Neutrophil extracellular traps (NETs) are large structures composed of chromatin, histones and granule-derived proteins released extracellularly by neutrophils. They are generally considered to be a part of the antimicrobial defense strategy, preventing the dissemination of pathogens. However, overproduction of NETs or their ineffective clearance can drive various pathologies, many of which are associated with advanced age and involve uncontrolled inflammation, oxidative, cardiovascular and neurodegenerative stress as underlying mechanisms. Targeting NETs in the elderly as an anti-aging therapy seems to be a very attractive therapeutic approach. Therapeutic apheresis with a specific filter to remove NETs could be a promising strategy worth considering.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

A continual increase in cases of Long/Post COVID constitutes a medical and socioeconomic challenge to health systems around the globe. While the true extent of this problem cannot yet be fully evaluated, recent data suggest that up to 20% of people with confirmed SARS-CoV-2 suffer from clinically relevant symptoms of Long/Post COVID several weeks to months after the acute phase. The clinical presentation is highly variable with the main symptoms being chronic fatigue, dyspnea, and cognitive symptoms. Extracorporeal apheresis has been suggested to alleviate symptoms of Post/COVID. Thus, numerous patients are currently treated with apheresis. However, at present there is no data from randomized controlled trials available to confirm the efficacy. Therefore, physicians rely on the experience of practitioners and centers performing this treatment. Here, we summarize clinical experience on extracorporeal apheresis in patients with Post/COVID from centers across Germany.

Diagnosis of pheochromocytomas and paragangliomas in patients receiving hemodialysis is troublesome. The aim of the study was to establish optimal conditions for blood sampling for mass spectrometric measurements of normetanephrine, metanephrine and 3-methoxytyramine in patients on hemodialysis and specific reference intervals for plasma metanephrines under the most optimal sampling conditions. Blood was sampled before and near the end of dialysis, including different sampling sites in 170 patients on hemodialysis. Plasma normetanephrine concentrations were lower (P < 0.0001) and metanephrine concentrations higher (P < 0.0001) in shunt than in venous blood, with no differences for 3-methoxytyramine. Normetanephrine, metanephrine and 3-methoxytyramine concentrations in shunt and venous blood were lower (P < 0.0001) near the end than before hemodialysis. Upper cut-offs for normetanephrine were 34% lower when the blood was drawn from the shunt and near the end of hemodialysis compared to blood drawn before hemodialysis. This study establishes optimal sampling conditions using blood from the dialysis shunt near the end of hemodialysis with optimal reference intervals for plasma metanephrines for the diagnosis of pheochromocytomas/paragangliomas among patients on hemodialysis.

Abstract Background Diagnosis of pheochromocytomas and paragangliomas in patients receiving hemodialysis is troublesome. Aim To establish optimal conditions for blood sampling for mass spectrometric measurements of normetanephrine, metanephrine and 3-methoxytyramine in patients on hemodialysis and specific reference intervals for plasma metanephrines under the most optimal sampling conditions. Methods Blood was sampled before and near the end of dialysis, including different sampling sites in 170 patients on hemodialysis. Results Plasma normetanephrine concentrations were lower (P < 0.0001) and metanephrine concentrations higher (P < 0.0001) in shunt than in venous blood, with no differences for 3-methyxytyramine. Normetanephrine, metanephrine and 3-methoxytyramine concentrations in shunt and venous blood were lower (P < 0.0001) near the end than before hemodialysis. Upper cut-offs for normetanephrine were 34% lower when the blood was drawn from the shunt and near the end of hemodialysis compared to blood drawn before hemodialysis. Conclusion This study establishes optimal sampling conditions using blood from the dialysis shunt near the end of hemodialysis with optimal reference intervals for plasma metanephrines for the diagnosis of pheochromocytomas/paragangliomas among patients on hemodialysis.

