Increased Expression of Proinflammatory Genes in Peripheral Blood Cells Is Associated with Cardiac Cachexia in Patients with Heart Failure with Reduced Ejection Fraction.

Background: Cardiac cachexia (CC) in chronic heart failure with reduced ejection fraction (HFrEF) is characterized by catabolism and inflammation predicting poor prognosis. Levels of responsible transcription factors like signal transducer and activator of transcription (STAT)1, STAT3, suppressor of cytokine signaling (SOCS)1 and SOCS3 in peripheral blood cells (PBC) are underinvestigated in CC. Expression of mediators was related to patients' functional status, body composition (BC) and metabolic gene expression in skeletal muscle (SM). Methods: Gene expression was quantified by qRT-PCR in three cohorts: non-cachectic patients (ncCHF, n = 19, LVEF 31 ± 7%, BMI 30.2 ± 5.0 kg/m2), cachectic patients (cCHF; n = 18, LVEF 27 ± 7%, BMI 24.3 ± 2.5 kg/m2) and controls (n = 17, LVEF 70 ± 7%, BMI 27.6 ± 4.6 kg/m2). BC was assessed by dual-energy X-ray absorptiometry. Blood inflammatory markers were measured. We quantified solute carrier family 2 member 4 (SLC2A4) and protein degradation by expressions of proteasome 20S subunit beta 2 and calpain-1 catalytic subunit in SM biopsies. Results: TNF and IL-10 expression was higher in cCHF than in ncCHF and controls (all p < 0.004). cCHF had a lower fat mass index (FMI) and lower fat-free mass index (FFMI) compared to ncCHF and controls (p < 0.05). STAT1 and STAT3 expression was higher in cCHF vs. ncCHF or controls (1.1 [1.6] vs. 0.8 [0.9] vs. 0.9 [1.1] RU and 4.6 [5.5] vs. 2.5 [4.8] vs. 3.0 [4.2] RU, all ANOVA-p < 0.05). The same applied for SOCS1 and SOCS3 expression (1.1 [1.5] vs. 0.4 [0.4] vs. 0.4 [0.5] and 0.9 [3.3] vs. 0.4 [1.1] vs. 0.8 [0.9] RU, all ANOVA-p < 0.04). In cCHF, higher TNF and STAT1 expression was associated with lower FMI (r = 0.5, p = 0.053 and p < 0.05) but not with lower FFMI (p > 0.4). In ncCHF, neither cytokine nor STAT/SOCS expression was associated with BC (all p > 0.3). SLC2A4 was upregulated in SM of cCHF vs. ncCHF (p < 0.03). Conclusions: Increased STAT1, STAT3, SOCS1 and SOCS3 expression suggests their involvement in CC. In cCHF, higher TNF and STAT-1 expression in PBC were associated with lower FMI. Increased SLC2A4 in cachectic SM biopsies indicates altered glucose metabolism.

Urinary Dickkopf-3 (DKK3) Is Associated with Greater eGFR Loss in Patients with Resistant Hypertension.

