In contrast, the blood velocity was not significantly different among the three types of veins. BCVA was correlated with the diameter of the occluded vein  but not with the RBF and blood velocity. The time from the initial visit, the time from the last injection, and the total number of anti-VEGF injections were not associated with any RBF parameters on the occluded vein. Conclusions: The RBF was significantly lower in the occluded veins than that in the other veins, and the diameter of the occluded vein was significantly smaller than that of the other veins in patients with BRVO. However, neither the time from the initial visit, nor the time from the last injection, nor the number of anti-VEGF injections were correlated with the RBF parameters on the occluded vein.Background: Doppler optical coherence tomography (DOCT) flowmeter can be used to measure retinal blood flow (RBF) parameters, including vessel diameter, blood velocity, and the absolute value of RBF within 2.0 s. We investigated the RBF parameters in eyes with branch retinal vein occlusion (BRVO) using a DOCT flowmeter. Methods: Seventeen patients with unilateral BRVO were enrolled. All subjects underwent comprehensive ophthalmologic examinations. The RBF parameters were assessed from three veins, i.e., (1) an occluded vein, (2) a non-occluded vein in the BRVO eyes, and (3) an equivalent (superior or inferior) vein in the fellow eye (non-affected vein), using prototype DOCT flowmeter . Moreover, the correlation between RBF parameters and the best corrected visual acuity (BCVA) was examined. We investigated the correlation between (1) the RBF parameters and the time from the initial visit, (2) the RBF parameters and the time from the last injection, and (3) the RBF parameters and the number of anti-vascular endothelial growth factor injections (VEGF). Results: The diameter of the occluded vein (95.9 ± 24.7 µm) was smaller than that of the non-occluded vein (127.9 ± 23.7 µm) and that of the healthy veins (116.4 ± 13.9 µm). The RBF was lower in the occluded veins (4.7 ± 3.7 µL/min) than that in the non-occluded veins (10.3 ± 5.1 µL/min;  Retinal vein occlusion (RVO) is the second most common circulatory disease, and branch RVO (BRVO) represents most the cases of RVO.  PreviousSeveral clinical studies have suggested that the reduction in the retinal blood velocity measured by various devices could be related to the pathophysiology of BRVO ,7,8,9. HPreviously, we developed a Doppler optical coherence tomography (DOCT) flowmeter method by modifying spectral-domain optical coherence tomography (SD-OCT) system , which can measure retinal arterial and vein blood velocity noninvasively, as blood velocity waveforms .The aims of the study were (1) to assess the characteristics of RBF as measured by DOCT flowmeter on the occluded vein in eyes with BRVO and (2) to evaluate the correlation between the RBF and best corrected visual acuity (BCVA) in eyes with BRVO.The ethics committee of Asahikawa Medical University  approved the study protocol , which adhered to the tenets of the Declaration of Helsinki. All patients provided written informed consent.Seventeen consecutive patients with BRVO  were recruited from 1 December 2017 through to 31 March 2019 at the medical retina clinic of Asahikawa Medical University. Two retina specialists (KS and KT) established the diagnosis of BRVO with the following diagnostic criteria: the presentation of feather or flame-shaped hemorrhage on fundus due to an occlusion of branch retinal veins. All patients received one initial intravitreal injection (IVI), and patients with persistent macular edema (ME) at subsequent follow-up visits received additional intravitreal anti-VEGF injection following a pro re nata (PRN) regimen. Patients with glaucoma, diabetes, fundus abnormalities not caused by BRVO, pre-existing retinal dystrophies, uncontrolled hypertension (blood pressure > 160/100 mmHg), and any history and evidence of past events or the presence of hypertensive retinopathy or vascular distress were excluded. We also excluded the patients who underwent the anti-VEGF injection due to ME on the day of the DOCT flowmeter measurement. Eyes with intraocular surgeries other than cataract surgery were also excluded from the study.We evaluated the vessel diameter, blood velocity, and RBF using a DOCT flowmeter according to the established method  10,11,1,13. Our According to the previously described segmental method, the image-capturing software was upgraded for Doppler imaging, and the image-processing software was newly developed to measure the RBF . One hunRBF was evaluated according to the established method  10,11,1,111,12. All the measurements using the DOCT flowmeter were performed by KT. After the dilation of the pupils using a 0.5% tropicamide eye drop , the subjects rested for at least 5 min in a dimly lit room at a temperature of 25 °C and their blood pressure was measured in the left arm. All subjects underwent comprehensive eye examinations, such as BCVA: logMAR , intraocular pressure (IOP), slit-lamp examination, and optical coherence tomography  to measure the central macular thickness. The mean ocular perfusion pressure was calculated at 2/3 mean blood pressure (MBP)–IOP. At least 24 h before the measurements, the subjects were instructed to refrain from intaking caffeine-containing drinks, such as coffee. RBF was measured using a DOCT flowmeter on three veins, i.e., 1. an occluded vein in BRVO eyes; 2. a non-occluded vein on the opposite hemisphere of the occluded vein in the BRVO eye; and 3. a vein in an equivalent area  in the fellow eyes. The RBF was measured at veins at a half disc diameter away from the optic disc.The data were analyzed using the JMP software version 14.0.0 . All the data are expressed as the mean ± standard deviation (SD). A Steel–Dwass test was used for non-parametric multiple comparisons of the RBF parameters among the veins. Spearman’s rank correlation coefficient was calculated to examine the associations between (1) the RBF parameters and the BCVA, (2) the RBF parameters and the time from the initial visit, (3) the RBF parameters and the time from the last anti-VEGF injection, and (4) the RBF parameters and the number of anti-VEGF injections.p < 0.001). The IOP was not significantly different between the BRVO (14.9 ± 2.3 mmHg) and the fellow eyes .The demographics of the study participants are summarized in p < 0.01) and in the vein in the fellow eyes . There were no significant differences in the blood velocity among the veins . The diameter of the occluded vein (95.9 ± 24.7 µm) was significantly smaller than that of the non-occluded vein  and that of the vein in fellow eyes (117.8 ± 14.5 µm p = 0.022).p = 0.001)  .The time from the initial visit, the time from the last anti-VEGF injection and the number of anti-VEGF injections were not associated with any of the RBF parameters .The current study showed that the RBF in the occluded vein was lower than that in the non-occluded and the healthy veins. The diameter of the occluded vein was smaller than that of the non-occluded and healthy veins, while there was no significant difference in the blood velocity among the veins. These results suggest that the reduction in RBF was associated with the diameter of the veins rather than with the blood velocity. In addition, the diameter of the occluded vein was correlated with the BCVA, implying that the diameter of the occluded vein in the BRVO eyes may be an important index for BRVO.A previous study using scanning laser Doppler flowmetry reported that the RBF and blood velocity in the occluded vein were significantly lower than they were in the non-occluded and the equivalent (in fellow eye) veins in treatment-naïve BRVO . MoreoveSeveral previous studies have reported that the presence of macular ischemia is an important prognostic factor for the final VA outcomes in patients with BRVO ,4. ConvePrevious reports have described changes in retinal vein diameter in patients with BRVO, in whom anti-VEGF injection causes the vasoconstriction of the retinal vein ,17,18. HOur study had several limitations. First, although the current study revealed that the RBF reduction was affected by the diameter of, rather than the blood velocity in, the occluded vein in the BRVO eye, we did not provide data pertaining to the longitudinal changes of RBF parameters. Secondly, although we understand BRVO can occur at any location and any diameter of retinal veins, we chose a half-disc diameter away from the optic disc for RBF measurement consistency. Third, as the patients did not always have the fluorescein angiography, the current study could not demonstrate the association between RBF and retinal ischemia. Fourth, we could not investigate the direct relationship between RBF and anti-VEGF treatment in BRVO although there were no correlations between RBF parameters and the number of anti-VEGF injections, and the time from the initial visit. Finally, we recruited a relatively small sample. Therefore, further longitudinal studies with a larger cohort are warranted.In BRVO eyes, the RBF and diameter of the occluded vein were significantly lower than those in the non-occluded and the healthy veins. We found that the diameter of the occluded vein was correlated with the BCVA, while neither the time from the initial visit, nor the time from the last injection nor the number of anti-VEGF injections were correlated with the RBF parameters on the occluded vein.