Purpose: To assess the kidney safety profile of mannitol in patients with malignant middle cerebral artery (MCA) infarction. Material and methods: We studied consecutive patients with malignant MCA infarction (01/2008-01/2018). Malignant MCA infarction was defined according to DESTINY criteria. We compared clinical endpoints including acute kidney injury (AKI; according to Kidney Disease: Improving Global Outcomes [KDIGO]) and dialysis between patients with and without mannitol. Multivariable model was built to explore predictor variables of AKI and in-hospital death. Results: Overall, 219 patients with malignant MCA infarction were included. Mannitol was administered in 93/ 219 (42.5%) patients with an average dosage of 650 g (250-950 g). Patients treated with mannitol more frequently suffered from AKI (39.8% vs. 11.9%; p < 0.001) and required hemodialysis (7.5% vs. 0.8%; p = 0.01) than patients without mannitol. At discharge, more patients in the mannitol group had persistent AKI than control patients (23.7% vs. 6.4%, p < 0.001). In multivariable model, mannitol emerged as independent predictor of AKI (OR 5.02, 95%CI 2.36-10.69; p < 0.001). Conclusions: Acute kidney injury appears to be a frequent complication of hyperosmolar therapy with mannitol in patients with malignant MCA infarction. Given the lack of evidence supporting effectiveness of mannitol in these patients, its routine use should be carefully considered. (c) 2021 Elsevier Inc. All rights reserved.

OBJECTIVE:Recently, dynamic retinal vessel analysis (DVA) has gained interest for investigation of microvascular function but comparative measurements with standard methods like the forearm blood flow technique (FBF) are uncommon till now.METHODS:We recruited 23 high-risk cardiovascular patients (Risk) and 17 healthy persons (Ctrl). During the FBF experiment, postocclusive reactive hyperaemia (RH) as well as endothelium-dependent and independent vasodilation was measured by infusion of acetylcholine (ACh) and sodium nitroprusside (SNP) into the brachial artery. The dynamic vessel analyzer was applied for measurement of the retinal arterial and venous response to flickering light during DVA and for determination of the central retinal arterial (CRAE) and venous equivalent (CRVE).RESULTS:Forearm blood flow technique was significantly attenuated in the patient group during postocclusive RH (p < .005). The increase of FBF in response to SNP did not differ significantly between the two groups (p = .09). In contrast, the FBF response to ACh was significantly blunted in the patient group (p < .05), indicating endothelial dysfunction. DVA did not detect any difference of retinal arterial (p = .68) or retinal venous (p = .93) vasodilation between both groups. The CRAE (p = .55) and CRVE (p = .83) did not differ significantly in either group.CONCLUSIONS:Forearm blood flow and DVA cannot be regarded as equivalent methods for testing of microvascular function. Possible explanations include differences in the vascular beds and vessel diameters examined as well as differences in the trigger mechanisms applied. Further studies are needed to define the role of DVA in this context.

CONTEXT:Adrenalectomy is the preferred treatment for unilateral primary aldosteronism but the results of long-term control of blood pressure (BP) are far from optimal. One possible explanation relates to the quality of the assessment of treatment effects on BP.PURPOSE OF THE STUDY:To examine the quality of reporting BP measurements in studies assessing the outcome of adrenalectomy on BP.METHODS:We conducted a systematic review searching 3 databases (PubMed, EMBASE, Web of Science) for articles published from January 1, 1990, onwards. Sixty-six studies, each reporting on more than 50 adrenalectomized patients, were eligible for full analysis.RESULTS:In 37 of the analyzed 66 studies (56.1%) BP values both before and after adrenalectomy were reported. In 19.7% (13/66) of the studies the method of BP measurement was described. The number of visits and number of BP recordings per visit on which BP results were based were reported in <15% of papers. The criteria for the diagnosis of hypertension were described in 72.7% (48/66) of the studies. The used definitions of improvement of BP control after adrenalectomy were variable, with 84.8% of the studies not providing any quantitative criteria to define reduction in BP.CONCLUSION:We conclude that the quality of reporting on BP control after adrenalectomy for primary aldosteronism shows substantial deficiencies and inconsistencies, thus impacting negatively on accurate assessment of effects of adrenalectomy on BP control. Future studies should adhere to accepted recommendations of correct BP measurement and should provide detailed description of the methods used for BP measurement.

