25 results on '"Klaus Stahl"'
Search Results
2. Effect of therapeutic plasma exchange on endothelial activation and coagulation-related parameters in septic shock
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Klaus Stahl, Bernhard M W Schmidt, Hermann Haller, Ulrich Budde, Christian Bode, Sascha David, Tobias Welte, Marius M. Hoeper, Julius J. Schmidt, and Benjamin Seeliger
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Adult ,Male ,medicine.medical_specialty ,Hemangioblasts ,Antithrombin III ,ADAMTS13 Protein ,Extracorporeal treatment ,030204 cardiovascular system & hematology ,von Willebrand factor ,Critical Care and Intensive Care Medicine ,Gastroenterology ,Sepsis ,Endothelial activation ,03 medical and health sciences ,0302 clinical medicine ,Von Willebrand factor ,Internal medicine ,Septic shock ,medicine ,Humans ,Platelet ,Prospective Studies ,ADAMTS-13 ,Blood Coagulation ,biology ,Plasma Exchange ,business.industry ,Research ,lcsh:Medical emergencies. Critical care. Intensive care. First aid ,030208 emergency & critical care medicine ,Plasmapheresis ,lcsh:RC86-88.9 ,Middle Aged ,medicine.disease ,Shock, Septic ,ADAMTS13 ,biology.protein ,Female ,Fresh frozen plasma ,business ,Protein C ,medicine.drug - Abstract
Background A dysbalanced coagulation system is part of the pathological host response to infection in sepsis. Activation of pro-coagulant pathways and attenuation of anti-coagulant activity ultimately lead to microvascular stasis and consequent organ failure. No treatment approaches specifically targeting this axis are available. We explored the effects of therapeutic plasma exchange (TPE) on microvascular coagulation dysbalance in septic shock. Methods We conducted a prospective single-center study enrolling 31 patients with early septic shock (onset 0.4 μg/kg/min). Clinical and biochemical data, including measurement of protein C; a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS13); and von Willebrand factor antigen (vWF:Ag), were obtained before and after TPE against fresh frozen plasma. Results Antithrombotic acting proteins such as antithrombin-III (ATIII) and protein C were markedly reduced in septic patients, but their activity increased after TPE (ATIII, 51% (41–61) vs. 63% (48–70), p = 0.029; protein C, 47% (38–60) vs. 62% (54–69), p = 0.029). Median ADAMTS13 activity was increased by TPE from 27 (21–42) % before to 47 (38–62) % after TPE (p p p = 0.001, R2 = 0.316). Conclusions Septic shock was associated with activation of pro-coagulant pathways and simultaneous depletion of anti-coagulant factors. TPE partially attenuated this dysbalance by removing pro- and by replacing anti-coagulant factors. Trial registration ClinicalTrials.gov, NCT03065751. Retrospectively registered on 28 February 2017.
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- 2020
3. Modulation of The Permeability-Inducing Factor Angiopoietin-2 Through Bifonazole in Systemic Inflammation
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Hermann Haller, Valerie Etzrodt, Klaus Stahl, Benjamin Seeliger, Temitayo O Idowu, Sascha David, Thorben Pape, and University of Zurich
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Antifungal Agents ,Bifonazole ,Stimulation ,610 Medicine & health ,Pharmacology ,Critical Care and Intensive Care Medicine ,Systemic inflammation ,Angiopoietin-2 ,Capillary Permeability ,Sepsis ,In vivo ,medicine ,Humans ,MTT assay ,Cells, Cultured ,Barrier function ,Inflammation ,business.industry ,Imidazoles ,Endothelial Cells ,medicine.disease ,In vitro ,Emergency Medicine ,medicine.symptom ,10023 Institute of Intensive Care Medicine ,business ,medicine.drug - Abstract
BACKGROUND Vascular barrier breakdown in sepsis represents a key component of the maladaptive host response to infection and the release of endothelial Angiopoietin-2 (Angpt-2) is a mechanistic driver of endothelial hyperpermeability. Angpt-2 is associated with morbidity and mortality but a targeted therapeutic approach is not available. We screened for U.S. Food and Drug Administration (FDA) approved drugs that might have off-target effects decreasing Angpt-2 and therefore, ameliorating capillary leakage. METHODS Endothelial cells were isolated from human umbilical veins (HUVECs) and used for in vitro studies at baseline and after stimulation (FDA-library screening, RT-PCR, ELISA, immunocytochemistry, MTT assay). On the functional level, we assessed real-time transendothelial electrical resistance (TER) using an ECIS (electric cell-substrate impedance sensing) device. RESULTS We found that the anti-fungal Bifonazole (BIFO) reduces spontaneous Angpt-2 release in a time- and dose-dependent manner after 8, 12 and 24 h (24 h: veh: 15.6 ± 0.7 vs. BIFO: 8.6 ± 0.8 ng/mL, p
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- 2021
4. Effects of therapeutic plasma exchange on the endothelial glycocalyx in septic shock
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Hermann Haller, Julius J. Schmidt, Sascha David, Heiko Schenk, Marius M. Hoeper, Tobias Welte, Bernhard M W Schmidt, Uta Hillebrand, Christian Bode, Heiner Wedemeyer, Klaus Stahl, Malgorzata Wygrecka, Benjamin Seeliger, Thorben Pape, Agnes Sauer, Yulia Kiyan, and University of Zurich
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medicine.medical_specialty ,medicine.medical_treatment ,Stimulation ,Extracorporeal treatment ,Heparan sulfate ,610 Medicine & health ,Critical Care and Intensive Care Medicine ,Gastroenterology ,Internal medicine ,Medicine ,DAMP ,Heparanase ,Research Articles ,business.industry ,Septic shock ,RC86-88.9 ,Medical emergencies. Critical care. Intensive care. First aid ,Plasmapheresis ,medicine.disease ,Biomarker (medicine) ,Therapeutic plasma exchange ,Fresh frozen plasma ,10023 Institute of Intensive Care Medicine ,business ,Ex vivo - Abstract
Background Disruption of the endothelial glycocalyx (eGC) is observed in septic patients and its injury is associated with multiple-organ failure and inferior outcomes. Besides this biomarker function, increased blood concentrations of shedded eGC constituents might play a mechanistic role in septic organ failure. We hypothesized that therapeutic plasma exchange (TPE) using fresh frozen plasma might influence eGC-related pathology by removing injurious mediators of eGC breakdown while at the time replacing eGC protective factors. Methods We enrolled 20 norepinephrine-dependent (NE > 0.4 μg/kg/min) patients with early septic shock (onset Results SDF demonstrated a decrease in eGC thickness in septic patients compared to healthy individuals (p = 0.001). Circulating HS levels were increased more than sixfold compared to controls and decreased significantly following TPE [controls: 16.9 (8–18.6) vs. septic patients before TPE: 105.8 (30.8–143.4) μg/ml, p p p = 0.001; vs. septic patients after TPE: 13.2 (11.2–31.8), p Conclusions Septic shock results in profound degradation of the eGC and an acquired deficiency of the protective regulator Hpa-2. TPE removed potentially injurious eGC degradation products and partially attenuated Hpa-2 deficiency. Trial registration clinicaltrials.gov NCT04231994, retrospectively registered 18 January 2020
