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Zusammenfassung Hintergrund Obwohl allergologische Erkrankungen zu den wichtigen Gesundheitsstörungen laut ärztlicher Approbationsordnung zählen, ist die Allergologie in Deutschland nicht als selbstständiges Fach im Studium der Humanmedizin verankert. Ziel der Arbeit Da sämtliche Universitäts- und Hochschulstandorte mit dieser Herausforderung umgehen müssen, war es Ziel unseres Lehrprojekts, eine exemplarische und mit allen beteiligten Kliniken und Instituten abgestimmte Koordination und Verzahnung der allergologischen Lehre an einem Standort zu etablieren. Insbesondere Comprehensive Allergy Centers (CAC) bieten eine bereits vorhandene Infrastruktur, in der diese Neukonzeption der allergologischen Lehre auf andere Standorte übertragen werden könnte. Material und Methoden Nach umfangreicher Bestandsaufnahme der aktuellen allergologischen Lehre an der Universitätsmedizin Göttingen wurde im interdisziplinären Konsens ein neues Lehrkonzept entwickelt, durch die Bereitstellung zusätzlicher digitaler Lehr- und Lernanteile ergänzt („blended learning“) und schließlich evaluiert. Ergebnisse Die allergologische Lehre im klinischen Studienabschnitt zeigte eine starke Fragmentierung, die ohne Koordination der zwölf beteiligten Kliniken/Institute und ohne Abstimmung der jeweiligen Lerninhalte stattfand. In der etablierten Struktur des interdisziplinären CAC erfolgte eine Neukonzeption, Koordination und Schwerpunktsetzung der studentischen Lehre zur klinischen Allergologie. Die Bereitstellung von neuen interaktiven Lerneinheiten sowie ergänzender Materialien zum Selbststudium wurden von den Studierenden positiv bewertet. Eine vergleichende Evaluation von Studierenden nach Absolvieren der unterschiedlichen Curricula zeigte signifikante Verbesserungen im Erreichen der gewünschten Lernziele.

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 addition to the early detection of an acute kidney injury (AKI), several problems or questions have to be addressed. These include the identification of the etiology, the severity (functional or structural), the prognosis (recovery or transition to chronic renal failure), the course of the disease (dialysis or not), and the identification of specific treatment options for AKI. The following article provides an overview of established and new AKI biomarkers as well as an outlook on the potential of future biomarker-associated models of AKI.

Baroreflex activation therapy (BAT) is a sympathoinhibitory procedure for treatment of therapy-resistant hypertension (rsHTN) and severe heart failure with reduced ejection fraction (HFrEF) that been available for several years. The double-blind, randomized Rheos Pivotal Trial demonstrated a blood pressure lowering effect in patients with rsHTN for the first-generation BAT device. A smaller randomized study in heart failure showed that the Barostim Neo system is safe and can improve heart failure symptoms and decrease neuroendocrine activation. However, for this unilateral system, which is currently in clinical use, no data from large randomized trials exist. Despite existing data for BAT in rsHTN and HFrEF, large randomized trials, showing reduction of blood pressure and cardiovascular events are still lacking. Therefore, BAT's efficacy and safety cannot be conclusively assessed.

Acute decompensated heart failure (ADHF) is one of the biggest challenges in the management of chronic heart failure. Despite several advances in medical and device therapy, high readmission and mortality rates continue to be a burden on healthcare systems worldwide. The aim of the current review is to provide an overview on current as well as future approaches in cardiorenal interactions in patients with ADHF. One of the strongest predictors of adverse outcomes in ADHF is renal dysfunction, referred to as cardiorenal syndromes (CRS) or cardiorenal interactions. Patients with ADHF frequently develop worsening of renal function (WRF) and/or acute kidney injury (AKI). Recent studies brought new information about biomarkers in diagnosing and predicting prognosis of CRS. Among others, dry weight at hospital discharge is considered a surrogate marker of successful treatment in ADHF patients with/without renal dysfunction. The etiology of WRF appears to be an important factor for determining risk related to WRF as well as clinical management. The hypertonic saline used as adjunctive therapy for intravenous loop diuretics and/or induction of aquaresis (e.g., using tolvaptan) may be promising and efficient approaches in the future.