Patients with resistant hypertension (HTN) demonstrate an increased risk of chronic kidney disease and progression to end-stage renal disease; however, the individual course of progression is hard to predict. Assessing the stress-induced, urinary glycoprotein Dickkopf-3 (uDKK3) may indicate ongoing renal damage and consecutive estimated glomerular filtration rate (eGFR) decline. The present study aimed to determine the association between uDKK3 levels and further eGFR changes in patients with resistant HTN. In total, 31 patients with resistant HTN were included. Blood pressure and renal function were measured at baseline and up to 24 months after (at months 12 and 24). uDKK3 levels were determined exclusively from the first available spot urine sample at baseline or up to a period of 6 months after, using a commercial ELISA kit. Distinctions between different patient groups were analyzed using the unpaired t-test or Mann-Whitney test. Correlation analysis was performed using Spearman's correlation. The median uDKK3 level was 303 (interquartile range (IQR) 150-865) pg/mg creatinine. Patients were divided into those with high and low eGFR loss (≥3 vs. <3 mL/min/1.73 m²/year). Patients with high eGFR loss showed a significantly higher median baseline uDKK3 level (646 (IQR 249-2555) (n = 13) vs. 180 (IQR 123-365) pg/mg creatinine (n = 18), p = 0.0412 (Mann-Whitney U)). Alternatively, patients could be classified into those with high and low uDKK3 levels (≥400 vs. <400 pg/mg creatinine). Patients with high uDKK3 levels showed significantly higher eGFR loss (-6.4 ± 4.7 (n = 11) vs. 0.0 ± 7.6 mL/min/1.73 m2/year (n = 20), p = 0.0172 (2-sided, independent t-test)). Within the entire cohort, there was a significant correlation between the uDKK3 levels and change in eGFR at the latest follow-up (Spearman's r = -0.3714, p = 0.0397). In patients with resistant HTN, high levels of uDKK3 are associated with higher eGFR loss up to 24 months later.

Effect of baroreflex activation therapy on dipping pattern in patients with resistant hypertension.

A relevant number of patients with resistant hypertension do not achieve blood pressure (BP) dipping during nighttime. This inadequate nocturnal BP reduction is associated with elevated cardiovascular risks. The aim of this study was to evaluate whether a nighttime intensification of BAT might improve nocturnal BP dipping. In this prospective observational study, non-dippers treated with BAT for at least 6 months were included. BAT programming was modified in a two-step intensification of nighttime stimulation at baseline and week 6. Twenty-four hours ambulatory BP (ABP) was measured at inclusion and after 3 months. A number of 24 patients with non- or inverted dipping pattern, treated with BAT for a median of 44 months (IQR 25-52) were included. At baseline of the study, patients were 66 ± 9 years old, had a BMI of 33 ± 6 kg/m2 , showed an office BP of 135 ± 22/72 ± 10 mmHg, and took a median number of antihypertensives of 6 (IQR 4-9). Nighttime stimulation of BAT was adapted by an intensification of pulse width from 237 ± 161 to 267 ± 170 µs (p = .003) while frequency (p = .10) and amplitude (p = .95) remained unchanged. Uptitration of BAT programming resulted in an increase of systolic dipping from 2 ± 6 to 6 ± 8% (p = .03) accompanied with a significant improvement of dipping pattern (p = .02). Twenty four hours ABP, day- and nighttime ABP remained unchanged. Programming of an intensified nighttime BAT interval improved dipping profile in patients treated with BAT, while the overall 24 h ABP did not change. Whether the improved dipping response contributes to a reduction of cardiovascular risk beyond the BP-lowering effects of BAT, however, remains to be shown.

Impact of Elevated LDH on Cystatin C-Based Glomerular Filtration Rate Estimates in Patients with Cancer.