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- 2021
5. Report On Complete Endpoints and Predictors of Response to Plasma Exchange – Results From a Randomized Controlled Trial in Septic Shock Patients
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Wolfgang Schmidt, Benjamin Seeliger, Christian Putensen, Sascha David, Christian Bode, Felix Lehmann, Julius J. Schmidt, Tobias Welte, Hermann Haller, Heiner Wedemeyer, Markus Busch, Andrea Sauer, Marius M. Hoeper, Klaus Stahl, Olaf Wiesner, Ulrich Budde, Philipp Wand, and Bernhard M.W. Schmidt
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Randomized controlled trial ,business.industry ,Septic shock ,law ,Anesthesia ,Medicine ,business ,medicine.disease ,law.invention - Abstract
Background: Recently, a randomized controlled trial (RCT) demonstrated rapid but individually variable hemodynamic improvement with therapeutic plasma exchange (TPE) in patients with septic shock. Prediction of clinical efficacy in specific sepsis treatments is fundamental for individualized sepsis therapy.Methods: In the original RCT patients with septic shock of < 24 h duration and norepinephrine (NE) requirement ≥ 0.4 μg/kg/min received standard of care (SOC) or SOC + one single TPE. Here we report all clinical and biological endpoints of this study. Subgroup analysis of NE reduction and 28-day mortality was performed to investigate characteristics that could be associated with clinical response.Results: Early hemodynamic stabilization was preserved in the TPE group for 24 hours and was accompanied by a reduction of lactate suggestive for shock reversal. A reduction of injurious mediators (such as PCT, vWF:Ag, Angpt-2, sTie-2) and a repletion of exhausted protective factors (such as AT-III, Protein C, ADAMTS-13) could be observed in the TPE but not in the SOC group. Significant NE reduction (> 50% from baseline) upon TPE occurred more often in patients with 1) a pulmonary focus of infection, 2) profound respiratory failure (pO2/FiO2 0.6 μg/kg/min and lactate >0.4 mmol/l) as well as 4) substantial degree of organ failure (SOFA Score > 16) at randomization. Patients with a pulmonary focus of infection had a 28-day mortality of 15% in the TPE group while it was 42% in the SOC group. Conclusions: Adjunctive TPE is associated with the removal of injurious mediators and repletion of consumed protective factors altogether leading to preserved hemodynamic stabilization in refractory septic shock. It is We identified potential response predictors (lung focus, PF ratio < 150, higher SOFA score etc.) that might guide future designing of large RCTs that will further evaluate TPE with regard to hard endpoints. Trial registration: Retrospectively registered 18th January 2020 at clinicaltrials.gov (Identifier: NCT04231994), https://clinicaltrials.gov/ct2/show/NCT04231994?term=NCT04231994&draw=2&rank=1
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- 2021
6. Unraveling the secret of re-balancing homeostasis in sepsis: a critical view on extracorporeal blood purification modalities
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Sascha David, Klaus Stahl, Christian Bode, Pedro David Wendel-Garcia, University of Zurich, and Stahl, Klaus
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medicine.medical_specialty ,Pain medicine ,MEDLINE ,610 Medicine & health ,Critical Care and Intensive Care Medicine ,Sepsis ,Extracorporeal blood purification ,Anesthesiology ,Correspondence ,Medicine ,Homeostasis ,Humans ,Intensive care medicine ,Modalities ,business.industry ,Shock ,medicine.disease ,Shock, Septic ,Hemoperfusion ,Cytokines ,Adsorption ,10023 Institute of Intensive Care Medicine ,Hemofiltration ,2706 Critical Care and Intensive Care Medicine ,business - Published
- 2021
7. The Janus Face of Coronavirus Disease 2019-Associated Coagulopathy
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Benjamin Seeliger, Klaus Stahl, Michael R.G. Doebler, Sascha David, Christian Bode, Daniel A. Hofmaenner, and University of Zurich
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Online Letters to the Editor ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Coagulopathy ,Medicine ,610 Medicine & health ,10023 Institute of Intensive Care Medicine ,Critical Care and Intensive Care Medicine ,business ,medicine.disease ,Virology - Published
- 2021
8. Case Report: Convalescent Plasma Therapy Induced Anti-SARS-CoV-2 T Cell Expansion, NK Cell Maturation and Virus Clearance in a B Cell Deficient Patient After CD19 CAR T Cell Therapy
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Berislav Bošnjak, Ivan Odak, Christiane Ritter, Klaus Stahl, Theresa Graalmann, Lars Steinbrück, Rainer Blasczyk, Christine S. Falk, Thomas F. Schulz, Hans Heinrich Wedemeyer, Markus Cornberg, Arnold Ganser, Reinhold Förster, Christian Koenecke, and CiiM, Zentrum für individualisierte Infektionsmedizin, Feodor-Lynen-Str.7, 30625 Hannover.
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viruses ,T cell ,Immunology ,Case Report ,CD19 CAR-T cell ,Virus ,CD19 ,Cell therapy ,Immune system ,medicine ,Immunology and Allergy ,NK cell ,B cell ,biology ,business.industry ,COVID – 19 ,RC581-607 ,medicine.disease ,Lymphoma ,medicine.anatomical_structure ,convalescent plasma (CP) ,biology.protein ,SARS – CoV – 2 ,Immunologic diseases. Allergy ,business ,Viral load - Abstract
Here, we described the case of a B cell-deficient patient after CD19 CAR-T cell therapy for refractory B cell Non-Hodgkin Lymphoma with protracted coronavirus disease 2019 (COVID-19). For weeks, this patient only inefficiently contained the virus while convalescent plasma transfusion correlated with virus clearance. Interestingly, following convalescent plasma therapy natural killer cells matured and virus-specific T cells expanded, presumably allowing virus clearance and recovery from the disease. Our findings, thus, suggest that convalescent plasma therapy can activate cellular immune responses to clear SARS-CoV-2 infections. If confirmed in larger clinical studies, these data could be of general importance for the treatment of COVID-19 patients.
