Multi-Omic Candidate Screening for Markers of Severe Clinical Courses of COVID-19.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) disease courses are characterized by immuno-inflammatory, thrombotic, and parenchymal alterations. Prediction of individual COVID-19 disease courses to guide targeted prevention remains challenging. We hypothesized that a distinct serologic signature precedes surges of IL-6/D-dimers in severely affected COVID-19 patients. METHODS: We performed longitudinal plasma profiling, including proteome, metabolome, and routine biochemistry, on seven seropositive, well-phenotyped patients with severe COVID-19 referred to the Intensive Care Unit at the German Heart Center. Patient characteristics were: 65 ± 8 years, 29% female, median CRP 285 ± 127 mg/dL, IL-6 367 ± 231 ng/L, D-dimers 7 ± 10 mg/L, and NT-proBNP 2616 ± 3465 ng/L. RESULTS: Based on time-series analyses of patient sera, a prediction model employing feature selection and dimensionality reduction through least absolute shrinkage and selection operator (LASSO) revealed a number of candidate proteins preceding hyperinflammatory immune response (denoted ΔIL-6) and COVID-19 coagulopathy (denoted ΔD-dimers) by 24-48 h. These candidates are involved in biological pathways such as oxidative stress/inflammation (e.g., IL-1alpha, IL-13, MMP9, C-C motif chemokine 23), coagulation/thrombosis/immunoadhesion (e.g., P- and E-selectin), tissue repair (e.g., hepatocyte growth factor), and growth factor response/regulatory pathways (e.g., tyrosine-protein kinase receptor UFO and low-density lipoprotein receptor (LDLR)). The latter are host- or co-receptors that promote SARS-CoV-2 entry into cells in the absence of ACE2. CONCLUSIONS: Our novel prediction model identified biological and regulatory candidate networks preceding hyperinflammation and coagulopathy, with the most promising group being the proteins that explain changes in D-dimers. These biomarkers need validation. If causal, our work may help predict disease courses and guide personalized treatment for COVID-19.

Cardiologist-Directed Sedation Management in Patients Undergoing Transvenous Lead Extraction: A Single-Centre Retrospective Analysis.

BACKGROUND: The demand for transvenous lead extraction (TLE) has increased. In line with this, the safety of such procedures has also increased. Traditionally, TLE is performed under resource-intensive general anaesthesia. This study aims to evaluate the safety and outcomes of Cardiologist-lead deep sedation for TLE. METHODS: We retrospectively analysed 328 TLE procedures performed under deep sedation from 2016 to 2019. TLE procedures were performed by experienced electrophysiologists. Sedation was administered by a specifically trained cardiologist (bolus midazolam/fentanyl and propofol infusion). Procedural sedation data including blood pressure, medication administration and sedation time were collected. Complications related to sedation and the operative component of the procedure were analysed retrospectively. RESULTS: The sedation-associated complication rate during TLE was 22.0%. The most common complication (75% of complications) was hypotension requiring noradrenaline, followed by bradycardia requiring atropine (13% of complications). Additionally, the unplanned presence of an anaesthesiologist was needed in one case (0.3%). Deep sedation was achieved with midazolam (mean dose 42.9 ± 26.5 µg/kg), fentanyl (mean dose 0.4 ± 0.6 µg/kg) and propofol (mean dose 3.5 ± 1.2 mg/kg/h). There was no difference in medication dosage between those with a sedation-associated complication and those without. Sedation-associated complications appeared significantly more in patients with reduced LVEF (p = 0.01), renal impairment (p = 0.01) and a higher American Society of Anaesthesiologists (ASA) class (p = 0.01). CONCLUSION: Deep sedation for TLE can be safely performed by a specifically trained cardiologist, with a transition to general anaesthesia required in only 0.3% of cases. We continue to recommend the on-call availability of an anaesthesiologist and cardiac surgeon in case of major complications.

De Novo Lipogenesis-Related Monounsaturated Fatty Acids in the Blood Are Associated with Cardiovascular Risk Factors in HFpEF Patients.