Background: The determination of renal function is crucial for the clinical management of patients with cancer. The glomerular filtration rate (GFR) serves as a key parameter, estimated by creatinine clearance determination in 24-h collected urine (CrCl) as well as equation-based approaches (eGFR) relying on serum creatinine (eGFR CKD EPIcrea) or serum cystatin C (eGFR cystatin C). Serum creatinine and serum cystatin C levels differentially depend on muscle and tumor mass, respectively. Although muscle and tumor mass may thus represent confounding factors, comparative studies for eGFR estimate approaches in cancer patients are lacking. Methods: The present study retrospectively analyzed GFR estimates based on equations of creatinine (eGFRcr), cystatin C (eGFRcys) and combined creatinine-cystatin C levels (eGFRcr-cys) in a subset of patients. The associations of LDH with cystatin C or LDH with eGFRcr, eGFRcys and GFRcr-cys were explored. Results: The laboratory values of 123 consecutive patients were included. The median age was 59 (24−87) and 47.2% were female. There was a statistically significant difference in the mean of CKD EPIcrea (85.17 ± 21.63 mL/min/1.73 m2), CKD EPIcys (61.16 ± 26.03 mL/min/1.73 m2) and CKD EPIcrea-cys (70.42 ± 23.89 mL/min/1.73 m2) (p < 0.0001). Spearman's correlation analysis revealed a significant correlation of elevated plasma LDH >1.5 UNV and cystatin C values (r = 0.270, p < 0.01, n = 123). LDH values >1.5 UNV were associated with significantly lower CKD EPIcys (r = 0.184, p < 0.01) or CKD EPIcrea-cys (r = 0.226, p < 0.05) estimates compared to CKD EPIcrea. Conclusions: The inclusion of cystatin C as a biomarker led to a lower eGFR estimates compared to creatinine alone or in a combination of both cystatin C and creatinine. The level of cystatin C correlated with the level of LDH, suggesting that the use of cystatin C-based calculations of GFR in cancer patients with elevated LDH should be used with caution.

Impact of medication adherence on the efficacy of Baroreflex activation therapy.

Therapy adherence significantly determines the success of antihypertensive therapy, especially in patients with resistant hypertension. Our study investigates the impact of drug adherence on the efficacy of Baroreflex-activation-therapy (BAT). In this retrospective analysis, the authors measured blood pressure (BP) and antihypertensive medication adherence (by gas chromatography-mass spectrometry [GC-MS] urine analysis) before and 6 months after BAT initiation. Adherence was defined as detection of ≥80% intake of prescribed medication at the time of follow-up. Response to BAT was defined as BP drop ≥5 mmHg in systolic 24 h-ambulatory BP (ABP) after 6 months. Overall patients (n = 38) median medication adherence was low, but rose from 60% (IQR 25%-100%) to 75% (IQR 38%-100%; p = .0194). After 6 months of BAT, mean systolic and diastolic office BP (-21 ± 25 mmHg and -9 ± 15 mmHg; p < .0001 and .0004) as well as 24 h-ABP dropped significantly (-9 ± 17 mmHg and -5 ± 12 mmHg; p = .0049 and .0280). After 6 months of BAT, 21 patients (60%) could be classified as responders. There was neither significant difference in mean office systolic (-21 ± 23 mmHg vs. -21 ± 28 mmHg; p = .9581) nor in 24 h-systolic ABP decrease (-11 ± 19 mmHg vs. -7 ± 15 mmHg; p = .4450) comparing adherent and non-adherent patients. Whereas Antihypertensive Therapeutic Index (ATI) was unchanged in non-responders, it significantly decreased in responders (from 50 ± 16 to 46 ± 16; p = .0477). These data are the first to show that BAT-initiation leads to a clear BP reduction independently of patients´ medication adherence. Response to BAT is associated with a significant lowering of ATI, which might contribute to an underestimation of BAT efficacy.

The Rapid Atrial Swirl Sign for Ultrasound-Guided Tip Positioning of Retrograde-Tunneled Hemodialysis Catheters: A Cross-Sectional Study from a Single Center.

