TY - JOUR A1 - Rickert, V. A1 - Wagenhäuser, L. A1 - Nordbeck, P. A1 - Wanner, C. A1 - Sommer, C. A1 - Rost, S. A1 - Üçeyler, N. T1 - Stratification of Fabry mutations in clinical practice: a closer look at α‐galactosidase A‐3D structure JF - Journal of Internal Medicine N2 - Background Fabry disease (FD) is an X‐linked lysosomal storage and multi‐system disorder due to mutations in the α‐galactosidase A (α‐GalA) gene. We investigated the impact of individual amino acid exchanges in the α‐GalA 3D‐structure on the clinical phenotype of FD patients. Patients and methods We enrolled 80 adult FD patients with α‐GalA missense mutations and stratified them into three groups based on the amino acid exchange location in the α‐GalA 3D‐structure: patients with active site mutations, buried mutations and other mutations. Patient subgroups were deep phenotyped for clinical and laboratory parameters and FD‐specific treatment. Results Patients with active site or buried mutations showed a severe phenotype with multi‐organ involvement and early disease manifestation. Patients with other mutations had a milder phenotype with less organ impairment and later disease onset. α‐GalA activity was lower in patients with active site or buried mutations than in those with other mutations (P < 0.01 in men; P < 0.05 in women) whilst lyso‐Gb3 levels were higher (P < 0.01 in men; <0.05 in women). Conclusions The type of amino acid exchange location in the α‐GalA 3D‐structure determines disease severity and temporal course of symptom onset. Patient stratification using this parameter may become a useful tool in the management of FD patients. KW - Fabry disease KW - Fabry genotype KW - Fabry phenotype KW - lyso‐Gb3 KW - α‐GalA 3D‐structure Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218125 VL - 288 IS - 5 SP - 593 EP - 604 ER - TY - JOUR A1 - Kraft, Peter A1 - Drechsler, Christiane A1 - Gunreben, Ignaz A1 - Heuschmann, Peter Ulrich A1 - Kleinschnitz, Christoph T1 - Regulation of Blood Coagulation Factors XI and XII in Patients with Acute and Chronic Cerebrovascular Disease: A Case-Control Study JF - Cerebrovascular Diseases N2 - Background: Animal models have implicated an integral role for coagulation factors XI (FXI) and XII (FXII) in thrombus formation and propagation of ischemic stroke (IS). However, it is unknown if these molecules contribute to IS pathophysiology in humans, and might be of use as biomarkers for IS risk and severity. This study aimed to identify predictors of altered FXI and FXII levels and to determine whether there are differences in the levels of these coagulation factors between acute cerebrovascular events and chronic cerebrovascular disease (CCD). Methods: In this case-control study, 116 patients with acute ischemic stroke (AIS) or transitory ischemic attack (TIA), 117 patients with CCD, and 104 healthy volunteers (HVs) were enrolled between 2010 and 2013 at our University hospital. Blood sampling was undertaken once in the CCD and HV groups and on days 0, 1, and 3 after stroke onset in patients with AIS or TIA. Correlations between serum FXI and FXII levels and demographic and clinical parameters were tested by linear regression and analysis of variance. Results: The mean age of AIS/TIA patients was 70 ± 12. Baseline clinical severity measured with NIHSS and Barthel Index was 4.8 ± 6.0 and 74 ± 30, respectively. More than half of the patients had an AIS (58%). FXI levels were significantly correlated with different leukocyte subsets (p < 0.05). In contrast, FXII serum levels showed no significant correlation (p > 0.1). Neither FXI nor FXII levels correlated with CRP (p > 0.2). FXII levels were significantly higher in patients with CCD compared with those with AIS/TIA (mean ± SD 106 ± 26% vs. 97 ± 24%; univariate analysis: p < 0.05); these differences did not reach significance in