De novo lipogenesis (DNL)-related monounsaturated fatty acids (MUFAs) in the blood are associated with incident heart failure (HF). This observation's biological plausibility may be due to the potential of these MUFAs to induce proinflammatory pathways, endoplasmic reticulum stress, and insulin resistance, which are pathophysiologically relevant in HF. The associations of circulating MUFAs with cardiometabolic phenotypes in patients with heart failure with a preserved ejection fraction (HFpEF) are unknown. In this secondary analysis of the Aldosterone in Diastolic Heart Failure trial, circulating MUFAs were analysed in 404 patients using the HS-Omega-3-Index® methodology. Patients were 67 ± 8 years old, 53% female, NYHA II/III (87/13%). The ejection fraction was ≥50%, E/e' 7.1 ± 1.5, and the median NT-proBNP 158 ng/L (IQR 82-298). Associations of MUFAs with metabolic, functional, and echocardiographic patient characteristics at baseline/12 months follow-up (12 mFU) were analysed using Spearman's correlation coefficients and linear regression analyses, using sex/age as covariates. Circulating levels of C16:1n7 and C18:1n9 were positively associated with BMI/truncal adiposity and associated traits (dysglycemia, atherogenic dyslipidemia, and biomarkers suggestive of non-alcoholic-fatty liver disease). They were furthermore inversely associated with functional capacity at baseline/12 mFU. In contrast, higher levels of C20:1n9 and C24:1n9 were associated with lower cardiometabolic risk and higher exercise capacity at baseline/12 mFU. In patients with HFpEF, circulating levels of individual MUFAs were differentially associated with cardiovascular risk factors. Our findings speak against categorizing FA based on physicochemical properties. Circulating MUFAs may warrant further investigation as prognostic markers in HFpEF.

Mechanistic assessment and ablation of left ventricular assist device related ventricular tachycardia in patients with severe heart failure.

Aims: Left-ventricular-assist-devices (lvad) are an established treatment for patients with severe heart failure with reduced ejection fraction (HF) and reduce mortality. However, HF patients have significant substrate for ventricular tachycardia (VT) and the lvad itself might be pro-arrhythmogenic. We investigated the mechanism of VT in lvad-patients in relation to the underlying etiology and provide in silico and ex-vivo data for ablation in these HF patients. Methods and Results: We retrospectively analyzed invasive electrophysiological (EP) studies of 17 patients with VT and lvad. The mechanism of VT was determined using electroanatomical, entrainment and activation time mapping. Ischemic cardiomyopathy was present in 70% of patients. VT originated from the lvad region in >30%. 1/6 patients with VT originating from the lvad region had episodes before lvad implantation, while 7/11 patients with VT originating from other regions had episodes before implantation. Number and time of radiofrequency (RF)-ablation lesions were not different between VTs originating from the lvad or other regions. Long-term freedom from VT was 50% upon ablation in patients with VT originating from the lvad region and 64% if ablation was conducted in other regions. To potentially preemptively mitigate lvad related VT in patients undergoing lvad implantation, we obtained in silico derived data and performed ex-vivo experiments targeting ventricular myocardium. Of the tested settings, application of 25 W for 30 s was safe and associated with optimal lesion characteristics. Conclusion: A significant percentage of patients with lvad undergoing VT ablation exhibit arrhythmia originating in close vicinity to the device and recurrence rates are high. Based on in silico and ex-vivo data, we propose individualized RF-ablation in selected patients at risk for/with lvad related VT.

Trans-fatty acid blood levels of industrial but not natural origin are associated with cardiovascular risk factors in patients with HFpEF: a secondary analysis of the Aldo-DHF trial.

BACKGROUND: Industrially processed trans-fatty acids (IP-TFA) have been linked to altered lipoprotein metabolism, inflammation and increased NT-proBNP. In patients with heart failure with preserved ejection fraction (HFpEF), associations of TFA blood levels with patient characteristics are unknown. METHODS: This is a secondary analysis of the Aldo-DHF-RCT. From 422 patients, individual blood TFA were analyzed at baseline in n = 404 using the HS-Omega-3-Index® methodology. Patient characteristics were: 67 ± 8 years, 53% female, NYHA II/III (87/13%), ejection fraction ≥ 50%, E/e' 7.1 ± 1.5; NT-proBNP 158 ng/L (IQR 82-298). A principal component analysis was conducted but not used for further analysis as cumulative variance for the first two PCs was low. Spearman's correlation coefficients as well as linear regression analyses, using sex and age as covariates, were used to describe associations of whole blood TFA with metabolic phenotype, functional capacity, echocardiographic markers for LVDF and neurohumoral activation at baseline and after 12 months. RESULTS: Blood levels of the naturally occurring TFA C16:1n-7t were inversely associated with dyslipidemia, body mass index/truncal adiposity, surrogate markers for non-alcoholic fatty liver disease and inflammation at baseline/12 months. Conversely, IP-TFA C18:1n9t, C18:2n6tt and C18:2n6tc were positively associated with dyslipidemia and isomer C18:2n6ct with dysglycemia. C18:2n6tt and C18:2n6ct were inversely associated with submaximal aerobic capacity at baseline/12 months. No significant association was found between TFA and cardiac function. CONCLUSIONS: In HFpEF patients, higher blood levels of IP-TFA, but not naturally occurring TFA, were associated with dyslipidemia, dysglycemia and lower functional capacity. Blood TFAs, in particular C16:1n-7t, warrant further investigation as prognostic markers in HFpEF. Higher blood levels of industrially processed TFA, but not of the naturally occurring TFA C16:1n-7t, are associated with a higher risk cardiometabolic phenotype and prognostic of lower aerobic capacity in patients with HFpEF.