Die therapieresistente und -refraktare arterielle Hypertonie unterscheiden sich in der Haufigkeit, Pathogenese, Prognose und dem therapeutischen Vorgehen. In beiden Fallen bedarf es eines strukturierten Vorgehens mit Ausschluss einer Pseudoresistenz und daran anschliesend einer sekundaren Hypertonie. Die resistente Hypertonie spricht erfahrungsgemas besser auf eine intensivierte diuretische Therapie an, wohingegen die refraktare Hypertonie mutmaslich einer sympathoinhibitorischen Therapie bedarf. Sind Allgemeinmasnahmen und die medikamentose Step-up-Therapie ausgeschopft, stehen interventionelle Verfahren zur Verfugung.

Heart failure and kidney dysfunction are common comorbidities with overlapping and synergizing mechanisms. Coincidence of both pathologies aggravates disease progression rates, symptoms, and outcomes. The treatment of patients with advanced renal insufficiency is faced with limited evidence for therapies that are standard of care in patients with normal and moderate kidney failure, frequent deterioration of kidney function during therapy, and onset of hyperkalemia, which pose challenges for clinical care, requiring intensified physician-patient contacts. A special challenge is the so-called diuretic resistance, which may require extracorporeal drainage.

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.

Sympathetic overactivity is one critical factor associated with the development of arterial hypertension, impaired insulin secretion and resistance. Some antihypertensives exert beneficial effects on glucose metabolism, whereas others lead to an impairment of metabolic state with consecutive weight gain. In resistant hypertension, baroreflex activation therapy (BAT) reduces arterial blood pressure (BP) by inhibition of the sympathetic nervous system. The objective of this study was to evaluate whether BAT influences metabolic state in patients with resistant hypertension. Thirty patients with resistant hypertension (10 with known diabetes mellitus) were prospectively included into this study. Blood pressure, BMI, weight, fasting glucose, insulin, C-peptide, hemoglobin A1c, HOMA-IR, HOMA-β, ISQuickI, and glucose levels during oral glucose tolerance test were measured at baseline and 6 months after BAT activation. Fasting glucose was significantly reduced after 6 months of BAT, whereas mean 2-h glucose levels during oral glucose tolerance test, fasting insulin levels, C-peptide levels, hemoglobin A1c, HOMA-IR, HOMA-β, ISQuickI, weight, and BMI remained unchanged. Despite improvement in fasting glucose, BAT exerts neither sustained additional beneficial effects nor an impairment of metabolic state. Thus, chronic BAT might be an effective interventional method to reduce BP without metabolic disadvantages.

Je fortgeschrittener die Funktionseinschrankung der Niere ist, desto groser ist die Wahrscheinlichkeit einer Infertilitat oder des Auftretens von (Pra-)Eklampsie, Fruhgeburt, fetalen Wachstumsstorungen und langfristiger nephrologischer Probleme bei einer eingetretenen Schwangerschaft. Die Betreuung und Beratung nierenkranker Patientinnen sollte schon prakonzeptionell erfolgen. Eine fruhzeitige Bestimmung der Kreatinin-Clearance, der Proteinurie (optimal im Sammelurin) und des Blutdrucks helfen, bei geplanter oder eingetretener Schwangerschaft niereninsuffizienter Patientinnen den Verlauf besser zu beurteilen. Viele der aus nephrologischer Indikation eingesetzten Medikamente konnen wegen fetaler Nebenwirkungen nicht gegeben werden, bei eingeschrankter glomerularer Filtrationsrate muss zudem oft eine Dosisanpassung erfolgen. Eine interdisziplinare Betreuung nierenkranker Schwangerer sollte obligat erfolgen.

Die Sarkoidose ist eine Multisystemerkrankung. Wir berichten im Folgenden uber eine junge Patientin, die mit Lymphknotenschwellungen, B-Symptomatik, Erythema nodosum und Arthralgien vorstellig wurde. Die Erkrankung zeigte einen atypischen Verlauf ohne pulmonale Beteiligung und ohne sarkoidosetypische Serumveranderungen. Letzten Endes konnte sie nur histologisch gesichert werden. Differenzialdiagnostisch standen v. a. infektiologische und neoplastische Erkrankungen im Vordergrund. Eine orale Steroidtherapie fuhrte zu einer Remission.

