Serum Protein Profiling Reveals a Specific Upregulation of the Immunomodulatory Protein Progranulin in Coronavirus Disease 2019.

BACKGROUND: Severe courses of coronavirus disease 2019 (COVID-19) are associated with elevated levels of interleukin 6 (IL-6). However, there is a growing body of evidence pointing to a broad and more complex disorder of proinflammatory and antiviral responses with disturbed interferon signaling in COVID-19. METHODS: In this prospective, single-center registry, we included severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients and patients with similar symptoms and severity of disease but negative for SARS-CoV-2 admitted to the emergency department and compared their serum protein expression profiles. RESULTS: IL-6 abundance was similar in SARS-CoV-2-positive patients (n = 24) compared with SARS-CoV-2-negative controls (n = 61). In contrast, we observed a specific upregulation of the immunomodulatory protein progranulin (GRN). High GRN abundance was associated with adverse outcomes and increased expression of IL-6 in COVID-19. CONCLUSIONS: The data from this registry reveal that GRN is specifically upregulated in SARS-CoV-2-positive patients while IL-6 may serve as marker for disease severity. The potential of GRN as a biomarker and a possible impact of increased GRN expression on interferon signaling, virus elimination, and virus-induced lung tissue damage in COVID-19 should be further explored.

Medical history of coronary artery disease and time to electrocardiogram in the emergency department: a real-life, single-center, retrospective analysis.

BACKGROUND: Timely acquisition of 12-lead Electrocardiogram (ECG) in the emergency department (ED) is crucial and recommended by current guidelines. OBJECTIVES: To evaluate the association of medical history of coronary artery disease (hCAD) on door-to-ECG time in the ED. METHODS: In this single center, retrospective cohort study, patients admitted to ED for cardiac evaluation were grouped according to hCAD and no hCAD. The primary outcome was door-to-ECG time. A multivariate analysis adjusted for the cofounders sex, age, type of referral and shift was performed to evaluate the association of hCAD with door-to-ECG time. RESULTS: 1101 patients were included in this analysis. 362 patients (33%) had hCAD. Patients with hCAD had shorter door-to-ECG time (20 min. [Inter Quartile Range [IQR] 13-30] vs. 22 min. [IQR 14-37]; p < 0.001) when compared to patients with no hCAD. In a multivariable regression analysis hCAD was significantly associated with a shorter door-to-ECG time (- 3 min [p = 0.007; 95% confidence Interval [CI] - 5.16 to - 0.84 min]). CONCLUSION: In this single center registry, hCAD was associated with shorter door-to-ECG time. In patients presenting in ED for cardiac evaluation, timely ECG diagnostic should be facilitated irrespective of hCAD.

Accuracy and precision of transcardiopulmonary thermodilution in patients with cardiogenic shock.

Hemodynamic monitoring plays a crucial role in the supportive treatment of critically ill patients. In this setting, the use of the pulmonary artery catheter (PAC) is a standard procedure. In this study we prospectively compare the accuracy and precision of pulmonary thermodilution (PTD) by PAC and transcardiopulmonary thermodilution (TC-PTD) in patients with cardiogenic shock following an acute cardiac event. In this prospective study 77 hemodynamic measurements were taken in 11 patients presenting cardiogenic shock (CS) treated at the medical intensive care unit of our university hospital. Hemodynamic parameters were measured simultaneously by PTD and by TC-PTD. Both techniques assessed showed a strong correlation in the obtained hemodynamic parameters. The mean bias of cardiac index between measured by PTD (CIpa) and by TC-PTD (CIpi) was 0.04 ± 0.35 L/min/m2. During intra-aortic balloon pump (IABP) counterpulsation and therapeutic hypothermia (TH) in post-resuscitation care, mean bias between CIpa and CIpi was 0.04 ± 0.36 and 0.04 ± 0.34 L/min/m2, respectively. Similarly, patients presenting mitral or tricuspid regurgitation showed interchangeable parameters. Preload parameters obtained by TC-PTD showed significant differences in patients with left ventricular ejection fraction (LVEF) <35 %, compared to patients with LVEF ≥35 %. In contrast, pulmonary arterial occlusion pressure showed no significant difference. Hemodynamic measurements by PTD and TC-PTD are interchangeable during therapy of CS, including patients IABP, TH, mitral or tricuspid regurgitation. Preload parameters measured by TC-PTD seem to be more accurate in these patients than pressure parameters of PTD to gather the acute hemodynamic situation.

