Asthmatics included those with a slow forced expiratory volume in one second (FEV1) decline  and those with a fast FEV1 decline  in 5-year follow-up. Immunostaining expression of MMP-9 and TIMP-1 was detected in airway tissues. MMP-9 and TIMP-1 was measured from AMs cultured for 24 h. After the 5-year treatment, the methacholine airway hyperresponsiveness of the slow FEV1 decline group was decreased, but that of the fast FEV1 decline group was increased . AMs of asthma with a fast FEV1 decline released a higher level of MMP-9  than those of a slow FEV1 decline (0.99 ± 0.20 pg/mL). The MMP-9/TIMP ratio in the fast FEV1 decline group (0.089 ± 0.032) was higher than that of the slow FEV1 decline group . The annual FEV1 decline in 5 years was proportional to the level of MMP-9  and MMP-9/TIMP-1 ratio . The airways of asthma with greater yearly decline in FEV1 showed an increased thickness of submucosa and strong expression of MMP-9. An increase in MMP-9 and MMP-9/TIMP-1 in airways or AMs could be indicators of chronic airway inflammation and contribute to a greater decline in lung function of patients with chronic asthma.Chronic asthma is associated with progressive airway remodeling, which may contribute to declining lung function. An increase in matrix metalloproteinases-9 (MMP-9)/tissue inhibitor metalloproteinase-1 (TIMP-1) may indicate airway inflammation and bronchial injury. Bronchial biopsy specimens and alveolar macrophages (AMs) were obtained from patients with asthma under regular treatment with inhaled corticosteroids or combination therapy and normal subjects ( Asthma is a chronic respiratory disease of airway inflammation that manifests as variable airflow limitation . PatientMatrix metalloproteinases (MMPs) are a family of enzymes that can break down proteins of the extracellular matrix (ECM), thus contributing to pathological processes of inflammation, wound healing, and fibrosis . The MMP1) of asthmatic patients. Additionally, a previous report [1 improvement with the treatment of corticosteroids. Despite some reports [The tissue inhibitors of matrix metalloproteinase (TIMPs) inhibit enzymatic activity of MMPs through binding to the MMPs ,18. The s report  showed t reports ,23, whic reports , or posi reports ,26.1. We also investigate whether the ratio of MMP-9/TIMP-1 was correlated to the magnitude of yearly FEV1 decline. Our aim was to evaluate whether the ratio of MMP-9/TIMP-1 released from cultured alveolar macrophages was higher in chronic asthmatic patients who had a fast, yearly decline in FEV1) with inhaled albuterol (400 μg) and bronchial hyperreactivity to methacholine (provocative concentration (PC) causing a 20% decrease in FEV1, PC20 < 8 mg/L). These patients received anti-asthma medications, which included inhaled and/or oral corticosteroids, inhaled long-acting β2-agonist, or a combination of these, and had been followed up at our clinics for more than 5 years. All of the patients with asthma had used inhaled corticosteroids all the time. All patients had been stable for at least 3 months and were taking their usual medications before entry into the study. Inhaled β2-agonists were withheld for 12 hours before methacholine testing.Non-smoking asthmatic patients, aged 18 to 65 years, were recruited from outpatient clinics of the Chang Gung Memorial Hospital. Asthma was defined according to the American Thoracic Society criteria . All ast1 decline (< 30 mL/year) in the 5-year follow-up, and 8 asthmatic subjects  with a fast FEV1 (≥ 30 mL/year) in the 5-year follow-up, as previously described [1 decline and 4 asthmatics with a fast FEV1 decline experienced difficulty in controlling their asthma symptoms despite taking the maximum recommended dose of inhaled corticosteroids and inhaled long-acting β2-agonist. These patients needed additional therapy with long-term oral corticosteroids or a long-acting muscarinic antagonist. The calculation of annual FEV1 decline (mL/year) was determined by subtracting FEV1 at the first year by the second measurement 5 years later, then dividing this by 5 [The asthmatic subjects were divided into 2 groups: 13 asthmatic subjects  with a slow FEVescribed . During his by 5 .Ten normal non-smoking subjects , who had normal pulmonary function and no evidence of bronchial hyperresponsiveness, allergic rhinitis, or asthma, were recruited. Their total IgE levels and eosinophil counts were normal and their serum-specific IgE was negative. 2 agonist for 24–48 hours. Asthmatic subjects underwent the procedure of fiberoptic bronchoscopy with bronchial biopsy and bronchoalveolar lavage. Informed consent was obtained from all patients before entry into the study. The study was approved by the Chang Gung Memorial Hospital Ethics Committee (IRB number: 90-13).All patients who satisfied the enrollment criteria performed routine pulmonary function tests and methacholine provocation testing after abstaining from short-acting oral or metered-dose inhaler bronchodilator use for 6 h, and long-acting βAll study patients received fiberoptic bronchoscopy under sedation. The procedure of bronchoscopy under sedation and administering of local anesthesia was performed in the study institution. Sedation with intravenous midazolam (5–10 mg), and local anesthesia with 2% xylocaine solution was performed during bronchoscopy. Oxygen saturation, blood pressure, and electrocardiography (ECG) were monitored during bronchoscopy. The bronchoscope was advanced through the nose and larynx, and then into the tracheal and bronchial lumen; bronchial biopsies were taken from the 4th or 5th subsegmental bronchus. The specimens were fixed by 4% paraformaldehyde for immunocytochemistry. g for 20 min at 4 °C. The cell pellet was obtained after centrifugation followed by consecutive washes and finally resuspended at 106 cells per mL in RPMI-1640  containing 5% heat-inactivated fetal calf serum . Trypan blue exclusion was used to determine cell viability. Differential cell counts were determined by counting 500 cells on cytocentrifuge preparations using a modified Wright–Giemsa stain. BAL fluids were stored at −70 °C until analysis. The purified alveolar macrophages were placed in 6-well plates at 106 cells/mL for 24 h at 37 °C and 5% CO2. The culture supernatant was collected and frozen at −70 °C until use. Bronchoalveolar lavage (BAL) was completed in subjects using 300 mL of 0.9% saline solution . SterileImmunoreactivity for tissues was performed with the use of the avidin–biotin peroxidase complex method. Tissue sections (5 μm) from asthmatic subjects were incubated overnight at 4 °C with a variety of primary antibodies, including anti-human MMP-9  and TIMP-1 antibodies  . Mouse iThe thickness of the epithelium, basement membrane, and subepithelial layer was investigated by H and E staining for 20 min at room temperature. The results were visualized using an Olympus BX51 microscope .IL, USA) according to the manufacturer’s instructions. The optical density was measured with a spectrophotometer set to 450 mM for all assays. Quantification was performed by interpolation from a standard curve. Quantitative sandwich-type enzyme-linked immunoassay techniques (ELISA) were used to assay the secretory products in macrophage supernatants . MMP-9 at-test for paired or unpaired data. For data with even or uneven or variation, a Mann–Whitney U test or Wilcoxon signed rank test was used for unpaired or paired data, respectively. ANOVA with post hoc analysis was used when comparing data from three groups; p < 0.05 was considered significant.Data were presented as mean ± SEM. The data were analyzed using a Student’s 1, and levels of PC20 in methacholine tests demonstrated no difference between the two groups of asthmatics. Initially, the PC20 was similar in both asthmatic groups. After 5 years, airway hyperresponsiveness of patients with a slow FEV1 decline was significantly decreased , while that of asthmatics with a fast FEV1 decline demonstrated an increased airway hyperresponsiveness  ( < 0.05) .1 .The cellularity of lavage fluid was similar between the asthmatic groups but was significantly lower in normal subjects. Compared to normal subjects, there was an increase in the percentage of eosinophils and lymphocytes and a corresponding decrease in the proportion of alveolar macrophages in asthmatics with either a fast or a slow decline in FEV1 . The celsubjects . In addi1 decline had a significantly higher immunohistochemistry (IHC) score of MMP-9 , when compared with asthmatic patients with a slow FEV1 decline   and subepithelial layer  in asthmatics with a fast FEV1 decline was significantly increased  than those of asthma with a slow FEV1 decline  or normal subjects . The level of MMP-9 was significantly higher in asthma with a slow FEV1 decline compared to normal subjects  from chronic asthma with a fast FEVsubjects A. Comparsubjects B. A signsubjects B. When do in AMs . The ratollow-up .1    A. Howeve0.01) (1 B. When t < 0.01) C. 1 decline. The higher levels of TIMP-1 released from cultured AM were observed in clinically stable asthmatics. The magnitude of annual FEV1 decline was proportional to the MMP-9 generation and the ratio of MMP-9/TIMP-1 released from alveolar macrophages, even though the patients had regularly received inhaled corticosteroids. An increased thickness of the basement membrane and subepithelial layer was observed in asthmatics with a fast FEV1 decline. Taken together, MMPs (mainly MMP-9) and TIMP-1 may contribute to progressive loss of lung function and increased cellular matrix fibrosis of the airway wall in chronic asthmatics who demonstrated a poor response to anti-asthma treatments. We demonstrated that the levels of MMP-9 expression in the epithelium, inflammatory cells, and submucosa as determined from immunostaining showed upregulation in asthmatic patients who regularly received inhaled corticosteroids and who had a rapid decline in pulmonary function at 5-year follow-up. The alveolar macrophages from these unstable asthmatics also spontaneously released higher amounts of MMP-9. Most importantly, the MMP-9 level and MMP-9/TIMP-1 ratio produced from AMs were significantly decreased in chronic asthma with a slow FEV1 decline in chronic asthma, which is in agreement with the data of Vignola et al. [1 exhibited a higher amount of neutrophils, while that of stable asthmatics did not show an increased amount