BACKGROUND: Chronic kidney disease (CKD) is a common medical problem in patients worldwide, with an increasing prevalence of patients with end-stage kidney disease (ESKD) requiring renal replacement therapy (RRT). In patients requiring RRT for more than two weeks or those who develop ESKD, tunneled hemodialysis catheter (HDC) insertion is preferred, based on a lower risk for infectious complications. While the efficacy of ultrasound (US)-guided tip positioning in antegrade-tunneled HDCs has previously been shown, its application for the insertion of retrograde-tunneled HDCs has not been described yet. This is especially important, since the retrograde-tunneled technique has several advantages over the antegrade-tunneled HDC insertion technique. Therefore, we here report our first experience of applying the rapid atrial swirl sign (RASS) for US-guided tip positioning of retrograde-tunneled HDCs. METHODS: We performed a cross-sectional study to assess the feasibility of applying the RASS for US-guided tip positioning of retrograde-tunneled HDCs. We performed a total number of 24 retrograde-tunneled HDC insertions in 23 patients (requiring placement of a HDC for the temporary or permanent treatment of ESKD) admitted to our Department of Nephrology and Rheumatology at the University Medical Center Göttingen, Germany. RESULTS: The overall success rate of applying the RASS for US-guided tip positioning of retrograde-tunneled HDCs was 24/24 (100%), with proper tip position in the right atrium in 18/23 (78.3%), or cavoatrial junction in 5/23 (21.7%) when RASS was positive and improper position when RASS was negative in 1/1 (100%), confirmed by portable anterior-posterior chest radiography, with only minor post-procedural bleeding in 2/24 (8.3%). In addition, this insertion technique allows optimal HDC flow, without any observed malfunction. CONCLUSION: This is the first study to investigate the efficacy of the RASS for US-guided tip positioning of retrograde-tunneled HDCs in patients with ESKD. Application of the RASS for US-guided tip positioning is an accurate and safe procedure for the proper placement of retrograde-tunneled HDCs.

Cystatin C predicts renal function impairment after partial or radical tumor nephrectomy.

PURPOSE: To test the value of preoperative and postoperative cystatin C (CysC) as a predictor on kidney function after partial (PN) or radical nephrectomy (RN) in renal cell carcinoma (RCC) patients with normal preoperative renal function. METHODS: From 01/2011 to 12/2014, 195 consecutive RCC patients with a preoperative estimated glomerular filtration rate (eGFR) > 60 ml/min/1.73m2 underwent surgical RCC treatment with either PN or RN. Logistic and linear regression models tested for the effect of CysC as a predictor of new-onset chronic kidney disease in follow-up (eGFR < 60 ml/min/1.73m2). Moreover, postoperative CysC and creatinine values were compared for kidney function estimation. RESULTS: Of 195 patients, 129 (66.2%) underwent PN. In postoperative and in follow-up setting (median 14 months, IQR 10-20), rates of eGFR < 60 ml/min/1.73m2 were 55.9 and 30.2%. In multivariable logistic regression models, preoperative CysC [odds ratio (OR): 18.3] and RN (OR: 13.5) were independent predictors for a reduced eGFR < 60 ml/min/1.73m2 in follow-up (both p < 0.01), while creatinine was not. In multivariable linear regression models, a difference of the preoperative CysC level of 0.1 mg/dl estimated an eGFR decline in follow-up of about 5.8 ml/min/1.73m2. Finally, we observed a plateau of postoperative creatinine values in the range of 1.2-1.3 mg/dl, when graphically depicted vs. postoperative CysC values ('creatinine blind area'). CONCLUSION: Preoperative CysC predicts renal function impairment following RCC surgery. Furthermore, CysC might be superior to creatinine for renal function monitoring in the early postoperative setting.

Eligibility for Baroreflex Activation Therapy and medication adherence in patients with apparently resistant hypertension.