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- 2021
9. SIGNR1 promotes immune dysfunction in systemic candidiasis by modulating neutrophil lifespan via T cell-derived histones and G-CSF
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Venizelos Papayannopoulos, Marianna Ioannou, Mia I. Temkin, Klaus Stahl, Spyros I. Vernardis, Sascha David, Dennis Hoving, Nathalia M. De Vasconcelos, Iker Valle Aramburu, Markus Ralser, Theodora-Dorita Tsourouktsoglou, Stefan Boeing, Christian Bode, Qian Wang, Robert L. Goldstone, and Vadim Demichev
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biology ,T cell ,medicine.disease ,T cell deficiency ,Chromatin ,Respiratory burst ,Sepsis ,medicine.anatomical_structure ,Histone ,Myeloperoxidase ,Immunology ,medicine ,biology.protein ,Systemic candidiasis - Abstract
SummaryThe mechanisms regulating immune dysfunction during sepsis are poorly understood. Here, we show that neutrophil-derived myeloperoxidase delays the onset of immune dysfunction during systemic candidiasis by controlling microbes captured by splenic marginal zone (MZ) macrophages. In contrast, SIGNR1-mediated microbe capture accelerates MZ colonization and immune dysfunction by triggering T cell death, T cell-dependent chromatin release and the synergistic induction of G-CSF by histones and fungi. Histones and G-CSF promote the prevalence of immature Ly6Glow neutrophils with defective oxidative burst, by selectively shortening the lifespan of mature Ly6Ghigh neutrophils. Consistently, T cell deficiency, or blocking SIGNR1, G-CSF or histones delayed neutrophil dysfunction. Furthermore, histones and G-CSF in the plasma of sepsis patients, shortened neutrophil lifespan and correlated with neutrophil mortality markers associated with a poor prognosis. Hence, the compromise of internal antimicrobial barrier sites drives neutrophil dysfunction by selectively modulating neutrophil lifespan via pathogenic T cell death, extracellular histones, and G-CSF.
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- 2021
10. A Retrospective Analysis of Nonocclusive Mesenteric Ischemia in Medical and Surgical ICU Patients: Clinical Data on Demography, Clinical Signs, and Survival
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Marius M. Hoeper, Sascha David, Bernhard C. Meyer, Olaf Wiesner, Jan Fuge, Michael P. Manns, Jan B. Hinrichs, Markus Busch, Sabine K Maschke, Klaus Stahl, and Andrea Schneider
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Icu patients ,Organ Dysfunction Scores ,shock ,030204 cardiovascular system & hematology ,Nonocclusive mesenteric ischemia ,Critical Care and Intensive Care Medicine ,Sepsis ,sepsis ,03 medical and health sciences ,0302 clinical medicine ,intestinal failure ,Intestinal failure ,Intensive care ,medicine ,Retrospective analysis ,Humans ,Aged ,Demography ,Retrospective Studies ,business.industry ,Original Articles ,nonocclusive mesenteric ischemia ,Middle Aged ,medicine.disease ,Intensive Care Units ,030220 oncology & carcinogenesis ,Shock (circulatory) ,Mesenteric Ischemia ,medicine.symptom ,business - Abstract
Background: To analyze demography, clinical signs, and survival of intensive care patients diagnosed with nonocclusive mesenteric ischemia (NOMI) and to evaluate the effect of a local intra-arterial prostaglandin therapy. Methods: Retrospective observational study screening 455 intensive care patients with acute arterial mesenteric perfusion disorder in a tertiary care hospital within the past 8 years. Lastly, 32 patients with NOMI were enrolled, of which 11 received local intra-arterial prostaglandin therapy. The diagnosis of NOMI was based on the clinical presentation and established biphasic computed tomography criteria. Clinical and biochemical data were obtained 24 hours before, at the time, and 24 hours after diagnosis. Results: Patients were 60.5 (49.3-73) years old and had multiple comorbidities. Most of them were diagnosed with septic shock requiring high doses of norepinephrine (NE: 0.382 [0.249-0.627] μg/kg/min). The Sequential Organ Failure Assessment (SOFA) score was 18 (16-20). A decrease in oxygenation (Pao 2/Fio 2), pH, and bicarbonate and an increase in international normalized ratio, lactate, bilirubin, leucocyte count, and NE dose were early indicators of NOMI. Median SOFA score significantly increased in the last 24 hours before diagnosis of NOMI (16 vs 18, P < .0001). Overall, 28-day mortality was 75% (81% nonintervention vs 64% intervention cohort; P = .579). Median SOFA scores 24 hours after intervention increased by +5% in the nonintervention group and decreased by 5.5% in the intervention group ( P = .0059). Conclusions: Our data suggest that NOMI is a detrimental disease associated with progressive organ failure and a high mortality. Local intra-arterial prostaglandin application might hold promise as a rescue treatment strategy. These data encourage future randomized controlled trials are desirable.