of neutrophils. The cellularity of neutrophils in BAL was highly correlated to the annual FEV1 decline in asthmatics. These observations raise the possibility that neutrophils may cause injury to the airway and result in further remodeling of chronic unstable asthma, as has been suggested by studies showing persistent bronchial neutrophilia in severe asthma and status asthmatics [1. We reported that the generation of MMP-9 from alveolar macrophages and the ratio of MMP-9/TIMP-1 are strongly associated with the magnitude of FEVa et al. . The sama et al. . We alsothmatics . Our res1 decline presented with higher airway hyperresponsiveness. Therefore, macrophages from these unstable asthmatics may release more MMP-9, leading to collagen deposition or neovascularization in the basement membrane of airways and contributing to airway hyperresponsiveness.It is thought that the imbalance between MMPs and TIMPs may play an important role in the process of the degradation and synthesis of the extracellular matrix of the airway. Hoshino et al.  reportedThe TIMPs could bind to MMPs and inhibit their enzymatic activity. In our study, alveolar macrophages from chronic stable asthma patients responsive to inhaled corticosteroids released higher amounts of TIMP-1 than those of chronic unstable asthma patients who do not respond to inhaled corticosteroids or healthy subjects. Hoshino and colleagues  found th1. Thus, inhaled corticosteroids cannot inhibit the airway remodeling of chronic asthma. Several reports have shown that neutrophil levels may increase in the airways in severe asthmatics or in patients with chronic asthma who exhibit a poor response to inhaled steroids [Although our patients have received inhaled corticosteroids for more than 5 years, some of these patients still demonstrated a progressive decline in pulmonary function and persistent airway structure change. A report showed that a high dose of inhaled corticosteroids did not change the levels of MMP-1, MMP-9, and TIMP-1 in induced sputum , althougsteroids ,43. PersPrevious reports revealed that MMP-9 increases in severe asthma ,44, and Extensive studies have revealed the role of MMPs in the pathogenesis of asthma, airway hyperresponsiveness (AHR), and asthma-associated airway remodeling ,46. MMP-Alveolar macrophages are the predominant immune cells in the lung and are represented by the classically activated (or M1) and the alternatively activated (or M2) phenotypes according to their function . Increas1 decline, despite having been regularly treated with inhaled corticosteroids. An increase in MMP-9 and MMP-9/TIMP-1 in airways or AMs could contribute to a greater decline in lung function in cases of chronic asthma and could therefore be used as an indicator of chronic airway inflammation.We concluded that there was an increase in MMP-9 and MMP-9/TIMP-1 in airways and alveolar macrophages from chronic asthmatics with a rapid FEV


According to the Cox regression model, fatal cardiovascular events were associated with the following cardiac geometric classifications; eccentric hypertrophy (p = 0.050); concentric hypertrophy (p = 0.041), and serum phosphate ≥ 3.6 mg/dL (p = 0.025), FGF-23 ≥ 168 (p = 0.0149), α-klotho < 313 (p = 0.044). Conclusions: In our population, Klotho and FGF23 are associated with cardiovascular risk in the early stages of CKD.Background: Research over the past decade has focused on the role of Klotho as a cardio protective agent that prevents the effects of aging on the heart and reduces the burden of cardiovascular disease CVD. The role of the interaction between fibroblast growth factor 23-(FGF-23)/Klotho in Klotho-mediated actions is still under debate. The main objective was to ascertain the potential use of plasmatic Klotho and FGF23 as markers for CKD-associated cardiac disease and mortality. Methods: This was a prospective analysis conducted in an outpatient diabetic nephropathy clinic, enrolling 107 diabetic patients with stage 2–3 CKD. Patients were divided into three groups according to their left ventricular mass index and relative wall thickness. Results: Multinomial regression analysis demonstrated that low Klotho and higher FGF-23 levels were linked to a greater risk of concentric hypertrophy. In the generalized linear model (GLM), Klotho, FGF-23 and cardiac geometry groups were statistically significant as independent variables of cardiovascular hospitalization ( Aging is the result of a complex interplay between genetics, environment and lifestyle. It encompasses intricate body physiologic alterations that hamper organs’ function and compromises their long-term viability. As major regulators of many vital physiologic processes, the kidneys are often the first organs to express the effects of aging. Reduced glomerular filtration rate (GFR) and/or diminished production of several hormones and communication mediators usually appear first and are the triggers of major consequent alterations that frequently result in chronic kidney disease (CKD), anemia, osteoporosis and left ventricular hypertrophy (LVH) ,2,3,4. CKD is known to be related to cardiac overload, which reconfigures the architecture and physiology of the myocardium, inducing hypertrophy and fibrosis ,5. TheseResearch over the past decade has focused on the role of Klotho as a cardio protective agent that prevents the effects of aging on the heart and reduces the burden of CVD ,8. Wheth2 (range: 67–189). This study enrolled one hundred and seven (107) consenting patients with stage 2–3 CKD, who were cleared of all exclusion criteria. The mean age was 57.2 ± 7.1 years (range: 41–68) and the mean LVMI level was 99.31 ± 23.45 g/mThe demographic and clinical parameters of the study subjects are presented in In terms of allocation of patients into groups according to their LVH and RWT values, 41 (38.3%) had normal geometry, 38 (35.5%) had eccentric hypertrophy and 28 (26.2%) had concentric hypertrophy.All the assessed variables, except age and BMI, showed significant differences between the three groups .r = −0.440, p = 0.0001), and directly proportional to Pi , and to FGF-23 .A simple linear regression analysis  revealedMultinomial regression analysis demonstrated that diminished eGFR and elevated Pi levels were associated with a greater risk of eccentric hypertrophy but not with concentric hypertrophy. In fact, hyperphosphatemia seemed to increase the risk of eccentric hypertrophy threefold. Contrarily, low α-Klotho and higher FGF-23 levels were linked with a greater risk of concentric hypertrophy, with higher Klotho levels associated with a 26% lower risk .p = 0.009). In our study, the cause of mortality was coronary and cerebrovascular disease in eccentric and concentric hypertrophy.p = 0.007). The results showed that the α-Klotho group (<313), compared to the group at ≥313, had higher odds of hospitalization ORa = 1.491, p = 0.014. In addition, the FGF-23 group (≥168), compared to the group at <168, had higher odds of hospitalization, ORa = 1.689, p = 0.004. The concentric hypertrophy group compared to the no hypertrophy group had higher odds of hospitalization, ORa = 4.889, p = 0.023. The optimized model as a function of α-Klotho groups, eGFR, age, gender, phosphorus, PTH, IL6, vitamin D, FGF-23 and cardiac geometry groups allowed for a final and statistically significant model (p < 0.001), which included Klotho groups, FGF-23 and cardiac geometry variables. The area under the receiver operating characteristic curve (ROC curve) for this optimized model was 0.980 (p < 0.001), revealing an elevated discriminating capacity of the model. The obtained estimates showed that the group with low levels of α-Klotho , higher levels of FGF-23  and the concentric hypertrophy group  had greater odds of cardiovascular hospitalization , Klotho, FGF-23 and cardiac geometry groups were statistically significant as independent variables of cardiovascular hospitalization (lization .p = 0.050); concentric hypertrophy (p = 0.041), and Pi ≥ 3.6 (p = 0.025), FGF-23 ≥ 168 (p = 0.0149), α-klotho < 313 (p = 0.044).According to Cox regression models , fatal cROC curve analysis demonstrated that α-Klotho < 313 and FGF-23 ≥ 168 are the best cut-off values associated with cardiovascular mortality , , respectively.The current study shows that both Klotho and FGF23 are independently altered and associated with concentric hypertrophy in CKD patients, thus being suitable as indicators of cardiac disease in this population. Particularly, it provides evidence that CKD-associated cardiac hypertrophy correlates with reduced eGFR and soluble Klotho and Vitamin D levels, and is indicative of a generalized pro-inflammatory status, as evidenced by increased levels of IL-6, ACR, PTH, P and FGF23. Furthermore, it shows that concentric hypertrophy in particular is associated with a more severe phenotype with a shorter survival rate.CKD is a very well-established inducer of cardiac hypertrophy, as it increases the heart burden in an attempt to accommodate kidney failure  . Aiming As recently argued by Neyra and Hu, there is an urgent need to identify sensitive and/or more specific diagnostic and prognostic biomarkers for CKD . In factFurthermore, in the generalized linear model, concentric hypertrophy was found to independently predict patient survival, with increased risk of hospitalization ,24,25.Regarding the interaction between α-Klotho and FGF-23, our results seem to corroborate those of Grabner et al., suggesting independent roles for each protein. These authors demonstrated that FGF-23-mediated activation of FGFR4 in cardiomyocytes stimulates phospholipase Cc/calcineurin-NFAT signaling, independently triggering LV hypertrophy . MoreoveThe cardiac hypertrophic effects of FGF-23 are mediated by FGFR-dependent activation of the calcineurin nuclear factor of the activated T-cell (NFAT) signaling cascade, but do not require Klotho as a co-receptor . As to Klotho, the exact pathophysiologic mechanisms behind its association with CKD progression are yet to be identified. This protein, which is mainly produced by the kidneys, consists of a long extracellular domain connected to a small intracellular C-terminal domain through a membrane-spanning segment. Its signaling properties depend upon the segment of the protein involved ,28. In fThe elucidation of Klotho- and FGF-23-mediated functions in CKD paved the way for the development of