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Article ; Online: Slow ventricular tachycardia presenting with acute liver failure

Andreas Wannhoff / Christian Nusshag / Wolfgang Stremmel / Uta Merle

SAGE Open Medical Case Reports, Vol

2017 Volume 5

Abstract: Objectives: Cardiac hepatopathy is an important differential diagnosis of acute liver failure. Slow ventricular tachycardia (slow VT) is a ventricular tachycardia (VT), in which heart rate is below the typical frequency of VT. We here report a case of ... ...

Abstract	Objectives: Cardiac hepatopathy is an important differential diagnosis of acute liver failure. Slow ventricular tachycardia (slow VT) is a ventricular tachycardia (VT), in which heart rate is below the typical frequency of VT. We here report a case of acute liver failure in a patient with slow VT. Methods: The 64-year old male patient with history of cardiac pacemaker implantation for complete atrioventricular block was referred to our intensive care unit because of acute liver failure. Results: Workup identified cardiac failure as cause of hepatopathy; however, reason for cardiac failure remained unknown even after left heart catheterization with coronary angiography. Finally, the analysis of cardiac pacemaker recordings led to the diagnosis of slow VT. This could not be terminated with either electric cardioversion or pharmacological treatment, and the patient died of cardiac failure. Conclusion: Diagnosis of VT can be challenging if occurring at unexpected slow heart rates. Analysis of pacemaker recordings could help to make the diagnosis of slow VT.
Keywords	Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2017-07-01T00:00:00Z
Publisher	SAGE Publishing
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Membranous nephropathy followed by anti-glomerular basement disease

Claudius Speer / Matthias Martin Gaida / Rüdiger Waldherr / Christian Nusshag / Florian Kälble / Martin Zeier

SAGE Open Medical Case Reports, Vol

A case report and review of clinical presentation and treatment

2018 Volume 6

Abstract: Membranous nephropathy is a common cause of nephrotic syndrome in adults and can be primary or secondary through autoimmune disease, medication, infection, or malignancy. Rapidly progressive glomerulonephritis with crescent formation is rare in patients ... ...

Abstract	Membranous nephropathy is a common cause of nephrotic syndrome in adults and can be primary or secondary through autoimmune disease, medication, infection, or malignancy. Rapidly progressive glomerulonephritis with crescent formation is rare in patients with membranous nephropathy. Thus, in cases with rapid decline in renal function, after excluding complications such as malignant hypertension, acute hypersensitivity interstitial nephritis, and bilateral renal vein thrombosis, the simultaneous occurrence of a superimposed glomerulonephritis should be considered. We report a 55-year-old man suffering from a biopsy-confirmed primary membranous nephropathy, who developed rapidly progressive glomerulonephritis with anti-glomerular basement membrane antibodies after being affected with membranous nephropathy for 8 years. The kidney biopsy revealed a concurrence of membranous nephropathy and anti-glomerular basement membrane disease. Clinical presentation and treatment of membranous nephropathy followed by anti-glomerular basement membrane disease are discussed based on our observation with promising follow-up.
Keywords	Medicine (General) ; R5-920
Subject code	616
Language	English
Publishing date	2018-10-01T00:00:00Z
Publisher	SAGE Publishing
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Effect of plasma exchange on COVID-19 associated excess of von Willebrand factor and inflammation in critically ill patients

Felix S. Seibert / Arturo Blazquez-Navarro / Bodo Hölzer / Adrian A. N. Doevelaar / Christian Nusshag / Uta Merle / Christian Morath / Panagiota Zgoura / Rita Dittmer / Sonja Schneppenheim / Jochen Wilhelm / Nina Babel / Ulrich Budde / Timm H. Westhoff

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 8

Abstract: Abstract Ubiquitous microthromboses in the pulmonary vasculature play a crucial role in the pathogenesis of COVID-19 associated acute respiratory distress syndrome (ARDS). Excess of Willebrand factor (vWf) with intravascular multimer formation was ... ...