Aortic Dissection Presenting as "Hysteria".

BACKGROUND: Patients with medical conditions may present with psychiatric symptoms, which may lead to worse physical health care. Here we present the case of a patient with acute aortic dissection masked by psychiatric symptoms after a stressful event. CASE REPORT: A 29-year-old female medical student presented to the Emergency Department (ED) complaining about the feeling of "hysteria" after an argument with her boyfriend earlier the same day. She did not report other symptoms or pain. Careful physical examination, initially impeded by the patient's agitation, revealed pulseless extremities. Blood gas analysis showed metabolic acidosis. Transthoracic echocardiography and computed tomography ultimately led to the correct diagnosis: Stanford Type-A aortic dissection. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Medical conditions requiring acute diagnostic work-up and therapy may present with psychiatric symptoms. Increased awareness and the use of standardized operating procedures in the ED may prevent fatal misdiagnoses in these patients.

Early SARS-CoV-2 infection: Platelet-neutrophil complexes and platelet function.

Background: Conflicting results have been reported on platelet activity ex vivo and responsiveness in vitro among patients with COVID-19 with or without thromboembolic complications. Objectives: To assess platelet reactivity in patients with moderate disease at early stages of COVID-19. Methods: We performed a prospective, descriptive analysis of 100 consecutive patients presenting with suspected SARS-CoV-2 infection at University Medical Center Freiburg during the first or second wave of the pandemic. Following polymerase chain reaction testing and compliance with study inclusion criteria, 20 SARS-CoV-2-positive and 55 SARS-CoV-2-negative patients (serving as patient controls) were enrolled. In addition, 15 healthy subjects were included. Platelet reactivity was assessed using whole-blood impedance aggregometry and flow cytometry in response to various agonists. Results: Platelet aggregation was significantly impaired in the patients with COVID-19 compared with that in the patient controls or healthy subjects. The reduced platelet responsiveness in the patients with COVID-19 was associated with impaired activation of GPIIb/IIIa (αIIbß3). In contrast, low expression of P-selectin at baseline and intact secretion upon stimulation in vitro suggest that no preactivation in vivo, leading to "exhausted" platelets, had occurred. The proportion of circulating platelet-neutrophil complexes was significantly higher in the patients with COVID-19 (mean ± SD, 41% ± 13%) than in the patient controls (18% ± 7%; 95% CI, 11.1-34.1; P = .0002) or healthy subjects (17% ± 4%; 95% CI, 13.8-33.8; P < .0001). An analysis of neutrophil adhesion receptors revealed upregulation of CD11b (α-subunit of αMß2) and CD66b (CEACAM8) but not of CD162 (PSGL-1) in the patients with COVID-19. Conclusion: Despite reduced platelet responsiveness, platelet-neutrophil complexes are increased at early stages of moderate disease. Thus, this cellular interaction may occur during COVID-19 without preceding platelet activation.

Serum ACE2, Angiotensin II, and Aldosterone Levels Are Unchanged in Patients With COVID-19.

BACKGROUND: The role of the renin-angiotensin-aldosterone system (RAAS) in coronavirus disease 2019 (COVID-19) is controversially discussed. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells by binding to angiotensin-converting enzyme 2 (ACE2) and activity of the RAAS may affect susceptibility to SARS-CoV-2 infection and outcome of patients with COVID-19. METHODS: In this prospective single-center study, we determined the serum levels of ACE2, angiotensin II, and aldosterone in patients with COVID-19 compared with control patients presenting with similar symptoms in the emergency unit. RESULTS: We analyzed serum samples from 24 SARS-CoV-2 positive and 61 SARS-CoV-2 negative patients. SARS-CoV-2 positive and control patients did not differ in baseline patients characteristics, symptoms, and clinical presentation. Mean serum concentrations of ACE2, angiotensin II, and aldosterone did not differ between the SARS-CoV-2 positive and the control group. In line with this, serum potassium as surrogate parameter for RAAS activity and blood pressure were similar in both groups. CONCLUSIONS: In summary, we did not find evidence for altered RAAS activity including angiotensin II, aldosterone, or potassium levels, and blood pressure in patients with COVID-19. CLINICAL TRIALS REGISTRATION: Trial Number DRKS00021206.

Suicide attempt by intravenous injection of gasoline: a case report.