targeted therapies. For instance, Di Marco et al. showed that the progression of cardiac hypertrophy and cardiac fibrosis could be reduced by antibody-mediated blockage of the FGF receptor , which wIn our study, the group with concentric hypertrophy had a higher cardiovascular mortality when compared to the group with eccentric hypertrophy and normal left ventricular geometry. Elevated levels of FGF-23 are implicated in elevated cardiovascular mortality in CKD when adjusted for the traditional risk factors and other mineral metabolism markers. The role of FGF-23 in cardiovascular mortality is not yet fully understood . Pi et aDespite acknowledging the small sample size, the sparse number of cardiovascular events and the limited statistical power of these analyzes as the main limitations of this study, the current study presents preliminary results of a long term project. Notwithstanding this, the role that these new markers may play in cardiovascular morbidity and mortality in this particular population with diabetes and mild to moderate CKD is evident in the study.Subsequent research is expected to evaluate the role of Klotho and FGF-23 in left ventricular diastolic dysfunction and progression to heart failure in patients with chronic renal disease.This prospective analysis was conducted in the outpatient diabetic nephropathy (DN) clinic of the Centro Hospitalar Universitário do Algarve in Faro, Portugal, from 2012 to 2017, enrolling a total of 107  adult diabetic patients with stage 2–3 CKD. Before its implementation, the study was granted ethical approval by the Hospital’s Ethics Committee (November 2011), ensuring that all principles of the Declaration of Helsinki of 1973 (revised in 2000) were followed. All procedures were implemented after obtaining patients’ written informed consent. Diabetes was classified as per the American Diabetes Association guidelines .2 or ≥ 89 mL/min/1.73 m2; parathyroid hormone (PTH) ≥ 350 pg/mL; phosphorus (Pi) > 5.5; type 1 diabetes; non-diabetic renal disease; neoplastic or infectious diseases.The exclusion criteria were: age > 65 years; previous CVD–defined as a history of one or more of the following: non-fatal myocardial infarction, angina pectoris (stable or unstable), stroke or transient ischemic attacks, peripheral vascular disease or congestive heart failure; atrial fibrillation, severe coronary heart disease associated with the presence of a wall motion abnormality by two dimensional echocardiography, left bundle branch block, severe valvular heart disease confirmed with echocardiogram; changes in the GFR of more than 30% in the previous 3 months, changes in antihypertensive therapy 2 weeks before study, uncontrolled hypertension (BP ≥ 140/90 mmHg); albumin/creatinine ratio (ACR) ≥ 500 mg/g assessed on two occasions with an interval of 3 months; estimated glomerular filtration rate (eGFR) ≤ 29 mL/min/1.73 mMedical history, laboratory data, and current therapy were collected during the initial visit.The blood pressure (BP) was determined with oscillometric methods, with the patient in dorsal decubitus. Three measurements were taken with an interval of 5 min between them.Echocardiographic evaluation was obtained using standard M mode and two-dimensional images . Offline analysis was obtained using the workstation Echopac PC’08 version 7.0.0 GE Vingmed Ultrasound , and the measurements were consistently obtained by the same physician. Images were digitally stored and analyzed by two independent experienced cardiologists. Quality control procedures included blind rereading and patient reexamination to allow assessment of intra-reader variability, inter-reader variability, and intra-patient variability. An average of three measurements was made for each variable.Patients were divided into three groups according to the left ventricular mass index (LVMI) and the relative wall thickness (RWT) values, calculated using the following equations:(1) Regression equation from Penn convention:2 in women and 131 g/m2 in men [LVH and RWT were used to categorize LV geometry: normal , eccentric hypertrophy , and concentric hypertrophy (LVH and increased RWT). Patients were classified as having LVH if they had a left ventricular mass index (LVMI)of 100 g/m2 in men , and RWT2 in men .The Centro Hospitalar Universitário do Algarve – Unidade de Faro outpatients’ DN clinic is the Algarve’s reference center for nephrology and guarantees a regular follow-up for patients with DN. Patients with a more severe condition are monitored every 3 months and those with a milder disease every 6 months. Mean duration of follow-up was 33.8 ± 8.6 months. 2D3 (vitamin D), soluble α-Klotho (Klotho) and oxidized low density lipoprotein (oxLDL). Serum levels of vitamin D  were determined by radioimmunoassay . The vitamin D levels were the average of three measurements conducted in winter, spring and summer. Serum levels of FGF23 were quantified using the enzyme-linked immunosorbent assay Human FGF-23 (C-Term) enzyme-linked immunoassay (ELISA) kit . Soluble α-Klotho serum levels were determined by ELISA using the Human soluble α-Klotho kit , by adapting the manufacturer’s instructions to the Triturus microplate automatic system . Two blood samples were collected for the validation of the circadian variability of Klotho and FGF-23, P and Ca were assayed by the ARCHITECT c and the AEROSET Systems . IL-6 and oxLDL determination was performed with a sandwich ELISA kit . HbA1c and PTH levels were measured using a spectrophotometry technique and electrochemiluminescent immunoassay (ECLIA), respectively. PTH concentrations were measured on an Immulite 2000 Intact PTH assay . The degree of insulin resistance was estimated using the homeostasis model assessment (HOMA-IR) described by Matthews et al. [® device . We estimated the GFR according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Equation [Fasting samples were drawn from all subjects and plasma was frozen at −80 °C in order to measure eGFR, phosphorus (Pi), calcium (Ca), parathyroid hormone (PTH), glycated hemoglobin (HbA1c), insulin resistance index, interleukin-6 (IL-6), fibroblast growth factor-23 (FGF23), 1,25(OH)s et al. . Serum cEquation .® albumin/creatinine assay system  kit. A laboratory immunoturbidimetric assay was used for albumin and creatinine determinations and the results are reported as ACR (μg/mg). Intra individual variation of ACR was assessed in 8 of the 16 subjects for 7 consecutive days.The ACR was determined from a first-morning urine collected on the 1st and the 8th day of the inclusion period. Urinary albumin and creatinine were determined immediately using the DCA 2000The primary cardiovascular outcome of this study was cardiovascular mortality. Deaths were confirmed by review of autopsy reports, death certificates, medical records, or information obtained from the next of kin or family members and classified, according to its cause, as cardiovascular or non-cardiovascular death. Cardiovascular deaths were defined as caused by coronary heart disease, heart failure, peripheral vascular disease and cerebrovascular disease.n = 26), and G-2—without cardiovascular hospitalization (n = 81).The secondary outcome evaluated the predictive factors of cardiovascular hospitalizations/admissions. These were classified upon discharge, considering only admissions caused by coronary heart disease , congestive heart failure, peripheral vascular disease and cerebrovascular disease (stroke or transient ischemic attacks) based on recent international guidelines  . AccordiContinuous variables are presented as mean and standard deviation and categorical variables are expressed as percentages and compared using the chi-squared test. Demographic and clinical factors associated with LVH were evaluated by ANOVA and the Kruskal–Wallis H test, respectively. Patients’ demographic and clinical characteristics at baseline were grouped according to their level of cardiac hypertrophy.Simple linear regressions were used to investigate possible correlations between these variables and LVMI, while multivariable nominal logistic regression identified factors associated to eccentric and concentric hypertrophy, using as a reference, patients with normal geometry.We evaluated time to fatal CV end point by Kaplan–Meier survival analysis compared by log-rank test among the three patterns of LV geometry for measuring patients’ survival rate and a comparison between the three groups was based on the log rank test. The null hypothesis was rejected below the 5% level. Statistical analysis was performed using SPSS .The generalized linear model (GLM) for binary dependent variables was used  with a logistic link function. The exponentials of the model parameters were the adjusted odds ratio (ORa) to other variables of the model. The test was used to determine whether Klotho, FGF-23 and cardiac geometry were important predictive factors in the determination of cardiovascular hospitalization. Prior to conducting the GLM, we calculated the median level of Klotho serum and FGF-23 in the current study population. The subjects were categorized in the following classes: Klotho (≥313 pg/mL or <313 pg/mL), and FGF-23 (≥168 RU/mL or <168 RU/mL). The independent variables associated with cardiovascular mortality were identified by Cox regression models. Variables included in these models were: age , gender, median: PTH , Pi , 1.25(OH)2D3 , α-klotho , FGF-23 , ACR , IL-6 , stratified renal disease  and cardiac geometric classification .We used the receiver operating characteristic (ROC) curve to identify klotho and FGF-23 cut-offs associated with the highest cardiovascular death in this population.The role of emerging factors like FGF-23 and Klotho in cardiovascular risk in both the early and late stages of chronic kidney disease is not entirely understood. The entire process involves direct and indirect mechanisms that contribute to this high cardiovascular risk. Moreover, these proteins seem to have independent roles in the pathophysiology of cardiovascular disease and CKD and have recently been considered relevant potential therapeutic agents in this disease. The early identification of CKD onset and risk stratification of CKD progression and/or CKD-related complications are essential for early treatment of CKD patients to ameliorate their comorbidity burden, particularly CVD, and prevent the development of ESRD.