Die Hemmung eines erhöhten Sympathikotonus stellt für verschiedene Erkrankungen ein effektives und in vielen Fällen kausales Therapieprinzip dar. Neben pharmakologischen Ansätzen mit Betablockern oder zentralen Sympatholytika sind in den letzten Jahren zunehmend auch interventionelle Verfahren, wie die renale Sympathikusdenervation oder die Baroreflexaktivierungstherapie (BAT) v. a. in der Behandlung der therapierefraktären arteriellen Hypertonie zur Anwendung gekommen. Kontroverse Studienergebnisse zur Wirksamkeit dieser Verfahren haben jedoch die Diskussion um Patientenselektion und Qualitätsstandards in der Anwendung entfacht. Infolge der aktuellen Indikationserweiterung findet zudem die BAT zunehmend Verbreitung in der Behandlung der systolischen Herzinsuffizienz. Eine Gruppe führender Anwender und Wissenschaftler auf dem Gebiet der BAT hat daher zusammen mit interdisziplinären Hypertensiologen in einer Konsensuskonferenz Voraussetzungen für die Etablierung eines BAT-Programms und Standards zur Implantation, Programmierung und Nachsorge definiert.

To the Editor: The diagnostic work-up of pheochromocytoma/paraganglioma (PPGL) among patients with chronic kidney disease (CKD) is a clinical challenge. Impaired renal elimination of catecholamines and their metabolites confounds urinary tests, while increased plasma concentrations of free metanephrines in patients with CKD also complicate interpretation of plasma tests.1, 2, 3 We therefore aimed to establish optimal reference intervals for plasma free metanephrines and 3-methoxytyramine in patients with CKD stages 3 and 4 or receiving hemodialysis (HD).This prospective multicenter study included 234 patients (79 CKD3, 48 CKD4, and 107 receiving HD) and an aged-matched reference population of 173 individuals (Table 1; Item S1). Measurements of plasma free normetanephrine, metanephrine, and 3-methoxytyramine were performed using liquid chromatography–tandem mass spectrometry (LC-MS/MS).4

ABO incompatible (ABOi) organ transplantation requires pre-transplant reduction of the recipient's IgG and IgM isoagglutinin titer against the donor to prevent hyperacute rejection. Over the past four years we primarily used unspecific IgG immunoadsorption (IA) for this purpose and combined this selectively with membrane filtration (IAc) to reduce IgM isoagglutinines. In patients with an initial IgG titer against donor below 1:64, plasma exchange (PE) was initiated. In this retrospective analysis covering January 2012 to August 2015 we compared how efficiently IgG and IgM isoagglutinines in a total of 22 ABOi kidney transplant recipients were reduced by either IA (n = 75 sessions), IAc (n = 14 sessions) or PE (n = 40 sessions). Median pre-treatment IgG isoagglutinin titers were 32 (4-4096) while IgM titers were 16 (1-256) respectively. Mean IgG reduction by either treatment modality was 1.3 ± 0.9 (IA), 1.8 ± 1.0 (IAc) and 2.6 ± 1.3 (PE) titer steps per session (p < 0.001 IA vs. PE; p < 0.04 PE vs. IAc). Mean IgM reduction was 0.6 ± 0.6 (IA), 1.8 ± 0.8 (IAc) and 2.4 ± 1.9 (PE) titer steps (p < 0.001 for both IA vs. PE and IA vs. IAc). Our data indicate that PE efficiently removed IgG- and IgM isoagglutinines. By processing only half the plasma volume per treatment PE was twice as effective as IA in terms of IgG-type isoagglutinin removal in our patient group. This is best explained by the presence of soluble AB0 antigens in the FFP used as plasma replacement. These advantages in efficacy have to be weighed against the potential hazards of PE. Combination of IA and plasma filtration effectively removes IgM-type and even enhances net IgG-type isoagglutinin elimination compared to IA alone. When trying to avoid PE, combined application of IA and IAc is a possible and effective way to reduce isoagglutinin titers before ABOi transplantation.