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- 2019
11. Comparison of anticoagulation strategies for veno-venous ECMO support in acute respiratory failure
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Marius M. Hoeper, Christian Kühn, Johann Bauersachs, Jens-Christian Schewe, Andreas Tiede, Benjamin Seeliger, Christian Bode, Klaus Stahl, Sascha David, Stefan F. Ehrentraut, Christian Putensen, Folkert Steinhagen, Robert Friedrich, Michael Döbler, Tobias Welte, University of Zurich, David, Sascha, and Bode, Christian
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Adult ,Male ,ARDS ,Letter ,Organ Dysfunction Scores ,medicine.medical_treatment ,Activated clotting time ,610 Medicine & health ,030204 cardiovascular system & hematology ,Critical Care and Intensive Care Medicine ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Extracorporeal Membrane Oxygenation ,Thromboembolism ,Germany ,Extracorporeal membrane oxygenation ,medicine ,Humans ,Oxygenator ,Blood Coagulation ,Retrospective Studies ,Simplified Acute Physiology Score ,medicine.diagnostic_test ,business.industry ,Bleeding ,lcsh:Medical emergencies. Critical care. Intensive care. First aid ,Anticoagulants ,030208 emergency & critical care medicine ,Retrospective cohort study ,lcsh:RC86-88.9 ,Middle Aged ,medicine.disease ,Heparinization ,Treatment Outcome ,SAPS II ,Anesthesia ,Female ,Blood Coagulation Tests ,ECMO ,10023 Institute of Intensive Care Medicine ,business ,Respiratory Insufficiency ,2706 Critical Care and Intensive Care Medicine ,Cohort study ,Partial thromboplastin time - Abstract
Background Extracorporeal membrane oxygenation (ECMO) support in acute respiratory failure may be lifesaving, but bleeding and thromboembolic complications are common. The optimal anticoagulation strategy balancing these factors remains to be determined. This retrospective study compared two institutional anticoagulation management strategies focussing on oxygenator changes and both bleeding and thromboembolic events. Methods We conducted a retrospective observational cohort study between 04/2015 and 02/2020 in two ECMO referral centres in Germany in patients receiving veno-venous (VV)-ECMO support for acute respiratory failure for > 24 h. One centre routinely applied low-dose heparinization aiming for a partial thromboplastin time (PTT) of 35–40 s and the other routinely used a high-dose therapeutic heparinization strategy aiming for an activated clotting time (ACT) of 140–180 s. We assessed number of and time to ECMO oxygenator changes, 15-day freedom from oxygenator change, major bleeding events, thromboembolic events, 30-day ICU mortality, activated clotting time and partial thromboplastin time and administration of blood products. Primary outcome was the occurrence of oxygenator changes depending on heparinization strategy; main secondary outcomes were the occurrence of severe bleeding events and occurrence of thromboembolic events. The transfusion strategy was more liberal in the low-dose centre. Results Of 375 screened patients receiving VV-ECMO support, 218 were included in the analysis (117 high-dose group; 101 low-dose group). Disease severity measured by SAPS II score was 46 (IQR 36–57) versus 47 (IQR 37–55) and ECMO runtime was 8 (IQR 5–12) versus 11 (IQR 7–17) days (P = 0.003). There were 14 oxygenator changes in the high-dose group versus 48 in the low-dose group. Freedom from oxygenator change at 15 days was 73% versus 55% (adjusted HR 3.34 [95% confidence interval 1.2–9.4]; P = 0.023). Severe bleeding events occurred in 23 (19.7%) versus 14 (13.9%) patients (P = 0.256) and thromboembolic events occurred in 8 (6.8%) versus 19 (19%) patients (P = 0.007). Mortality at 30 days was 33.3% versus 30.7% (P = 0.11). Conclusions In this retrospective study, ECMO management with high-dose heparinization was associated with lower rates of oxygenator changes and thromboembolic events when compared to a low-dose heparinization strategy. Prospective, randomized trials are needed to determine the optimal anticoagulation strategy in patients receiving ECMO support.
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- 2021
12. Adjuvant therapeutic plasma exchange in septic shock
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Christian Bode, Tobias Welte, Klaus Stahl, Sascha David, and Christian Putensen
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2019-20 coronavirus outbreak ,Letter ,Coronavirus disease 2019 (COVID-19) ,Plasma Exchange ,Septic shock ,business.industry ,medicine.medical_treatment ,Plasmapheresis ,Pharmacology ,Critical Care and Intensive Care Medicine ,medicine.disease ,Shock, Septic ,Sepsis ,Shock (circulatory) ,medicine ,Humans ,Therapeutic plasma exchange ,medicine.symptom ,business ,Adjuvant - Published
- 2020
13. First do no harm—beware the risk of therapeutic plasma exchange in severe COVID-19
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Christian Bode, Klaus Stahl, and Sascha David
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2019-20 coronavirus outbreak ,Do no harm ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,biology ,business.industry ,lcsh:Medical emergencies. Critical care. Intensive care. First aid ,lcsh:RC86-88.9 ,Critical Care and Intensive Care Medicine ,medicine.disease ,biology.organism_classification ,medicine.disease_cause ,Pneumonia ,Pandemic ,medicine ,Therapeutic plasma exchange ,Intensive care medicine ,business ,Betacoronavirus ,Coronavirus - Published
- 2020
14. Non-occlusive mesenteric ischemia (NOMI): evaluation of 2D-perfusion angiography (2D-PA) for early treatment response assessment
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Christian von Falck, Frank Wacker, Timo C Meine, Lena S Becker, Markus Busch, Klaus Stahl, Bernhard C. Meyer, Cornelia L A Dewald, Sascha David, Nina Rittgerodt, and Jan B. Hinrichs
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medicine.medical_specialty ,Urology ,2D-Perfusion angiography ,Digital subtraction angiography ,030204 cardiovascular system & hematology ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Ischemia ,Internal medicine ,medicine.artery ,Interventional Radiology ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Superior mesenteric artery ,Prostaglandin E1 ,Retrospective Studies ,Aorta ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,business.industry ,Gastroenterology ,Area under the curve ,Angiography, Digital Subtraction ,medicine.disease ,Perfusion ,chemistry ,Mesenteric ischemia ,Treatment efficacy ,Case-Control Studies ,Mesenteric Ischemia ,Angiography ,Cardiology ,Non-occlusive mesenteric ischemia ,business - Abstract
Purpose To evaluate the feasibility of 2D-perfusion angiography (2D-PA) for the analysis of intra-procedural treatment response after intra-arterial prostaglandin E1 therapy in patients with non-occlusive mesenteric ischemia (NOMI). Methods Overall, 20 procedures in 18 NOMI patients were included in this retrospective case–control study. To evaluate intra-procedural splanchnic circulation changes, post-processing of digital subtraction angiography (DSA) series was performed. Regions of interest (ROIs) were placed in the superior mesenteric artery (SMA; reference), the portal vein (PV; ROIPV), as well as the aorta next to the origin of the SMA (ROIAorta). Peak density (PD), time to peak (TTP), and area under the curve (AUC) were assessed, and parametric ratios ‘target ROIPD, TTP, AUC/reference ROI’ were computed and compared within treatment and control group. Additionally, a NOMI score was assessed pre- and post-treatment compared to 2D-PA. Results Vasodilator therapy leads to a significant decrease of the 2D-PA-derived values PDAorta (p = 0.04) and AUCAorta (p = 0.03). These findings correlated with changes of the simplified NOMI score, both for overall (4 to 1, p PV (p = 0.04) and TTPPV was accelerated without reaching statistical significance (p = 0.13). When compared to a control group, all 2D-PA values in the NOMI group (pre- and post-intervention) differed significantly (p Aorta/PV and lower AUCAorta/PV and PD Aorta/PV. Conclusion 2D-PA offers an objective approach to analyze immediate flow and perfusion changes following vasodilatory therapies of NOMI patients and may be a valuable tool for assessing treatment response.