Abstract	Abstract Ubiquitous microthromboses in the pulmonary vasculature play a crucial role in the pathogenesis of COVID-19 associated acute respiratory distress syndrome (ARDS). Excess of Willebrand factor (vWf) with intravascular multimer formation was identified as a key driver of this finding. Plasma exchange (PLEX) might be a therapeutic option to restore the disbalance between vWf and ADAMTS13. We report the effects of PLEX on vWf, ADAMTS13, inflammatory cytokines and parameters of ventilation. We investigated 25 patients, who were on mechanical ventilation for COVID-19 pneumonia with ARDS at two German university hospitals. All patients received PLEX as an ultima ratio measure for refractory ARDS. VWf antigen (vWf:Ag), ADAMTS13 activity, a cytokine panel mirroring the inflammatory situation and clinical parameters were assessed before and after three to six PLEX therapies with fresh frozen plasma. Before the PLEX sequence there was an excessive release of vWf:Ag (425.4 ± 167.5%) and mildly reduced ADAMTS13 activity (49.7 ± 23.3%). After the PLEX series, there was a significant increase of ADAMTS13 activity to 62.4 ± 17.7% (p = 0.029) and a significant decrease of vWf:Ag to 336.1 ± 138.2% (p = 0.041) resulting in a 63% improvement of the ADAMT13/vWf:Ag ratio from 14.5 ± 10.0 to 23.7 ± 14.6, p = 0.024. Comparison of parameters before and after individual PLEX sessions (n = 35) revealed a mean reduction of vWf from 387.8 ± 165.1 to 213.2 ± 62.3% (p = 0.001) and an increase of ADAMTS13 activity from 60.4 ± 20.1 to 70.5 ± 14.0% (p = 0.001). Parallelly, monocyte chemotactic protein-1 and interleukin-18 decreased significantly (p = 0.034 each). Along the PLEX sequence lactate dehydrogenase (p = 0.001), C-reactive protein (p = 0.001), and positive end expiratory pressure (p = 0.01) significantly decreased accompanied by an improvement of Horovitz index (p = 0.001). PLEX restores the disbalance between ADAMTS13 and vWf:Ag, a driver of immunothrombosis. Moreover, it reduces the inflammatory state and is associated with a benefit of ventilation parameters. These findings render a further rationale to regard PLEX as a therapeutic option in severe COVID-19.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Humoral response to SARS-CoV-2 mRNA vaccination in previous non-responder kidney transplant recipients after short-term withdrawal of mycophenolic acid

Frontiers in Medicine, Vol

2022 Volume 9

Abstract: Seroconversion rates after COVID-19 vaccination are significantly lower in kidney transplant recipients compared to healthy cohorts. Adaptive immunization strategies are needed to protect these patients from COVID-19. In this prospective observational ... ...

Abstract	Seroconversion rates after COVID-19 vaccination are significantly lower in kidney transplant recipients compared to healthy cohorts. Adaptive immunization strategies are needed to protect these patients from COVID-19. In this prospective observational cohort study, we enrolled 76 kidney transplant recipients with no seroresponse after at least three COVID-19 vaccinations to receive an additional mRNA-1273 vaccination (full dose, 100 μg). Mycophenolic acid was withdrawn in 43 selected patients 5–7 days prior to vaccination and remained paused for 4 additional weeks after vaccination. SARS-CoV-2-specific antibodies and neutralization of the delta and omicron variants were determined using a live-virus assay 4 weeks after vaccination. In patients with temporary mycophenolic acid withdrawal, donor-specific anti-HLA antibodies and donor-derived cell-free DNA were monitored before withdrawal and at follow-up. SARS-CoV-2 specific antibodies significantly increased in kidney transplant recipients after additional COVID-19 vaccination. The effect was most pronounced in individuals in whom mycophenolic acid was withdrawn during vaccination. Higher SARS-CoV-2 specific antibody titers were associated with better neutralization of SARS-CoV-2 delta and omicron variants. In patients with short-term withdrawal of mycophenolic acid, graft function and donor-derived cell-free DNA remained stable. No acute rejection episode occurred during short-term follow-up. However, resurgence of prior anti-HLA donor-specific antibodies was detected in 7 patients.
Keywords	SARS-CoV-2 ; kidney transplantation ; variants of concern ; delta variant ; omicron variant ; SARS-CoV-2 vaccination ; Medicine (General) ; R5-920
Language	English
Publishing date	2022-08-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: suPAR links a dysregulated immune response to tissue inflammation and sepsis-induced acute kidney injury

JCI Insight, Vol 8, Iss

2023 Volume 7

Abstract: Acute kidney injury (AKI) secondary to sepsis results in poor outcomes and conventional kidney function indicators lack diagnostic value. Soluble urokinase plasminogen activator receptor (suPAR) is an innate immune–derived molecule implicated in ... ...