Progressive renal disease is characterized by histological changes in the kidney and fibrosis is a common outcome. Renal biopsy is the only diagnostic tool to evaluate these histopathological changes. Pentraxin-2 (PTX-2) is an anti-inflammatory constitutive plasma protein associated with the innate immune system. Recently, as a biomarker, the circulating level of PTX-2 is shown to be decreased in chronic fibrotic diseases. In this study, we aimed to investigate the relationship between renal fibrosis severity and serum PTX-2 levels in patients undergoing renal biopsy.This cross-sectional study included 45 patients and 16 healthy individuals (HIs). The severity of renal fibrosis was evaluated according to the Banff and Sethi scoring systems by the same pathologist. PTX-2 was measured by an enzyme-linked immunosorbent assay and compared with the demographical, clinical, biochemical, and histopathological data of the patients and HIs.p=0.12). Patients with moderate renal fibrosis had significantly lower serum PTX-2 levels than those in patients with minimal and mild fibrosis . PTX-2 concentrations were correlated with serum albumin , and were negatively correlated with serum creatinine levels  and body mass index .PTX-2 levels were lower in the biopsy group than in the HI group (The results indicated that PTX-2 levels are significantly lower in patients with renal fibrosis than HIs, and declining further in patients with severe fibrosis. Chronic kidney disease (CKD) has been a growing health-care problem with increasing prevalence. More than 10% of the population in developed countries is considered to have CKD, with a variety of etiologies such as hypertension, diabetes, glomerulonephritis, and so on .Pentraxin-2 (PTX-2), also named as serum amyloid P component, is a constitutive, anti-inflammatory plasma protein associated with the innate immune system. Recently, the circulating level of this protein was shown to be decreased in chronic fibrotic diseases . PTX-2 hThis cross-sectional study was performed at the Sisli Hamidiye Etfal Teaching and Research Hospital between April 2016 and April 2017 in Istanbul, Turkey. The study included 45 patients who were older than 18 years and had an indication for renal biopsy  along with 16 healthy individuals . Informed consent was obtained from all subjects and the study protocol was approved by the Hospital’s Ethical Committee.2). Proteinuria at more than 3.5 g/day and serum albumin below 3.0 g/L were defined as nephrotic syndrome. Non-nephrotic proteinuria was defined as proteinuria lower than 3.5 g/day or proteinuria with concomitant hematuria. Biopsy indications for patients with type 2 diabetes including unexplained rapid worsening of renal function, microscopic hematuria, and proteinuria without diabetic retinopathy. Patients who were clinically suspected for non-diabetic renal disease were selected, examined, and a biopsy was performed if a patient fulfilled the above-mentioned criteria.The indications assessed by a nephrologist for renal biopsy included acute kidney injury, non-nephrotic proteinuria, proteinuria with coexisting hematuria, isolated hematuria, nephrotic syndrome, and progressive CKD , solitary kidney, multiple and bilateral cysts or renal tumors, anatomical kidney anomalies, active renal, perirenal, or biopsy site infection, malignancy, severe resistant hypertension, or uncontrollable bleeding disorder were excluded. Medications altering the coagulation cascade were withheld until an appropriate time before the procedure. Patients in the biopsy group were evaluated using ultrasonography by an experienced radiologist for kidney biopsy eligibility. The biopsies were performed by an experienced nephrologist or interventional radiologist. After the biopsy, all patients were kept under observation in the hospital for a day in case of complications.2. Proteinuria was excluded in the control group by examining a random morning urine sample.On the day of the kidney biopsy, fasting serum samples for biochemical evaluation were obtained at 08:00 a.m. in all cases. Values of laboratory parameters including complete blood cell counts and serum levels of creatinine, albumin, C-reactive protein (CRP), C3, and C4 were measured using standard enzymatic procedures. Proteinuria was quantified based on 24-h urinary protein excretion measurements. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to determine the estimated glomerular filtration rate (eGFR). The severity of kidney failure was estimated according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines. The body mass index (BMI) was defined as the weight in kilograms/(height in meter)Blood samples for PTX-2 quantification were obtained on the same day when the patients underwent percutaneous renal biopsy. The sera were kept at -80°C until use. The levels of PTX-2 were determined by enzyme-linked immunosorbent assay (ELISA)  as per the manufacturer's recommendations.The biopsy specimens of the patients were examined by a single experienced pathologist using light and immunofluorescence microscopy. Routine staining analyses, including hematoxylin and eosin, periodic Schiff-methenamine, periodic acid-Schiff reagent, and Masson trichrome staining, were performed. Congo red and methyl violet staining analyses were also performed for samples from some patients. Immunofluorescence staining was performed for IgA, IgG, IgM, C3, C4, C1q, and kappa/lambda light chains.Interstitial fibrosis and tubular atrophy were scored according to the Banff 97 criteria, with scores from 0 to 3 based on the percentage of cortical parenchyma involved .p<0.05 was considered statistically significant.SPSS 21.0 for Windows was used for statistical analysis. Descriptive statistics were presented as number and percentage for categorical changes: as average, standard deviation, minimum, maximum, and median for numerical variations. When the numerical variations maintained the normal distribution conditions, the two independent groups were compared using the Student’s t-test, and when the numerical variations did not maintain the normal distribution conditions, three or more groups were compared using the Kruskal-Wallis test. The study group analysis was performed with Mann Whitey U test and interpreted with Bonferroni correction. The ratios in the groups were compared using Chi-Square analysis. As the relations between numerical variations did not meet the parametrical test condition, Spearman Correlation analysis was used. p=0.012).This study included 45 patients in the Biopsy Group (BG) and 16 HIs. Their demographic, clinical, and laboratory data are shown in The stage of kidney failure was determined for each subject. The numbers of patients with stages 1-5 of kidney failure were: 9 (20%), 16 (35.6%), 8 (17.8%), 6 (13.3%), and 6 (13.3%), respectively. There was no correlation between the stage of kidney failure and PTX-2 level. The pathological diagnosis of the patients was as follows: focal segmental glomerulosclerosis (FSGS) (n=18), IgA nephropathy (n=9), membranous glomerulonephritis (MGN) (n=6), amyloidosis (n=3), tubulointerstitial nephritis (n=3), lupus nephritis (n=2), myeloma cast nephropathy (n=1), cholesterol crystal embolism (n=1), membranoproliferative glomerulonephritis (n=1), and diabetic glomerulosclerosis (n=1).p=0.017 and p=0.010, respectively) (p=0.016), and negatively with serum creatinine  and BMI   . There wp=0.011) .Pentraxins such as pentraxin-2  regulate various features of the innate immune system. PTX-2 increases the migration of immune-regulatory macrophages, suppresses the differentiation of monocyte-derived fibroblast-like cells, and inhibits neutrophil adhesion to extracellular matrix proteins .A prognostic marker for CKD has been explored for years. A large number of serum and urinary molecules such as NGAL, KIM-1, MCP-1, MMP-9, interleukin-18, clusterin, MMP-9, TIMP-1, Procollagen I alpha 1, FGF-23, suPAR, as well as PTX-2 are under investigation to predict CKD progression  was found to be a natural inhibitor of fibrosis during kidney injury via the downregulation of fibrotic collagen gene transcription. On the contrary, fibrocytes were infrequently seen in injured kidneys following treatment with hSAP, proving that fibrocytes do not play a major role in fibrosis. A correlation between loss of kidney function and lower hSAP concentrations has also been reported in mice .-1Col4a3-mice) (Another study focused on recombinant PTX-2 treatment in mice deficient in the kidney microvascular basement membrane protein collagen type IV (α)3 (1-mice) . This pr1-mice) . The mut1-mice) .All the subjects enrolled in our study were indicated for renal biopsy, and fibrosis was found ranging from the minimal to severe grade in all the specimens. Thus, in agreement with animal studies, PTX-2 levels were lower in patients with renal fibrosis than in HIs. We also found significantly lower PTX-2 levels in patients with moderate renal fibrosis than in those with minimal and mild fibrosis. As the number of patients with severe renal fibrosis was small, we could not perform a subgroup analysis; however, it is noteworthy that this group had the lowest PTX-2 level.We also found that the level of PTX-2 was negatively correlated with the BMI. Although the sample size was small, there were no associations between BMI and the pathological diagnosis of patients. However, it is expected that patients with FSGS may have higher BMI. Obesity-associated FSGS is a well-known phenomenon, and is also called obesity-related glomerulopathy. The pathological components of this disease include glomerulomegaly, FSGS (particularly the perihilar variant), reduced glomerular and podocyte density, and diabetoid changes . IsolateBased on the potential role of PTX-2 in wound healing and fibrosis, an increasing number of studies are testing PTX-2 as a therapeutic agent. For instance, Blink et al. performed a study of 21 patients with idiopathic pulmonary fibrosis (IPF) and did not report any benefit of PTX-2 (PRM-151) administration . Raghu eThis study has a few limitations; it was a single center study with a small cohort size and a limited number of unmatched healthy controls. As the number of patients with severe renal fibrosis was small, we could not perform a subgroup analysis. Further, because there were only a few patients for each pathological diagnosis, we could not evaluate the difference between the serum PTX-2 levels in various specific diseases.In conclusion, we report the first study in human subjects investigating the level of PTX-2 in patients who underwent renal biopsy. This study demonstrated that PTX-2 levels are lower in patients with renal fibrosis than HIs and declining further in patients with more severe fibrosis. Therefore, PTX-2 may be a biomarker of fibrosis, and could be used as a prognostic indicator to guide treatment. However, extensive additional studies are required to firmly establish the relationship between serum PTX-2 levels and renal fibrosis.th National Congress of Nephrology, Antalya, Turkey on 19th October 2019.The article was presented as an oral presentation at the 36Basturk T and Ahbap E contributed in research idea and study design. Ojalvo D, Mazi EE, Ozagari AA and Hasbal NB contributed with data acquisition, analysis and interpretation. Ojalvo D and Ahbap E were responsible for statistical analysis. Basturk T, Ahbap E, Sakaci T, Koc Y, Sevinc M, Unsal A contributed to supervision or mentorship.