Uncontrolled hypertension is a main risk factor for cardiovascular morbidity. Baroreflex activation therapy (BAT) is an effective therapy option addressing true resistant hypertension. We evaluated patients' eligibility for BAT in a staged assessment as well as adherence to antihypertensive drug therapy. Therefore, we analyzed files of 345 patients, attending the hypertension clinic at University Medicine Göttingen. Additionally, gas chromatographic-mass spectrometric urine analyses of selected individuals were performed evaluating their adherence. Most common cause for a revoked BAT recommendation was blood pressure (BP) control by drug adjustment (54.2%). Second leading cause was presence of secondary hypertension (31.6%). Patients to whom BAT was recommended (59 (17.1%)) were significantly more often male (67.8% vs. 43.3%, P = .0063), had a higher body mass index (31.8 ± 5.8 vs. 30.0 ± 5.7 kg/m², P = .0436), a higher systolic office (168.7 ± 24.7 vs. 147.7 ± 24.1 mmHg, P < .0001), and 24h ambulatory BP (155.0 ± 14.6 vs. 144.4 ± 16.8 mmHg, P = .0031), took more antihypertensive drugs (5.8 ± 1.3 vs. 4.4 ± 1.4, P < .0001), and suffered more often from numerous concomitant diseases. Eventually, 27 (7.8%) received a BAT system. In the toxicological analysis of 75 patients, mean adherence was 75.1%. 16 patients (21.3%) showed non-adherence. Thus, only a small number of patients eventually received a BAT system, as treatable reasons for apparently resistant hypertension could be identified frequently. This study is-to our knowledge-the first report of a staged assessment of patients' suitability for BAT and underlines the need for a careful examination and indication. Non-adherence was proven to be a relevant issue concerning apparently resistant hypertension and therefore non-eligibility for interventional antihypertensive therapy.

Cytokine adsorption therapy in lymphoma-associated hemophagocytic lymphohistiocytosis and allogeneic stem cell transplantation.

Lymphoma-associated Hemophagocytic lymphohistiocytosis (HLH) represents a severe complication of disease progression, mediated through cytokine release from the lymphoma cells. Cytokine adsorption may contribute as a supportive treatment to stabilize organ function by reduction of cytokine levels. So far, no experiences of cytokine adsorption and simultaneous stem cell transplantation were published. We report the case of a patient with aggressive lymphoma secondary to chronic lymphocytic leukemia with rapidly progressive HLH (Richter's transformation) upon conditioning chemotherapy prior to allogeneic stem cell transplantation (ASCT). Continuous hemodiafiltration was initiated in the treatment of shock with acute renal failure, lactacidosis and need for high-dose catecholamine therapy, integrating an additional cytokine-adsorbing filter (CytoSorb®) to reduce cytokine levels. This was followed by scheduled allogenic stem cell transplantation. We observed a marked decrease in interleukin-6 plasma levels, associated with a reduced need for vasopressor therapy and organ function stabilization. Hematopoietic engraftment was present at day 14 post-ASCT, leading to disease-free discharge at day 100 post-transplantation. Cytokine adsorption may serve as a safe adjunct to HLH/sepsis treatment during allogeneic stem cell transplantation. Clinical studies are required to make future treatment recommendations.

Type 2A von Willebrand disease and systemic sclerosis: Vonicog alfa reduced gastrointestinal bleeding.

Von Willebrand disease (VWD) is a bleeding disorder caused by qualitative or quantitative defects of von Willebrand factor (VWF). This case report of a patient with systemic sclerosis and gastrointestinal bleeding from angiodysplasias seeks to address the key clinical question of a useful diagnostic and therapeutic approach in this setting. The extent of vascular malformations and the frequency of bleeding episodes were unusually severe, and we reached a diagnosis of inherited type 2A VWD. After an insufficient effect of treatment with factor VIII (FVIII)/VWF, prophylactic administration of vonicog alfa, a recombinant VWF preparation without FVIII, was initiated. This therapy led to a substantial reduction of transfusion requirements and the improvement of angiodysplasias. In refractory gastrointestinal bleeding, hemostaseological evaluation is crucial, as inherited disorders of hemostasis may go unnoticed, especially in patients with underlying autoimmune diseases, where complications may be ascribed to the underlying disease.

Syndecan-4 as a Marker of Endothelial Dysfunction in Patients with Resistant Hypertension.