Blunt abdominal trauma in the setting of polycystic kidney disease is still scantly described in the literature and management guidelines of such patients are not well-established.The authors herein present a case of hypovolemic shock secondary to segmental renal artery bleed in a 75-year-old man with polycystic kidney disease after minimal blunt abdominal trauma, who underwent successful selective arterial embolization, and provide a thorough review of similar cases in the literature, while shedding the light on important considerations when dealing with such patients.It is important to suspect renal injury in patients with pre-existing renal lesions irrespective of the mechanism of injury; and, vice-versa to suspect an underlying abnormality in patients with a clinical deterioration that’s out of proportion to the mechanism of injury.The online version of this article (10.1186/s12873-018-0192-3) contains supplementary material, which is available to authorized users. The kidney is the most frequently injured genitourinary organ, with a female to male ratio of 1:3 . OverallWe report on the case of a patient with ADPKD who presented with shock to the Emergency Department secondary to trivial blunt abdominal trauma. In addition, we provide a review of patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) who sustain a kidney injury following trauma.The objective of this review is to describe a case of hypovolemic shock secondary to minimal blunt trauma to a kidney in a patient with Autosomal Dominant Polycystic Kidney Disease, and to summarize the relevant literature reporting on similar cases. Despite the presence of well-established protocols for the diagnosis and management of blunt renal trauma, managing emergencies with trauma to a kidney in patients with ADPKD is not common. This review will hopefully be an educational opportunity in the diagnosis and management of blunt trauma to kidneys in patients with ADPKD. We sought to add to the growing literature by focusing more on cases with ADPKD and describing an uncommon type of renal injury that was managed differently from the aforementioned cases.A literature review of the published cases of ADPKD kidneys that presented with blunt trauma was performed by searching the following databases: EMBASE, PubMed, Google Scholar, and Medline. Search terms included: “Abnormal Kidneys”, “Pathologic Kidneys”, “Polycystic Kidney”, “Autosomal Dominant Polycystic Kidney Disease”, “Trauma”, “Blunt Trauma”, “Wounds and Injuries”, “Blunt Abdominal trauma”, “Blunt Renal Trauma”, “Blunt Renal Injury” “Pre-Existing Renal Lesions”, “Intra-abdominal bleeding”, “Intra-abdominal hemorrhage”, “Non-penetrating injury”.The literature search revealed 12 published cases of trauma to pre-existing kidneys in patients with ADPKD. We suspect that the scarcity of case reports found in the literature is partly due to under-reporting. Table This is the case of a 75-year-old male with a history of ADPKD, hypertension, dyslipidemia, Crohn’s disease, Benign Prostatic Hyperplasia and a left nephrectomy who presented with generalized malaise, mild diaphoresis, right lower quadrant abdominal pain 10 min after tripping and falling on an outstretched arm while walking down the street. Immediately after the fall, he complained of right wrist pain, walked a short distance back home and started complaining of malaise. He was subsequently evaluated by a neighbor Emergency Medicine attending physician who suspected hypovolemic shock, and transported him in the back of a car to a nearby tertiary care Emergency Department (ED). In route to the hospital, he became pre-syncopal, improving on Trendelenburg positioning. Upon arrival to the ED, his vital signs were as follows:Temperature = 36.2 (degrees Celsius), Blood Pressure: 100/62 mmHg (130/72 Trendelenberg), Heart Rate = 53 beats/min, Oxygen saturation = 100%, Respiratory Rate = 27 breaths/min.On physical exam, he was profusely diaphoretic, lethargic but alert and oriented to person, place and time. He had right lower quadrant abdominal tenderness with no rebound or guarding. Due to suspicion of shock, he immediately received two boluses of 0.9% Normal Saline (1 l each). Next, 2 units of O negative packed Red Blood Cells were prepared and he was immediately transfused. The patient was not receiving anticoagulation, so reversing the latter was not envisioned. He reported that his baseline creatinine is 1.6 mg/dL.His home medications included Irbesartan, Budesonide, Fenofibrate, Ezetimibe, Allopurinol, Nebivolol, Calcium Carbonate and Finasteride.A large hematoma measuring 11 × 7 × 7.5 cm inseparable from the medial aspect of the right lower renal pole and extending into the right perinephric space, displacing the kidney superiorly and anteriorly; with associated significant perinephric blood and associated minimal retroperitoneal bleed.Active contrast extravasation along the posterior aspect of the hematoma extending into its most dependent aspect Figs. , 2 on thA 12-min delay image demonstrated pelvic contrast extravasation from the proximal ureter, indicating urinary extravasation  irrespective of the mechanism of injury; and, vice-versa to suspect a PREL in patients with a clinical deterioration that’s out of proportion to the mechanism of injury.Report on the uncommon injury pattern observed in our patient, and its management; along with the available management options.Highlight the importance of maintaining a high index of suspicion for intra-abdominal injury and bleeding in elderly patients, irrespective of anticoagulant use.This paper reports on a patient with ADPKD who exhibited rapid clinical deterioration after minimal trauma, and compares the case to other similar cases reported in the literature. The main motives behind writing this case report were as follows:The kidneys are the most frequently injured genitourinary organ secondary to trauma. Renal injury occurs in up to 5% of trauma victims, and is responsible for 24% of traumatic abdominal solid organ injuries –9. The kPKD1 or PKD2 genes eventually develop renal cysts that are visible by ultrasonography and cause enlargement of the kidneys . Mo. Mo27]. In the presence of renal vasculature injury, multiple severe associated injuries can be present most of the time, with a mortality rate reaching 44%. Despite urgent radiologic evaluation leading to rapid diagnosis, most patients are usually not candidates for vascular repair because of the frequent incidence of severe associated injuries to the same kidney. In spite of vascular repair, kidney function does not usually return to normal . In addiAll the cases that underwent nephrectomies, had CT abdomen findings of ruptured cysts , 31–33. In addition, several studies validate the importance of the AAST organ injury scale but have also found that perinephric hematoma size and contrast extravasation were independently associated with urological intervention , 37, botFinally, follow-up CT imaging (after 48 h) is judicious in patients with deep renal injuries (AAST Grade IV-V) because they are prone to developing troublesome complications such as urinomas or hemorrhage , 39. Of Cases of traumatic injuries in patients with polycystic disease are a rare occurrence and therefore management guidelines are still not established. Further studies and expert consensus opinions are required to come up with recommendations on optimal management of this vulnerable patient population. Currently the majority of patients are managed according to the underlying abnormality and injuries, such as described in the above case. Rapid clinical deterioration after minimal trauma should raise suspicion of an underlying abnormality. In the right circumstances, selective renal artery embolization is a safe option in patients who sustain a renovascular injury.Additional file 1: Axial CT scan 12-min delay image demonstrating urine extravasation from the proximal ureter (highlighted by the white arrow). (DOCX 761 kb)


The correct affiliation is Department of Medicine, Stanford University, Palo Alto, California. This article has been corrected.1In the Original Investigation titled “Assessment of Risk of Harm Associated With Intensive Blood Pressure Management Among Patients With Hypertension Who Smoke: A Secondary Analysis of the Systolic Blood Pressure Intervention Trial,”


To explore the relationship between blood pressure control and autonomic nervous function assessing by heart rate variability (HRV) and heart rate turbulence (HRT) in hypertensive patients. A total of 120 consecutive hypertensive patients and 80 nonhypertensive patients (N-HP group) were enrolled in this study. The hypertensive patients were divided into controlled blood pressure and uncontrolled blood pressure groups according to their blood pressure on admission. All subjects underwent 24-hour Holter monitoring. This study compared HRV and HRT in nonhypertensive and hypertensive patients and hypertensive patients with controlled and uncontrolled blood pressure. HRV parameters include square root of mean of the sum of squares of successive NN interval differences (rMSSD), number of successive NN intervals differing by > 50ms divided by the total number of successive NN intervals (pNN50), very low frequency (VLF) at frequency between 0.0033 and 0.04 Hz, low frequency (LF) at frequency between 0.04 and 0.15 Hz, and high frequency (HF) at frequency between 0.15 and 0.4 Hz. Turbulence slope (TS) belongs to HRT parameters. TS, rMSSD, pNN50, VLF, LF, and HF values were significantly lower in the HP group than in the N-HP group. Multiple logistic regression analysis showed that reduced TS, rMSSD, pNN50, LF, and HF values were risk factors of hypertension. TS, rMSSD, pNN50, VLF, LF, and HF values were significantly lower in hypertensive patients with uncontrolled blood pressure than in hypertensive patients with controlled blood pressure. Multiple logistic regression analysis showed that reduced TS, rMSSD, pNN50, VLF, LF, and HF values were risk factors for uncontrolled blood pressure. This study indicates impaired autonomic nervous function in hypertensive patients, especially in hypertensive patients with uncontrolled blood pressure despite guideline recommended antihypertensive medications. Hypertension is a major disease that damages people's health. Long-term hypertension could impair major organs such as heart, brain, kidneys, and blood vessels, which is related to considerable mortality . SympathA total of 120 consecutive hospitalized hypertensive patients and 80 N-HP patients were included in this retrospective study from June 2016 to June 2018. The hypertensive patients were divided into controlled blood pressure (n=66) and uncontrolled blood pressure (n=54) groups according to their blood pressure on admission.Patients with Diabetes Mellitus (DM), Acute Coronary Syndrome (ACS), valvular heart disease and known nonischemic cardiomyopathy, atrial fibrillation, atrial flutter, 2nd- or 3rd-degree atrioventricular block, and pacemaker implantation and patients without premature ventricular contraction (PVC) of 24-hour Holter monitoring were excluded. All hypertensive patients received antihypertensive medication. All patients gave informed consent for participation in this study, and the study protocol was approved by the ethical committees of Wuhan Fourth Hospital, Puai Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.All participants underwent 24-hour Holter monitoring (GE MARS Software and Seer Light recording box). Quantitative HRV analysis was performed according to the guidelines of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology . HRV parHRT parameters were also derived from Holter monitoring including turbulence onset (TO) and turbulence slope (TS). TO was the amount of sinus acceleration following a PVC. TO was expressed as a percentage and was calculated with the following formula: TO (%) = 100 × [(RR1 + RR2) − (RR−1 +RR−2)]/(RR−1 + RR−2), where RR1 and RR2 were the first and second sinus RR intervals after the PVC, and RR−1 and RR−2 were the first and second sinus intervals preceding the PVC. TO value < 0% indicated early sinus acceleration and was considered normal. TO ≥ 0% indicated that normal sinus heart rate acceleration phenomenon after PVC disappeared and was described as abnormal . TS was  t-test. Nonnormal distribution data were tested by two-tailed Mann–Whitney U test. The chi-square test was used to compare categorical variables as percentages. The risk factors for hypertension were determined by multivariate logistic regression model after adjusting for age, gender, and beta-blockers use. Spearman correlation analysis of the hypertensive patients was performed between HRV and HRT. P values less than 0.05 were considered statistically significant. Statistical analyses were performed using IBM SPSS (version 22.0) for Windows (SPSS).Continuous data were presented as mean ± standard deviation (SD). Normal distribution of continuous variables was performed by Kolmogorov-Smirnov test. Continuous variables with normal distribution were assessed by Student'sBMI, triglyceride level, interventricular septum (IVS) thickness, and incidence of stable CAD were significantly higher in the HP group compared to the N-HP group. Blood pressure on admission was significantly higher in the HP group compared to the N-HP group. The proportions of beta-blockers and diuretics uses were higher in the HP group than in the N-HP group . TS, rMSThe percentage of hypertensive patients receiving combined antihypertensive drug therapy was significantly higher and percentage of patients treating with monotherapy was significantly lower in hypertensive patients with uncontrolled blood pressure compared to hypertensive patients with controlled blood pressure . TS, rMSSpearman correlation analysis of the hypertensive patients showed that LF and LF/HF were negatively correlated with TO, while SDNN, SDANN, rMSSD, PNN50, VLF, LF, and HF were positively correlated with TS .The present study found that TS, rMSSD, pNN50, VLF, LF, and HF values were significantly lower in hypertensive patients compared to N-HP patients, and TS, rMSSD, pNN50, VLF, LF, and HF values were significantly lower in hypertensive patients with uncontrolled blood pressure compared to hypertensive patients with controlled blood pressure. Our study results thus indicate impaired autonomic nervous function in hypertensive patients, especially in hypertensive patients with uncontrolled blood pressure despite guideline recommended antihypertensive medications. To the best of our knowledge, this is the first study describing the association between autonomic nervous function, evaluated by HRV and HRT changes, and blood pressure control in hypertensive patients.HRV and HRT changes could reflect sympathetic and vagal function in hypertensive patients. HRV reflects the fluctuation of heart rate as time changes in response to external environmental stimulation; HRV changes were related to various cardiovascular diseases . HRT refPrevious studies found that DM and beta-blockers use might affect the HRV , 17. PatHRV mainly reflected the interaction between neural modulatory and sinus node function, while HRT could be considered as parameter reflecting the physiological response to endogenous stimulus. Spearman correlation analysis between HRV and HRT showed that LF and LF/HF were negatively correlated with TO, and SDNN, SDANN, rMSSD, PNN50, VLF, LF, and HF were positively correlated with TS, which suggested the close correlation between HRV and TS, and HRV and HRT could be considered as complementary parameters reflecting autonomic nervous function change.Impaired autonomic function played an important role in the pathogenesis of hypertension. Long-term sympathetic excitation might lead to left ventricular remodeling and atherosclerosis. Poreba et al.  found thThere were some limitations in this study. First, this was a retrospective single-center clinical study with a small number of patients. Our results need to be confirmed by a multicenter prospective clinical study with larger patient cohort to explore the impact of autonomic nervous dysfunction on prognosis of hypertensive patients. Second, HRV and HRT evaluation was not suitable to hypertensive patients with nonsinus rhythm such as atrial fibrillation, atrial flutter or pacemaker implantation, or 2nd- or 3rd-degree atrioventricular block and without PVC on Holter monitoring. Third, we did not quantify cardiac remodeling parameters including left ventricular posterior wall thickness and diastolic function parameters as E/A and E/e' in this patient cohort. Finally, this study did not analyze potential impact of the disease stage as well as the duration of antihypertensive medication on HRV and HRT because many elderly patients in this patient cohort could not provide us with the inquired data. Above study limitations should be considered when interpreting results demonstrated in this study.The present study shows that autonomic nervous dysfunction, as expressed by reduced HRV and HRT, exists in hypertensive patients, especially in hypertensive patients with uncontrolled blood pressure. Monitoring HRV and HRT parameters, which jointly reflect autonomic nervous system's regulation and response to internal and external stimuli, might be helpful to evaluate the autonomic nervous function status of the patients and supply useful information to optimize therapeutic efficacy aiming to improve autonomic nervous function balance for hypertensive patients. Future studies are warranted to explore if targeting the autonomic nervous function on top of antihypertensive medication might obtain better clinical efficacy on blood pressure control for patients with refractory hypertension.