Simultaneous hemorrhagic and ischemic strokes have been previously reported in the literature. Typically, these occur in patients secondary to dialysis, cerebral amyloid angiopathy, or thrombotic thrombocytopenic purpura. The occurrence of ischemic stroke in those with flow-limiting intracranial atherosclerotic stenosis is well documented and continues to be one of the most common causes of stroke worldwide.A 62-year-old, right-handed, Asian female with history of known refractory hypertension and diabetes mellitus was brought into the ED via emergency medical services (EMS) as a stroke alert soon after experiencing sudden onset of neurologic symptoms. The patient was driving with her husband from San Francisco to Miami when she experienced confusion, slurred speech, and right-sided weakness, which subsequently progressed to unresponsiveness. En route to the ED, EMS reported a blood pressure of 240/120 millimeters of mercury (mmHg) and a glucose level of 133 milligrams per deciliter (mg/dL).2) (reference range 18.5–24.9 kg/m2). The patient was started on a nicardipine infusion with a goal systolic blood pressure less than 190–200 mmHg and a propofol infusion for sedation before being taken for imaging.Upon arrival, her Glasgow Coma Scale was seven. Her neurologic examination demonstrated right-sided hemiplegia, left-sided withdrawal to pain, a rightward gaze preference, and reactive pupils. The patient was immediately intubated in the ED for airway protection. Initial vital signs following intubation were as follows: blood pressure 270/159 mmHg; pulse 78 beats per minute; temperature 36.7 degrees Celsius; respiratory rate 18 breaths per minute (on ventilator); pulse oximetry 100% (on 100% fraction of inspired oxygen); and body mass index of 23.5 kilograms per meter squared  of the brain revealed an ICH that arose in the pons and extended into the fourth ventricle. Her only risk factor for developing the hemorrhagic stroke was the known refractory hypertension. The size of the hemorrhage measured 3.4 centimeters (cm) by 2.0 cm with a volume less than 30 milliliters (mL) . An ICH CTA showed a near occlusion of the left M1  segment of the middle cerebral artery (MCA), which appeared to be chronic . The patWhat do we already know about this clinical entity?There are established guidelines for blood pressure management, imaging modalities, and definitive treatment options to manage either ischemic or hemorrhagic stroke.What makes this presentation of disease reportable?This report discusses the novel presentation of a patient with simultaneous ischemic and hemorrhagic strokes secondary to hypertension from intracranial atherosclerotic stenosis.What is the major learning point?Clarity is needed for clinical parameters and treatment options in the dual-lesion patient.How might this improve emergency medicine practice?Care will be improved with better-defined management standards and other special consideration, given the unique pathophysiology in dual ischemic and hemorrhagic lesions.On hospital day three, due to concern for developing hydrocephalus, an external ventricular drain was placed, which measured normal intracranial pressure. On hospital day five, increased lethargy was noted while the patient was off of sedative medication. A repeat non-contrast CT of the brain at this time demonstrated a new, low attenuated area involving the high posterior aspect of the left frontal lobe in a MCA watershed area . The patSome of the common risk factors for developing intracranial atherosclerotic disease are hypertension, smoking, diabetes mellitus, and hyperlipidemia.10Intracranial arteries are made up of endothelium with smooth muscle cells and an extracellular matrix comprised mostly of collagen and elastin. Stroke due to intracranial atherosclerotic disease is caused by hemodynamic failure, in-situ thrombus from plaque disruption, and/or distal thromboembolism.Previous reports have discussed the occurrence of simultaneous hemorrhagic and ischemic events in patients secondary to dialysis, cerebral amyloid angiopathy, or thrombotic thrombocytopenic purpura.This patient had severe refractory secondary hypertension due to flow-limiting intracranial atherosclerotic disease. We hypothesize this to be the major contributing factor to her hypertensive ICH. This has implications regarding ideal blood pressure management in the emergent setting. Questions arise whether to decrease blood pressure to limit hemorrhage extension and rebleeding or whether to maintain blood pressure to allow perfusion of the oligemic watershed parenchyma. Ideal blood pressure parameters in patients with both intracranial atherosclerotic disease and intracranial hemorrhage is currently unknown. Current American Stroke Association guidelines for ICH recommend lowering systolic blood pressure to 140 mmHg.Another important point concerns the timing of CTA in the ED for patients with ICH. The common benefits of routine CTA imaging would include evaluation for aneurysm, malformations, and other intracranial vascular anomalies often seen in spontaneous hemorrhage. CTA also assists in the selection of aneurysmal treatment planning. An additional benefit of CTA in the ED during ICH would be identifying intracranial stenosis, similar to this case, which may be the underlying cause of secondary hypertension.This is a case of intracranial hemorrhage secondary to refractory hypertension due to severe intracranial atherosclerotic stenosis. Further exploration is needed of the critical questions that arise, such as ideal blood pressure parameters for management, timeliness and routine use of CTA in the ED, and subsequent selection of treatment plan in the dual-lesion patient populations.


Significant numbers of chronic obstructive respiratory disease patients are readmitted for Acute Exacerbation (AE) within 30 days of discharge. And these early readmissions have serious clinical and socioeconomic consequences. The objective of our study was to determine the rate of readmission within 30 days of discharge and it’s predictors among patients treated for acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD).A prospective cohort study involving 130 patients  was conducted from April-September, 2019, in Jimma Medical Center (JMC), South-West Ethiopia. Socio-demographic, clinical, laboratory, and drug-related data were recorded at admission and during hospital stay. Cox regression analysis was performed to identify risk factors for readmissions following an AE of asthma and COPD.During the study period, 130 ) patients were admitted with AE of asthma and COPD. The median age was 59 years. Of 130 patients, 21(18.10%) had a new AE of asthma and COPD that required hospitalization in the 30 days after discharge. The overall median survival time to 30-day readmission was 20 days . Multivariate analysis revealed prolonged use of oxygen therapy  to be independent risk factors for early readmissions.Early hospital readmission rates for AE of asthma and COPD were alarmingly high. Frequent hospital admission and long-term oxygen therapy during hospital stay were independent predictors of 30-day readmission. Asthma and Chronic Obstructive Pulmonary Disease (COPD), commonly called chronic respiratory diseases, are common diseases with a heterogeneous distribution worldwide. The clinical course is punctuated by intermittent episodes of acute worsening of symptoms, termed exacerbations . ExacerbAccording to the Global Burden ofDisease (GBD) report in 2015, asthma and COPD affected an estimated 358.2 and 174.5 million people, respectively .The overall median time to 30-day readmission was 20 days . The median time to 30-day readmission for AECOPD was 20 days , while 21.5days (IQR.16-29) for acute exacerbation of asthma, (p = 0.773). .Several variables such as history of hospital admission, use of high dose salbutamol inhaler, chest clinic physician visit, occupational status, residence, and other four variables  were omitted from analysis due to violation of cell adequacy test and two variables (comorbidity and living status) removed due to co-linearity effect. Therefore, nine variables were candidates for bivariate Cox-regression analysis (p<0.25) depicted in Accordingly, patients who were on oxygen therapy for ≥16hrs per 24hrs had 5 times increased hazard of 30-day readmission  .This prospective cohort study summarized the rate of 30-day readmission and it’s predictors among patient treated for acute exacerbation of chronic obstructive respiratory disease, asthma, and COPD. During the study period, 21(18.01%) patients were readmitted, making an overall incidence rate of 55.8 per100, 000 person-years (COPD = 7(6.03%), asthma = 14(12.07%). It was 59.9 per 100,000 person-year, 95% CI,  for AE of COPD and Asthma, respectively. The overall median survival time to 30-day readmission was 20 days . The median survival time to 30-day readmission for AECOPD was 20 days , and that of AE of asthma was 21.5 days (IQR.16-29). Prolonged use of oxygen therapy and frequent hospital admissions were independent predictors for 30-day readmission.Regarding an overall rate of 30-days readmission, our finding (21(18.01%)) was almost similar with studies conducted in Chicago , Ohio 3, Spain , and USAIn this study, one hundred sixteen (89.23%) patients were adherent (efficient) to inhalation technique. This adherence rate is relatively better than the study conducted by Kebede et al, 87(62.14%) . In a stGuerrero M et al., [Although we have evaluated a wide range of risk factors for hospital readmission, only two clinical factors were found to be independent predictors of 30-days readmission in the current study. In our study, patients who were on oxygen therapy for ≥16hrs per day had 5 times increased hazard of 30-day readmission Click here for additional data file.S2 File(DOCX)Click here for additional data file.