multivariate analysis adjusted for sex and age. FXI levels did not differ significantly between study groups. Sex and age were significantly associated with FXI and/or FXII levels in patients with AIS/TIA (p < 0.05). In contrast, no statistical significant influence was found for treatment modality (thrombolysis or not), pre-treatment with platelet inhibitors, and severity of stroke. Conclusions: In this study, there was no differential regulation of FXI and FXII levels between disease subtypes but biomarker levels were associated with patient and clinical characteristics. FXI and FXII levels might be no valid biomarker for predicting stroke risk. KW - biomarker KW - factor XI KW - factor XII KW - ischemic stroke KW - chronic cerebrovascular disease Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-199076 SN - 1015-9770 SN - 1421-9786 N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. VL - 38 IS - 5 ER - TY - JOUR A1 - Hock, Michael A1 - Terekhov, Maxim A1 - Stefanescu, Maria Roxana A1 - Lohr, David A1 - Herz, Stefan A1 - Reiter, Theresa A1 - Ankenbrand, Markus A1 - Kosmala, Aleksander A1 - Gassenmaier, Tobias A1 - Juchem, Christoph A1 - Schreiber, Laura Maria T1 - B\(_{0}\) shimming of the human heart at 7T JF - Magnetic Resonance in Medicine N2 - Purpose Inhomogeneities of the static magnetic B\(_{0}\) field are a major limiting factor in cardiac MRI at ultrahigh field (≥ 7T), as they result in signal loss and image distortions. Different magnetic susceptibilities of the myocardium and surrounding tissue in combination with cardiac motion lead to strong spatio‐temporal B\(_{0}\)‐field inhomogeneities, and their homogenization (B0 shimming) is a prerequisite. Limitations of state‐of‐the‐art shimming are described, regional B\(_{0}\) variations are measured, and a methodology for spherical harmonics shimming of the B\(_{0}\) field within the human myocardium is proposed. Methods The spatial B\(_{0}\)‐field distribution in the heart was analyzed as well as temporal B\(_{0}\)‐field variations in the myocardium over the cardiac cycle. Different shim region‐of‐interest selections were compared, and hardware limitations of spherical harmonics B\(_{0}\) shimming were evaluated by calibration‐based B0‐field modeling. The role of third‐order spherical harmonics terms was analyzed as well as potential benefits from cardiac phase–specific shimming. Results The strongest B\(_{0}\)‐field inhomogeneities were observed in localized spots within the left‐ventricular and right‐ventricular myocardium and varied between systolic and diastolic cardiac phases. An anatomy‐driven shim region‐of‐interest selection allowed for improved B\(_{0}\)‐field homogeneity compared with a standard shim region‐of‐interest cuboid. Third‐order spherical harmonics terms were demonstrated to be beneficial for shimming of these myocardial B\(_{0}\)‐field inhomogeneities. Initial results from the in vivo implementation of a potential shim strategy were obtained. Simulated cardiac phase–specific shimming was performed, and a shim term‐by‐term analysis revealed periodic variations of required currents. Conclusion Challenges in state‐of‐the‐art B\(_{0}\) shimming of the human heart at 7 T were described. Cardiac phase–specific shimming strategies were found to be superior to vendor‐supplied shimming. KW - 7 T KW - B KW - cardiac MRI KW - shimming KW - ultrahigh field Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218096 VL - 85 IS - 1 SP - 182 EP - 196 ER - TY - JOUR A1 - Schneider, Andreas A1 - Gutjahr-Lengsfeld, Lena A1 - Ritz, Eberhard A1 - Scharnagl, Hubert A1 - Gelbrich, Götz A1 - Pilz, Stefan A1 - Macdougall, Iain C. A1 - Wanner, Christoph A1 - Drechsler, Christiane T1 - Longitudinal Assessments of Erythropoietin-Stimulating Agent Responsiveness and the Association with Specific Clinical Outcomes in Dialysis Patients