Abstract	Acute kidney injury (AKI) secondary to sepsis results in poor outcomes and conventional kidney function indicators lack diagnostic value. Soluble urokinase plasminogen activator receptor (suPAR) is an innate immune–derived molecule implicated in inflammatory organ damage. We characterized the diagnostic ability of longitudinal serum suPAR levels to discriminate severity and course of sepsis-induced AKI (SI-AKI) in 200 critically ill patients meeting Sepsis-3 criteria. The pathophysiologic relevance of varying suPAR levels in SI-AKI was explored in a polymicrobial sepsis model in WT, (s)uPAR-knockout, and transgenic suPAR-overexpressing mice. At all time points studied, suPAR provided a robust classification of SI-AKI disease severity, with improved prediction of renal replacement therapy (RRT) and mortality compared with established kidney biomarkers. Patients with suPAR levels of greater than 12.7 ng/mL were at highest risk for RRT or death, with an adjusted odds ratio of 7.48 (95% CI, 3.00–18.63). suPAR deficiency protected mice against SI-AKI. suPAR-overexpressing mice exhibited greater kidney damage and poorer survival through inflamed kidneys, accompanied by local upregulation of potent chemoattractants and pronounced kidney T cell infiltration. Hence, suPAR allows for an innate immune–derived and kidney function–independent staging of SI-AKI and offers improved longitudinal risk stratification. suPAR promotes T cell–based kidney inflammation, while suPAR deficiency improves SI-AKI.
Keywords	Inflammation ; Nephrology ; Medicine ; R
Subject code	616
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	American Society for Clinical investigation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Living Donor Kidney Transplantation in Patients With Donor-Specific HLA Antibodies After Desensitization With Immunoadsorption

Florian Kälble / Caner Süsal / Luiza Pego da Silva / Claudius Speer / Louise Benning / Christian Nusshag / Lien Pham / Hien Tran / Matthias Schaier / Claudia Sommerer / Jörg Beimler / Arianeb Mehrabi / Martin Zeier / Christian Morath

Frontiers in Medicine, Vol

2021 Volume 8

Abstract: Due to the current organ shortage, living donor kidney transplantation is increasingly performed across HLA (human leukocyte antigen) or ABO antibody barriers. There is still uncertainty about the risk of antibody-mediated rejection (AMR) episodes, which ...

Abstract	Due to the current organ shortage, living donor kidney transplantation is increasingly performed across HLA (human leukocyte antigen) or ABO antibody barriers. There is still uncertainty about the risk of antibody-mediated rejection (AMR) episodes, which may limit long-term graft survival. From March 2007 to December 2016, 58 sensitized living donor kidney transplant candidates were identified and 38 patients eventually included in the study: 36 patients (95%) had pre-transplant and pre-desensitization Luminex-detected donor-specific HLA antibodies (DSA), and 17/36 patients (47%) in addition had a positive crossmatch result. Two patients had no detectable DSA but a positive CDC B-cell crossmatch result. Patients were treated with pre- and post-transplant apheresis and powerful immunosuppression including the anti-CD20 antibody rituximab (N = 36) in combination with thymoglobulin (N = 20) or anti-IL2 receptor antibody (N = 18). The results of the 38 successfully desensitized and transplanted patients were retrospectively compared to the results of 76 matched standard-risk recipients. Desensitized patients showed patient and graft survival rates similar to that of standard-risk recipients (P = 0.55 and P = 0.16, respectively). There was a trend toward reduced death-censored graft survival in desensitized patients (P = 0.053) which, however, disappeared when the 34 patients who were transplanted after introduction of sensitive Luminex testing were analyzed (P = 0.43). The incidence of rejection episodes without borderline changes were in desensitized patients with 21% similar to the 18% in standard-risk patients (P = 0.74). Thirty-six patients had pre-transplant HLA class I and/or II DSA that were reduced by 85 and 81%, respectively, during pre-transplant desensitization (P < 0.001 for both). On day 360 after transplantation, 20 of 36 (56%) patients had lost their DSA. The overall AMR rate was 6% in these patients, but as high as 60% in 5 (14%) patients with persistent and de novo DSA during year 1; 2 (40%) of whom lost their graft due to AMR. Eleven (31%) patients with persistent DSA but without de novo DSA had an AMR rate of 18% without graft loss while one patient lost her graft without signs of AMR. Our desensitization protocol for pre-sensitized living donor kidney transplant recipients with DSA resulted in good graft outcomes with side effects and rejection rates similar to that of standard-risk recipients. Adequate patient selection prior to transplantation and frequent immunological monitoring thereafter is critical to minimize rejection episodes and subsequent graft loss.
Keywords	desensitization ; immunoadsorption ; donor-specific antibody (DSA) ; antibody-mediated rejection (AMR) ; kidney transplantation ; Medicine (General) ; R5-920
Subject code	610 ; 616
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Application of regularized regression to identify novel predictors of mortality in a cohort of hemodialysis patients

Stanislas Werfel / Georg Lorenz / Bernhard Haller / Roman Günthner / Julia Matschkal / Matthias C. Braunisch / Carolin Schaller / Peter Gundel / Stephan Kemmner / Salim S. Hayek / Christian Nusshag / Jochen Reiser / Philipp Moog / Uwe Heemann / Christoph Schmaderer

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 12

Abstract: Abstract Cohort studies often provide a large array of data on study participants. The techniques of statistical learning can allow an efficient way to analyze large datasets in order to uncover previously unknown, clinically relevant predictors of ... ...