Stage 5 chronic kidney disease (CKD-5) patients on haemodialysis (HD) are at high risk of accidental falls. Previous research has shown that frailty is one of the primary contributors to the increased risk of falling in this clinical population. However, HD patients often present with abnormalities of cardiovascular function such as baroreflex impairment and orthostatic dysregulation of blood pressure (BP) which may also be implicated in the aetiology of falling. Therefore, we aimed to explore the relative importance of frailty and cardiovascular function as potential exercise-modifiable predictors of falls in these patients.Ninety-three prevalent CKD-5 patients on HD from three Renal Units were recruited for this prospective cohort study, which was conducted between October 2015 and August 2018. At baseline, frailty status was assessed using the Fried’s frailty phenotype, while physical function was evaluated through timed up and go (TUG), five repetitions chair sit-to-stand (CSTS-5), objectively measured physical activity, and maximal voluntary isometric strength. Baroreflex and haemodynamic function at rest and in response to a 60° head-up tilt test (HUT-60°) were also assessed by means of the Task Force Monitor. The number of falls experienced was recorded once a month during 12 months of follow-up.p = 0.003) and other physical function determinants were associated with a higher number of falls. In multivariate analysis however, only worse baroreflex function , and orthostatic decrements of BP to HUT-60°  remained significantly associated with a greater number of falls. Eighty falls were recorded during the study period and the majority of them (41.3%) were precipitated by dizziness symptoms, as reported by participants.In univariate negative binomial regression analysis, frailty . Stage 5 chronic kidney disease (CKD-5) patients receiving maintenance haemodialysis (HD) are at high risk of falls and fall-related injuries –3, with The prevalence of physical frailty in the CKD-5 population is 36.8% and is approximately five-fold higher than in community-dwelling older adults , 10. FroThe objective of this investigation was to explore the relative importance of frailty and cardiovascular function as potential exercise-modifiable predictors of falls in CKD-5 patients on HD. We hypothesised that 1) frailty and cardiovascular function would be associated with a higher number of falls, and that 2) modelling the risk of falling by adding a cardiovascular function variable to frailty would improve the prediction of falls sustained and recorded over a 12-month period in CKD-5 patients on HD.An observational prospective study design was used to investigate the association between potential predictors of falls  and the number of falls sustained over a 12-month follow-up period in CKD-5 patients on HD.The study was conducted in three National Health Service (NHS) Renal Units located in North Lanarkshire and Fife, United Kingdom, between October 2015 and August 2018. Recruitment started in October 2015 and continued on a rolling basis until December 2017. All potential predictors and clinical variables were assessed (during a single session of 2 hours duration) at baseline for each participant between October 2015 and December 2017, while the follow-up period ran from November 2015 to August 2018.ClinicalTrials.gov .This research project abided by the ethical principles for medical research involving human participants, as set out by the world medical association declaration of Helsinki, and received ethical approval by the West of Scotland NHS and Queen Margaret University Research Ethics Committees (NHS REC reference number: 15/WS/0079). This research project was prospectively registered in Prevalent ambulatory CKD-5 patients stable on HD therapy for at least 3 months, fluent in spoken and written English, and ≥ 18 years of age were considered eligible to participate in the study.Exclusion criteria were lower limb amputation without prosthesis, unstable dialysis and medication treatment, unstable cardiac condition, clinically severe left ventricular outflow obstruction, suspected or known aneurysm, critical mitral stenosis, critical cerebrovascular stenosis, critical proximal coronary artery stenosis, pregnancy and severe cognitive impairment.All patients who agreed to take part in the study provided written informed consent.Patient demographics , and clinical characteristics  were extracted from the patients’ medical records. Height and weight were measured on the assessment day.A fall was operationally defined as an unexpected event in which the participant comes to rest on the ground, floor, or lower level . One resA modified version of the Fried’s frailty phenotype was used to assess frailty . Patient1) The 3-m timed up and go (TUG) test was used to assess dynamic balance . 2) The The arterial baroreflex was assessed during quiet rest (in supine position) and in response to a five-minute head-up tilt test at 60° (HUT-60°) . The TasBaroreflex function variables taken for the analysis were i) number of up (up-events) and down (down-events) baroreceptor events, defined as the simultaneous coupling of a contSBP ramp (+/− 1 mmHg for 3 consecutive beats) with either an increase or decrease of the RRI of at least 4 ms. The total number of baroreceptor events  were then calculated as the sum of all down-events and up-events, ii) the down/up/total baroreceptor effectiveness index (BEI), representing the ratio of occurred down/up/total baroreceptor events and detected down/up/total BP ramps expressed as a percentage , and iiiStatistical analyses were performed with SPSS . The Kolmogorov-Smirnov Test (K-S) was used to assess whether data were normally distributed. Differences between fallers and non-fallers in demographic, clinical, frailty, and cardiovascular characteristics were analysed by means of a Chi-Squared test for categorical variables, and by either Mann-Whitney U or independent t-tests, as appropriate, for continuous variables.p-value ≤ .05) were taken forward to the multivariate stage. The multivariate analysis consisted of a first model (Model 1), in which all factors were adjusted for clinical confounders, while a second model was designed to assess the second research hypothesis. In this second model (Model 2), frailty and physical function factors were adjusted for all variables in Model 1 and for the cardiovascular function variable showing the highest correlation (R2) with number of falls, while cardiovascular factors were adjusted for all variables in Model 1 and for frailty. In a further analysis, we calculated the relative change in Akaike’s Information criterion (AIC) to explore the goodness of fit of negative binomial regression models where only frailty and cardiovascular function variables were entered simultaneously.The association between baseline factors and the number of falls recorded during follow-up was analysed by means of negative binomial regression with an overdispersion parameter estimated on the actual distribution of the dependent variable . All frailty and cardiovascular factors were initially entered in a univariate negative binomial regression model, and those factors reaching statistical significance  analysis of those potential factors associated with falls (yes or no), and the area under the curve (AUC) was used to compare the predictive ability of frailty alone with a model composed of frailty and a cardiovascular predictor. Statistical limits for significance were set at an alpha level of n = 7; 7.5%), ii) deterioration of health conditions  and iii) death . The remaining 76 patients completed all baseline assessments and were enrolled in the study. Seven participants (9.2%) were lost to follow-up due to renal transplantation  and death . Therefore, 69 patients were entered in the final analysis.Ninety-three patients undergoing outpatient HD therapy at the Renal Units provided written informed consent. Seventeen patients (18.3%) did not complete baseline assessments due to i) change of mind or inability to schedule an assessment appointment within a couple of months from consent .Figure We hypothesised that frailty and cardiovascular function would be associated with a higher number of falls in CKD-5 patients on HD. Additionally, we hypothesised that modelling the risk of falling by adding a cardiovascular function variable to frailty would improve the prediction of falls sustained over 12 months in this patient population.The univariate negative binomial regression analysis revealed that frailty and other physical function measures, such as number of daily steps and sit to stands, handgrip strength, gait speed, and TUG were associated with a higher number of falls in the study population. In addition, cardiovascular function indices such as total-BEI, CO and OscDBP responses to HUT-60°, were also associated with a higher number of falls Table . HoweverThe overall implications of these findings are that the addition of a baroreflex function index to an exclusively physical frailty-based model, did not only improve the prediction of falls, but it also highlighted the greater relative importance of a cardiovascular function index, implicated in the short-term regulation of BP, in predicting the occurrence of these falls. In particular, the forced entry modelling performed in Model 2 of the negative binomial regression analysis Table , as wellThe predominant role of these cardiovascular factors appeared to be also indirectly confirmed by the fall-related symptomatology reported by study participants Fig. . The mosAnother interesting finding was that BEI but not BRS was associated with a higher number of falls. The BEI is a measure that describes how often the baroreflex is activated , in contMany dialysis-specific or idiopathic risk factors may be involved in the dysregulation of BP which could possibly lead to dizziness symptoms and falls in this clinical population. First of all, the uremia-related cardiac autonomic dysfunction, characterised by alterations of the sympathetic, parasympathetic, and baroreflex components of the autonomic nervous system, is a factor that has been linked to symptomatic hypotension in CKD-5 patients . MoreoveImportantly, a systematic review with meta-analysis has recently concluded that exercise training can ameliorate autonomic regulation in CKD patients . In partThe estimates of association between frailty and number of falls experienced emerging from this study are similar to those observed by previous research , 12. In Interestingly, the exploratory independent comparisons of fallers and non-fallers revealed that those who fell were more likely to use antidepressants (50% vs 23.8%) and had higher CRP levels (37.6 ± 59.2 mg/L vs 18.3 ± 32.7 mg/L). Because both antidepressant use and high CRP levels have been linked to a higher risk of falling by previous research conducted on HD patients , we adjup = 0.084), and it is possible that a larger sample size may have also resulted into better chances of detecting a significant association between OscSBP decrements and falls, by decreasing the chances of committing a type II error. The lack of relationship between contBP and falls may also be explained in light of the orthostatic challenge used in our study, as previous research has shown that the initial response of contBP to passive tilting is less pronounced or even absent compared to active stand procedures [It should be acknowledged that because the sample size was relatively small, we could not apply a more exhaustive multivariate negative binomial regression analysis to more robustly test the interrelationships between frailty/physical function, cardiovascular function, and falls. In addition, we should also acknowledge that, while orthostatic decrements of OscDBP were significantly associated with falls Table , orthostocedures , 46. Addocedures , 47. Preocedures . TherefoThis prospective cohort study indicates that by adding a cardiovascular index, implicated in the short-term regulation of BP, to a frailty-only model it was possible to improve significantly the prediction of falls in CKD-5 patients on HD. Baroreflex function, as assessed by means of BEI, and orthostatic decrements of BP showed a higher impact, and thus greater relative importance, than frailty in predicting number of falls in the study population. The clinical implications of these findings indicate that a simple non-invasive, time-efficient, assessment consisting of a continuous and simultaneous recording of BP and HR may be more useful than frailty assessment alone when predicting falls in HD patients. A high number of falls appear to be mediated by a degree of cardiovascular dysregulation, evidenced by the predominance of self-reported dizziness symptoms. We therefore recommend that interventions designed to improve baroreflex function/short-term regulation of BP should be considered when implementing falls prevention programmes in this patient population.Additional file 1: Table S1. Multicollinearity analysis: correlations among baroreflex function variables; Table S2. Negative binomial regression analysis: sensitivity analyses.