BACKGROUND: There is much experience with intoxication by aspiration of volatile hydrocarbon products, whereas intravenous injection of these distillates is rare. There are only few reports that describe a wide variety of associated pathological changes, predominantly in the pulmonary system. OBJECTIVES: We report the case of an intravenous self-injection of gasoline by a young man in a suicide attempt. CASE REPORT: Immediately after injecting gasoline, the 22-year-old man developed bradycardia, hypotension, and increasing dyspnea. Computed tomography scan of the chest showed signs consistent with diffuse alveolar-toxic damage to the lung. These symptoms and radiological findings are similar to those commonly observed after inhalation of this type of substance. This may have been due to diffusion of gasoline into the alveoli, where its presence leads to this characteristic damage. In this patient, gasoline entered the intramuscular tissue, and the patient developed a soft-tissue phlegmon at the forearm. At operation, gas emanation and superficial necrosis were noted. Nevertheless, the patient's outcome was good, with full recovery within 3 weeks. CONCLUSIONS: The major changes in this patient after intravenous injection of gasoline were in the pulmonary system, including hypoxemia and radiological findings that could be related to an exhalation of the volatile substance. In addition, gas in the musculature of the injection area caused a soft-tissue phlegmon.

Perturbation of the endothelial glycocalyx in post cardiac arrest syndrome.

BACKGROUND: The prognosis of immediate survivors of cardiac arrest remains poor, as the majority of these patients develops an inflammatory disorder known as the post-cardiac arrest syndrome (PCAS). Recently, the endothelial glycocalyx has been shown to be a key modulator of vascular permeability and inflammation, but its role in PCAS remains unknown. METHODS: Plasma levels of the glycocalyx components syndecan-1, heparan sulfate and hyaluronic acid were measured in 25 patients after immediate survival of cardiac arrest during different phases of PCAS. Twelve hemodynamically stable patients with acute coronary syndrome served as controls. RESULTS: Cardiac arrest resulted in a significant increase in syndecan-1, heparan sulfate and hyaluronic acid levels compared to controls, indicating a shedding of the endothelial glycocalyx as a pathophysiological component of the post cardiac arrest syndrome. The time course differed between the individual glycocalyx components, with a higher increase of syndecan-1 in the early phase of PCAS (2.8-fold increase vs. controls) and a later peak of heparan sulfate (1.7-fold increase) and hyaluronic acid (2-fold increase) in the intermediate phase. Only the plasma levels of syndecan-1 correlated positively with the duration of CPR and negatively with the glycocalyx-protective protease inhibitor antithrombin III. Plasma levels of both syndecan-1 and heparan sulfate were higher in eventual non-survivors than in survivors of cardiac arrest. CONCLUSION: Our data for the first time demonstrates a perturbation of the endothelial glycocalyx in immediate survivors of cardiac arrest and indicate a potential important role of this endothelial surface layer in the development of post-cardiac arrest syndrome.

Leptin augments cerebral hemodynamic reserve after three-vessel occlusion: distinct effects on cerebrovascular tone and proliferation in a nonlethal model of hypoperfused rat brain.

The adipocytokine leptin has distinct functions regulating vascular tone, inflammation, and collateral artery growth. Arteriogenesis is an inflammatory process and provides a mechanism to overcome the effects of vascular obstruction. We, therefore, tested the effects of leptin in hypoperfused rat brain (three-vessel occlusion). Systemic leptin administration for 1 week after occlusion surgery increased cerebral hemodynamic reserve similar to granulocyte-macrophage colony-stimulating factor (GM-CSF), as indicated by improved CO(2) reactivity (vehicle 0.53%±0.26% versus leptin 1.05%±0.6% per mm Hg arterial pCO(2), P<0.05). Infusion of microspheres under maximal vasodilation failed to show a positive effect of leptin on cerebral perfusion (vehicle 64.9%±4.5% versus leptin 66.3%±7.0%, occluded/nonoccluded hemisphere). Acute treatment with GM-CSF led to a significant increased CO(2) reactivity and cerebral perfusion (79.2%±8.1% versus 64.9%±4.5%, P<0.05). Vasoconstrictive response of isolated rat carotid artery rings, after phenylephrine was attenuated at 24 hours following preincubation with leptin, was unaffected by removal of endothelium but abrogated by coculture with N-(omega)-nitro-L-arginine methylester, pointing toward an inducible nitric oxide synthase-mediated mechanism. In chronic cerebral hypoperfusion, acute leptin treatment restored the hemodynamic reserve of the cerebral vasculature through its effects on vascular tone, while leaving vascular outward remodeling unaffected. Our results, for the first time, reveal a protective role of leptin on vascular function in hemodynamically compromised brain tissue.