Hypertension, particularly pulse pressure [PP] is a major risk factor for end-stage renal disease. However, the effect of individual components of hypertension namely PP, systolic [SBP] and diastolic blood pressure [DBP] on kidney function, in the general African population is unknown. Data were collected on 944 participants [aged 40-75 y], living in villages in the area around the city of Kumasi, Ghana, on demographics, medications, height, weight, BP and 24-hour creatinine clearance (CrCl).2, 24-hourCrCl as a measure of glomerular filtration rate (GFR) 84(23) ml/min/1.73 m2. 29% had BP >140/90 mmHg; SBP and DBP were 125/74(26/14) mmHg, PP was 51(17) mmHg. PP increased with age by 0.55 mmHg/year. PP was higher (53(17) v 49(15) mmHg; p < 0.001) in the semiurban participants. GFR decreased both with increasing PP  but there was no significant relationship with DBP [-0.04 ]. After adjusting for SBP, the relationship between GFR and PP became steeper . Using multivariate regression analysis that included PP, age, gender, BMI, only increasing age [-0.75 ] and decreasing BMI [0.49 ] were associated with decreased kidney function. The demographic and clinical characteristics were: age 55(11) [mean (SD)] years, females 62%, rural village-dwellers 52%, diabetes 1·5%, BMI 21(4) kg/m In this homogeneous West-African population, PP increased with age and had a steeper relationship with declining kidney function than SBP or DBP. Hypertension is a major risk factor for chronic kidney damage, and while both systolic (SBP) and diastolic blood pressure (DBP) have been implicated as causal factors, it is now clear that SBP is a much stronger predictor of chronic kidney disease than DBP –3. IsolaPP has a stronger relationship than SBP alone with cardiovascular deaths in end-stage renal disease (ESRD) patients , 8, 9. AHypertension is common in Ghana, with estimated prevalence of about 29%, and hence a major cause of morbidity and mortality , 12. HowThe present report uses data on 944 individuals  from the 1,103 participants of the baseline survey for a cluster-randomised trial in 12 communities in the Ejisu-Juabeng and Kumasi Districts of the Ashanti Region, clustered around Kumasi, the second largest city in Ghana –13. In tParticipants attended a registration centre in their village. After details of the study had been explained in the local language (Twi), individual written consent was obtained. All participants, with the help of a project assistant, completed the questionnaire, which included sections on demographic background, socioeconomic status, health, diet, lifestyle and past and current drug treatment. Ethical approval was granted by the Committee on Human Research Publication and Ethics of the School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, and by Wandsworth Research Ethics Committee, London.Methods are described in detail elsewhere –14. In bVenous blood samples were taken fasting from each participant. The samples were put into Vacutainer tubes and transported without delay to Komfo Anokye Teaching Hospital. The tubes were centrifuged at 1,500 rpm for 10 minutes at room temperature, and the serum transferred into 5 ml aliquot tubes, which were kept frozen at −20°C until analysed. Serum and urine creatinine were measured using a Jaffe alkaline picrate method (Beckman–Coulter). Our method has been validated against isotope dilution mass spectrometry (IDMS) values for creatinine measurement .Two consecutive timed 24-hour urine collections were obtained from each participant and the excretion of sodium, potassium and creatinine clearance were measured.2 [kg/m2]. Data were analysed using SPSS v.17 . Results are presented as mean ± SD or median (interquartile range) for continuous variables and relationships between variables using correlation and regression coefficients with 95% confidence intervals. A two-sided p value < 0.05 is taken as statistically significant.GFR was measured as the mean of two creatinine clearances based on 24-hour urine collections and adjusted for body surface area. 24-hour urinary sodium and potassium were also measured. Body mass index (BMI) was calculated from the equation: BMI = weight/height2, haemoglobin 12.2 (1.7) g/dl, and creatinine clearance 84 (22) ml/min/1.73 m2. 24-urine sodium/potassium ratio was 2.3 (1.2) mmol/mmol. The mean BP of the study population was 125/74 (26/14) mmHg with a PP of 51 (17) mmHg. The overall prevalence of hypertension in the population was 28.7%, which higher than in other parts of Africa  mmHg/year in the overall population. PP also increased with age [0.55  mmHg/year]. DBP did not increase significantly with age particularly in subjects 55 years or older . The increase in blood pressure was seen in both men and women. However, a steeper rise of SBP and PP was noted in women than men at an older age Figures . The womβ = -0.18 (95% CI: -0.27 to -0.10) ml/min/1.73 m2/mmHg, p < 0.001] and SBP , but there was no significant association between creatinine clearance and DBP  , compared to men .Creatinine clearance showed a strong inverse correlation with age; it also correlated inversely with PP and directly with BMI . On univ = 0.43] . Creatin2/mmHg, p = 0.001]. In contrast, although creatinine clearance increased with an increase in SBP, the relationship no longer held after adjusting for PP .Using multivariate analysis, after adjusting for SBP the relationship between creatinine clearance and PP became stronger . On multivariate regression analysis with creatinine clearance as dependent variable, and age, sex, pulse pressure, BMI and presence of diabetes as independent variables, only age  and BMI  were independent predictors of creatinine clearance.There was no significant difference in creatinine clearance between men and women. [83 ± 21 v 85 ± 23 ml/min/1.73 mThis is the first study investigating the effects of age, gender, and demographic factors on blood pressure components, along with the effect of blood pressure on kidney function in a rural African population.Our study shows that hypertension is common in Ghana. We have shown an increase in SBP and PP with age, in both men and women. Both SBP and PP rose with age, the rise being more marked in the women that in the men. Both SBP and PP were higher in the semiurban than in the rural population.The increase in PP with age is well known, and has been ascribed to increasing central arterial stiffness. The trajectory of rise in PP with age may be gender related and is steeper in women than in men . We haveThere is evidence that the higher PP in semiurban populations may be as a consequence of altered dietary habits and sedentary lifestyle leading to an increase in body weight . In our PP is a better predictor of CVD than SBP and DBP among middle age Caucasian populations , 19. In In summary our study was directed to assessing the role of PP in predicting GFR. PP preformed slightly better than SBP, and both were highly correlated with GFR, unlike DBP, which showed no significant relationship. However, we have found age to be a significant confounder while assessing the impact of blood pressure parameters on GFR. The relationship of pulse pressure with decreasing kidney function was stronger than that with systolic blood pressure. Diastolic blood pressure had no relationship with kidney function.This is the first population study showing gender and demographic differences in blood pressure parameters in a homogeneous West-African population from central Ghana. Sub-Saharan Africans have a higher PP when compared to Caucasians of similar age. We have also demonstrated that PP, a measure of arterial compliance, has a better relationship with declining renal function than measurement of either systolic or diastolic blood pressure. This study does provide support for the notion that in the prevention of cardiovascular disease (including stroke and chronic kidney disease) blood pressure reduction is a vital component of public health policy in Sub-Saharan Africa.