JF - Nephron Clinical Practice N2 - Background: Dose requirements of erythropoietin-stimulating agents (ESAs) can vary considerably over time and may be associated with cardiovascular outcomes. We aimed to longitudinally assess ESA responsiveness over time and to investigate its association with specific clinical end points in a time-dependent approach. Methods: The German Diabetes and Dialysis study (4D study) included 1,255 diabetic dialysis patients, of whom 1,161 were receiving ESA treatment. In those patients, the erythropoietin resistance index (ERI) was assessed every 6 months during a median follow-up of 4 years. The association between the ERI and cardiovascular end points was analyzed by time-dependent Cox regression analyses with repeated ERI measures. Results: Patients had a mean age of 66 ± 8.2 years; 53% were male. During follow-up, a total of 495 patients died, of whom 136 died of sudden death and 102 of infectious death. The adjusted and time-dependent risk for sudden death was increased by 19% per 5-unit increase in the ERI (hazard ratio, HR = 1.19, 95% confidence interval, CI = 1.07-1.33). Similarly, mortality increased by 25% (HR = 1.25, 95% CI = 1.18-1.32) and infectious death increased by 27% (HR = 1.27, 95% CI = 1.13-1.42). Further analysis revealed that lower 25-hydroxyvitamin D levels were associated with lower ESA responsiveness (p = 0.046). Conclusions: In diabetic dialysis patients, we observed that time-varying erythropoietin resistance is associated with sudden death, infectious complications and all-cause mortality. Low 25-hydroxyvitamin D levels may contribute to a lower ESA responsiveness. KW - dialysis KW - erythropoietin KW - diabetes KW - epidemiology Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196511 SN - 1660-2110 N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. VL - 128 IS - 1-2 ER - TY - JOUR A1 - de Zeeuw, Dick A1 - Akizawa, Tadao A1 - Agarwal, Rajiv A1 - Audhya, Paul A1 - Bakris, George L. A1 - Chin, Melanie A1 - Krauth, Melissa A1 - Lambers Heerspink, Hiddo J. A1 - Meyer, Colin J. A1 - McMurray, John J. A1 - Parving, Hans-Henrik A1 - Pergola, Pablo E. A1 - Remuzzi, Giuseppe A1 - Toto, Robert D. A1 - Vaziri, Nosratola D. A1 - Wanner, Christoph A1 - Warnock, David G. A1 - Wittes, Janet A1 - Chertow, Glenn M. T1 - Rationale and Trial Design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: The Occurrence of Renal Events (BEACON) JF - American Journal of Nephrology N2 - Background: Chronic kidney disease (CKD) associated with type 2 diabetes mellitus constitutes a global epidemic complicated by considerable renal and cardiovascular morbidity and mortality, despite the provision of inhibitors of the renin-angiotensin-aldosterone system (RAAS). Bardoxolone methyl, a synthetic triterpenoid that reduces oxidative stress and inflammation through Nrf2 activation and inhibition of NF-κB was previously shown to increase estimated glomerular filtration rate (eGFR) in patients with CKD associated with type 2 diabetes mellitus. To date, no antioxidant or anti-inflammatory therapy has proved successful at slowing the progression of CKD. Methods: Herein, we describe the design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: the Occurrence of Renal Events (BEACON) trial, a multinational, multicenter, double-blind, randomized, placebo-controlled Phase 3 trial designed to determine whether long-term administration of bardoxolone methyl (on a background of standard therapy, including RAAS inhibitors) safely reduces renal and cardiac morbidity and mortality. Results: The primary composite endpoint is time-to-first occurrence of either end-stage renal disease or cardiovascular death. Secondary endpoints include the change in eGFR and time to occurrence of cardiovascular events. Conclusion: BEACON will be the first event-driven trial to evaluate the