The management of resistant hypertension presents several challenges in everyday clinical practice. During the past few years, several studies have been performed to identify efficient and safe pharmacological and non-pharmacological options for the management of such patients. The Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2) trial demonstrated significant benefits with the use of spinorolactone as a fourth-line drug for the treatment of resistant hypertension over doxazosin and bisoprolol. In addition, recent data support that spironolactone may demonstrate superiority over central acting drugs in such patients, as well. Based on the European guidelines, spironolactone is recommended as the fourth-line drug option, followed by amiloride, other diuretics, doxazosin, bisoprolol or clonidine.  Among several device-based approaches, renal sympathetic denervation had fallen into hibernation after the disappointing results of the Renal Denervation in Patients With Uncontrolled Hypertension (SYMPLICITY HTN) 3 trial. However, the technique re-emerged at the epicenter of the clinical and research interest after the favorable results of three sham-controlled studies, which facilitated novel catheters and techniques to perform the denervation. Significant results of iliac anastomosis on blood pressure levels have also been demonstrated. Nevertheless, the technique-related adverse events resulted in withdrawal of this interventional approach. Last, the sympatholytic properties of the carotid baroreceptor activation therapy were associated with significant blood pressure reductions in patients with resistant hypertension, which need to be verified in larger controlled trials. Currently device-based approaches are recommended only in the setting of clinical trials until more safety and efficacy data become available. However, the true prevalence of resistant hypertension after applying a strict definition and having excluded causes of pseudo-resistant hypertension is less than 10% of the patients with treated hypertension1. Importantly, resistant hypertension is related with higher risk for cardiovascular morbidity and mortality, chronic kidney disease, and other hypertension-mediated target organ damage2.The prevalence of resistant hypertension ranges from 5 to 30% on the basis of the definition used by relevant studies1.Based on the European guidelines, resistant hypertension is defined as the failure to reduce systolic or diastolic blood pressure (BP) levels (or both) below 140 and 90 mm Hg, respectively, despite treatment with optimal doses (or best-tolerated doses) of an appropriate therapeutic strategy with the triple combination of an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker with a calcium channel blocker and a thiazide/thiazide-type diuretic. As stated in the guidelines, home or ambulatory BP measurements should be used to confirm inadequate BP control, and exclusion of pseudo-resistant hypertension and secondary hypertension is mandatory to establish the diagnosis3. During the past few years, several studies in resistant hypertension, and especially the spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2) trial4, resulted in changes in the recommendations for the management of resistant hypertension. Specifically, the addition of “low-dose spironolactone to existing treatment, or the addition of further diuretic therapy if intolerant to spironolactone, with either eplerenone, amiloride, higher-dose thiazide/thiazide-like diuretic or a loop diuretic, or the addition of bisoprolol or doxazosin” is now recommended1. Similarly, the consensus document of the American Heart Association for the management of resistant hypertension recommends the use of either spironolactone or eplerenone as a fourth-line agent, followed by a beta-blocker, a dual beta- and alpha-blocker, clonidine, or diltiazem5. The purposes of this review are to report and critically discuss the findings of recent studies that resulted in a stronger recommendation for the treatment of resistant hypertension and to report treatments under investigation that could prove to be useful in such patients.In the previous European guidelines (2013), the use of mineralocorticoid receptor antagonists, amiloride, and the alpha-1 blocker doxazosin were considered for the management of resistant hypertension1. A 2016 study demonstrated that readings performed in a routine triage setting were higher than the readings performed by trained physicians and resulted in a misdiagnosis of uncontrolled resistant hypertension in 33% of the patients6. Under-treatment is also a common cause of pseudo-resistant hypertension, and studies indicate that a lack of BP control is often attributable to the absence of treatment intensification7.The exclusion of pseudo-hypertension is of paramount importance for the establishment of an accurate diagnosis. BP is often measured inaccurately; wrong-sized cuffs, measurement of BP only once, placement the cuff over the patient’s clothes, and wrong position of the patient are common mistakes performed in everyday clinical practice8.Another important cause of pseudo-resistant hypertension is poor medication adherence. The recent Renal Sympathetic Denervation as a New Treatment for Therapy Resistant Hypertension (SYMPATHY) trial examined drug adherence with the detection of drug concentrations in blood samples in patients with uncontrolled hypertension on three or more anti-hypertensive drugs or with documented intolerance to two or more of the four major anti-hypertensive drug classes; 16% were non-adherent and 52% were poorly adherent9. Abstinence in heavy alcohol drinkers may decrease 24 hours systolic and diastolic ambulatory BP levels by up to 7.2 and 6.6 mm Hg, respectively10. Usually, patients with resistant hypertension present an average sodium intake that exceeds 10 g per day11. Salt not only increases BP levels but also blunts the anti-hypertensive effect of the BP-lowering drugs12. In salt-sensitive patients , these effects are much more pronounced13. Moreover, obesity and increased body mass index in general increase significantly BP levels1. The mechanisms that induce hypertension in those patients include the activation of sympathetic nervous system and renin–angiotensin–aldosterone system and also insulin resistance and impaired sodium excretion14. The adoption of current European Society of Cardiology/European Society of Hypertension guidelines on lifestyle changes may significantly decrease BP levels in those patients and contribute to BP control.Lifestyle factors such as excessive alcohol and salt intake contribute to the presence of resistant hypertension. Large amounts of alcohol consumption (three or more drinks per day) have an important dose-related effect on BP levels in both normotensive and hypertensive patients1. The use of NSAIDs not only increases BP levels but also can blunt the effect of various anti-hypertensive drugs such as diuretics, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers1. The hypertensive effect of NSAIDs is more pronounced in patients with chronic kidney disease1. Other substances that can increase BP levels are decongestants and stimulant agents used for weight loss and also contraceptives, cyclosporine, erythropoietin, and cortisone that increase BP levels mainly through fluid retention. A proposed work-up for patients with resistant hypertension is shown inFinally, several drugs and substances may increase BP levels. Non-steroidal anti-inflammatory drugs (NSAIDs) represent probably the most common agents in terms of worsening BP control4. The study was a double-blind four-way crossover study that assessed the use of spironolactone (25 or 50 mg) versus bisoprolol (5 to 10 mg), doxazosin (5 to 10 mg), or placebo. To exclude non-adherence, the study was monitored with pill count and measurement of serum angiotensin-converting enzyme activity. Spironolactone was superior to both active treatments and placebo, and mean reductions in BP were 8.70, 4.48, and 4.03 mm Hg with spironolactone, bisoprolol, and doxazosin, respectively. Importantly, about 60% of the spironolactone users achieved BP control versus 43.3% of the bisoprolol and 41.5% of the doxazosin users4.The landmark PATHWAY-2 study found significant benefits with the use of spironolactone in patients with resistant hypertension on a standard three-drug therapy with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker, amlodipine, and indapamide1. Second, uptitration of spironolactone dose from 25 to 50 mg resulted in a greater reduction in BP at week 12 of the study. The BP-lowering effect of spironolactone uptitration was higher compared with the corresponding increases in the dose of either bisoprolol or doxazosin . Last, while spironolactone reduced BP levels irrespective of renin levels, an enhanced benefit in patients with suppressed renin levels was observed, and there was up to a 20 mm Hg reduction in home BP in patients with the lowest renin levels4.Apart from the beneficial effect of spironolactone in patients with resistant hypertension, the PATHWAY-2 study offered three important findings. First, despite the superiority of spironolactone over bisoprolol and doxazosin, the use of the latter two drugs was associated with significant reductions in BP compared with placebo. Thus, the European guidelines recommend the use of bisoprolol and doxazosin for the treatment of resistant hypertension when spironolactone is contraindicated or not tolerated1. In the third substudy, the effect of amiloride on systolic BP was examined in a 6- to 12-week open-label run-out phase, in which patients on spironolactone were crossed over from spironolactone to amiloride (146 patients). Amiloride use resulted in a remarkable reduction in BP levels of 20.4 mm Hg, comparable to the 18.3 mm Hg observed with spironolactone, suggesting that amiloride might be an effective alternative agent for these patients. Based on these findings, the European guidelines propose the use of amiloride as an alternative option if spironolactone is contraindicated or not well tolerated15.Important clinical information for the management of resistant hypertension arose from three recent substudies of the PATHWAY-2 trial. In the first substudy, the plasma aldosterone, renin, and aldosterone-to-renin ratio were assessed as predictors of home systolic BP response in 126 patients. Plasma aldosterone-to-renin ratio and plasma renin levels were found to be predictors of BP response to spironolactone. In the second one, the impact of each drug on the thoracic fluid content (an index of fluid retention) and vascular resistance was examined (226 patients). Thoracic fluid content was significantly reduced (by 6.8%) from baseline with spironolactone but not with the other active treatments. Given the overall outcomes of the PATHWAY-2 study, this finding supports the theory that patients with resistant hypertension are characterized by volume overload, secondary to aldosterone excess, explaining the greater benefits observed with spironolactone16. BP control assessed with office and 24-hour ambulatory BP monitoring was similar across the two groups of patients. However, the 24-hour systolic and diastolic BP reduction and the daytime diastolic BP reductions observed with spironolactone were significantly greater than those observed with clonidine. Given the easier dosage scheme of spironolactone and the greater benefits in various ambulatory BP parameters, spironolactone seems to be a preferable option over clonidine17.Although concrete evidence supports the superiority of mineralocorticoid receptor antagonists over alpha- and beta-blockers for patients with resistant hypertension, there is a lack of evidence regarding the use of central acting drugs in such patients. In this setting, the recent Resistant Hypertension Optimal Treatment (ReHOT) study compared the impact of spironolactone and clonidine in 187 patients with resistant hypertension16. A meta-analysis of 662 patients and five trials found that the addition of spironolactone in patients with resistant hypertension resulted in a reduction in office BP levels of 15.73/6.21 mm Hg compared with placebo, but compared with other drugs , spironolactone reduced home systolic BP by 4.5 mm Hg18. In a meta-analysis of five studies and 553 patients with resistant hypertension, spironolactone reduced 24-hour, daytime, nighttime, and office BP by 10.50/4.09, 10.20/4.14, 10.02/3.21, and 16.99/6.18 mm Hg, respectively19. Last, a meta-analysis of five studies and 755 patients with resistant hypertension found a greater reduction in systolic BP levels of 7.4 mm Hg (in the randomized studies) and 11.9 mm Hg (in the non-randomized studies) with mineralocorticoid receptor antagonists compared with other fourth-line options 20.Important information emerged from meta-analytic data for the use of mineralocorticoid receptor antagonists in patients with resistant hypertension. In 869 patients from four trials, spironolactone as add-on therapy was associated with a reduction in BP of 16.67/6.11 mm Hg21, although strong data with eplerenone use are currently missing. Given the substantial fluid retention observed in these patients and the findings of the PATHWAY-2 study, amiloride is an alternative option, while treatment with doxazosin, bisoprolol, or clonidine may also be considered when either