Publications by authors named "Daniel Zickler"

Medial vascular calcification in chronic kidney disease (CKD) involves pro-inflammatory pathways induced by hyperphosphatemia. Several interleukin 6 family members have been associated with pro-calcific effects in vascular smooth muscle cells (VSMCs) and are considered as therapeutic targets. Therefore, we investigated the role of leukemia inhibitory factor (LIF) during VSMC calcification.

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Background: Identifying candidates for extracorporeal cardiopulmonary resuscitation (eCPR) is challenging, and novel predictive markers are urgently needed. Hyperfibrinolysis is linked to tissue hypoxia and is associated with poor outcomes in out-of-hospital cardiac arrest (OHCA). Rotational thromboelastometry (ROTEM) can detect or rule out hyperfibrinolysis, and could, therefore, provide decision support for initiation of eCPR.

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Aims: Expanded hemodialysis (HDx) therapy with improved molecular cut-off dialyzers exerts beneficial effects on lowering uremia-associated chronic systemic microinflammation, a driver of endothelial dysfunction and cardiovascular disease (CVD) in hemodialysis (HD) patients with end-stage renal disease (ESRD). However, studies on the underlying molecular mechanisms are still at an early stage. Here, we identify the (endothelial) transcription factor Krüppel-like factor 2 (KLF2) and its associated molecular signalling pathways as key targets and regulators of uremia-induced endothelial micro-inflammation in the HD/ESRD setting, which is crucial for vascular homeostasis and controlling detrimental vascular inflammation.

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Background: Corona Virus Disease 2019 (COVID-19) patients display risk factors for intensive care unit acquired weakness (ICUAW). The pandemic increased existing barriers to mobilisation. This study aimed to compare mobilisation practices in COVID-19 and non-COVID-19 patients.

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Purpose: For patients with severe renal impairment (CrCl ≤ 30 ml/min) or end-stage renal disease (ESRD), olaparib intake is not recommended as the pharmacokinetics and safety of olaparib have not been evaluated in this patient group. Therefore, this valuable patient group is generally excluded from poly(ADP-ribose) polymerase inhibitor (PARPi) therapy. Here we report the pharmacokinetics (PK), efficacy, safety and tolerability of olaparib capsules 200 mg BID in a patient with recurrent epithelial ovarian cancer (EOC) and ESRD requiring hemodialysis.

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Article Synopsis
  • The COVID-19 pandemic has stressed global healthcare systems, highlighting the need for better methods to allocate treatment and resources in intensive care for critically ill patients.
  • Current risk assessment tools like SOFA and APACHE II have shown limited effectiveness in predicting outcomes for severe COVID-19 patients, necessitating additional monitoring tools, especially for those undergoing experimental therapies.
  • A study analyzing plasma proteins from critically ill COVID-19 patients identified 14 proteins that could predict survival more accurately than existing methods, achieving high classification accuracy, especially in relation to coagulation and complement processes.
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  • This study looked at how safe and possible it is to move seriously ill patients in a hospital when they are given a medicine called norepinephrine.
  • Researchers checked the records of over 12,000 patients from 16 different ICUs in Germany to see how often and when they were able to mobilise or move around.
  • The results showed that higher doses of norepinephrine made it less likely for patients to move out of bed, but it didn't seem to affect how many patients survived or cause more problems.
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BACKGROUNDResults of many randomized trials on COVID-19 convalescent plasma (CCP) have been reported, but information on long-term outcome after CCP treatment is limited. The objectives of this extended observation of the randomized CAPSID trial are to assess long-term outcome and disease burden in patients initially treated with or without CCP.METHODSOf 105 randomized patients, 50 participated in the extended observation.

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Objectives: To determine the profile of cytokines in patients with severe COVID-19 who were enrolled in a trial of COVID-19 convalescent plasma (CCP).

Methods: Patients were randomized to receive standard treatment and 3 CCP units or standard treatment alone (CAPSID trial, ClinicalTrials.gov NCT04433910).

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Medial vascular calcification is common in chronic kidney disease (CKD) and is closely linked to hyperphosphatemia. Vascular smooth muscle cells (VSMCs) can take up pro-calcific properties and actively augment vascular calcification. Various pro-inflammatory mediators are able to promote VSMC calcification.

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Morbidity and mortality of COVID-19 is increased in patients with inborn errors of immunity (IEI). Age and comorbidities and also impaired type I interferon immunity were identified as relevant risk factors. In patients with primary antibody deficiency (PAD) and lack of specific humoral immune response to SARS-CoV-2, clinical disease outcome is very heterogeneous.

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Peritoneal dialysis (PD) is a valuable 'home treatment' option, even more so during the ongoing Coronavirus pandemic. However, the long-term use of PD is limited by unfavourable tissue remodelling in the peritoneal membrane, which is associated with inflammation-induced angiogenesis. This appears to be driven primarily through vascular endothelial growth factor (VEGF), while the involvement of other angiogenic signaling pathways is still poorly understood.