effect of an oral antioxidant and anti-inflammatory drug in advanced CKD. KW - clinical trial KW - diabetes mellitus KW - glomerular filtration rate KW - trial design KW - bardoxolone methyl KW - Nrf2 KW - end-stage renal disease KW - cardiovascular death KW - chronic kidney disease Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196832 SN - 0250-8095 SN - 1421-9670 N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. VL - 37 IS - 3 ER - TY - JOUR A1 - Eiringhaus, Jörg A1 - Wünsche, Christoph M. A1 - Tirilomis, Petros A1 - Herting, Jonas A1 - Bork, Nadja A1 - Nikolaev, Viacheslav O. A1 - Hasenfuss, Gerd A1 - Sossalla, Samuel A1 - Fischer, Thomas H. T1 - Sacubitrilat reduces pro‐arrhythmogenic sarcoplasmic reticulum Ca\(^{2+}\) leak in human ventricular cardiomyocytes of patients with end‐stage heart failure JF - ESC Heart Failure N2 - Aims Inhibition of neprilysin and angiotensin II receptor by sacubitril/valsartan (Val) (LCZ696) reduces mortality in heart failure (HF) patients compared with sole inhibition of renin–angiotensin system. Beneficial effects of increased natriuretic peptide levels upon neprilysin inhibition have been proposed, whereas direct effects of sacubitrilat (Sac) (LBQ657) on myocardial Ca\(^{2+}\) cycling remain elusive. Methods and results Confocal microscopy (Fluo‐4 AM) was used to investigate pro‐arrhythmogenic sarcoplasmic reticulum (SR) Ca\(^{2+}\) leak in freshly isolated murine and human ventricular cardiomyocytes (CMs) upon Sac (40 μmol/L)/Val (13 μmol/L) treatment. The concentrations of Sac and Val equalled plasma concentrations of LCZ696 treatment used in PARADIGM‐HF trial. Epifluorescence microscopy measurements (Fura‐2 AM) were performed to investigate effects on systolic Ca\(^{2+}\) release, SR Ca\(^{2+}\) load, and Ca\(^{2+}\)‐transient kinetics in freshly isolated murine ventricular CMs. The impact of Sac on myocardial contractility was evaluated using in toto‐isolated, isometrically twitching ventricular trabeculae from human hearts with end‐stage HF. Under basal conditions, the combination of Sac/Val did not influence diastolic Ca\(^{2+}\)‐spark frequency (CaSpF) nor pro‐arrhythmogenic SR Ca\(^{2}\) leak in isolated murine ventricular CMs (n CMs/hearts = 80/7 vs. 100/7, P = 0.91/0.99). In contrast, Sac/Val treatment reduced CaSpF by 35 ± 9% and SR Ca\(^{2+}\) leak by 45 ± 9% in CMs put under catecholaminergic stress (isoproterenol 30 nmol/L, n = 81/7 vs. 62/7, P < 0.001 each). This could be attributed to Sac, as sole Sac treatment also reduced both parameters by similar degrees (reduction of CaSpF by 57 ± 7% and SR Ca2+ leak by 76 ± 5%; n = 101/4 vs. 108/4, P < 0.01 each), whereas sole Val treatment did not. Systolic Ca2+ release, SR Ca\(^{2+}\) load, and Ca\(^{2+}\)‐transient kinetics including SERCA activity (k\(_{SERCA}\)) were not compromised by Sac in isolated murine CMs (n = 41/6 vs. 39/6). Importantly, the combination of Sac/Val and Sac alone also reduced diastolic CaSpF and SR Ca\(^{2+}\) leak (reduction by 74 ± 7%) in human left ventricular CMs from patients with end‐stage HF (n = 71/8 vs. 78/8, P < 0.05 each). Myocardial contractility of human ventricular trabeculae was not acutely affected by Sac treatment as the developed force remained unchanged over a time course of 30 min (n trabeculae/hearts = 3/3 vs. 4/3). Conclusion This study demonstrates that neprilysin inhibitor Sac directly improves Ca\(^{2+}\) homeostasis in human end‐stage HF by reducing pro‐arrhythmogenic SR Ca\(^{2+}\) leak without acutely affecting systolic Ca\(^{2+}\) release and inotropy. These effects might contribute to the mortality benefits observed in the PARADIGM‐HF trial. KW - heart failure KW - entresto KW - Neprilysin inhibition KW - Ca cycling KW - SR Ca leak KW - arrhythmia Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218479 VL - 7 IS - 5 SP - 2992 