mineralocorticoid receptor antagonists or amiloride is contraindicated or adverse events occur.Collectively, accumulating evidence suggests that mineralocorticoid receptor antagonists are the optimal choice as the fourth-line option in patients with resistant hypertension, and data favor their use over central acting drugs, alpha- and beta-blockers. Most data come from studies with spironolactone. However, eplerenone may be considered as an alternative when adverse effects  are observed with spironolactone therapy24. The resistance of the arterial tree walls is another important factor contributing to the rise of BP. Recently, the creation of arteriovenous anastomosis between the distal iliac vein and artery to add a low resistance compartment to the arterial tree was investigated in patients with resistant hypertension25.Interventional approaches represent a novel potential addition on lifestyle interventions and pharmacological therapy for the management of resistant hypertension. The neurogenic mechanisms implicated in BP elevation have been the target of several interventional approaches such as renal sympathetic denervation (RSD) and carotid baroreceptor activation therapy26 and -227 showed impressive reductions in BP and created high expectations for the future of the procedure in the hypertension treatment field. However, the first randomized sham-controlled study (SYMPLICITY HTN-3) failed to show any significant benefits of RSD over sham control in the reduction of both office and ambulatory BP in patients with drug-resistant hypertension28, and the technique fell into hibernation. Although several pitfalls were identified, the incomplete denervation and lack of circumferential, four-quadrant sympathetic fiber interruption were the main factors pointed out as causes of the negative findings of the study29. Three recent randomized sham-controlled studies used improved technologies and techniques to achieve optimal renal denervation and offered encouraging results.The early RSD studies SYMPLICITY HTN-130. Similar results were observed in the SPYRAL HTN-ON MED trial, a randomized sham control study (of patients with uncontrolled hypertension on one to three anti-hypertensive drugs) that used the same techniques described for SPYRAL-OFF MED. RSD resulted in a greater reduction in office and ambulatory BP compared with the sham technique group . No reports of renal artery stenosis or worsening of renal function were reported31. The RADIANCE-HTN SOLO study was the third study that examined whether RSD performed with endovascular ultrasound reduces ambulatory BP in patients with hypertension in the absence of anti-hypertensive medication. After 2 months, significantly greater decreases in BP of −6.5/−4.1, −4.1/−1.8, and −7.1/−3.6 mm Hg in office, ambulatory, and home BP were reported with RSD compared with the sham control group32.The first one was the SPYRAL HTN-OFF MED trial, a randomized sham-controlled study of patients with untreated hypertension. Patients were randomly assigned to RSD of all accessible renal arterial vessels with the Symplicity Spyral multi-electrode catheter or the Symplicity G3 S (n = 38) or a sham procedure (n = 42). After 3 months, RSD resulted in significantly greater reductions in office and ambulatory BP levels compared with those of the sham control group . Importantly, no patient reported any safety concerns33. Particularly, patients with resistant hypertension were assigned to either treatment with radiofrequency RSD of the main renal arteries, side branches, and accessories or an endovascular ultrasound-based RSD of the main renal artery. After 3 months, BP levels were significantly more reduced in the ultrasound ablation group compared with the radiofrequency ablation group of the main renal artery . Importantly, no significant difference was found between the radiofrequency ablation groups  or between the ultrasound and the side branch ablation groups, suggesting potential superiority of ultrasound over radiofrequency ablation of the main artery in reducing BP levels33. However, larger studies are needed to confirm or dispute the superiority of one technique over the other. Up to then, no approach could be considered the preferred or first-choice option.A recent study assessed the efficacy of different ablation methods in reducing BPCollectively, these studies resurfaced the clinical and research interest for RSD in the management of resistant hypertension. Although more patients demonstrated BP reduction with RSD than with the sham procedure, in several study participants who underwent RSD, an increase in BP was noticed, suggesting that some patients are not eligible for RSD. The quest of patient eligibility requires the identification of reliable and accurate predictors of BP response, a very demanding step with unknown outcome. Studies with larger study populations and longer follow-up periods are needed to establish the safety and efficacy of the technique, and several such studies are either planned or being conducted. The results of these studies will either re-enforce the concept of RSD or put the final nail in the coffin of this interventional approach.34. After 12 months, office BP and ambulatory BP were reduced by 25/20.8 and 12.6/15.3 mm Hg, respectively, suggesting that the technique might offer long-lasting benefits in BP levels. Nevertheless, the percentage of patients who presented venous stenosis increased to 33%, who were treated successfully with venous stenting35. In conclusion, although iliac anastomosis showed promise in terms of efficacy, the safety concerns were significant and this approach was recently abandoned.The ROX CONTROL HTN study randomly assigned 83 patients with resistant hypertension to either pharmacological treatment plus placement of an arteriovenous coupler or pharmacological therapy alone. After 6 months, significant reductions in office and ambulatory systolic BP of 26.9 and 13.5 mm Hg were noted with the anastomosis device group, respectively. In contrast, such benefits were not observed in the control group . Similarly, a significant reduction in diastolic BP was reported with the device. However, implantation of the arteriovenous coupler was associated with ipsilateral venous stenosis in 29% of the patients, who received venoplasty or stenting37. The potential benefits might be due to the reduction of heart rate (and thus cardiac workload and energy demands) and the manifestation of arterial dilation, which results in reduction of the peripheral resistance and enhancement of renal blood flow and natriuresis.Carotid baroreceptor activation therapy is a device-based approach aiming to activate the baroreceptors that signal the brain to activate a sympatholytic response. Such approaches might be useful in conditions characterized by sympathetic overactivity, such as hypertension, heart failure, and arrhythmias38.The Rheos Pivotal Trial assessed the impact of the Rheos system, a device that uses electrical impulses from a pulse generator to chronically activate the baroreflex at the carotid sinus, on BP levels in 265 patients with resistant hypertension. In the first group of patients, treatment was applied for the first 6 months, whereas in the second group, a delayed treatment initiation was implemented at the 6-month visit; 42% of patients in the first group versus 24% in the second group achieved systolic BP of less than 140 mm Hg at 6 months, and more than 50% in both groups had a systolic BP of less than 140 mm Hg at 12 months. However, the procedural safety endpoints of the study were not met since procedural complications occurred in 25% of the patients 39. The Barostim Neo System in the Treatment of Heart Failure/Barostim Hope for Heart Failure and the recent Baroreflex Activation Therapy in Patients with Heart Failure and a Reduced Ejection Fraction trials41 demonstrated significant benefits in the functional status, quality of life, and exercise capacity in patients with heart failure and reduced injection fraction. Importantly, these studies met the safety endpoints; thus, the device was granted approval by the US Food and Drug Administration39. The device has also been approved in Europe for the management of resistant hypertension; the Barostim Neo trial demonstrated a persistent reduction in BP after 6 months (of a systolic BP of approximately 26 mm Hg) and an adequate safety profile42.However, the same company developed a second-generation device of smaller size, the Barostim Neo, which uses a smaller electrode on the surface of only one of the sinuses, thus reducing the invasiveness of the procedure and extending the battery life and replacement periodOverall, baroreflex activation therapy is approved for the treatment of resistant hypertension in Europe and for the treatment of heart failure with reduced ejection fraction in the US. However, it is more invasive than RSD, the safety of the procedure is not unequivocally proven, and thus it has not gained either wide application or general acceptance by hypertensive experts for the management of resistant hypertension.43. Importantly, the device demonstrated an acceptable safety profile43. Two other trials—the CALM-FIM_US44 and the Controlling and Lowering Blood Pressure with the MobiusHD (CALM-2)45 studies—are examining the use of the MobiusHD device in patients with resistant hypertension. The results of these studies are eagerly awaited to further clarify the efficacy and safety of this approach and strengthen its role in the management of resistant hypertension.The MobiusHD carotid bulb expansion device is an under-examination device that is used to reduce BP through stretching of the carotid artery at the bulb, which in turn activates the carotid baroreceptors. The Controlling and Lowering Blood Pressure with the MOBIUSHD (CALM-FIM_EUR) study recently reported pronounced reduction in BP levels of 24/12 mm Hg in office and 21/12 mm Hg in ambulatory BP with the use of the MobiusHD device in patients with resistant hypertension51. It has been suggested that the increased fluid retention and consequent upper airway edema may explain the high prevalence of OSA in these patients53. In addition, central fluid accumulation during sleep seems to significantly contribute to the manifestation and worsening of OSA56. Treatment of OSA with continuous positive airway pressure (CPAP) in patients with resistant hypertension was found to induce a modest but significant reduction in BP levels. In a study of patients with resistant hypertension and OSA, CPAP treatment resulted in a reduction in ambulatory BP of 3.1/3.2 mm Hg, an effect that was even greater in patients more adherent to CPAP therapy (reduction in ambulatory BP of 4.4/4.1 mm Hg with at least 4 hours of CPAP treatment per night)57. In contrast, a favorable impact of CPAP treatment on the prevention of cardiovascular events has not yet been demonstrated58.Obstructive sleep apnea (OSA) is highly prevalent in patients with resistant hypertension59. Refractory hypertension is defined as failure of BP control with the use of five or more anti-hypertensive drugs of different drug classes, including a long-acting thiazide diuretic, such as chlorthalidone, and a mineralocorticoid receptor antagonist59. This novel type of uncontrolled hypertension seems to be rare, affecting less than 5% of the patients referred to a specialized clinic for uncontrolled hypertension. Furthermore, refractory hypertension was found to be more frequent in African-American, younger, and female patients62. There is evidence suggesting that the cause of treatment failure in patients with refractory hypertension, in contrast to resistant hypertension, is the increased sympathetic tone, rather than fluid retention, as indicated by the increased heart rate levels and urine norepinephrine excretion in such patients62. Therefore, intensification of diuretic therapy may not be effective, and sympatholytic agents or device-based therapy may be preferable62. However, data in such patients are still missing and studies are needed to identify optimal management options.The term refractory hypertension has been recently re-introduced and was included in the 2017 American guidelines for the management of hypertensionDuring the past few years, important data for the management of resistant hypertension have emerged. Most data support that mineralocorticoid antagonists  present more favorable BP-lowering properties in patients with resistant hypertension compared with central acting drugs, alpha- and beta-blockers. In case of contraindications or adverse events, amiloride should be used as an alternative option followed by doxazosin, bisoprolol, or clonidine.Several device-based approaches are being investigated, and recent RSD trials have rekindled interest in the interventional therapy of resistant hypertension. The few studies implementing carotid baroreceptor stimulation have shown favorable results, which need to be verified in controlled trials with a long follow-up period, while safety concerns need to be adequately addressed. Iliac anastomosis devices are no longer available in our therapeutic armamentarium. Overall, we are living in exciting times in the resistant hypertension field, and a lot of data, especially about the role of interventional approaches in the treatment of resistant hypertension, are eagerly expected in the near future.