(1) Background: Arterial hypertension (HTN) is one of the most relevant cardiovascular risk factors. Nowadays multiple pharmaceutical treatment options exist with novel interventional methods (e.g., baroreflex activation therapy (BAT)) as a last resort to treat patients with resistant HTN. Although pathophysiology behind resistant HTN is still not fully understood. There is evidence that selected biomarkers may be involved in the pathophysiology of HTN. (2) Methods: We investigated serum SDC4-levels in patients suffering from resistant HTN before and 6 months after BAT implantation. We collected 19 blood samples from patients with resistant HTN and blood pressure above target and measured serum SDC4-levels. (3) Results: Our results showed high serum SDC4-levels in patients with resistant HTN as compared to a healthy population. Patients with both, resistant HTN and diabetes mellitus type II, demonstrated higher serum SDC4-levels. ß-blockers had lowering effects on serum SDC4-levels, whereas calcium channel blockers were associated with higher levels of serum SDC4. BAT implantation did not lead to a significant difference in serum SDC4-levels after 6 months of therapy. (4) Conclusion: Based on our results we propose SDC4 is elevated in patients suffering from resistant HTN. Thus, SDC4 might be a potential marker for endothelial dysfunction in patients with resistant hypertension.

Plasma Exchange or Immunoadsorption in Demyelinating Diseases: A Meta-Analysis.

Multiple sclerosis (MS) is an inflammatory disease mainly affecting the central nervous system. In MS, abnormal immune mechanisms induce acute inflammation, demyelination, axonal loss, and the formation of central nervous system plaques. The long-term treatment involves options to modify the disease progression, whereas the treatment for the acute relapse has its focus in the administration of high-dose intravenous methylprednisolone (up to 1000 mg daily) over a period of three to five days as a first step. If symptoms of the acute relapse persist, it is defined as glucocorticosteroid-unresponsive, and immunomodulation by apheresis is recommended. However, several national and international guidelines have no uniform recommendations on using plasma exchange (PE) nor immunoadsorption (IA) in this case. A systematic review and meta-analysis was conducted, including observational studies or randomized controlled trials that investigated the effect of PE or IA on different courses of MS and neuromyelitis optica (NMO). One thousand, three hundred and eighty-three patients were included in the evaluation. Therapy response in relapsing-remitting MS and clinically isolated syndrome was 76.6% (95%CI 63.7-89.8%) in PE- and 80.6% (95%CI 69.3-91.8%) in IA-treated patients. Based on the recent literature, PE and IA may be considered as equal treatment possibilities in patients suffering from acute, glucocorticosteroid-unresponsive MS relapses.

Urine E-cadherin: A Marker for Early Detection of Kidney Injury in Diabetic Patients.

Diabetic nephropathy (DN) is the main reason for end-stage renal disease. Microalbuminuria as the non-invasive available diagnosis marker lacks specificity and gives high false positive rates. To identify and validate biomarkers for DN, we used in the present study urine samples from four patient groups: diabetes without nephropathy, diabetes with microalbuminuria, diabetes with macroalbuminuria and proteinuria without diabetes. For the longitudinal validation, we recruited 563 diabetic patients and collected 1363 urine samples with the clinical data during a follow-up of 6 years. Comparative urinary proteomics identified four proteins Apolipoprotein A-I (APOA1), Beta-2-microglobulin (B2M), E-cadherin (CDH1) and Lithostathine-1-alpha (REG1A), which differentiated with high statistical strength (p < 0.05) between DN patients and the other groups. Label-free mass spectrometric quantification of the candidates confirmed the discriminatory value of E-cadherin and Lithostathine-1-alpha (p < 0.05). Immunological validation highlighted E-cadherin as the only marker able to differentiate significantly between the different DN stages with an area under the curve (AUC) of 0.85 (95%-CI: [0.72, 0.97]). The analysis of the samples from the longitudinal study confirmed the prognostic value of E-cadherin, the critical increase in urinary E-cadherin level was measured 20 ± 12.5 months before the onset of microalbuminuria and correlated significantly (p < 0.05) with the glomerular filtration rate measured by estimated glomerular filtration rate (eGFR).

Long-term effects of baroreflex activation therapy: 2-year follow-up data of the BAT Neo system.