EP - 3002 ER - TY - JOUR A1 - Rogowski-Lehmann, Natalie A1 - Geroula, Aikaterini A1 - Prejbisz, Aleksander A1 - Timmers, Henri J. L. M. A1 - Megerle, Felix A1 - Robledo, Mercedes A1 - Fassnacht, Martin A1 - Fliedner, Stephanie M. J. A1 - Reincke, Martin A1 - Stell, Anthony A1 - Januszewicz, Andrzej A1 - Lenders, Jacques W. M. A1 - Eisenhofer, Graeme A1 - Beuschlein, Felix T1 - Missed clinical clues in patients with pheochromocytoma/paraganglioma discovered by imaging JF - Endocrine Connections N2 - Background: Pheochromocytomas and paragangliomas (PPGLs) are rare but potentially harmful tumors that can vary in their clinical presentation. Tumors may be found due to signs and symptoms, as part of a hereditary syndrome or following an imaging procedure. Objective: To investigate potential differences in clinical presentation between PPGLs discovered by imaging (iPPGLs), symptomatic cases (sPPGLs) and those diagnosed during follow-up because of earlier disease/known hereditary mutations (fPPGL). Design: Prospective study protocol, which has enrolled patients from six European centers with confirmed PPGLs. Data were analyzed from 235 patients (37 iPPGLs, 36 sPPGLs, 27% fPPGLs) and compared for tumor volume, biochemical profile, mutation status, presence of metastases and self-reported symptoms. iPPGL patients were diagnosed at a significantly higher age than fPPGLs (P<0.001), found to have larger tumors (P=0.003) and higher metanephrine and normetanephrine levels at diagnosis (P=0.021). Significantly lower than in sPPGL, there was a relevant number of self-reported symptoms in iPPGL (2.9 vs 4.3 symptoms, P< 0.001). In 16.2% of iPPGL, mutations in susceptibility genes were detected, although this proportion was lower than that in fPPGL (60.9%) and sPPGL (21.5%). Patients with PPGLs detected by imaging were older, have higher tumor volume and more excessive hormonal secretion in comparison to those found as part of a surveillance program. Presence of typical symptoms indicates that in a relevant proportion of those patients, the PPGL diagnosis had been delayed. Precis: Pheochromocytoma/paraganglioma discovered by imaging are often symptomatic and carry a significant proportion of germline mutations in susceptibility genes. KW - pheochromocytoma KW - paraganglioma KW - imaging KW - signs and symptoms KW - prospective KW - Biochemical-Diagnosis KW - Plasma KW - MASS KW - Normetanephrine KW - Metanephrine KW - Paraganglioma KW - Society KW - Utility Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226481 VL - 7 IS - 11 ER - TY - JOUR A1 - Sailer, Clara Odilia A1 - Wiedemann, Sophia Julia A1 - Strauss, Konrad A1 - Schnyder, Ingeborg A1 - Fenske, Wiebke Kristin A1 - Christ-Crain, Mirjam T1 - Markers of systemic inflammation in response to osmotic stimulus in healthy volunteers JF - Endocrine Connections N2 - Osmotic stimulus or stress results in vasopressin release. Animal and human in vitro studies have shown that inflammatory parameters, such as interle ukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha), increase in parallel in the central nervous system and bronchial, corneal or intestinal epithelial cell lines in response to osmotic stimulus. Whether osmotic stimulus directly causes a systemic inflammatory response in humans is unknown. We therefore investigated the influence of osmotic stimulus on circulatory markers of systemic inflammation in healthy volunteers. In this prospective cohort study, 44 healthy volunteers underwent a standardized test protocol with an osmotic stimulus leading into the hyperosmotic/hypernatremic range (serum sodium >= 150 mmol/L) by hypertonic saline infusion. Copeptin - a marker indicating vasopressin activity - serum sodium and osmolality, plasma IL-8 and TNF-alpha were measured at baseline and directly after osmotic stimulus. Median (range) serum sodium