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- 2020
15. Therapeutic plasma exchange in acute on chronic liver failure
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Marius M. Hoeper, Klaus Stahl, Florian W. R. Vondran, Julius J. Schmidt, Sascha David, Bernhard M W Schmidt, Benjamin Seeliger, Markus Busch, Olaf Wiesner, Andrea Schneider, Richard Taubert, Jan Fuge, and Michael P. Manns
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Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Cirrhosis ,medicine.medical_treatment ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,Liver transplantation ,Gastroenterology ,law.invention ,Tertiary Care Centers ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,Germany ,medicine ,Humans ,Decompensation ,Retrospective Studies ,Plasma Exchange ,business.industry ,Organ dysfunction ,Acute-On-Chronic Liver Failure ,Hematology ,General Medicine ,Plasmapheresis ,Middle Aged ,medicine.disease ,Prognosis ,Intensive Care Units ,Treatment Outcome ,Immune System ,Cohort ,Therapeutic plasma exchange ,Female ,medicine.symptom ,business ,030215 immunology - Abstract
Background Acute on chronic liver failure (ACLF) has been identified as a distinct syndrome due to acute decompensation of liver cirrhosis accompanied by extra-hepatic organ failure, primarily caused by an overwhelming systemic immune response. Therapeutic plasma exchange (TPE) has been demonstrated in a randomized controlled trial to improve transplant free survival in acute liver failure. Here we investigated if TPE might have comparable beneficial effects in patients with ACLF. Methods Thirty-one patients with ACLF that were treated with TPE were enrolled into this retrospective analysis and 1:1 matched to an ACLF cohort treated with standard medical therapy (SMT) only. Results Patients considered for a bridge to recovery (n = 21 each group) approach had a 30-day mortality >90% that was not improved by TPE (P = .185). Deaths occurred in the SMT group at significant earlier time points compared to the patients treated with TPE (mortality at 5 days: 33.3% for TPE and 66.7% for SMT, P = .048). However, patients who received TPE as a bridge to transplant strategy (n = 10) survived in 60% of cases and demonstrated 24 hours after study inclusion a stabilization of organ dysfunction (organ failures at inclusion: 4 (3-5) vs 24 hours after inclusion: 3 (2-4), P = .031 and CLIF-C-ACLF score: 64 (49-76) vs 54 (49-66), P = .043) not seen in SMT patients. Conclusions Although these retrospective data need to be interpreted with caution, they suggest that TPE in ACLF patients is feasible but not suitable as a bridge to recovery strategy. In selected patients TPE might assist as bridge to transplant.
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- 2020
16. Immunoglobulin Deficiency as an Indicator of Disease Severity in Patients with COVID-19
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Michael Sander, Horst Walter Birk, Faeq Husain-Syed, Rory E. Morty, Birgit Jennert, Heiko Slanina, Fiorenza Ferrari, Benjamin Seeliger, Janina Trauth, Werner Seeger, Khodr Tello, Hartmut Dietrich, Klaus Stahl, Hans Dieter Walmrath, Klaus Warnatz, John Ziebuhr, Jochen Wilhelm, Marius M. Hoeper, Claudio Ronco, Susanne Herold, Christian G. Schüttler, Shadi Kassoumeh, István Vadász, Sascha David, Tobias Welte, and University of Zurich
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Pulmonary and Respiratory Medicine ,Male ,medicine.medical_specialty ,immunodysregulation ,Physiology ,Immunoglobulins ,610 Medicine & health ,Gastroenterology ,Severity of Illness Index ,Immunoglobulin G ,Cohort Studies ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Risk Factors ,Physiology (medical) ,Internal medicine ,Medicine ,Humans ,030212 general & internal medicine ,030304 developmental biology ,0303 health sciences ,Creatinine ,biology ,business.industry ,SARS-CoV-2 ,Incidence (epidemiology) ,Acute kidney injury ,respiratory failure ,COVID-19 ,cytokine release syndrome ,Cell Biology ,Middle Aged ,medicine.disease ,Ferritin ,Intensive Care Units ,Respiratory failure ,chemistry ,Cohort ,biology.protein ,IgG deficiency ,Female ,10023 Institute of Intensive Care Medicine ,business ,Research Article ,severe acute respiratory syndrome coronavirus 2 - Abstract
Despite the pandemic status of COVID-19, there is limited information about host risk factors and treatment beyond supportive care. Immunoglobulin G (IgG) could be a potential treatment target. Our aim was to determine the incidence of IgG deficiency and associated risk factors in a cohort of 62 critically ill patients with COVID-19 admitted to two German ICUs (72.6% male, median age: 61 yr). Thirteen (21.0%) of the patients displayed IgG deficiency (IgG < 7 g/L) at baseline (predominant for the IgG1, IgG2, and IgG4 subclasses). Patients who were IgG-deficient had worse measures of clinical disease severity than those with normal IgG levels (shorter duration from disease onset to ICU admission, lower ratio of [Formula: see text] to [Formula: see text], higher Sequential Organ Failure Assessment score, and higher levels of ferritin, neutrophil-to-lymphocyte ratio, and serum creatinine). Patients who were IgG-deficient were also more likely to have sustained lower levels of lymphocyte counts and higher levels of ferritin throughout the hospital stay. Furthermore, patients who were IgG-deficient compared with those with normal IgG levels displayed higher rates of acute kidney injury (76.9% vs. 26.5%; P = 0.001) and death (46.2% vs. 14.3%; P = 0.012), longer ICU [28 (6–48) vs. 12 (3–18) days; P = 0.012] and hospital length of stay [30 (22–50) vs. 18 (9–24) days; P = 0.004]. Univariable logistic regression showed increasing odds of 90-day overall mortality associated with IgG-deficiency (odds ratio 5.14, 95% confidence interval 1.3–19.9; P = 0.018). IgG deficiency might be common in patients with COVID-19 who are critically ill, and warrants investigation as both a marker of disease severity as well as a potential therapeutic target.
