Activation of baroreceptors in the carotid modulates the autonomic nervous system. Baroreflex activation therapy (BAT), which activates baroreceptors in the carotid, has become available in the ...treatment of resistant hypertension. Besides this, a carotid implant modulating baroreceptors as well as pharmacological modulation of carotid bodies were quite recently presented. This review will underscore currently available and promising approaches that activate baroreceptors in the carotid, and thereby contribute to beneficial effects in patients with arterial hypertension, and discusses potential organoprotective BAT effects beyond blood pressure (BP) reduction. A systematic review and meta-analysis was conducted including observational studies or randomized controlled trials that investigated the effect of BAT on BP in resistant hypertension. Nine studies, seven observational and two randomized, with a total of 444 patients, were included in the evaluation. Analysing the longest follow-up visit from the different studies, there was a significant reduction of systolic BP after BAT of -36 mmHg 95% confidence interval (CI) -42 to -30 mmHg. Separate meta-analysis of the short-term (1-6 months) and long-term effects (≥12 months) revealed a reduction of -21 mmHg (95% CI -26 to -17 mmHg) and -38 mmHg (95% CI -46 to -30 mmHg), respectively. There are promising data both in the experimental and the clinical application for BAT. Though the present meta-analysis suggests beneficial effects of BAT on BP, the results must be interpreted extremely carefully. Considering that evidence from controlled trials is very limited, it is evident that there is a strong need for further investigation.
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.
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.
Baroreflex activation therapy (BAT) has been demonstrated to decrease office blood pressure (BP) in the randomized, double-blind Rheos trial. There are limited data on 24-hour BP changes measured by ...ambulatory BP measurements (ABPMs) using the first generation rheos BAT system suggesting a significant reduction but there are no information about the effect of the currently used, unilateral BAT neo device on ABPM. Patients treated with the BAT neo device for uncontrolled resistant hypertension were prospectively included into this study. ABPM was performed before BAT implantation and 6 months after initiation of BAT. A total of 51 patients were included into this study, 7 dropped out from analysis because of missing or insufficient follow-up. After 6 months, 24-hour ambulatory systolic (from 148 ± 17 mm Hg to 140 ± 23 mm Hg, P<0.01), diastolic (from 82 ± 13 mm Hg to 77 ± 15 mm Hg, P<0.01), day- and night-time systolic and diastolic BP (all P ≤ 0.01) significantly decreased while the number of prescribed antihypertensive classes could be reduced from 6.5 ± 1.5 to 6.0 ± 1.8 (P=0.03). Heart rate and pulse pressure remained unchanged. BAT was equally effective in reducing ambulatory BP in all subgroups of patients. This is the first study demonstrating a significant BP reduction in ABPM in patients undergoing chronically stimulation of the carotid sinus using the BAT neo device. About that BAT-reduced office BP and improved relevant aspects of ABPM, BAT might be considered as a new therapeutic option to reduce cardiovascular risk in patients with resistant hypertension. Randomized controlled trials are needed to evaluate BAT effects on ABPM in patients with resistant hypertension accurately.
Abstract
Background
Risk of kidney function decline in immunoglobulin A (IgA) nephropathy (IgAN) is significant and may not be predicted by available clinical and histological tools. To serve this ...unmet need, we aimed at developing a urinary biomarker-based algorithm that predicts rapid disease progression in IgAN, thus enabling a personalized risk stratification.
Methods
In this multicentre study, urine samples were collected in 209 patients with biopsy-proven IgAN. Progression was defined by tertiles of the annual change of estimated glomerular filtration rate (eGFR) during follow-up. Urine samples were analysed using capillary electrophoresis coupled mass spectrometry. The area under the receiver operating characteristic curve (AUC) was used to evaluate the risk prediction models.
Results
Of the 209 patients, 64% were male. Mean age was 42 years, mean eGFR was 63 mL/min/1.73 m2 and median proteinuria was 1.2 g/day. We identified 237 urine peptides showing significant difference in abundance according to the tertile of eGFR change. These included fragments of apolipoprotein C-III, alpha-1 antitrypsin, different collagens, fibrinogen alpha and beta, titin, haemoglobin subunits, sodium/potassium-transporting ATPase subunit gamma, uromodulin, mucin-2, fractalkine, polymeric Ig receptor and insulin. An algorithm based on these protein fragments (IgAN237) showed a significant added value for the prediction of IgAN progression AUC 0.89; 95% confidence interval (CI) 0.83–0.95, as compared with the clinical parameters (age, gender, proteinuria, eGFR and mean arterial pressure) alone (0.72; 95% CI 0.64–0.81).
Conclusions
A urinary peptide classifier predicts progressive loss of kidney function in patients with IgAN significantly better than clinical parameters alone.
Graphical Abstract
Graphical Abstract
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.
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.
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.
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.
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.
In multiple sclerosis relapses refractory to intravenous corticosteroid therapy, plasma exchange is recommended. Immunoadsorption (IA) is regarded as an alternative therapy, but its efficacy and ...putative mechanism of action still needs to be established.
We prospectively treated 11 patients with multiple sclerosis who had optical neuritis and fulfilled the indications for apheresis therapy (Trial registration DE/CA25/00007080-00). In total, five IA treatments were performed using tryptophan-IA. Clinical activity (visual acuity, Expanded Disability Status Scale, Incapacity Status Scale), laboratory values and visual evoked potentials were measured before, during and after IA, with a follow-up of six months. Moreover, proteomic analyses were performed to analyze column-bound proteins as well as corresponding changes in patients' sera.
After the third IA, we detected an improvement of vision in eight of eleven patients, whom we termed responders. Amongst these, the mean visual acuity improved from 0.15 ± 0.12 at baseline to 0.47 ± 0.32 after the third IA (P = 0.0252) up to 0.89 ± 0.15 (P < 0.0001) at day 180 ± 10 after IA. Soluble interleukin-2 receptor decreased in responders (P = 0.03), whereas in non-responders it did not. Proteomic analyses of proteins adsorbed to IA columns revealed that several significant immunological proteins as well as central nervous system protein fragments, including myelin basic protein, had been removed by IA.
IA was effective in the treatment of corticosteroid-refractory optic neuritis. IA influenced the humoral immune response. Strikingly, however, we found strong evidence that demyelination products and immunological mediators were also cleared from plasma by IA.
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.
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