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.

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.

Baroreceptors in the carotid and hypertension-systematic review and meta-analysis of the effects of baroreflex activation therapy on blood pressure.

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.

Urinary free light chains may help to identify infection in patients with elevated systemic inflammation due to rheumatic disease.

The risk of infection in patients with rheumatic diseases is elevated, but a clear marker to differentiate the cause of the systemic inflammation is missing. We assessed the ability urinary immunoglobulin free light chains (FLCs) to indicate the presence of infection in patients with rheumatic disease. We performed a retrospective analysis of patients with rheumatic disease attending the Georg-August University Hospital in Goettingen, Germany, from January 2011 to December 2013. Subjects were included if they had urine levels of κ and λ FLCs available. A reference group of patients without autoimmune disease, but with documented infection, was constructed. A total of 1500 patients had their urinary FLCs quantified during the study period. Of the 382 patients with rheumatic disease, 172 (45%) displayed no systemic inflammation, 162 (42%) had inflammation due to the underlying disease activity, and 48 (13%) had inflammation due to a confirmed infection. Urinary FLC concentrations were much higher in patients with rheumatic diseases and infection (κ 68.8 ± 81.8 mg/L, λ 31.4 ± 53.5 mg/L) compared to those with inflammation due to rheumatic disease activity (κ 22.7 ± 26.3 mg/L, λ 8.1 ± 9.1 mg/L, κ p < 0.001, λ p = 0.004). Urinary κ FLCs demonstrated good ability to predict infection, with a sensitivity of 63% and specificity of 84%. Urinary λ FLCs gave similar values, with a sensitivity of 65% and specificity of 81%. FLCs may be useful for distinguishing inflammation due to rheumatic disease activity from that due to the additional presence of infection. The ability to quantify these proteins in urine provides a simple alternative to the use of blood.

FABP1 and FABP3 Have High Predictive Values for Renal Replacement Therapy in Patients with Acute Kidney Injury.

BACKGROUND/AIMS: Early initiation of renal replacement therapy (RRT) is recommended in order to improve the clinical outcome of patients who develop an acute kidney injury (AKI). However, markers that guide an early RRT initiation do not really exist currently. METHODS: Urine and serum samples were prospectively collected from 120 AKI patients. Depending on the necessity of initiating RRT, patients were divided into 2 different groups: dialysis (n = 52) and non-dialysis (n = 68). RESULTS: Comparative urinary proteomic analyses identified 4 different proteins (fatty acid binding proteins 1 and 3 (FABP1 and FABP3), ß-2-microglobulin (B2M), cystatin-M (CST6)) that discriminate AKI patients with high risk for RRT. Western blot analysis confirmed the proteomics data for FABP1 and FABP3 but not for B2M and CST6. Validation analysis confirmed that the FABP1 and FABP3 fulfilled the requirement of functioning as markers for AKI patients with risk to dialysis (p < 0.001). CONCLUSION: The release of high amounts of FABP1 and FABP3 in urine of AKI patients could serve as a diagnostic/prognosis marker for RRT initiation in these patients.

Impact of baroreflex activation therapy on renal function--a pilot study.

BACKGROUND/AIMS: Resistant hypertension and chronic kidney disease (CKD) are interlinked via sympathetic overdrive. Baroreflex activation therapy (BAT) has been shown to chronically reduce blood pressure (BP) in patients with resistant hypertension. The effect of BAT on renal function in CKD patients with resistant hypertension has not been reported. The aim of this study was to investigate the effect of sympathetic inhibition on renal function in CKD patients. METHODS: 23 CKD patients with resistant hypertension were prospectively treated with BAT. Analyses were performed before and 6 months after the start of BAT. The renal function was analyzed by creatinine, cystatin C, glomerular filtration rate (GFR), renin, aldosterone, fractioned and 24-hour sodium excretion and analyses of urine marker proteins. The purpose of the control group was to investigate the influence of treating patients in a center for hypertension and regression to the mean on investigated variables. RESULTS: The office mean BP decreased from 116.9 ± 20.9 mm Hg to 104.2 ± 22.2 mm Hg (p < 0.01), while the number of prescribed antihypertensive classes decreased from 6.6 ± 1.6 to 6.1 ± 1.7 (p = 0.02). Proteinuria and albuminuria decreased from a median of 283.9 and 47.7 to 136.5 (p = 0.01) and 45.0 mg/g creatinine (p = 0.01) with pronounced effects in higher CKD stage III + IV compared to I + II (p < 0.01). CKD-EPI cystatin C equation improved from 53.6 ± 22.7 to 60.4 ± 26.1 ml/min (p = 0.02). While creatinine and GFR were impaired after a period of 6 months, no changes of proteinuria, albuminuria, or BP were obtained in control patients. CONCLUSION: The data of this prospective trial demonstrate potential nephroprotective effects of BAT in therapy-resistant hypertension in CKD patients by a reduction of BP, proteinuria and moreover, a stabilization of estimated GFR.

Lipoprotein apheresis reduces biomarkers of plaque destabilization and cardiovascular risk.