Abstract	Abstract Cohort studies often provide a large array of data on study participants. The techniques of statistical learning can allow an efficient way to analyze large datasets in order to uncover previously unknown, clinically relevant predictors of morbidity or mortality. We applied a combination of elastic net penalized Cox regression and stability selection with the aim of identifying novel predictors of mortality in a cohort of prevalent hemodialysis patients. In our analysis we included 475 patients from the “rISk strAtification in end-stage Renal disease” (ISAR) study, who we split into derivation and confirmation cohorts. A wide array of examinations was available for study participants, resulting in over a hundred potential predictors. In the selection approach many of the well established predictors were retrieved in the derivation cohort. Additionally, the serum levels of IL-12p70 and AST were selected as mortality predictors and confirmed in the withheld subgroup. High IL-12p70 levels were specifically prognostic of infection-related mortality. In summary, we demonstrate an approach how statistical learning can be applied to a cohort study to derive novel hypotheses in a data-driven way. Our results suggest a novel role of IL-12p70 in infection-related mortality, while AST is a promising additional biomarker in patients undergoing hemodialysis.
Keywords	Medicine ; R ; Science ; Q
Subject code	310
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Longitudinal Humoral Responses after COVID-19 Vaccination in Peritoneal and Hemodialysis Patients over Twelve Weeks

Claudius Speer / Matthias Schaier / Christian Nusshag / Maximilian Töllner / Mirabel Buylaert / Florian Kälble / Paula Reichel / Julia Grenz / Caner Süsal / Martin Zeier / Paul Schnitzler / Christian Morath / Katrin Klein / Louise Benning

Vaccines, Vol 9, Iss 1130, p

2021 Volume 1130

Abstract: It has been demonstrated that patients on hemo- or peritoneal dialysis are particularly susceptible to SARS-CoV-2 infection and impaired seroconversion compared to healthy controls. Follow-up data on vaccination response in dialysis patients is limited ... ...

Abstract	It has been demonstrated that patients on hemo- or peritoneal dialysis are particularly susceptible to SARS-CoV-2 infection and impaired seroconversion compared to healthy controls. Follow-up data on vaccination response in dialysis patients is limited but is greatly needed to individualize and guide (booster) vaccination strategies. In this prospective, multicenter study we measured anti-spike S1 and neutralizing antibodies in 124 hemodialysis patients, 41 peritoneal dialysis patients, and 20 age- and sex-matched healthy controls over 12 weeks after homologous BNT162b2 vaccination. Compared to healthy controls, both hemodialysis and peritoneal dialysis patients had lower anti-S1 IgG antibodies (median (IQR) 7.0 (2.8–24.3) and 21.8 (5.8–103.9) versus 134.9 (23.8–283.6), respectively; p < 0.001 and p < 0.05) and a reduced SARS-CoV-2 spike protein–ACE2 binding inhibition caused by vaccine-induced antibodies (median (IQR) 56% (40–81) and 77% (52–89) versus 96% (90–98), respectively; p < 0.001 and p < 0.01) three weeks after the second vaccination. Twelve weeks after the second vaccination, the spike protein–ACE2 binding inhibition significantly decreased to a median (IQR) of 45% (31–60) in hemodialysis patients and 55% (36–78) in peritoneal dialysis patients, respectively ( p < 0.001 and p < 0.05). Peritoneal dialysis patients mounted higher antibody levels compared with hemodialysis patients at all time points during the 12-week follow-up. Individual booster vaccinations in high-risk individuals without seroconversion or rapidly waning neutralizing antibody levels are required and further data on the neutralization of emerging variants of concern in these patients are urgently needed.
Keywords	COVID-19 ; COVID-19 vaccination ; hemodialysis ; peritoneal dialysis ; humoral response ; BNT162b2 ; Medicine ; R
Subject code	610
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Heterologous ChAdOx1 nCoV-19/BNT162b2 Prime-Boost Vaccination Induces Strong Humoral Responses among Health Care Workers

Louise Benning / Maximilian Töllner / Asa Hidmark / Matthias Schaier / Christian Nusshag / Florian Kälble / Paula Reichel / Mirabel Buylaert / Julia Grenz / Gerald Ponath / Katrin Klein / Martin Zeier / Caner Süsal / Paul Schnitzler / Christian Morath / Claudius Speer

Vaccines, Vol 9, Iss 857, p

2021 Volume 857

Abstract: Despite limited data on safety and immunogenicity, heterologous prime-boost vaccination is currently recommended for individuals with ChAdOx1 nCoV-19 prime immunization in certain age groups. In this prospective, single-center study we included 166 ... ...