increased from 141 mmol/L (136, 147) to 151 mmol/L (145, 154) (P < 0.01), serum osmolality increased from 295 mmol/L (281, 306) to 315 mmol/L (304, 325) (P < 0.01). Median (range) copeptin increased from 4.3 pg/L (1.1, 21.4) to 28.8 pg/L (19.9, 43.4) (P < 0.01). Median (range) IL-8 levels showed a trend to decrease from 0.79 pg/mL (0.37, 1.6) to 0.7 pg/mL (0.4, 1.9) (P < 0.09) and TNF-alpha levels decreased from 0.53 pg/mL (0.11, 1.1) to 0.45 pg/mL (0.1 2, 0.97) (P < 0.036). Contrary to data obtained in vitro, circulating proinflammatory cytokines tend to or decrease in human plasma after osmotic stimulus. In this study, osmotic stimulus does not increase circulating markers of systemic inflammation. KW - TNF-alpha KW - interleukin-8 KW - interleukin-6 KW - copeptin KW - hyperosmolality KW - Hyperosmotic Stress KW - Interleukin-6 KW - Expression KW - Protein KW - Neurons Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227204 VL - 8 IS - 9 ER - TY - JOUR A1 - Refardt, Julie A1 - Sailer, Clara Odilia A1 - Winzeler, Bettina A1 - Betz, Matthias Johannes A1 - Chifu, Irina A1 - Schnyder, Ingeborg A1 - Fassnacht, Martin A1 - Fenske, Wiebke A1 - Christ-Crain, Mirjam T1 - FGF-21 levels in polyuria-polydipsia syndrome JF - Endocrine Connections N2 - The pathomechanism of primary polydipsia is poorly understood. Recent animal data reported a connection between fibroblast growth factor 21 (FGF-21) and elevated fluid intake independently of hormonal control by the hormone arginine-vasopressin (AVP) and osmotic stimulation. We therefore compared circulating FGF-21 levels in patients with primary polydipsia to patients with AVP deficiency (central diabetes insipidus) and healthy volunteers. In this prospective cohort study, we analyzed FGF-21 levels of 20 patients with primary polydipsia, 20 patients with central diabetes insipidus and 20 healthy volunteers before and after stimulation with hypertonic saline infusion targeting a plasma sodium level >= 150 mmol/L. The primary outcome was the difference in FGF-21 levels between the three groups. Baseline characteristics were similar between the groups except for patients with central diabetes insipidus being heavier. There was no difference in baseline FGF-21 levels between patients with primary polydipsia and healthy volunteers (122 pg/mL (52,277) vs 193 pg/mL (48,301), but higher levels in patients with central diabetes insipidus were observed (306 pg/mL (114,484); P=0.037). However, this was not confirmed in a multivariate linear regression analysis after adjusting for age, sex, BMI and smoking status. Osmotic stimulation did not affect FGF-21 levels in either group (difference to baseline: primary polydipsia -23 pg/mL (-43, 22); central diabetes insipidus 17 pg/mL (-76, 88); healthy volunteers -6 pg/mL (-68, 22); P=0.45). To conclude, FGF-21 levels are not increased in patients with primary polydipsia as compared to central diabetes insipidus or healthy volunteers. FGF-21 therefore does not seem to be causal of elevated fluid intake in these patients. KW - FGF21 KW - diabetes insipidus KW - primary polydipsia KW - osmotic stimulation KW - copeptin KW - Fibroblast Growth Factor-21 KW - Klotho-related molecules KW - Copeptin KW - Diagnosis KW - PF-05231023 KW - Resistance KW - Men Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225085 VL - 7 IS - 12 ER - TY - JOUR A1 - Notz, Quirin A1 - Lotz, Christopher A1 - Herrmann, Johannes A1 - Vogt, Marius A1 - Schlesinger, Tobias A1 - Kredel, Markus A1 - Muellges, Wolfgang A1 - Weismann, Dirk A1 - Westermaier, Thomas A1 - Meybohm, Patrick A1 - Kranke, Peter T1 - Severe neurological complications in critically ill COVID‑19 patients JF - Journal of Neurology N2 - No abstract available. KW - COVID-19 KW - neurological complications Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232429 SN - 0340-5354 ER -