Das Tubulointerstitium macht etwa 85–90% des Nierenvolumens aus, es besteht aus Tubuli und dem dazwischen liegenden Interstitium. Das Tubulussystem reguliert die Ausscheidung der mit der Nahrung aufgenommenen Salze und halt die Konzentration dieser Ionen und die Osmolalitat des Blutes innerhalb enger Grenzen konstant, es reguliert den Wasser-, den Saure-Basen- und den Kalzium-Phosphat-Haushalt, bildet Hormone und baut sie ab, ist an der Blutdruckregulation und ubernimmt Funktionen im Prozess der Endharnbildung. Als Tubulopathien werden ganz allgemein tubulare Funktionsstorungen beschrieben, deren Manifestationen und Auspragungen wiederum sehr unterschiedlich sein konnen. Das Interstitium besteht im Wesentlichen aus extrazellularer Matrix und residenten interstitiellen Fibroblasten, selten auch aus anderen zellularen Elementen. Entzundungen des Tubulointerstitiums konnen in akute und chronische Formen differenziert werden, daruber hinaus in primare und sekundare Formen. Zur Therapie der medikamentos induzierten akuten interstitiellen Nephritis bietet sich neben dem Weglassen des induzierenden Medikamentes eine fruhe Glukokortikoidtherapie an.

Ein 69-jahriger Patient wurde mit einem Kreatininanstieg von 1,4 auf 4,9 mg/dl innerhalb von 4 Monaten, lividen, schmerzhaften Effloreszenzen an den Fusen, rezidivierender Epistaxis und Gleichgewichtsstorungen aufgenommen. In der Vorgeschichte waren drei kurzlich aufgetretene transitorische ischamische Attacken sowie ein metabolisches Syndrom bekannt. Im kranialen Magnetresonanztomogramm zeigten sich fleckformige vaskulitisahnliche zerebrale Signalanhebungen. Laborchemisch bestanden eine Eosinophilie sowie eine geringgradige Proteinurie vom tubularen Typ. Haut- und Nierenbiopsien erbrachten die Diagnose einer Cholesterinembolie als Ursache der Nierenfunktionsverschlechterung. Als mutmasliche Quelle der rezidivierenden Cholesterinkristallembolien lies sich eine massive Sklerose der Aorta sichern. Auch ohne vorausgehende angiographische Intervention muss bei rasch progredienter Niereninsuffizienz eines Atherosklerosepatienten insbesondere in hoherem Alter die Differentialdiagnose Cholesterinkristallembolie in Betracht gezogen werden.

Patients with severe multiple sclerosis (MS) relapses which do not respond sufficiently to corticosteroids can undergo escalating immunotherapy with plasma exchange. We review the course of 14 apheresis cycles in 13 adult patients and three pediatric cases from our center between 2004 and 2005. Nine cases were due to optic neuritis, five had experienced clinically isolated syndromes, and two suffered from Devic's disease. Of the adult patients, 71% had good or very good outcome. The mean time point of improvement was after the third plasmapheresis session, and early initiation of plasma exchange therapy (within 1 month after begin of relapse) was associated with better outcome. In pediatric MS, two of three patients showed clear improvement. These data argue for a very good therapeutic effect of plasma exchange if performed early and with adequate indication.

Catheter-based renal denervation (RD) offers a relative new approach targeting the renal sympathetic nerves in order to decrease the blood pressure (BP) in patients with resistant hypertension associated with an increased risk of cardiovascular events. According to available evidence and expert suggestions, patients with treatment-resistant hypertension defined by office systolic BP C 160 mmHg (C 150 mmHg in type 2 diabetes) despite treatment with at least three antihypertensive drugs (including one diuretic) are eligible for RD [1, 2]. Secondary hypertension, including renal artery stenosis [ 50 %, must be ruled out and both-side denervation procedure is usually performed and some reports suggest higher responder rates in order to decrease the BP [3, 4]. Here, we report a RD procedure in a 47-year-old woman (BMI of 31.2 kg/m) with medically resistant hypertension on a treatment of seven antihypertensive drugs (b-blocker, angiotensin-II-blocker, calcium channel blocker, thiazide, a2-agonist, direct vasodilatator, ablocker). A secondary cause for the hypertension was excluded. No direct or indirect signs of hemodynamic relevant renal artery stenosis were seen in duplex sonography. End-organ damage was present with the detection of hypertensive cardiomyopathy, retinopathy and nephropathy with micro-albuminuria. Automated blood pressure measurement over the daytime indicated baseline systolic/diastolic BP of 187 ± 16 mmHg/108 ± 8 mmHg (n = 9) before RD; the corresponding heart rate (HR) was 68 ± 7 bpm. For performing RD, access via the right femoral artery with a 6F-sheath was used and fluoroscopic angiography indicated a normal configuration of the left renal artery (Fig. 1a), whereas the right renal artery with high-angle junction from abdominal aorta had a proximal stenosis of approximate 50 % (Fig. 1b). Left artery denervation was performed with the application of five 8-W-radiofrequency ablation points using the standard solid-tip renal denervation catheter (Simplicity catheter; Medtronic/Ardian Inc.). Mean temperature was 59.4 ± 4.5 C with a mean impedance drop of 19.6 ± 1.7 % during the 120 s of ablation at each point. Remarkable intimal oedema and/or vasospasm without compromising the blood flow could be seen after the radiofrequency ablation procedure in the left renal artery (Fig. 1c). Due to right renal artery proximal stenosis, difficulty to advance the ablation catheter into the distal artery (using a ‘RDC guiding catheter’) and the patient’s wish to not further elongate the procedure time, only a left-sided RD approach was chosen. Post-procedural performed controls revealed that the blood pressure could be significantly reduced 2 days after the RD procedure compared to the BP measured before the procedure in the same clinical environment (141 ± 12 mmHg systolic and 85 ± 8 mmHg diastolic; n = 7; P \ 0.001 vs. systolic and diastolic BP before RD); the HR was also reduced (57 ± 4 bpm; n = 3; P = 0.048 vs. HR before RD). Moreover, 1 month after the RD, ambulatory BP measurement revealed a mean systolic blood pressure of 122 ± 17 mmHg and diastolic of 77 ± 20 mmHg at daytime (n = 45; P \ 0.001 vs. systolic and diastolic RR M. R. Schroeter (&) Universitatsmedizin Gottingen, Herzzentrum, Abt. Kardiologie und Pneumologie, Robert-Koch-Str. 40, 37099 Gottingen, Germany e-mail: mschroeter@med.uni-goettingen.de