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- 2020
17. Early therapeutic plasma exchange in septic shock: a prospective open-label nonrandomized pilot study focusing on safety, hemodynamics, vascular barrier function, and biologic markers
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Hermann Haller, Temitayo O Idowu, Hannah Knaup, Klaus Stahl, Bernhard M W Schmidt, Olaf Wiesner, Sascha David, Jan T. Kielstein, Marius M. Hoeper, Markus Busch, and Tobias Welte
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Male ,Time Factors ,Organ Dysfunction Scores ,medicine.medical_treatment ,Hemodynamics ,Pilot Projects ,Extracorporeal treatment ,030204 cardiovascular system & hematology ,Critical Care and Intensive Care Medicine ,Blood purification ,Norepinephrine ,0302 clinical medicine ,Fresh frozen plasma ,Germany ,Vasoconstrictor Agents ,Prospective Studies ,APACHE ,Plasma Exchange ,lcsh:Medical emergencies. Critical care. Intensive care. First aid ,Plasmapheresis ,Middle Aged ,Shock, Septic ,Renal Replacement Therapy ,Female ,Patient Safety ,Adult ,Mean arterial pressure ,medicine.medical_specialty ,Multiple Organ Failure ,Urology ,Proinflammatory cytokine ,03 medical and health sciences ,medicine ,Humans ,Endothelium ,Adverse effect ,Biologic marker ,Septic shock ,business.industry ,Research ,Endothelial Cells ,030208 emergency & critical care medicine ,lcsh:RC86-88.9 ,medicine.disease ,Respiration, Artificial ,business ,Biomarkers - Abstract
Background Given the pathophysiological key role of the host response to an infection rather than the infection per se, an ideal therapeutic strategy would also target this response. This study was designed to demonstrate safety and feasibility of early therapeutic plasma exchange (TPE) in severely ill individuals with septic shock. Methods This was a prospective single center, open-label, nonrandomized pilot study enrolling 20 patients with early septic shock (onset 0.4 μg/kg/min) out of 231 screened septic patients. Clinical and biochemical data were obtained before and after TPE. Plasma samples were taken for ex-vivo stimulation of human umbilical vein endothelial cells (HUVECs) to analyze barrier function (immunocytochemistry and transendothelial electrical resistance (TER)). Cytokines were measured by cytometric bead array (CBA) and enzyme-linked immunosorbent assays (ELISAs). An immediate response was defined as > 20% NE reduction from baseline to the end of TPE. Results TPE was well tolerated without the occurrence of any adverse events and was associated with a rapid reduction in NE (0.82 (0.61–1.17) vs. 0.56 (0.41–0.78) μg/kg/min, p = 0.002) to maintain mean arterial pressure (MAP) above 65 mmHg. The observed 28-day mortality was 65%. Key proinflammatory cytokines and permeability factors (e.g., interleukin (IL)-6, IL-1b, and angiopoietin-2) were significantly reduced after TPE, while the protective antipermeability factor angiopoietin-1 was not changed. Ex-vivo stimulation of HUVECs with plasma obtained before TPE induced substantial cellular hyperpermeability, which was completely abolished with plasma obtained after TPE. Conclusions Inclusion of early septic shock patients with high doses of vasopressors was feasible and TPE was safe. Rapid hemodynamic improvement and favorable changes in the cytokine profile in patients with septic shock were observed. It has yet to be determined whether early TPE also improves outcomes in this patient cohort. An appropriately powered multicenter randomized controlled trial is desirable. Trial registration Clinicaltrials.gov, NCT03065751. Retrospectively registered on 28 February 2017. Electronic supplementary material The online version of this article (10.1186/s13054-018-2220-9) contains supplementary material, which is available to authorized users.
- Published
- 2018
18. Extracorporeal cytokine removal in severe CAR-T cell associated cytokine release syndrome
- Author
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Christine S. Falk, Nora Möhn, Matthias Eder, Sascha David, Christian Koenecke, Bernhard M W Schmidt, Marius M. Hoeper, Gernot Beutel, Arnold Ganser, Tobias Welte, Thomas Skripuletz, and Klaus Stahl
- Subjects
Male ,Resuscitation ,Chemokine ,medicine.medical_treatment ,T-Lymphocytes ,Receptors, Antigen, T-Cell ,Pharmacology ,Critical Care and Intensive Care Medicine ,Immunotherapy, Adoptive ,Endothelial activation ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Longitudinal Studies ,Receptors, Chimeric Antigen ,biology ,business.industry ,Interleukin-6 ,Endothelial Cells ,030208 emergency & critical care medicine ,Middle Aged ,medicine.disease ,Hemoperfusion ,Immunohistochemistry ,Cytokine release syndrome ,Cytokine ,Treatment Outcome ,030228 respiratory system ,Methylprednisolone ,biology.protein ,Cytokines ,Adsorption ,business ,Cytokine Release Syndrome ,Ex vivo ,medicine.drug - Abstract
Purpose Life-threatening complications of CD-19 Chimeric antigen receptor - T (CAR-T) cells such as the cytokine release syndrome (CRS)) have been reported. Treatment is limited to IL-6 blockade and steroids although global removal of elevated soluble inflammatory factors might be more effective. Methods Clinical course of a CRS patient treated with extracorporeal cytokine adsorption (Cytosorb®). A panel of 48 cytokines, chemokines and endothelial markers has been analyzed longitudinally. Ex vivo stimulation of endothelial cells to visualize (immunocytochemistry) and quantify (ECIS, TER) endothelial barrier effects. Results Following CAR-T cell application a 65 years old male developed grade 4 CRS with refractory shock (3 vasopressors) and severe capillary leakage (+37 L/24 h resuscitation). Treatment included IL-6 blockade, methylprednisolone and additionally Cytosorb hemoperfusion. While multiple soluble inflammatory factors were elevated and most of them decreased by more than 50% following Cytosorb, markers of endothelial injury increased steadily (e.g. Angpt-2/Angpt-1) leading to profound endothelial activation and leakage in ex vivo assays. Conclusion This is the first reported use of cytokine adsorption for CRS showing efficacy in absorption of various cytokines but not endothelial growth factors. A randomized controlled trial to evaluate additional Cytosorb treatment in CRS is currently recruiting at our institution ( NCT04048434 ).
- Published
- 2019
19. To remove and replace—a role for plasma exchange in counterbalancing the host response in sepsis
- Author
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Sascha David and Klaus Stahl
- Subjects
Extracorporeal Circulation ,medicine.medical_specialty ,Letter ,Critical Illness ,Host response ,Review ,Critical Care and Intensive Care Medicine ,Sepsis ,Immune System Phenomena ,Extracorporeal technique ,High volume hemofiltration ,Medicine ,Humans ,Intensive care medicine ,Plasma Exchange ,business.industry ,Renal replacement therapy ,lcsh:Medical emergencies. Critical care. Intensive care. First aid ,lcsh:RC86-88.9 ,Coupled plasma filtration adsorption ,medicine.disease ,Acute kidney injury ,High cut-off membranes ,Adsorption ,Hemofiltration ,business - Abstract
Sepsis is one of the leading causes of morbidity and mortality worldwide. It is characterized by a dysregulated immune response to infections that results in life-threatening organ dysfunction and even death. Bacterial cell wall components (endotoxin or lipopolysaccharide), known as pathogen-associated molecular patterns (PAMPs), as well as damage-associated molecular patterns (DAMPs) released by host injured cells, are well-recognized triggers resulting in the elevation of both pro-inflammatory and anti-inflammatory cytokines. Understanding this complex pathophysiology has led to the development of therapeutic strategies aimed at restoring a balanced immune response by eliminating/deactivating these inflammatory mediators. Different extracorporeal techniques have been studied in recent years in the hope of maximizing the effect of renal replacement therapy in modulating the exaggerated host inflammatory response, including the use of high volume hemofiltration (HVHF), high cut-off (HCO) membranes, adsorption alone, and coupled plasma filtration adsorption (CPFA). These strategies are not widely utilized in practice, depending on resources and local expertise. The literature examining their use in septic patients is growing, but the evidence to support their use at this stage is considered of low level. Our aim is to provide a comprehensive overview of the technical aspects, clinical applications, and associated side effects of these techniques.