OBJECTIVE: Baroreflex activation therapy (BAT) reduces office blood pressure (BP) in patients with resistant hypertension (HTN). Whereas sustained effects from the BAT Rheos device have already been reported, no long-term data on 24-h ambulatory BP (ABP) are currently available for the unilateral BAT Neo device. METHODS: Patients treated with the BAT neo device for resistant hypertension were prospectively included into this observational study. Office and ABP measurements were performed before BAT implantation as well as 6, 12 and 24 months after initiation of BAT. RESULTS: A total of 60 patients with resistant HTN (office BP 172 ± 25/90 ± 17 mmHg, 24-h ABP 150 ± 16/80 ± 12 mmHg, median of antihypertensive drugs 7 (IQR 6-8)) were included. After 24 months, there was a significant reduction of - 25 ± 33/- 9 ± 18 mmHg (n = 50, both p < 0.01) in office BP and - 8 ± 23/- 5 ± 13 mmHg (n = 46, both p = 0.02) in 24-h ABP, while the number of antihypertensive medications was reduced to a median of 5 (4-6) drugs (p < 0.01). Patients with isolated systolic HTN (ISH) experienced a BP-lowering effect in office BP, but not in ABPM at month 24. Using unadjusted BP values, BAT seems to be more effective in combined hypertension (CH) than in ISH. After adjustment for baseline BP values, there was no significant difference in BP reduction between ISH and CH patients. Ambulatory SBP at baseline was the only independent correlate of BP response at month 24. CONCLUSION: BAT reduced office BP and improved relevant parameters of ABP, which is associated with a high cardiovascular risk, in patients with resistant HTN, whereas, after adjustment for baseline BP, BP reduction was not different in patients with CH compared with patients with ISH. However, randomized controlled trials are needed to confirm the effects of BAT on 24-h ABP.

Efficacy of Electrical Baroreflex Activation Is Independent of Peripheral Chemoreceptor Modulation.

Arterial baroreflex activation through electrical carotid sinus stimulation has been developed for the treatment of resistant hypertension. Previous studies suggested that the peripheral chemoreflex is tonically active in hypertensive patients and may inhibit baroreflex responses. We hypothesized that peripheral chemoreflex activation attenuates baroreflex efficacy evoked by electrical carotid sinus stimulation. We screened 35 patients with an implanted electrical carotid sinus stimulator. Of those, 11 patients with consistent acute depressor response were selected (7 men/4 women, age: 67±8 years, body mass index: 31.6±5.2 kg/m2, 6±2 antihypertensive drug classes). We assessed responses to electrical baroreflex stimulation during normoxia, isocapnic hypoxia (SpO2: 79.0±1.5%), and hyperoxia (40% end-tidal O2 fraction) by measuring heart rate, blood pressure, ventilation, oxygen saturation, end-tidal CO2 and O2 fractions, and muscle sympathetic nerve activity. During normoxia, baroreflex activation reduced systolic blood pressure from 164±27 to 151±25 mm Hg (mean±SD, P<0.001), heart rate from 64±13 to 61±13 bpm (P=0.002), and muscle sympathetic nerve activity from 42±12 to 36±12 bursts/min (P=0.004). Hypoxia increased systolic blood pressure 8±12 mm Hg (P=0.057), heart rate 10±6 bpm (P<0.001), muscle sympathetic nerve activity 7±7 bursts/min (P=0.031), and ventilation 10±7 L/min (P=0.002). However, responses to electrical carotid sinus stimulation did not differ between hypoxic and hyperoxic conditions: systolic blood pressure: -15±7 versus -14±8 mm Hg (P=0.938), heart rate: -2±3 versus -2±2 bpm (P=0.701), and muscle sympathetic nerve activity: -6±4 versus -4±3 bursts/min (P=0.531). We conclude that moderate peripheral chemoreflex activation does not attenuate acute responses to electrical baroreflex activation therapy in patients with resistant hypertension. These patients provided insight into human baroreflex-chemoreflex interactions that could not be gained otherwise.