Die Kombination aus initial hohem Fieber verbunden mit starkem Krankheitsgefuhl, Splenomegalie, Transaminasenerhohungen und akutem Nierenversagen muss auch in Deutschland differenzialdiagnostisch an eine Leptospirose denken lassen. Die Diagnose erfolgt im Regelfall serologisch uber den Titerverlauf. Die renale Beteiligung ist haufig, mit allerdings im Regelfall guter Prognose, insbesondere bei fehlendem Ikterus. Eine Therapie mit Doxycyclin oder Penizillin kann Krankheitsdauer und Ausscheidung, evtl. auch die Nephritis verkurzen bzw. verhindern.

Introduction Sepsis is characterized by systemic microvascular dysfunction. Endothelial progenitor cells (EPCs) are critically involved in maintaining vascular homeostasis under both physiological and pathological conditions. The aim of the present study was to analyze the endothelial progenitor cell system in patients suffering from sepsis with acute renal dysfunction. Methods Patients with newly diagnosed sepsis were recruited from the ICU in a nonrandomized prospective manner. Blood samples were obtained within the first 12 hours after the diagnosis of sepsis. For quantifying endothelial progenitor cells (EPCs), CD133+/Flk-1+ cells were enumerated by cytometric analysis. Analysis of EPC proliferation was performed by a colony-forming units (CFU) assay. Blood concentrations of proangiogenic mediators were measured by ELISA. Acute renal dysfunction was diagnosed according to the Acute Kidney Injury Network (AKIN) criteria. Depending on the overall mean creatinine concentration during the stay at the ICU, patients were either assigned to a 'normal creatinine group' or to a 'high creatinine group'. Survival rates, frequency of dialysis, the simplified acute physiology score (SAPS) II scores, and different laboratory parameters were collected/used for further clinical characterization Results Circulating EPCs were significantly higher in all sepsis patients included in the study as opposed to healthy controls. Patients within the 'high creatinine group' showed an even more pronounced EPC increase. In contrast, EPC proliferation was severely affected in sepsis. Neither total circulating EPCs nor EPC proliferation differed between patients requiring dialysis and patients without renal replacement therapy. Cell numbers and cell proliferation also did not differ between surviving patients and patients with sepsis-related death. Serum levels of vascular endothelial growth factor (VEGF), stromal derived factor-1 (SDF-1), and Angiopoietin-2 were higher in sepsis than in healthy controls. Sepsis patients within the 'high creatinine group' showed significantly higher mean serum levels of uric acid. Conclusions Sepsis significantly affects the endothelial progenitor cell system, as reflected by increased EPC numbers, increased concentrations of proangiogenic mediators, and reduced proliferative capacity of the cells. This occurs independently from the frequency of dialysis and from patient survival. Increased serum levels of uric acid are possibly responsible for stronger EPC mobilization in sepsis patients with higher average creatinine levels. peerReviewed