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ObjectivesTo evaluate the impact of rapid diagnostic testing (RDT) combined with immediate infectious disease (ID) consultation on the treatment of septic patients with positive blood cultures in intensive care units in a setting without 24/7 service.MethodsAdult ICU patients in a tertiary care hospital with positive blood cultures were included from January 2019 to December 2020. The control group underwent routine laboratory testing, and for the intervention group, RDT was applied with immediate ID consultation.ResultsIn 77 out of the 91 patients in the intervention group, the pathogen was identified by RDT. Regarding antimicrobial susceptibility testing (AST), genotypic testing (ePlex®) was successful for Gram-positive cocci, but inadequate for Gram-negative rods. Phenotypic resistance testing with the Accelerate PhenoTest® took too long to be successfully integrated into the intervention. Adaptation of empirical antibiotic therapy was recommended for 72.7% of the patients. Adherence to the ID consultation post-RDT results was high at 82.3%. In the control group, adaptation of the initial antibiotic therapy would have been recommended for 81.8% of patients, if the species identification had been available. Overall adherence to the local antibiotic therapy guideline for sepsis was significantly lower in the control than in the intervention group (27.8% versus 89.3%, p

Critical care cardiology (CCC) in the modern era is shaped by a multitude of innovative treatment options and an increasingly complex, ageing patient population. Generating high-quality evidence for novel interventions and devices in an intensive care setting is exceptionally challenging. As a result, formulating the best possible therapeutic approach continues to rely predominantly on expert opinion and local standard operating procedures. Fostering the full potential of CCC and the maturation of the next generation of decision-makers in this field calls for an updated training concept, that encompasses the extensive knowledge and skills required to care for critically ill cardiac patients while remaining adaptable to the trainee’s individual career planning and existing educational programs. In the present manuscript, we suggest a standardized training phase in preparation of the first ICU rotation, propose a modular CCC core curriculum, and outline how training components could be conceptualized within three sub-specialization tracks for aspiring cardiac intensivists.

BackgroundThe new types of mRNA-containing lipid nanoparticle vaccines BNT162b2 and mRNA-1273 and the adenovirus-based vaccine AZD1222 were developed against SARS-CoV-2 and code for its spike (S) protein. Several studies have investigated short-term antibody (Ab) responses after vaccination.ObjectiveHowever, the impact of these new vaccine formats with unclear effects on the long-term Ab response – including isotype, subclass, and their type of Fc glycosylation – is less explored.MethodsHere, we analyzed anti-S Ab responses in blood serum and the saliva of SARS-CoV-2 naïve and non-hospitalized pre-infected subjects upon two vaccinations with different mRNA- and adenovirus-based vaccine combinations up to day 270.ResultsWe show that the initially high mRNA vaccine-induced blood and salivary anti-S IgG levels, particularly IgG1, markedly decrease over time and approach the lower levels induced with the adenovirus-based vaccine. All three vaccines induced, contrary to the short-term anti-S IgG1 response with high sialylation and galactosylation levels, a long-term anti-S IgG1 response that was characterized by low sialylation and galactosylation with the latter being even below the corresponding total IgG1 galactosylation level. Instead, the mRNA, but not the adenovirus-based vaccines induced long-term IgG4 responses – the IgG subclass with inhibitory effector functions. Furthermore, salivary anti-S IgA levels were lower and decreased faster in naïve as compared to pre-infected vaccinees. Predictively, age correlated with lower long-term anti-S IgG titers for the mRNA vaccines. Furthermore, higher total IgG1 galactosylation, sialylation, and bisection levels correlated with higher long-term anti-S IgG1 sialylation, galactosylation, and bisection levels, respectively, for all vaccine combinations.ConclusionIn summary, the study suggests a comparable “adjuvant” potential of the newly developed vaccines on the anti-S IgG Fc glycosylation, as reflected in relatively low long-term anti-S IgG1 galactosylation levels generated by the long-lived plasma cell pool, whose induction might be driven by a recently described TH1-driven B cell response for all three vaccines. Instead, repeated immunization of naïve individuals with the mRNA vaccines increased the proportion of the IgG4 subclass over time which might influence the long-term Ab effector functions. Taken together, these data shed light on these novel vaccine formats and might have potential implications for their long-term efficacy.