Abstract	Despite limited data on safety and immunogenicity, heterologous prime-boost vaccination is currently recommended for individuals with ChAdOx1 nCoV-19 prime immunization in certain age groups. In this prospective, single-center study we included 166 health care workers from Heidelberg University Hospital who received either heterologous ChAdOx1 nCoV-19/BNT162b2, homologous BNT162b2 or homologous ChAdOx1 nCoV-19 vaccination between December 2020 and May 2021. We measured anti-S1 IgG, SARS-CoV-2 specific neutralizing antibodies, and antibodies against different SARS-CoV-2 fragments 0–3 days before and 19–21 days after boost vaccination. Before boost, 55/70 (79%) ChAdOx1 nCoV-19-primed compared with 44/45 (98%) BNT162b2-primed individuals showed positive anti-S1 IgG with a median (IQR) anti-S1 IgG index of 1.95 (1.05–2.99) compared to 9.38 (6.26–17.12). SARS-CoV-2 neutralizing antibodies exceeded the threshold in 24/70 (34%) of ChAdOx1 nCoV-19-primed and 43/45 (96%) of BNT162b2-primed individuals. After boosting dose, median (IQR) anti-S1 IgG index in heterologous ChAdOx1 nCoV-19/BNT162b2 vaccinees was 116.2 (61.84–170), compared to 13.09 (7.03–29.02) in homologous ChAdOx1 nCoV-19 and 145.5 (100–291.1) in homologous BNT162b2 vaccinees. All boosted vaccinees exceeded the threshold for neutralization, irrespective of their vaccination scheme. Vaccination was well-tolerated overall. We show that heterologous ChAdOx1 nCoV-19/BNT162b2 vaccination is safe and induces a strong and broad humoral response in healthy individuals.
Keywords	COVID-19 ; COVID-19 vaccination ; heterologous vaccination ; humoral response ; mRNA vaccine ; BNT162b2 ; Medicine ; R
Subject code	360
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Glomerular filtration barrier dysfunction in a self-limiting, RNA virus-induced glomerulopathy resembles findings in idiopathic nephrotic syndromes

Christian Nusshag / Alisa Stütz / Stefan Hägele / Claudius Speer / Florian Kälble / Christoph Eckert / Thorsten Brenner / Markus A. Weigand / Christian Morath / Jochen Reiser / Martin Zeier / Ellen Krautkrämer

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 10

Abstract: Abstract Podocyte injury has recently been described as unifying feature in idiopathic nephrotic syndromes (INS). Puumala hantavirus (PUUV) infection represents a unique RNA virus-induced renal disease with significant proteinuria. The underlying ... ...

Abstract	Abstract Podocyte injury has recently been described as unifying feature in idiopathic nephrotic syndromes (INS). Puumala hantavirus (PUUV) infection represents a unique RNA virus-induced renal disease with significant proteinuria. The underlying pathomechanism is unclear. We hypothesized that PUUV infection results in podocyte injury, similar to findings in INS. We therefore analyzed standard markers of glomerular proteinuria (e.g. immunoglobulin G [IgG]), urinary nephrin excretion (podocyte injury) and serum levels of the soluble urokinase plasminogen activator receptor (suPAR), a proposed pathomechanically involved molecule in INS, in PUUV-infected patients. Hantavirus patients showed significantly increased urinary nephrin, IgG and serum suPAR concentrations compared to healthy controls. Nephrin and IgG levels were significantly higher in patients with severe proteinuria than with mild proteinuria, and nephrin correlated strongly with biomarkers of glomerular proteinuria over time. Congruently, electron microcopy analyses showed a focal podocyte foot process effacement. suPAR correlated significantly with urinary nephrin, IgG and albumin levels, suggesting suPAR as a pathophysiological mediator in podocyte dysfunction. In contrast to INS, proteinuria recovered autonomously in hantavirus patients. This study reveals podocyte injury as main cause of proteinuria in hantavirus patients. A better understanding of the regenerative nature of hantavirus-induced glomerulopathy may generate new therapeutic approaches for INS.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	Nature Publishing Group
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