Aim: The objectives of this study were to evaluate the effectiveness of information and administrative assistance regarding patient adherence to asthma guidelines and investigate the nature of the barriers in access to pharmaceutical care in Greece based on the case study of the out-of-hospital management of patients with acute asthma.Materials and Methods: The sample of the study consisted of 100 patients with acute asthma who visited the Emergency Department of a General Hospital of Athens. A comparative cross-sectional study using convenience sampling was conducted during October 2014 and June 2015 regarding the adherence to the follow up.Results: Patients who complied with the follow up visit constituted 61% of the total sample (82% of the patients from the intervention group and 40% from the control group) and for those for whom the follow up visit had been scheduled by the researchers had been compliant with the physician's instructions more often than patients for whom the follow up had not been scheduled by the researchers . Patients with increased hospitalization days during the previous year and who did not consume the appropriate medication prescribed for asthma due to lack of a prescription, visited the ED more frequently than the rest of the patients . More than one out of three patients (36.4%) reported that they had not bought their asthma medications because they had no prescription while almost one out of five stated that they had purchased their medications but had used them with savings in doses. Patients who had not taken their asthma medication due to lack of prescription, visited more than once the ED, resulting in non-admission, when compared to patients who had a prescription for their medications. .Discussion–Conclusions: Out-of-hospital management of asthma in Greece presents significant gaps and shortcomings, mainly due to important unresolved issues regarding availability, accessibility and use of services. The findings of the present study confirm the cause-effect relationship between ineffective out-of-hospital management of asthma and the increase in the frequency of the use of hospital emergency departments, resulting in an increase in health costs. Greece is currently undergoing the ninth consecutive year of continuous and profound economic crisis. During these years, the country's GDP fell by 24.8%  implemented in Greece after 2010 .Given the fact that the Greek health system has been in operation for many years with under-funding of vital sectors but also with insufficient organization, fragmented care and serious primary health care deficits, there are serious doubts about its ability to cope with increased morbidity needs in the coming years. In order to ensure the health system's viability, emphasis must be placed on strategies for optimal use of resources, which undoubtedly should include strengthening primary health care by providing comprehensive and effective out-of-hospital management of chronic diseases such as asthma.Greece has always been characterized as quite a “privatized” system, with high out of pocket payments particularly due to public health sector's under-financing. Private expenditure increased as a percentage of total health expenditure during the economic crisis (from 30.5% of THE in 2009 to 39.11% of THE in 2014), compared with a falling trend between 2005 and 2009, bringing Greece to the first position regarding private spending among the EU-15 countries, for which the mean private expenditure has been estimated to 23.6% of THE for 2014. Out-of-pocket payments, representing 35.47% of the total health expenditure  increased as a percentage of total health expenditure from 28.4% in 2009 to 35.47% in 2014  while for some other diseases  the user charges were increased from 10 to 25% .In general, average cost-sharing for pharmaceuticals rose from 13.3% in 2012 to 18% in 2013. Interestingly, only 8% of prescribed drugs (packets) were provided with 0% co-payment in 2013 compared with 13% in 2012  and the lack in research related to access of patients with chronic diseases to medication, such as asthmatic patients, in Greece  led the authors to focus on investigating the respective context and highlight, if proved, the necessity for the chronically ill to comply with their physicians guidelines and for the policy makers in the primary health care sector to support and introduce institutional changes toward improving out-of-hospital management of chronic diseases.The objectives of this study were to evaluate the effectiveness of information and administrative assistance regarding patient adherence to asthma guidelines  and inveThe sample of the study consisted of 100 patients with acute asthma who visited the Emergency Department (ED) of a General Hospital of Athens. A comparative cross-sectional study was conducted during October 2014 and June 2015 regarding patients' compliance to the follow up, using convenience sampling.Patients who visited the ED were divided into two groups:1)The intervention group (this group's follow up was scheduled by the researchers): in this group, the follow up visit was organized by the researchers who undertook the appointment planning procedures. The appointment was scheduled according to the doctor's instructions (approximately 30 days after the visit to the ED) and a reminder (sms) was sent two (2) days before the scheduled date of the follow up visit. Also, during their visit to the ED, they were provided with an information booklet on the factors that cause asthma symptoms and the importance of compliance with treatment, consistency in treatment and communication with the physician.2)The control group (this group's follow up was not scheduled by the researchers): in this group, no intervention was made by the researchers regarding the arrangement of their follow up; their compliance to the doctor's instructions and attending to the follow up visit was checked by phone.The questionnaire developed by the researchers included items on access to medication, use of services and socio-demographics. The independent variables of the study were the demographic (and other) characteristics  while the dependent variables (binary) were (a) patients' compliance to follow up or not, (b) visit to ED (due to asthma attacks) followed by admission and (c) visit to ED (>1 times), due to asthma attacks, followed by non-admission.p > 0.05 for all variables), histograms and normal probability plots. Bivariate analyses were conducted and included Pearson's X2 test (Fischer's exact test) and X2 test for trend to determine associations between categorical variables and student's t-test and Mann-Whitney test and to investigate group differences within continuous variables. Also, multivariate logistic regression was performed (the independent variable which were included in the regression models were those which were significant at the level of 0.2 (p < 0.2) in the bivariate analysis) and its results were presented by using the odds ratios, the 95% CIs and the corresponding p-values. A two-sided p-value of 0.05 was considered statistically significant. The Statistical Package for Social Sciences (IBM SPSS) program, version 20.0, was used for statistical analysis.Categorical variables are presented as absolute (n) and relative (%) frequencies. The normality assumption was evaluated using the Kolmogorov-Smirnov criterion  and 68% were female. Almost one out of three (31%) were primary school graduates, 52% were high school graduates and 17% were graduates of higher/upper secondary education. Fifty-one percent were working, 29% were unemployed and 20% were retired. The average working time in hours per week was 20.98 h (SD = 23.21) and 88% had insurance coverage   Table .A significant percentage of patients with asthma did not consume the medication prescribed either due to lack of a prescription or due to lack of economic means to buy the medication and/or to pay the cost-sharing expenses and a significant number of patients did not adhere to their physician's guidelines about the appropriate dosage in order to save doses and, thus, to extend the duration of the use of the medication. In particular, only 16% of the patients had received a prescription for their asthma medication each month (over the preceding 12 months) Table .During the 12 months which preceded the study, 22% of the study patients stated that they were absent from their work due to asthma from 1 to 7 days, while the self-estimated mean rate of decline in work, related to asthma was 39.5%; in fact, two out of five patients reported that their efficiency/performance at work dropped from 0 to 20% and 32% from 21 to 60% . Also one out of four patients reported that they did not visit their doctor because they were not able to pay him/her .From the above, it is clear that out-of-hospital management of asthma presents significant gaps and shortcomings either due to important unresolved issues with regards to availability, accessibility and use of services, either due to the fact that health policies have not preceded so as to strengthen these care dimensions. The findings of the present study confirm the cause-effect relationship between ineffective out-of-hospital management of asthma  and the increase in the frequency of the use of the EDs' health services, resulting in an increase in the health costs by the use of the EDs. The improper out-of-hospital management not only causes congestion in the functioning of the EDs, but also it contributes to increases in costs, compared to the cost of outpatient visits in order to monitor the course and management of the disease. It is therefore obvious that effective out-of-hospital management of the disease contributes to reducing the use of health services, resulting in a reduction in the cost of hospitalization and the use of EDs' services.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication. In particular, OK helped supervise the study, conducted the field research, performed the statistical analysis and wrote the manuscript with support from the co-authors. DK conceived the original idea and methodological design, supervised the study and the findings of this work, discussed the results and contributed to the final manuscript. CE discussed the results and contributed to the final manuscript. GC discussed the results and contributed to the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Standard measures of kidney function are only modestly useful for accurate prediction of risk for acute kidney injury (AKI).Clinical and biomarker data can predict AKI more accurately.Using Luminex xMAP technology, we measured 109 biomarkers in blood from 889 patients prior to undergoing coronary angiography. Procedural AKI was defined as an absolute increase in serum creatinine of ≥0.3 mg/dL, a percentage increase in serum creatinine of ≥50%, or a reduction in urine output (documented oliguria of <0.5 mL/kg per hour for >6 hours) within 7 days after contrast exposure. Clinical and biomarker predictors of AKI were identified using machine learning and a final prognostic model was developed with least absolute shrinkage and selection operator (LASSO).P < 0.001). The optimal score cutoff had 77% sensitivity, 75% specificity, and a negative predictive value of 98% for procedural AKI. An elevated score was predictive of procedural AKI in all subjects .Forty‐three (4.8%) patients developed procedural AKI. Six predictors were present in the final model: four  had a positive association with AKI risk, while two (CD5 antigen‐like and Factor VII) had a negative association with AKI risk. The final model had a cross‐validated area under the receiver operating characteristic curve (AUC) of 0.79 for predicting procedural AKI, and an in‐sample AUC of 0.82 (We describe a clinical and proteomics‐supported biomarker model with high accuracy for predicting procedural AKI in patients undergoing coronary angiography. Furthermore, the presence of comorbidities including diabetes, chronic kidney disease (CKD), and heart failure (HF) further increase the risk of AKI development.2All study procedures were approved by the Partners Healthcare Institutional Review Board and carried out in accordance with the Declaration of Helsinki.The design of the CASABLANCA (NCT NCT00842868) study has been detailed previously.After informed consent was obtained, detailed clinical and historical variables were recorded using a standardized case report form at the time of the angiographic procedure. This case report form included more than 100 clinical variables acquired at the