Serum concentrations of the uremic metabolites increased with kidney function deterioration. Gut microbial diversity did not differ among the examined patient and control groups. In moderate or higher stage CKD groups, Oscillibacter showed positive interactions with other microbiota, and the proportions of Oscillibacter were positively correlated with those of the uremic metabolites. The gut microbiota, particularly Oscillibacter, was predicted to contribute to pyruvate metabolism which increased with CKD progression. Relative abundance of Oscillibacter was significantly associated with both serum uremic metabolite levels and kidney function. Predicted functional analysis suggested that kidney-function-associated changes in the contribution of Oscillibacter to pyruvate metabolism in CKD may greatly affect the gut environment according to kidney function, resulting in dysbiosis concomitant with uremic toxin production. The gut microbiota could be associated with uremia progression in CKD. These results may provide basis for further metagenomics analysis of kidney diseases.Chronic kidney disease (CKD)-associated uremia aggravates—and is aggravated by—gut dysbiosis. However, the correlation between CKD severity and gut microbiota and/or their uremic metabolites is unclear. We enrolled 103 CKD patients with stage 1 to 5 and 46 healthy controls. We analyzed patients’ gut microbiota by MiSeq system and measured the serum concentrations of four uremic metabolites ( More than one trillion microbes are found in the human body , and theGut dysbiosis due to kidney impairment is specifically associated with an alteration in uremic toxin metabolism ,10. VariAlthough various studies have reported the relationship between gut dysbiosis and kidney function impairment, as well as the involvement of gut microbiota in uremic toxin metabolism ,19,20, fThis study was approved by the Medical Ethics Committee of Seoul National University Hospital (IRB number: 1808-153-967) and complied with the Declaration of Helsinki. The study included only participants who provided informed consent and agreed to submit fecal specimens to the human stool repository (IRB number: 1802-062-921). The human stool repository includes samples collected from patients who underwent percutaneous kidney biopsy (IRB number: 1508-046-694) and from kidney transplant donors and recipients prior to transplantation (IRB number: 1703-062-839). We also obtained serum samples at the same time as feces collection from registered participants. The serum samples for this study were provided by the Seoul National University Hospital Human Biobank, a member of the National Biobank of Korea. All samples derived from the National Biobank of Korea were obtained with informed consent under institutional review-board-approved protocols.We collected demographic information from the study participants, including details on age, sex, height, and weight, and established whether any of these individuals had comorbidities, including hypertension and diabetes mellitus, as determined from their clinical and medication histories compiled in an electronic medical record system. Participants who had used antibiotics within one month were excluded. Furthermore, given that gut microbiota may be affected by the systemic inflammation status, we also collected data on the serum levels of highly sensitive C-reactive protein, which is used as a marker of inflammation.Kidney function was assessed by measuring serum blood urea nitrogen and creatinine levels at the time of fecal sample collection. The presence of hematuria and amount of proteinuria were quantified based on urine microscopic examination and random urine protein to creatinine ratio determinations, respectively. Plasma hemoglobin and serum albumin concentrations were examined to evaluate the anemia and nutritional status, respectively. The etiologies of CKD were established by pathological confirmation, imaging studies, or clinical diagnosis. The estimated glomerular filtration rate was calculated using the Chronic Kidney Disease Epidemiology Collaboration calculation formula according to CKD staging.We divided the study participants into the following groups: kidney donors without evidence of kidney disease as healthy controls; patients with stage 1 and 2 CKD as mild CKD; patients with stage 3 and 4 CKD, and stage 5 CKD without dialysis, as moderate to severe CKD; and patients with stage 5 CKD requiring dialysis as end-stage renal disease (ESRD).® Fast DNA Stool Mini Kit  according to the manufacturer’s instructions [The stool samples collected from all study participants were immediately stored in a deep freezer at −80 °C. Stool DNA extraction was performed using a QIAampructions . The exthttp://www.drive5.com/usearch). Primer sequences were removed from the merged sequences, and filtered sequences were subsequently clustered into operational taxonomic units (OTUs) based on 97% sequence identity. The taxonomic positions of representative sequences in each OTU were assigned based on comparisons with the EzTaxon-e reference database [q < 0.05 (Benjamini–Hochberg-corrected). Networks were constructed for significantly different direct interactions among genera in the different patient groups, with the visualization of networks and calculations performed using CoNet with Cytoscape (v. 3.4.0).For microbiota analysis, the obtained sequence reads were analyzed using the Microbial Genomics Module of CLC genomic workbench v. 11.0.1 . Briefly, raw sequences were merged, and sequences with short read lengths (<400 base pairs of merged reads) or low-quality score and chimeric reads were removed using the USEARCH pipeline v. 11.0.667  was applied to correct for multiple testing and FDR-adjusted p-values of less than 0.05 were considered as significant. Statistical analyses were performed using R v. 3.5.0 (R Core Team), Stata v. 15.1 , and GraphPad Prism v. 8.1.1 .For the baseline characteristics, continuous variables are expressed as the means and standard deviations and categorical variables are expressed as percentages. Differences between samples were evaluated using the Mann–Whitney U and Kruskal–Wallis tests. The p = 0.003). The participants with lower kidney function had more comorbidities, including hypertension and diabetes mellitus . In line with expectations, we observed that plasma hemoglobin and serum albumin levels were negatively correlated with CKD severity . The proportion of patients with anemia increased significantly with worsening CKD severity (p < 0.001). However, serum levels of highly sensitive C-reactive protein did not differ significantly among the four groups.We analyzed samples collected from a total of 149 participants, among whom there were 46 controls and 103 patients with CKD. The patients with CKD comprised 36 subjects with mild CKD, 32 with moderate to severe CKD, and 35 with dialysis-dependent ESRD. The baseline characteristics, laboratory data, and uremic metabolite concentrations were compared among groups . We founp-cresyl sulfate, p-cresyl glucuronide, indoxyl sulfate, and TMAO in the sera revealed clear positive correlations with CKD severity , although there were no significant differences in the levels of these metabolites between participants in the control and mild CKD groups . When we evaluated the differences in genera among groups based on multiple group comparisons, the proportions of Alistipes, Oscillibacter, Lachnospira, Veillonella, and Dialister were shown to be significantly different among the four groups , whereas the abundance of Lachnospira, Veillonella, and Dialister decreased with increasing CKD severity .A total of 1,796 OTUs were detected in all patients. To compare the diversity indices among samples, read numbers were normalized to 6,400 by random subsampling, and we accordingly detected no significant differences in bacterial diversity among the different patient groups  in multivariable linear regression, p-cresyl sulfate showed a significant association with six major genera, with positive correlations observed with Alistipes, Oscillibacter, and Subdoligranulum  and negative correlations with Lachnospira, Veillonella, and Megamonas . Serum p-cresyl glucuronide and indoxyl sulfate levels were positively correlated with Alistipes  and Oscillibacter . Serum TMAO levels were associated only with Oscillibacter (q = 0.006). Unexpectedly, we found Oscillibacter to be associated with all four measured uremic toxins, although each of these metabolites is derived from different parent compounds.We subsequently analyzed differences in the relative abundance of gut microbiota according to the levels of uremic toxins in the sera of patients and controls. The genera found to be associated with the levels of uremic toxins are shown on a logarithmic scale in q < 0.05; The functions of the gut microbiota were predicted based on PICRUSt analysis and a comparison of pathways based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) categories among the different CKD groups. At KEGG Ortholog (KO) level 3, four pathways were predicted to be significantly different among groups  showed the highest proportional contribution of Oscillibacter (33.0% for K00161 and 33.1% for K00162). Among all genera, Oscillibacter also showed a high proportional contribution (21.3%) to the pyruvate dehydrogenase E2 component (K00627). These findings indicate that Oscillibacter is a primary source of pyruvate dehydrogenase, a key enzyme involved in glucose oxidation that converts pyruvate to acetyl-CoA. The proportional contributions of Oscillibacter to each orthologous gene involved in pyruvate metabolism compared with those of other genera are shown in As Oscillibacter to each of pyruvate metabolism orthologs according to CKD severity, we found that the contribution to pyruvate dehydrogenase E1 component decreased by approximately 10% in CKD groups compared with the control group . In contrast, we found that the contribution of Oscillibacter to lactate dehydrogenase, which converts pyruvate to lactate, was significantly increased , the relative abundances of which showed continuous change concomitant with changes in kidney function. Given that previous studies only investigated differences in OTUs at the family level or differences in OTUs between control and subjected with ESRD [Clostridia which includes Oscillibacter, was reported to show a significant elevation in patients with ESRD compared with control subjects, thereby indicating that our findings are at least partially consistent with those reported previously.Although several studies have analyzed the gut microbiota in patients with CKD, most studies focused on the differences between patients with ESRD and healthy controls. For example, Vaziri et al. identified a significant elevation in the relative abundance of 190 OTUs in patients with ESRD compared with healthy controls . Similarith ESRD ,31, it iith ESRD , the claOscillibacter and Veillonella appear to have important roles as network hubs for the other microbes in the analysis