- Published
- 2019
20. Staying Awake in Severe Acute Respiratory Distress Syndrome: A Perspective on Immunocompromised Patients
- Author
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Marius M. Hoeper, Sascha David, Heiko Schenk, Benjamin Seeliger, Christian Kühn, Klaus Stahl, and Olaf Wiesner
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,ARDS ,business.industry ,medicine.medical_treatment ,Perspective (graphical) ,Immunosuppression ,Acute respiratory distress ,Critical Care and Intensive Care Medicine ,medicine.disease ,Correspondence ,Medicine ,business ,Intensive care medicine - Published
- 2021
21. Kinetics of Rituximab Excretion into Urine and Peritoneal Fluid in Two Patients with Nephrotic Syndrome
- Author
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Michelle Duong, Klaus Stahl, Mario Schiffer, Annette D. Wagner, Roland Jacobs, Anke Schwarz, and Hermann Haller
- Subjects
medicine.medical_specialty ,030232 urology & nephrology ,Case Report ,Urine ,lcsh:RC870-923 ,Gastroenterology ,Excretion ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,Membranoproliferative glomerulonephritis ,medicine ,030203 arthritis & rheumatology ,Proteinuria ,business.industry ,Peritoneal fluid ,lcsh:Diseases of the genitourinary system. Urology ,medicine.disease ,Nephrology ,Immunology ,Rituximab ,medicine.symptom ,business ,Nephrotic syndrome ,Nephrotic range proteinuria ,medicine.drug - Abstract
Clinical observations suggest that treatment of Rituximab might be less effective in patients with nephrotic range proteinuria when compared to nonnephrotic patients. It is conceivable that the reason for this is that significant amounts of Rituximab might be lost in the urine in a nephrotic patient and that these patients require a repeated or higher dosage. However, this has not been systematically studied. In this case report we describe two different patients with nephrotic range proteinuria receiving Rituximab. The first patient received Rituximab for therapy resistant cryoglobulinemic membranoproliferative glomerulonephritis and the other for second line treatment of Felty’s syndrome. We employed flow cytometry to determine the amount of Rituximab excretion in both urine and peritoneal fluid specimens in these patients following administration of Rituximab. We found that a significant amount of Rituximab is lost from the circulation by excretion into the urine. Furthermore we saw a close correlation of the excretion of Rituximab to the excretion of IgG molecules suggesting selectivity of proteinuria as the determining factor of Rituximab excretion. Further larger scale clinical studies could have the potential to evaluate an optimal cut-off value of IgG urinary loss before a possible administration of Rituximab therefore contributing to a more individualized treatment approach in patients with nonselective and nephrotic range proteinuria.
- Published
- 2017
22. Nonocclusive Mesenteric Ischemia and Interventional Local Vasodilatory Therapy: A Meta-Analysis and Systematic Review of the Literature
- Author
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Markus Busch, Jan B. Hinrichs, Bernhard C. Meyer, Andrea Schneider, Sascha David, Michael P. Manns, Nina Rittgerodt, Jan Fuge, Sabine K Maschke, Marius M. Hoeper, and Klaus Stahl
- Subjects
medicine.medical_specialty ,Critical Care ,Vasodilator Agents ,Vasodilation ,030204 cardiovascular system & hematology ,Nonocclusive mesenteric ischemia ,Critical Care and Intensive Care Medicine ,Sepsis ,03 medical and health sciences ,0302 clinical medicine ,Emergency surgery ,Internal medicine ,Intensive care ,medicine ,Odds Ratio ,Humans ,Retrospective Studies ,business.industry ,Mortality rate ,Standard of Care ,medicine.disease ,Intensive Care Units ,Treatment Outcome ,030220 oncology & carcinogenesis ,Shock (circulatory) ,Meta-analysis ,Mesenteric Ischemia ,Cardiology ,medicine.symptom ,business - Abstract
Background:Intensive care patients with nonocclusive mesenteric ischemia (NOMI) show mortality rates of 70% to 90%. Besides emergency surgery, different interventional local vasodilatory treatment (LVT) attempts have been described. We performed a systematic review and a meta-analysis to evaluate feasibility, efficacy, and tolerability of LVT in patients with life-threatening NOMI.Methods:Searches of PubMed, EMBASE, Web of Science, and Cochrane Library databases were performed until February 2019. Measured outcomes included immediate technical success rates (as indicated by mesenteric vasodilation on angiography or clinical improvement) and adverse events (AEs). Therapeutic efficacy was measured by the assessment of overall mortality.Results:Twelve studies (335 patients, 245 received LVT) from 1977 to 2018 were included. All studies were retrospective (4 comparative and 8 noncomparative). Different intra-arterial vasodilators (4× papaverine, 6× prostaglandin E1, 1× tolazoline/heparin, 1× tolazoline + iloprost) were reported. Initial technical success rate was 75.9% (95% confidence interval [CI], 55.1%-89%, P = .017) with an AE rate of 2.9% (95% CI: 1.3%-6.6%; P = .983). Overall mortality in LVT patients was 40.3% (95% CI: 28.7%-53%, P = .134). In 4 studies, outcomes were compared between patients receiving LVT to those who received standard of care (odds ratio for death in LVT patients was 0.261 [95% CI: 0.095-0.712, P = .009]).Conclusions:Local vasodilatory treatment appears to be safe in patients with NOMI and might have the potential to at least partially reverse mesenteric vasoconstriction features in control angiographies. However, with no randomized and prospective studies available yet, the overall quality of published studies has to be considered as low; therefore, it is not possible to draw generalizable conclusions from the present data concerning clinical end points. Its application might hold promise as a rescue treatment strategy and deserves further evaluation in randomized controlled trials.