Lipoprotein apheresis (LA) is believed to exert anti-atherosclerotic effects beyond LDL-cholesterol reduction. We investigated 22 patients undergoing regular LA on a weekly basis (group A) before (AP) and after LA procedure (EP), 15 healthy individuals (group B), and 22 hyperlipoproteinemic patients with concomitant cardiovascular end organ damage treated without LA therapy (group C). Biomarkers of endothelial inflammation (hsCRP), plaque destabilization, and rupture (sVCAM, MMP-9, PAPP-A, ADMA) were quantified. Intergroup comparison revealed a statistically significant lower MMP-9 level in group A (AP and EP) compared with group C (P < 0.01), whereas PAPP-A levels were lower in group B compared with group A and C (P = 0.04). EP ADMA-levels and EP sVCAM levels in group A were statistically lower compared with group B and C. AP and EP values comparison revealed a significant reduction for hsCRP (mean 41.0 ± 16.7%, P < 0.01), sVCAM (mean 69.6 ± 14.0%, P < 0.01), PAPP-A (mean 88.7 ± 20.4%, P < 0.01), ADMA (mean 69.7 ± 18.4% P < 0.01). In conclusion, we observed a transient decrease in the plasma concentrations of several biomarkers expressed during plaque destabilization and elevated cardiovascular risk after a single LA treatment.

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.

Effects of baroreflex activation therapy on cardiac function and morphology.

AIMS: Arterial hypertension (aHTN) plays a fundamental role in the pathogenesis and prognosis of heart failure with preserved ejection fraction (HFpEF). The risk of heart failure increases with therapy-resistant arterial hypertension (trHTN), defined as inadequate blood pressure (BP) control ≥140/90 mmHg despite taking ≥3 antihypertensive medications including a diuretic. This study investigates the effects of the BP lowering baroreflex activation therapy (BAT) on cardiac function and morphology in patients with trHTN with and without HFpEF. METHODS: Sixty-four consecutive patients who had been diagnosed with trHTN and received BAT implantation between 2012 and 2016 were prospectively observed. Office BP, electrocardiographic and echocardiographic data were collected before and after BAT implantation. RESULTS: Mean patients' age was 59.1 years, 46.9% were male, and mean body mass index (BMI) was 33.2 kg/m2. The prevalence of diabetes mellitus was 38.8%, atrial fibrillation was 12.2%, and chronic kidney disease (CKD) stage ≥3 was 40.8%. Twenty-eight patients had trHTN with HFpEF, and 21 patients had trHTN without HFpEF. Patients with HFpEF were significantly older (64.7 vs. 51.6 years, P < 0.0001), had a lower BMI (30.0 vs. 37.2 kg/m2, P < 0.0001), and suffered more often from CKD-stage ≥3 (64 vs. 20%, P = 0.0032). After BAT implantation, mean office BP dropped in patients with and without HFpEF (from 169 ± 5/86 ± 4 to 143 ± 4/77 ± 3 mmHg [P = 0.0019 for systolic BP and 0.0403 for diastolic BP] and from 170 ± 5/95 ± 4 to 149 ± 6/88 ± 5 mmHg [P = 0.0019 for systolic BP and 0.0763 for diastolic BP]), while a significant reduction of the intake of calcium-antagonists, α2-agonists and direct vasodilators, as well as a decrease in average dosage of ACE-inhibitors and α2-agonists could be seen. Within the study population, a decrease in heart rate from 74 ± 2 to 67 ± 2 min-1 (P = 0.0062) and lengthening of QRS-time from 96 ± 3 to 106 ± 4 ms (P = 0.0027) and QTc-duration from 422 ± 5 to 432 ± 5 ms (P = 0.0184) were detectable. The PQ duration was virtually unchanged. In patients without HF, no significant changes of echocardiographic parameters could be seen. In patients with HFpEF, posterior wall diameter decreased significantly from 14.0 ± 0.5 to 12.7 ± 0.3 mm (P = 0.0125), left ventricular mass (LVM) declined from 278.1 ± 15.8 to 243.9 ± 13.4 g (P = 0.0203), and e' lateral increased from 8.2 ± 0.4 to 9.0 ± 0.4 cm/s (P = 0.0471). CONCLUSIONS: BAT reduced systolic and diastolic BP and was associated with morphological and functional improvement of HFpEF.

Nephrotic syndrome in a multiple sclerosis patient receiving long-term interferon beta therapy.

Recombinant interferon α (IFN-α) and interferon ß (IFN-ß) are efficient drugs for clinical use in multiple sclerosis, hepatitis C virus infection, and malignant diseases. We report a case of a 40-year-old woman with relapsing-remitting multiple sclerosis who was treated with interferon beta-1b for several years before being admitted to our department with nephrotic-range proteinuria (protein excretion, 8.3 g/d) and serum albumin level of 2.9 g/dL without any clinical and laboratory change typical for a systemic autoimmune disease. The kidney biopsy led to the diagnosis of immune complex-mediated membranoproliferative glomerulonephritis with immunoglobulin and complement deposits visible by immunohistology, as well as subendothelial deposits and tubuloreticular inclusions evident by electron microscopy. Subsequently replacing interferon beta-1b with glatiramer acetate resulted in partial remission, with proteinuria decreasing to protein excretion of 1.0 g/d 2 months thereafter. The association of a focal mesangiocapillary glomerular change and immunoglobulin-complement deposits with tubuloreticular inclusions suggests lupus nephritis. To our knowledge, this is the first report of an interferon beta-1b-induced immune complex glomerulonephritis characterized by histologic, immunohistologic, and ultrastructural features that resembled lupus nephritis, but that occurred in a patient without evidence of systemic lupus erythematosus. Our review of experimental data and earlier case reports suggests a pathogenic role of recombinant IFN in some autoimmune diseases, especially those with the potency to induce systemic lupus erythematosus-like syndromes.

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.

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.

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.

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.

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.

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.

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.