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Atherosclerotic artery disease is the major cause of death and an immense burden on healthcare systems worldwide. The formation of atherosclerotic plaques is promoted by high levels of low-density lipoproteins (LDL) in the blood, especially in the oxidized form. Circulating LDL is taken up by conventional and non-classical endothelial cell receptors and deposited in the vessel wall.

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Abstract: Systemic chronic microinflammation and altered cytokine signaling, with adjunct cardiovascular disease (CVD), endothelial maladaptation and dysfunction is common in dialysis patients suffering from end-stage renal disease and associated with increased morbidity and mortality. New hemodialysis filters might offer improvements. We here studied the impact of novel improved molecular cut-off hemodialysis filters on systemic microinflammation, uremia and endothelial dysfunction.

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Background: We compared filter survival and citrate-induced complications during continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in COVID-19 and Non-COVID-19 patients.

Methods: In this retrospective study we included all consecutive adult patients (n = 97) treated with RCA-CRRT. Efficacy and complications of RCA-CRRT were compared between COVID-19 and Non-COVID-19 patients.

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The interferon pathway, a key antiviral defense mechanism, is being considered as a therapeutic target in COVID-19. Both, substitution of interferon and JAK/STAT inhibition to limit cytokine storms have been proposed. However, little is known about possible abnormalities in STAT signaling in immune cells during SARS-CoV-2 infection.

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BACKGROUNDCOVID-19 convalescent plasma (CCP) has been considered a treatment option for COVID-19. This trial assessed the efficacy of a neutralizing antibody containing high-dose CCP in hospitalized adults with COVID-19 requiring respiratory support or intensive care treatment.METHODSPatients (n = 105) were randomized 1:1 to either receive standard treatment and 3 units of CCP or standard treatment alone.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) induces lung injury of varying severity, potentially causing severe acute respiratory distress syndrome (ARDS). Pulmonary injury patterns in COVID-19 patients differ from those in patients with other causes of ARDS. We aimed to explore the frequency and pathogenesis of cavitary lung lesions in critically ill patients with COVID-19.

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Article Synopsis
  • COVID-19 can lead to a hypercoagulable state, increasing the risk of thromboembolic complications in critically ill patients.
  • A study using ROTEM on 13 ICU patients showed significant coagulation issues during acute illness, but normal levels were observed after three months post-discharge.
  • The findings suggest that it may be safe to stop anticoagulation therapy in patients who demonstrate complete recovery of their coagulation profile.
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  • COVID-19 exhibits a wide range of symptoms, from none at all to severe complications, and this study looked at 139 hospitalized patients to understand its progression through 86 diagnostic measures.
  • An initial surge in inflammation was noted, which later gave way to indicators of tissue healing and immune system adjustments.
  • The researchers identified specific markers that could help tailor treatment plans and demonstrated that their machine learning models, based on protein data, could be used effectively across different patient groups.
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Antigen-detecting rapid diagnostic tests (Ag-RDT) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) offer new opportunities for the quick and laboratory-independent identification of infected individuals for control of the SARS-CoV-2 pandemic. Despite the potential benefits, nasopharyngeal sample collection is frequently perceived as uncomfortable by patients and requires trained healthcare personnel with protective equipment. Therefore, anterior nasal self-sampling is increasingly recognized as a valuable alternative.

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With an urgent need for bedside imaging of coronavirus disease 2019 (COVID-19), this study's main goal was to assess inter- and intraobserver agreement in lung ultrasound (LUS) of COVID-19 patients. In this single-center study we prospectively acquired and evaluated 100 recorded ten-second cine-loops in confirmed COVID-19 intensive care unit (ICU) patients. All loops were rated by ten observers with different subspeciality backgrounds for four times by each observer (400 loops overall) in a random sequence using a web-based rating tool.

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Article Synopsis
  • Thrombin activates the protease-activated receptor 1 (PAR1) in vascular endothelial cells, stimulating proangiogenic responses by inducing the production of vascular endothelial growth factor (VEGF).
  • Detailed studies revealed that the transcription factor c-FOS is essential for thrombin-induced VEGF synthesis and angiogenesis in human microvascular endothelial cells.
  • The activation of the PAR-1 receptor leads to ERK1/2 signaling, which in turn activates the AP-1/c-FOS complex, driving gene transcription and promoting angiogenic responses, providing insights into therapeutic strategies for conditions related to endothelial injury and thrombosis.
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Introduction: SARS-CoV-2 is a novel coronavirus that was first isolated in Wuhan, China, and resulted in a rapidly spreading pandemic worldwide. Currently there is only limited evidence on the effect of COVID-19 on pregnant women.

Case: Here we present one of the first serious COVID-19 cases in pregnancy at term with subsequent delivery.

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