time of study entry as well as results of coronary angiography. Angiographic results were based on visual interpretation by the operator, verified through the catheterization report.Median follow‐up was 4 years, with a maximum follow‐up of 6 years. Follow‐up was complete for all patients. Processes for identification and adjudication of clinical endpoints were as previously describedSpecific to this analysis, procedural AKI was defined as an abrupt reduction in kidney function with an absolute increase in serum creatinine of more than or equal to 0.3 mg/dL, a percentage increase in serum creatinine of ≥50%, or a reduction in urine output (documented oliguria of <0.5 mL/kg per hour for >6 hours), within 7 days after contrast exposure.t test or Wilcox Rank sum test.Baseline characteristics between those who developed procedural AKI and those who did not were compared. Dichotomous variables were compared using Fishers exact test, while continuous variables were compared using A total of 15 mL of blood was obtained immediately before the angiographic procedure through a centrally‐placed vascular access sheath. The blood was immediately centrifuged for 15 minutes, serum and plasma aliquoted on ice, and frozen at −80°C until biomarker measurement. The samples for the present study were analyzed after the first freeze‐thaw cycle for baseline biomarker values only. Luminex xMAP technology, is a bead‐based multiplexed immunoassay system in a microplate format. The multiplexed assays were developed by Myriad RBM at their Austin, Texas facility. Each analyte assay was individually designed in a single assay format. The individual assays were validated according to CLSI Standards and thoroughly tested at the simplex stage before multiplexing. After multiplexing key performance parameters, such as LLOQ, LDD, and precision were established prior to every kit release. During the assay runs, laboratory information management system (LIMS) provided chain of custody and data logging information for samples throughout the testing process. Sample plating was verified by two technicians and run in temperature‐controlled lab. Native controls were run in duplicate alongside samples. Standard curves were at the front and back of each plate to minimize between and within run impression. All samples and reagent handling were automated. A minimum of 50 beads were analyzed per analyte and a 8‐point standard curve fitting with advanced algorithms ensured accuracy for sample concentrations. Controls followed Westgard rules to monitor unwanted trending. Sample results were manually reviewed before release. The data was backed up on site with long‐term off‐site storage. We measured 109 biomarkers in blood  from 889 patients undergoing coronary angiographic procedures for various indications.A complete case analysis was performed; blood urea nitrogen, or creatinine values were missing with some patients (n = 167), so these patients were removed from the analysis. One other patient was removed from the analysis for having an insufficient quantity of sample, leaving 889 samples available for analysis. For any biomarker result that was below the limit of detection, we utilized a standard approach of imputing concentrations 50% below the limit of detection.To facilitate the machine learning analysis, the concentrations for all proteins underwent the following transformations: (a) they were log‐transformed to achieve a normal distribution, (b) outliers were clipped at the value of three times the median absolute deviation, and (c) the values were re‐scaled to a distribution with zero mean and unit variance. The starting sets of variables consisted of all 109 proteins, as well as clinical factors in the CASABLANCA dataset that were chosen for their possible clinical relevance. Clinical and biomarker predictors of AKI were identified using least‐angle regression. In this method, factors were included in the model one at a time, with their coefficients determined by their correlation with the outcome. This was repeated until all factors were included in the model, and the step at which the performance plateaued resulted in our initial panel of interest. Starting with this panel of interest, predictive analyses were run on the training set using least absolute shrinkage and selection operator (LASSO) with logistic regression, predicting the outcome of procedural AKI using only the variables in the panel of interest. This model‐development process was done through Monte Carlo cross‐validation, using 400 iterations with an 80:20 (training: test) split. If the performance of the least contributing variable in the panel was not statistically significant, it was removed from the panel and the analysis repeated until the predictive contribution of all variables was statistically significant. With our final panel, we evaluated its performance using the MCCV process described above, and we also determined its in‐sample performance using a final prognostic model developed on all of the available data with LASSO with logistic regression. A cutoff was determined using the optimal Youdens index.P‐value of <0.05 was considered statistically significant. All analyses were performed using the R statistical computing platform, version 3.4.4.In all statistical analyses, a two‐tailed 3P = 0.04) and more likely to have prevalent diabetes mellitus  or CKD  (Table P = 0.04) and a higher percentage of them were prescribed an angiotensin‐converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB) compared to those who did not develop AKI  (Table Forty‐three (4.8%) patients developed procedural AKI. Those who developed procedural AKI were older  and BUN/creatinine ratio  and lower eGFR  and hemoglobin  at baseline compared to those who did not develop procedural AKI. They also had higher baseline concentrations of C‐reactive protein (CRP) (8.8 vs 3.5 mg/L) and osteopontin (43 vs 27 ng/mL) and lower concentrations of Factor VII (350 vs 468 ng/mL) compared to those who did not develop procedural AKI . Those who developed procedural AKI had numerically lower concentrations of CD5 antigen‐like (3600 vs 3755 pg/mL) compared to those with did not develop procedural AKI   had a positive association with AKI risk; while two (CD5 antigen‐like and Factor VII) had a negative association with AKI risk. Using the model‐building procedure described above for subsets of variables, the addition of each biomarker provided a statistically significant improvement in the AUC and the likelihood ratio, while decreasing the AIC and the BIC Table .P < 0.001). The optimal score cutoff had 77% sensitivity, 75% specificity, and a negative predictive value of 98% for procedural AKI . In addition, we tested our model in several subgroups and found that in women (n = 358) the AUC = 0.76; in those whose age ≥ 75 years (n = 285) the AUC = 0.81; in those with eGFR <60 (n = 181) the AUC = 0.87; in those with diabetes (n = 285) the AUC = 0.75; in those with HF (n = 205) the AUC = 0.86; and in those with PAD (n = 273) the AUC = 0.89.The final model had a cross‐validated area under the receiver operating characteristic curve (AUC) of 0.79 for predicting procedural AKI, and an in‐sample AUC of 0.82 P < 0.00. The opt4Among a typical population of 889 patients undergoing coronary angiography with or without interventions for various acute and non‐acute indications, 4.8% of patients developed procedural AKI. We created a model that included six predictors of AKI: four  had a positive association with AKI risk; while two (CD5 antigen‐like and Factor VII) had a negative association with AKI risk. The final model had a high accuracy for predicting procedural AKI in patients undergoing coronary angiography.The rationale for our study is based on the fact that AKI following coronary angiographic procedures is associated with significant morbidity and mortality that has potential to alter patient management if predicted early.Prior work has examined this question, mostly based on clinical variables. Among patients in the Minnesota Registry of Interventional Cardiac Procedures, diabetes, increased age, higher dose and route of contrast administration, HF, hypertension, peri‐procedural shock, baseline anemia, post‐procedural drop in hematocrit, use of nephrotoxins, volume depletion, increased creatinine kinase‐muscle/brain enzyme, and need for cardiac surgery after contrast exposure were associated with increased risk of procedural AKI.While BUN and serum creatinine are most often used to predict procedural AKI, they are not very sensitive or specific for the diagnosis of AKI because they are affected by many renal and non‐renal factors that are independent of kidney injury or kidney function.P < 0.01) in patients with AKI; CRP concentrations subsequently fell after recovery from AKI.Inflammation may play an important role in presence and severity of AKI. CRP is an acute‐phase protein of hepatic origin that is a marker of inflammation synthesized in response to factors released by macrophages and adipocytes.P < 0.0001), sensitivity of 100%,and specificity of 61% for a cutoff value of 577 ng/mL.Osteopontin is an extracellular matrix protein and proinflammatory cytokine thought to facilitate the recruitment of monocytes/macrophages and to mediate cytokine secretion in leukocytes. It plays a role in many physiological and pathological processes, including biomineralization, tissue remodeling, and inflammation.CD5L gene that acts as a key regulator of lipid synthesis. It is mainly expressed by macrophages in lymphoid and inflamed tissues and regulates mechanisms in inflammatory responses, such as infection or atherosclerosis.CD5 antigen‐like is a secreted protein encoded by the P < 0.001), white blood count (P < 0.001), fibrinogen (P < 0.001), and Factor VII (P < 0.001) were associated with a subsequent rise in serum creatinine. Furthermore, CRP, white blood count, and Factor VII all independently predicted an eGFR decline of >3 mL/min/year/1.73 m2.Data regarding Factor VII and its ability to predict kidney dysfunction are scarce; however, it is well established as a marker of hypercoagulability and persistence of inflammatory response.Our AKI risk prediction model incorporated clinical and biomarker predictors all known to affect renal function and was based on an unbiased, machine learning approach for selection of model variables. Major advantages of our cohort are its detailed characterization and our experience working within this database, although limitations to our study exist. The CASABLANCA cohort was predominantly male, Caucasian, and representative of patients in a tertiary care referral center. In addition, we did not include the volume of contrast dye used during the coronary angiographic procedures, which clearly affects risk for AKI development or whether patients had prophylactic treatment for AKI prevention. In contrast to measures of kidney function (such as creatinine or eGFR), a theoretical advantage of our risk prediction model is the potential detection of AKI prior to change in measures of kidney function and the inclusion of several predictors associated with AKI development. Earlier prediction of AKI can allow for adjustments in patient/care management that might help to mitigate risk for severe kidney dysfunction.5In a typical at‐risk population undergoing coronary angiography for various acute and non‐acute indications, we describe a clinical and proteomics‐supported biomarker model with high accuracy for predicting procedural AKI in patients undergoing coronary angiography. The ability to predict AKI may allow for earlier interventions in at‐risk patients to reduce future AKI risk. We plan to test our risk prediction model in an external validation cohort in the future.Dr. Nasrien E. Ibrahim has received presentation fees from Novartis. Dr. Hanna K. Gaggin has received grant support from Roche Diagnostics and Jana Care, consulting income from Roche Diagnostics, and participates in clinical endpoint committees/data safety monitoring boards for Radiometer. Mr. Craig A. Magaret and Ms. Rhonda F. Rhyne are employed by Prevencio, Inc. Dr. James L. Januzzi has received grant support from Roche Diagnostics, Abbott, Singulex and Prevencio, consulting income from Roche Diagnostics, Critical Diagnostics, Janssen and Novartis, and participates in clinical endpoint committees/data safety monitoring boards for Novartis, Amgen, Pfizer, Janssen, AbbVie, and Boehringer‐Ingelheim. The other authors have nothing to disclose.Table S1. List of 109 biomarkers testedClick here for additional data file.