- Published
- 2019
23. Molecular Mechanisms and Treatment Strategies in Diabetic Nephropathy: New Avenues for Calcium Dobesilate—Free Radical Scavenger and Growth Factor Inhibition
- Author
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Jan Menne, Klaus Stahl, Hermann Haller, Anna Bertram, and Linong Ji
- Subjects
0301 basic medicine ,Calcium dobesilate ,lcsh:Medicine ,Inflammation ,Review Article ,Growth Factor Inhibition ,Disease ,Calcium Dobesilate ,Bioinformatics ,Antioxidants ,General Biochemistry, Genetics and Molecular Biology ,End stage renal disease ,Diabetic nephropathy ,03 medical and health sciences ,Diabetes mellitus ,medicine ,Humans ,Diabetic Nephropathies ,Endothelium ,General Immunology and Microbiology ,business.industry ,lcsh:R ,Free Radical Scavengers ,General Medicine ,medicine.disease ,Free radical scavenger ,Oxidative Stress ,030104 developmental biology ,Immunology ,Intercellular Signaling Peptides and Proteins ,medicine.symptom ,business ,medicine.drug - Abstract
Diabetic nephropathy is one of the most important microvascular complications of diabetes mellitus and is responsible for 40–50% of all cases of end stage renal disease. The therapeutic strategies in diabetic nephropathy need to be targeted towards the pathophysiology of the disease. The earlier these therapeutic strategies can bring about positive effects on vascular changes and prevent the vasculature in patients with diabetes from deteriorating, the better the renal function can be preserved. Studies evaluating anti-inflammatory and antioxidative strategies in diabetic nephropathy demonstrate the need and value of these novel treatment avenues. CaD is an established vasoactive and angioprotective drug that has shown a unique, multitarget mode of action in several experimental studies and in different animal models of diabetic microvascular complications. On the molecular level, CaD reduces oxidative stress and inhibits growth factors such as fibroblast growth factor and vascular endothelial growth factors. Recent findings have demonstrated a strong rationale for its use in reducing urine albumin excretion rate and markers of inflammation as well as improving endothelial function. Its beneficial effects make it an attractive therapeutic compound especially in the early stages of the disease. These findings, although promising, need further confirmation in prospective clinical trials with CaD.
- Published
- 2017
24. Extracorporeal membrane oxygenation for acute respiratory distress syndrome due to Pneumocystis pneumonia
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Marius M. Hoeper, Axel Haverich, Klaus Stahl, Christian Kühn, Sascha David, Johann Bauersachs, Julius J. Schmidt, Olaf Wiesner, Heiko Schenk, Benjamin Seeliger, and Tobias Welte
- Subjects
Pulmonary and Respiratory Medicine ,ARDS ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Pneumocystis jirovecii Pneumonia ,Conflict of interest ,Acute respiratory distress ,Pneumocystis pneumonia ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,030228 respiratory system ,Nothing ,Intensive care ,Extracorporeal membrane oxygenation ,Medicine ,030212 general & internal medicine ,business ,Intensive care medicine - Abstract
Pneumocystis jirovecii pneumonia (PcP) occurs exclusively in immunocompromised patients. About 50% of PcP is HIV-related, the other half associated with immunosuppression for other reasons [1]. If PcP progresses to an acute respiratory distress syndrome (ARDS) requiring intensive care and invasive mechanical ventilation, the prognosis is generally poor [1] and mortality is about 80% if additional veno-venous extracorporeal membrane oxygenation (VV-ECMO) support is necessary [1]. Despite lack of clear evidence [2], VV-ECMO has become an integral part in the rescue therapy of severe ARDS. Moreover, some centers start VV-ECMO at early time-points in order to rigorously follow (ultra-) protective ventilation strategies [3]. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Stahl has nothing to disclose. Conflict of interest: Dr. Schenk has nothing to disclose. Conflict of interest: Dr. Seeliger has nothing to disclose. Conflict of interest: Dr. Wiesner has nothing to disclose. Conflict of interest: Dr. Schmidt has nothing to disclose. Conflict of interest: Dr. Bauersachs has nothing to disclose. Conflict of interest: Dr. Welte reports personal fees from AstraZeneca, Boehringer, Berlin Chemie, Chiesi, GSK, Novartis, grants from AstraZeneca, Novartis, outside the submitted work. Conflict of interest: Dr. Kuhn has nothing to disclose. Conflict of interest: Dr. Haverich has nothing to disclose. Conflict of interest: Dr. Hoeper reports personal fees from Actelion, personal fees from Bayer, personal fees from MSD, personal fees from Pfizer, outside the submitted work. Conflict of interest: Dr. David has nothing to disclose.
- Published
- 2019
25. Finerenone: a New Mineralocorticoid Receptor Antagonist Without Hyperkalemia: an Opportunity in Patients with CKD?
- Author
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Klaus Stahl, Anna Bertram, Hermann Haller, and Jan Menne
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Finerenone ,medicine.drug_class ,030204 cardiovascular system & hematology ,Pharmacology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Mineralocorticoid receptor ,Internal medicine ,Internal Medicine ,medicine ,Animals ,Humans ,Naphthyridines ,Renal Insufficiency, Chronic ,Receptor ,Mineralocorticoid Receptor Antagonists ,Aldosterone ,business.industry ,medicine.disease ,Eplerenone ,Receptors, Mineralocorticoid ,030104 developmental biology ,Endocrinology ,chemistry ,Mineralocorticoid ,Spironolactone ,Hyperkalemia ,business ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug ,Kidney disease - Abstract
Aldosterone binds to the mineralocorticoid receptor and has an important regulatory role in body fluid and electrolyte balance. It also influences a variety of different cell functions such as oxidative stress, inflammation and organ fibrosis. The important role of the tissue-specific mineralocorticoid receptors in cardiovascular and renal injury has been shown in knockout animals and in clinical studies Mineralocorticoid receptor antagonists seem to exert their beneficial effects via anti-oxidative, anti-inflammatory and anti-fibrotic effects. Spironolactone and eplerenone were the first steroidal mineralocorticoid receptor antagonist. The established steroidal mineralocorticoid receptor antagonists show important therapeutic effects but are hampered by a variety of side effects, most importantly clinically significant hyperkaliemia. Selective non-steroidal mineralocorticoid receptor antagonists have been recently developed and demonstrate effectiveness in early clinical trials. Finereroneholds promise for the future application of this new mineralocorticoid receptor antagonist class in patients with chronic kidney disease since it has shown a significant reduction in UACR combined with a safety profile similar to that in the placebo group. However, further long-term studies investigating relevant clinical end points like reduction in cardiovascular or renal event rate are warranted.
- Published
- 2016
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