Zur Behandlung der therapierefraktären Hypertonie (trHTN) steht seit einigen Jahren die Möglichkeit der Barorezeptoraktivierungstherapie (BAT) zur Verfügung. Das Verfahren wird derzeit in Deutschland an einer begrenzten Anzahl von Standorten durchgeführt, auch mit dem Ziel, eine hohe Expertise durch ausreichende Erfahrung anzubieten. Durch eine wachsende Zahl von Patienten, die mit einer BAT behandelt werden, treten jedoch im ärztlichen Alltag immer wieder Probleme im Umgang mit diesen Patienten auf. Um diese Probleme zu adressieren, wurde im November 2016 eine Konsensuskonferenz mit Experten auf dem Gebiet der trHTN durchgeführt, die die aktuellen Evidenzen und Erfahrungen, aber auch Problembereiche im Umgang mit BAT-Patienten zusammenfasst.

Baroreceptor activation therapy (BAT) has been available for several years for treatment of therapy-refractory hypertension (trHTN). This procedure is currently being carried out in a limited number of centers in Germany, also with the aim of offering a high level of expertise through sufficient experience; however, a growing number of patients who are treated with BAT experience problems that treating physicians are confronted with in routine medical practice. In order to address these problems, a consensus conference was held with experts in the field of trHTN in November 2016, which summarizes the current evidence and experience as well as the problem areas in handling BAT patients.

Bernd Hohenstein1, Mirian Opgenoorth1, Jens Passauer1, Steffen Jahn2, Kerstin U Amann3, Michael Kirschfink4, Stefan Zastrow5, Manfred Wirth5 and Christian Hugo1 University Hospital Carl Gustav Carus, Department of Internal Medicine 3, Division of Nephrology, Dresden, Germany, University Hospital Carl Gustav Carus, Institute of Pathology, Dresden, Germany, University Hospital Erlangen, Institute of Pathology, Division of Nephropathology, Erlangen, Germany, University Hospital Heidelberg, Institute of Immunology, Heidelberg, Germany, University Hospital Carl Gustav Carus, Department of Urology, Dresden, Germany

In recent years, immunoadsorption is increasingly recognized as an alternative treatment approach replacing therapeutic plasma exchange in a variety of neurological disorders. While most experience is based on the application of single-use tryptophan adsorbers, less data exists on the application of more efficient regenerating adsorber columns. We here report the systematic use of a regenerating adsorber system in various neurological indications such as multiple sclerosis, encephalitis, myasthenia gravis and chronic inflammatory demyelinating polyneuropathy, providing the expected treatment success in regard to reduction of immunoglobulins and antibody clearance, together with a low rate of adverse events. As it has been shown for single-use columns before, immunoadsorption with regenerating adsorbers can be successfully applied in disorders without known specific antibodies such as multiple sclerosis. Regenerating systems offer the perspective to provide a more efficacious long term treatment perspective for such patients.

Objective: Antibody-mediated rejection (AMR) is associated with poor allograft survival. Therefore, effective treatment strategies are required. Extracorporeal strategies are increasingly included in treatment of antibody-mediated rejection to eliminate the detrimental alloantibodies. Yet, other mechanisms contributing to the beneficial effect of apheresis besides the removal of antibodies are under consideration.Methods: We retrospectively analyzed data of 427 transplant patients from 2006 to 2013 with special focus on occurrence, treatment - always including immunoadsorption - and 12-months outcome of antibody-mediated rejection.Besides, we prospectively monitored how the number and phenotype of endothelial progenitor cells in four patients experiencing antibody-mediated rejection changed during the treatment course of 6-20 sessions of immunoadsorption in comparison to seven patients subjected to immunoadsorption because of preparation for ABO-incompatible transplantation.Results: 24 patients were diagnosed with acute AMR and treated with immunoadsorption resulting in patient and allograft survival of 100% and 87.5%, respectively. In patients with antibody-mediated rejection, the endothelial progenitor cell number after successful immunoadsorption therapy was always transiently decreased and the adhesive and migratory ability improved. This regulation of circulating endothelial precursor cells was not seen in patients undergoing repetitive immunoadsorptions before ABO-incompatible transplantation.Conclusion: Combined therapy with immunoadsorption allows a successful treatment of AMR. Treatment seems to be associated with a transient regulation of circulating endothelial precursor cells. (C) 2015 Elsevier Ireland Ltd. All rights reserved.