To investigate clinical efficacy of transjugular intrahepatic portal shunt (TIPS) for the treatment of cirrhotic portal hypertension.71 cases of patients with cirrhotic portal hypertension and esophageal and gastric variceal bleeding hospitalized from January 2014 to June 2017 were enrolled and treated with TIPS. The change of portal pressure and serum biochemical indexes before and after TIPS were compared, and re-hemorrhage rate, ascites incidence, complications, and survival rate were calculated.P < 0.05). During the follow-up, the incidence of hepatic encephalopathy was 12.1%, the incidence of re-hemorrhage was 18.2%, and there were 4 cases of stent dysfunction, with 1 case of bare stent and 3 cases of dual stent.71 patients  with cirrhotic portal hypertension received TIPS. The success rate of TIPS was 93% (66/71). During 1–24 months (mean 12.5 ± 7 months) follow-up of 66 patients, 61 cases survived and 5 cases died. The portal pressure decreased significantly from 40.48 ± 3.15 cmH2O to 23.59 ± 4.41 cmH2O after TIPS (TIPS is an effective procedure for the treatment of cirrhotic portal hypertension complications, since it can reduce portal pressure and significantly alleviate ascites. Liver function is impaired in short-term after TIPS, but TIPS has no significant effect on liver function in middle-term. Portal hypertension is an increase in the pressure within the portal vein, which carries the blood from the digestive organs to the liver . Portal Transjugular intrahepatic portal shunt (TIPS) was proposed by Rosch in 1969 . The 200This study was approved by Ethics Committee of Xiangya Hospital of Central South University and all subjects provided informed consent. From January 2014 to June 2017, 71 patients with cirrhotic decompensated portal hypertension accompanied with EGVB and refractory ascites who were treated with TIPS at Xiangya Hospital of Central South University were enrolled.The general clinical data of the patients are shown in Table Ultrasound, CT or MRI examinations were performed before procedure to understand the anatomy of intrahepatic branches of hepatic vein and portal vein, and provide auxiliary support for choosing the puncture direction, angle of hepatic vein to portal vein, and the blood flow state of portal vein. The liver and kidney function, coagulation function, blood type, blood transfusion and other related biochemical indices were measured before procedure.After routine disinfection and local anesthesia, the right internal jugular vein was punctured, the guide wire was inserted into the inferior vena cava through the right atrium, the catheter was placed, and hepatic venous pressure was measured. According to preoperative imaging results, the right hepatic vein or the middle hepatic vein was selected as the initial puncture vein, and the proper puncture angle and plane were selected to enter the portal vein. The balloon was expanded and positioned, and the portal vein pressure was measured after the pigtail catheter was exchanged. According to the balloon dilatation pressure mark, the position and length of the punctured intrahepatic segment could be estimated. The RUS-100 puncture system was placed along the guide wire to the main portal vein, and the angiography was used to monitor blood flow and varicose veins of the main and branch of portal vein. The embolization treatment was performed with polyglycerol or anhydrous alcohol and a spring coil, and the embolization effect was determined by angiography. Under the guidance of the guide wire, a stent release system was placed between the hepatic vein and the portal vein puncture channel, an artificial shunt was established, and the stent was released after the position was determined. The portal vein pressure was measured again and the portal vein pressure significantly decreased, indicating that the procedure could be ended with compression hemostasis bandage.After the procedure, routine monitoring was performed, paying attention to the patients’ vital signs, abdominal pain, consciousness, gastrointestinal hemorrhage, and blood oozing of puncture site. All patients received routine anticoagulant therapy (subcutaneous injection of low molecular weight heparin 3000 U), and appropriate anti-inflammatory treatment.Clinical follow-up was performed at 1 week, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months after TIPS. The follow-up included the general condition, hemorrhage, hepatic encephalopathy, ascites, etc., and liver function and blood routine tests. Some patients were examined by abdominal color Doppler ultrasound or DSA to determine the situation of the stent.2 test. P < 0.05 was considered significant.All data were statistically analyzed using SPSS 25 software. The measurement data were expressed as χ ± SD. Preoperative and postoperative portal venous pressure, preoperative and postoperative hematology, and biochemical indices were analyzed by paired t test. The enumeration data were analyzed by χOf the 71 patients, 3 cases had failed stent placement due to their vascular anatomy; 2 cases had unstable circulation due to intraoperative hemorrhage, so the stent placement failed. The successful cases of TIPS were 66, and the success rate was 93%. During follow-up, 61 cases survived and five cases died, including one case died of abdominal thoracic hemorrhage 3 days after TIPS and 4 cases died of hepatic encephalopathy. Total 8 cases had hepatic encephalopathy, and 12 cases had recurrent hemorrhage. Total 4 cases had stent stenosis, 3 cases of them underwent the second TIPS and 1 case underwent hepatic vein balloon dilatation, and there was no hemorrhage during the follow-up period. The hematemesis and hematochezia of 53 patients with hemorrhage were effectively controlled after TIPS, and the short-term hemostatic rate was 100%. After TIPS, the therapeutic effect of 8 patients with refractory ascites was evaluated by color Doppler ultrasound and abdominal circumference measurement [12 cases used metal stents, 10 patients used Fluency covered stents, and 44 cases used dual stents. The diameter of all stents used in this study was 8 mm.P < 0.05, paired t-test).As shown in Table P < 0.05), while the platelet, prothrombin time, international normalized ratio (INR), and aspartate aminotransferase were not significantly different before and after TIPS (P > 0.05).As shown in Table P < 0.05) at 1 week, 3 months, and 12 months after TIPS, and the difference in alanine aminotransferase was statistically significant 1 week after TIPS (P < 0.05). The difference in total bilirubin was statistically significant at 1 week, 1 month and 3 months after TIPS (P < 0.05). However, the differences in serum albumin, alanine aminotransferase, aspartate aminotransferase, and total bilirubin were not statistically significant at 18 months and 24 months after TIPS (P > 0.05).As shown in Table 2 = 0.472, P = 0.79). There was 1 case of hepatic encephalopathy in early operation group, and 7 cases of hepatic encephalopathy in elective operation group, the difference was not statistically significant .As shown in Table 2 = 16.899, P = 0.001).As shown in Table Through the establishment of the portacaval shunt, TIPS can significantly reduce portal pressure and control EGVB . TIPS haThere is still no consensus on liver function changes after TIPS. Some studies suggested that liver function was impaired due to portal shunt , 10, whiThe complications of TIPS mainly include hepatic encephalopathy and stent dysfunction, and the incidence of hepatic encephalopathy after TIPS is 18–45% –17. A meDue to iatrogenic mechanical injury and portal shunt after TIPS, liver function may be impaired to a certain extent in short-term, but it has no significant effect on liver function in middle-term. The main complications after TIPS are hepatic encephalopathy and stent stenosis. Therefore, it is necessary to evaluate hepatic encephalopathy history in patients before TIPS, and use covered stents to reduce the incidence of postoperative stent dysfunction.TIPS is an effective procedure for the treatment of cirrhotic portal hypertension complications, since it can reduce portal pressure and significantly alleviate ascites. Liver function is impaired in short-term after TIPS, but TIPS has no significant effect on liver function in middle-term.


Hypertension contributes to high rates of mortality and morbidity in both developing and developed countries. It predisposes individuals to several chronic diseases including stroke and other cardiovascular diseases. Predisposing factors such as sedentary lifestyles, unhealthy dietary habits, and physical inactivity are associated with its growing prevalence over the years. Besides social-economic factors, increased incidence of diabetes and obesity as well as modernized lifestyles plays important roles in the growing prevalence of uncontrolled hypertension, in particular in developing countries.Currently, despite availability of several antihypertensive drugs, attaining an adequate blood pressure control is still a challenge. This can be attributed to several factors. For example, many of the existing antihypertensive agents do not modulate oxidative stress, which is an important pathophysiologic pathway for the development of hypertension and several of its complications. Poor medication adherence, reduced drug effectiveness, drug unaffordability or unavailability, and side/adverse effects of medications are additional important obstacles that weigh significantly in our ability to control the disease. To address some of these limitations, attention has been paid in recent years to the use of various nonpharmacologic interventions as a more viable alternative to treat the disease.This special issue reports on the current status of nonpharmacologic approaches taken thus far across the world, in the prevention and treatment of hypertension. Several contributions were received from researchers in most of the continents. After stringent and thorough reviewing process, nine manuscripts  were accepted for publication.H. H. Alhawari et al. assessed the frequency of hypertension among healthy university students and its association with gender, body mass index (BMI), smoking, and family history of both hypertension and cardiovascular diseases. They found significant gender differences in both systolic and diastolic blood pressure . Upon comparison of the mean difference in both systolic and diastolic blood pressure with BMI, there were significant differences in both systolic and diastolic blood pressure. First-degree family history of both hypertension and cardiovascular diseases was also found to affect systolic but not diastolic blood pressure. G. Musinguzi et al. investigated and identified factors influencing compliance and health seeking behavior among hypertensive patients, being related to health systems and patient socioeconomic and structural environment. These include self-medication and self-prescription of antihypertensive drugs as well as marketing of herbal remedies. H. Javadzade et al. assessed the effectiveness of a theory-based self-care intervention with the application of health literacy approaches in hypertensive patients and limited health literacy. The results have a potential to assist with the development of a theoretical framework for self-care intervention in patients with high blood pressure and limited health literacy. T. M. Dokunmu et al. assessed the risk of developing hypertension in healthy adult Nigerian population. Prehypertension was found in 36.8% population and elevated blood pressure in 31% individuals with hypertensive symptoms. The researchers found that age more than 35 years was an independent risk and this increases to 26.48 in the presence of prediabetes and random blood glucose greater than 100 mg/dL. Large scale screening and management of hypertension are recommended to reduce the burden of the disease. A. Larki et al. determined the factors that influence adherence to self-care behaviors among low health literacy hypertensive patients based on health belief model. The researchers found that designing and implementing educational programme to increase self-efficacy of patients and promote their beliefs about perceived susceptibility and severity of complications may improve self-care behaviors among low health literacy hypertensive patients.E. Drevenhorn proposed a middle-range theory of nursing in hypertension care. Patients related concepts such as attitude and beliefs concerning health were presented. The researcher highlighted the clinical and research implications of the theory. Hypertension is a chronic disease that necessitates long-term self-management. Using a semistructured interview guide, K. D. Wright et al. described the process in which African American older adults and nurse researchers cocreated an intervention to address stress in the self-management of hypertension. Based on participants feedback, four biweekly (2-hour) group sessions which incorporated patients suggestions and concerns were created. Though it may be of significant benefits, further studies are required to test the generalizability of this technique. M. Horiuchi et al. investigated the effects of resistance exercise under hypoxia on postexercise in eight healthy young males. The findings suggested that hypoxic condition elicits greater impact on hypotension following resistance exercise (in comparison to normoxia). The data also suggest that the underlying mechanisms for the attenuation of hypotension after resistance exercise may vary between normoxia and hypoxia. Romani presented a review paper that underscores the beneficial effects of magnesium on blood pressure maintenance.The issue highlights the importance of treatment and control of blood pressure via nonpharmacologic approaches. It thus reinforces the need for researchers to intensify more research in this aspect of hypertension management. This may help to reduce drastically the increasing prevalence and burden of hypertension worldwide.