Coronavirus disease 2019 (COVID-19) is a viral infection affecting multiple organ systems of great significance for metabolic processes. Thus, there is increasing interest in metabolic and lipoprotein signatures of the disease, and early analyses have demonstrated a metabolic pattern typical for atherosclerotic and hepatic damage in COVID-19 patients. However, it remains unclear whether this is specific for COVID-19 and whether the observed signature is caused by the disease or rather represents an underlying risk factor. To answer this question, we have analyzed 482 serum samples using nuclear magnetic resonance metabolomics, including longitudinally collected samples from 12 COVID-19 and 20 cardiogenic shock intensive care patients, samples from 18 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody-positive individuals, and single time point samples from 58 healthy controls. COVID-19 patients showed a distinct metabolic serum profile, including changes typical for severe dyslipidemia and a deeply altered metabolic status compared with healthy controls. Specifically, very-low-density lipoprotein and intermediate-density lipoprotein particles and associated apolipoprotein B and intermediate-density lipoprotein cholesterol were significantly increased, whereas cholesterol and apolipoprotein A2 were decreased. Moreover, a similarly perturbed profile was apparent when compared with other patients with cardiogenic shock who are in the intensive care unit when looking at a 1-week time course, highlighting close links between COVID-19 and lipid metabolism. The metabolic profile of COVID-19 patients distinguishes those from healthy controls and also from patients with cardiogenic shock. In contrast, anti-SARS-CoV-2 antibody-positive individuals without acute COVID-19 did not show a significantly perturbed metabolic profile compared with age- and sex-matched healthy controls, but SARS-CoV-2 antibody-titers correlated significantly with metabolic parameters, including levels of glycine, ApoA2, and small-sized low- and high-density lipoprotein subfractions. Our data suggest that COVID-19 is associated with dyslipidemia, which is not observed in anti-SARS-CoV-2 antibody-positive individuals who have not developed severe courses of the disease. This suggests that lipoprotein profiles may represent a confounding risk factor for COVID-19 with potential for patient stratification.

Immune checkpoint inhibitor (ICI) therapy has revolutionized the treatment of several human malignancies, particularly metastatic skin cancer. However, immune-related myocarditis (irM), an immune-mediated adverse event (irAE), is often fatal. In the absence of a reliable biomarker, measurement of pre-ICI therapy serum troponin concentration has been proposed to identify patients at risk of developing irM, although real-world studies examining this strategy are lacking. Thus, we retrospectively analyzed the case records of all patients who commenced ICI therapy between January 2018 and December 2019 in a single university skin cancer center (n = 121) to (i) determine the incidence of irM, (ii) establish the frequency of pretreatment serum hsTnT elevations, and (iii) to establish whether this identified patients who subsequently developed irM. Only one patient developed irM, resulting in an overall incidence of 0.8%. Pretreatment hsTnT was measured in 47 patients and was elevated in 13 (28%). Elevated serum hsTnT concentrations were associated with chronic renal failure (p = 0.02) and diabetes (p < 0.0002). Pretreatment hsTnT was not elevated in the patient who developed fulminant irM. Pre-immunotherapy serum hsTnT concentrations were often asymptomatically elevated in patients with advanced skin cancer, none of whom subsequently developed irM during ICI therapy. However, large studies are required to assess the positive and negative predictive values of hsTnT for the development of irM. In the meantime, elevated hsTnT concentrations should be investigated before initiation of immunotherapy and closely monitored during early treatment cycles, where the risk of irM is greatest.

Background: The coronavirus disease (COVID-19) pandemic imposed diverse challenges on the health care system. Morbidity and mortality of non-COVID-19 emergencies might also have changed because hospitals may not be able to provide optimal care due to restructured resources and uncertainties how to deal with potentially infected patients. It has been recommended to stratify treatment of cardiovascular emergencies according to cardiovascular risk. However, data on the prevalence of asymptomatic SARS-CoV-2 infection in patients presenting with cardiac emergencies remain scarce.Methods: We retrospectively analyzed patients' data from a tertiary cardiology department between April 15 and May 31, 2020. All patients were screened on admission for COVID-19 symptoms using a questionnaire and body temperature measurements. All hospitalized patients were routinely screened using nasopharyngeal swab testing.Results: In total, we counted 710 urgent and emergency admissions. Nasopharyngeal swab tests were available in 689 (97%) patients, 409 and 280 of which presented as urgent and emergency admissions, respectively. Among 280 emergency admissions, none tested positive for SARS-CoV-2.Conclusion: In cardiac emergency patients which were screened negative for COVID-19 symptoms, the prevalence of SARS-CoV-2 infection in regions with a modest overall prevalence is low. This finding might be helpful to better determine timing of emergency procedures and reasonable usage of protective equipment during the COVID-19 crisis and the future.

Besides mediating hemostatic functions, platelets are increasingly recognized as important players of inflammation. Data from experiments in mice and men revealed various intersection points between thrombosis, hemostasis, and inflammation, which are addressed and discussed in this review in detail. One such example is the intrinsic coagulation cascade that is initiated after platelet activation thereby further propagating and re-enforcing wound healing or thrombus formation but also contributing to the pathophysiology of severe diseases. FXII of the intrinsic pathway connects platelet activation with the coagulation cascade during immune reactions. It can activate the contact system thereby either creating an inflammatory state or accelerating inflammation. Recent insights into platelet biology could show that platelets are equipped with complement receptors. Platelets are important for tissue remodeling after injury has been inflicted to the endothelial barrier and to the subendothelial tissue. Thus, platelets are increasingly recognized as more than just cells relevant for bleeding arrest. Future insights into platelet biology are to be expected. This research will potentially offer novel opportunities for therapeutic intervention in diseases featuring platelet abundance.