of network co-occurrence. Particularly, Oscillibacter showed significant positive associations with diverse genera in patients with advanced CKD, indicating that the bacterial species in this genus interact with those in other bacteria in the gut microbiota of patients with advanced CKD. Moreover, we found that Oscillibacter showed common associations with the four uremic metabolites p-cresyl sulfate, p-cresyl glucuronate, indoxyl sulfate, and TMAO, which are derived from a diverse range of parent compounds, including phenols, indoles, and quaternary amines. These broad effects on uremic metabolites and other microbes suggest that Oscillibacter play a pivotal role in creating a favorable inflammatory environment that facilitates the proliferation and activation of a number of uremic toxin-producing pathogens. Although they are poorly represented in culture collections, the genus Oscillibacter was detected in human gut microbiota related to some pathologic state [Oscillibacter abundance had been found in patients with stroke and closely related to gut permeability and host inflammation [Oscillibacter with respect to kidney disease has not been reported. Veillonella, another core microbiota associated with CKD stages, has not been studied in gut microbiota from patients with kidney disease, although they were previously reported to be decreased in saliva and oral swab samples of patients with CKD [Of the bacterial taxa showing significant differences among the CKD groups, ic state ,33,34. Eammation . Howeverwith CKD .Oscillibacter-related genes. Moreover, we observed that the elevated abundance of Oscillibacter and their contribution to pyruvate metabolism were weighted toward anaerobic glycolysis (represented by lactate production) rather than to aerobic glycolysis as kidney function deteriorated. A recent metabolomics study revealed that citric acid metabolism in the tricarboxylic acid cycle, a subsequent pathway of pyruvate, is the most altered metabolic pathway in patients with nondiabetic CKD stages 3–4 compared to in healthy controls [Oscillibacter is significantly associated with serum lactate levels according to an animal study and the genus Veillonella is related to the metabolism of lactate to propionate in athletes [In the present study, we conducted predicted functional analyses to detect clues indicating the physiological role of the microbiota in the production of toxins associated with kidney dysfunction. We found that as kidney function deteriorated, there was an increase in the microbial contributions to pyruvate metabolism, particularly with regards to the proportional contribution of controls . Furtherathletes ,39. The athletes . Based oAlthough the present study has notable strengths, such as including an entire spectrum of CKD stages, there were also limitations. First, we did not establish any clear causal relationships among microbiota, microbial metabolites, and CKD. Although we demonstrated associations between microbes and specific metabolites within the microbiota, the causal mechanisms should be determined in further studies. Second, the number of participants registered in each group was relatively small. However, compared with previous studies of CKD and microbiomes, we evaluated a similar or larger number of participants. Furthermore, although we obtained comparative values at certain times during CKD progression, we did not observe serial changes in renal function over time. Finally, we did not assess interactions between the human host and observed microbiota as immunological factors or perform gene expression analyses. However, this study provides a possible association between gut microbiota and renal functions.Oscillibacter within the gut microbiota, the bacteria of which interact with other gut microbes. Based on our observations, Oscillibacter may create a favorable environment for the production of various uremic metabolites, and such action may be related to the altered contribution of Oscillibacter to the pyruvate metabolism pathway. Further studies are needed to confirm our results and perform more in-depth analyses of the various interrelationships among the gut microbiome, microbial metabolites, and CKD progression.In this study, we detected significant correlations among the gut microbiota, uremic metabolites, and renal functions in patients with CKD, providing insights into the role of the gut microbiome in the progression of kidney disease. Our findings indicate that the deterioration in renal function observed in patients with CKD is related to increases in the relative abundance of


Patient education is effective for HTN treatment. There are many methods of patient education improving HTN control. Are there additive effects of combination of different educational methods for HTN treatment?  To assess the effects of addition of the electronic educational material to doctor's face-to-face education for HTN control.  We designed a randomized single blind study to compare the doctor's face-to-face education alone and its combination with the electronic educational material over the cell phone. Participants were patients with a confirmed diagnosis of primary HTN. Electronic educational material over the cell phone was the intervention. Main measures were standard blood pressure measurements before and after 12 weeks of treatment.  The baseline characteristics of the intervention and control groups including the age, sex, SBP, DBP, and HTN control rate were not significantly different. After 12 weeks of follow-up, the blood pressure and the HTN control rate seemed worse in the combination group; however, the differences between the intervention group and the control group were not statistically significant.  There were no additive effects in the combination of the doctor's face-to-face education and the electronic educational material over the cell phone. Hypertension (HTN) is the most common chronic disease in the world . In addiTo assess the effects of addition of the electronic educational material to doctor's face-to-face education for HTN control.The research project was conducted at the Jingmi Community Health Service Center at Futian District, Shenzhen China, from September 2019 to December 2019. Patients were included with the following criteria: (1) patients with the diagnosis certificate of primary HTN from the hospital; (2) patients currently under the care of the community health service center where the research project was conducted; and (3) patients participating in the research project voluntarily with the signed informed consent for the research. The exclusion criteria were (1) patients with secondary HTN and (2) patients with hypertensive emergency.Using coin throwing method, 147 patients who were diagnosed with primary hypertension were randomized to two arms, the intervention arm consisting of 74 patients and the control arm consisting of 73 patients. All patients received antihypertensive drugs including calcium antagonists, angiotensin inhibitors, angiotensin receptor inhibitors, beta blockers, and diuretics, as the routine treatment. On average, 1-2 antihypertensive drugs were used for the majority of patients, and 3 antihypertensive drugs were used for the minority of patients. During the observation period, the quantity and dosage of drugs had no change, and the subjects visited the clinic 5 times averagely. Both arms received doctor's face-to-face education during the patient encounter, and the intervention arm received additional electronic educational material through WeChat and message over the cell phone biweekly. The electronic educational material was the electronic prescription of health education for HTN (see appendix A) and text message to ask patients to record home blood pressures.The clinic systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at the community health service center by the nurse who did not know the patient grouping (single blind) with the electronic blood pressure meter following the guideline for primary care of hypertension (2019) . The uppt-test of two independent samples for difference comparison. Because the gender and HTN control status were qualitative data, we used the chi-square test (χ2) for difference analysis. P < 0.05 was taken as the difference was statistically significant. HTN control status was separated into two situations, the controlled (blood pressure < 140/90 mmHg) and uncontrolled (blood pressure ≥ 140/90 mmHg). The HTN control rate was calculated by the number of HTN controlled patients to divide the number of the total patients.The Excel was used to input and sort out the research data, and the SPSS 25.0 statistical software was used for statistical analysis. Because the age, systolic blood pressure, and diastolic blood pressure of the two groups were quantitative data, obeying the normal distribution, we used the mean ± standard deviation for the statistical description and the Student's P > 0.05).The baseline characteristics of the intervention and control groups are summarized in P > 0.05).The SBP, DBP, and HTN control rate of patients after 12 weeks of follow-up are recorded in the Chronic diseases become the major cause of death of human being this century, and HTN is the most common chronic disease in the world . Many meThere are many articles reporting different methods of patient education effective to treat HTN . BecauseIt is necessary to initiate research to identify if the additive effect exists in the combination of different methods of patient education for HTN control. Because sending the electronic educational material over the cell phone  is a popThe results in the The control group received the traditional doctor's face-to-face education alone, and the intervention group received both the doctor's face-to-face education and the electronic educational material through WeChat and message over the cell phone. On the contrary to the original hypothesis in which we wished an additive effect in the intervention arm, after 12 weeks of follow-up, it seemed that the values of the SBP and DBP were higher, and HTN control rate was lower in the intervention arm; however, the differences between the two groups were not statistically significant.Patient education was demonstrated as one of the most effective and economic methods to assist to control HTN . Many meThe strength of the study include the randomized and single-blinded methodologies that simply decrease the confounding factors to compare the intervention arm and control arm. The limitations of the study include the limited sample size and no presentation of home blood pressures. We would like to extend the research in a large hypertensive population in the future. Although we asked patients to record the home blood pressures, the quality and quantity of the data for home blood pressures were not good enough for analysis to be included in the paper.There were no additive effects in the combination of the doctor's face-to-face education and the electronic educational material over the cell phone.