Risk factors for catheter-related infections in patients receiving permanent dialysis catheter.

BACKGROUND: Due to rising vascular comorbidities of patients undergoing dialysis, the prevalence of permanent hemodialysis catheters as hemodialysis access is increasing. However, infection is a major complication of these catheters. Therefore, identification of potential predicting risk factors leading to early infection related complications is valuable, in particular the significance the CRP (C-reactive protein)-value is of interest. METHODS: In this retrospective study 151 permanent hemodialysis catheters implanted in 130 patients were examined. The following data were collected at the time of catheter implantation: CRP-value, history of catheter-related infection, microbiological status, immunosuppression and diabetes mellitus. The primary outcomes were recorded over the 3 months following the implantation: catheter-related infection, days of hospital stay and death. Catheter removal or revision, rehospitalization and use of antibiotics were identified as secondary outcomes. RESULTS: We identified a total of 27 (17.9%) infections (systemic infection: 2.26 episodes/ 1000 catheter days, local infection: 0.6 episodes/ 1000 catheter days). The development of an infection was independent of the CRP-value (p = 0.66) as well as the presence of diabetes mellitus (p = 0.64) or immunosuppression (p = 0.71). Univariate analysis revealed that infection was more frequent in patients with MRSA-carriage (p < 0.001), in case of previous catheter-related infection (p < 0.05) and of bacteremia or bacteriuria in the period of 3 months before catheter implantation (p < 0.001). Catheter removal or revision (p = 0.002), rehospitalization (p = 0.001) and use of antibiotics (p = 0.02) were also more often observed in patients with MRSA-carriage. CONCLUSIONS: The CRP-value at the time of implantation of a permanent hemodialysis catheter is not associated with the development of early catheter related infections, but an individual history of catheter-related infection, MRSA-carriage and bacteremia or bacteriuria in the period of 3 months prior to catheter implantation are significant risk factors.

Effect of baroreflex activation therapy on renal sodium excretion in patients with resistant hypertension.

OBJECTIVE: Activation of the sympathetic nervous system increases sodium retention in resistant hypertension. Baroreflex activation therapy (BAT) is an interventional method to reduce sympathetic overactivity in patients with resistant hypertension. This study aimed to assess the effect of BAT on urinary sodium excretion. METHODS: From 2012 to 2015, consecutive patients with resistant hypertension and blood pressure (BP) above target despite polypharmacy strategies were consecutively included in this observational study. BAT was provided with the individual adaption of programmed parameters over the first months. 24-h urinary sodium excretion (UNa) was estimated at baseline and after 6 months using the Kawasaki formula in patients undergoing BAT. Additionally, the fractional sodium excretion, plasma renin activity, and aldosterone levels were assessed. RESULTS: Forty-two patients completed the 6-month follow-up period. Office systolic and ambulatory 24-h systolic BP at baseline were 169 ± 27 mmHg and 148 ± 16 mmHg despite a median intake of 7(3-9) antihypertensive drugs. After 6 months of BAT, systolic office BP decreased to 150 ± 29 mmHg (p < 0.01), 24-h systolic BP to 142 ± 22 mmHg (p = 0.04) and 24-h UNa increased by 37% compared to baseline (128 ± 66 vs. 155 ± 83 mmol/day, p < 0.01). These findings were accompanied by a significant increase in fractional sodium excretion (0.74% [0.43-1.47] to 0.92% [0.61-1.92]; p = 0.02). However, in contrast to the significant BP reduction, eGFR, plasma sodium, renin activity and aldosterone levels did not change during BAT. The increase in sodium excretion was correlated with the change in eGFR (r = 0.371; p = 0.015). CONCLUSION: The present study revealed a significant increase of estimated 24-h UNa which may contribute to the long-term BP-lowering effects of this interventional method.