Cardiac radiotherapy transiently alters left ventricular electrical properties and induces cardiomyocyte-specific ventricular substrate changes in heart failure.

AIMS: Ongoing clinical trials investigate the therapeutic value of stereotactic cardiac radioablation (cRA) in heart failure patients with ventricular tachycardia. Animal data indicate an effect on local cardiac conduction properties. However, the exact mechanism of cRA in patients remains elusive. Aim of the current study was to investigate in vivo and in vitro myocardial properties in heart failure and ventricular tachycardia upon cRA. METHODS AND RESULTS: High-density 3D electroanatomic mapping in sinus rhythm was performed in a patient with a left ventricular assist device and repeated ventricular tachycardia episodes upon several catheter-based endocardial radio-frequency ablation attempts. Subsequent to electroanatomic mapping and cRA of the left ventricular septum, two additional high-density electroanatomic maps were obtained at 2- and 4-month post-cRA. Myocardial tissue samples were collected from the left ventricular septum during 4-month post-cRA from the irradiated and borderzone regions. In addition, we performed molecular biology and mitochondrial density measurements of tissue and isolated cardiomyocytes. Local voltage was altered in the irradiated region of the left ventricular septum during follow-up. No change of local voltage was observed in the control (i.e. borderzone) region upon irradiation. Interestingly, local activation time was significantly shortened upon irradiation (2-month post-cRA), a process that was reversible (4-month post-cRA). Molecular biology unveiled an increased expression of voltage-dependent sodium channels in the irradiated region as compared with the borderzone, while Connexin43 and transforming growth factor beta were unchanged (4-month post-cRA). Moreover, mitochondrial density was decreased in the irradiated region as compared with the borderzone. CONCLUSION: Our study supports the notion of transiently altered cardiac conduction potentially related to structural and functional cellular changes as an underlying mechanism of cRA in patients with ventricular tachycardia.

Saturated Fatty Acid Blood Levels and Cardiometabolic Phenotype in Patients with HFpEF: A Secondary Analysis of the Aldo-DHF Trial.

BACKGROUND: Circulating long-chain (LCSFAs) and very long-chain saturated fatty acids (VLSFAs) have been differentially linked to risk of incident heart failure (HF). In patients with heart failure with preserved ejection fraction (HFpEF), associations of blood SFA levels with patient characteristics are unknown. METHODS: From the Aldo-DHF-RCT, whole blood SFAs were analyzed at baseline in n = 404 using the HS-Omega-3-Index® methodology. Patient characteristics were 67 ± 8 years, 53% female, NYHA II/III (87%/13%), ejection fraction ≥50%, E/e' 7.1 ± 1.5; and median NT-proBNP 158 ng/L (IQR 82-298). Spearman´s correlation coefficients and linear regression analyses, using sex and age as covariates, were used to describe associations of blood SFAs with metabolic phenotype, functional capacity, cardiac function, and neurohumoral activation at baseline and after 12-month follow-up (12 mFU). RESULTS: In line with prior data supporting a potential role of de novo lipogenesis-related LCSFAs in the development of HF, we showed that baseline blood levels of C14:0 and C16:0 were associated with cardiovascular risk factors and/or lower exercise capacity in patients with HFpEF at baseline/12 mFU. Contrarily, the three major circulating VLSFAs, lignoceric acid (C24:0), behenic acid (C22:0), and arachidic acid (C20:0), as well as the LCSFA C18:0, were broadly associated with a lower risk phenotype, particularly a lower risk lipid profile. No associations were found between cardiac function and blood SFAs. CONCLUSIONS: Blood SFAs were differentially linked to biomarkers and anthropometric markers indicative of a higher-/lower-risk cardiometabolic phenotype in HFpEF patients. Blood SFA warrant further investigation as prognostic markers in HFpEF. One Sentence Summary: In patients with HFpEF, individual circulating blood SFAs were differentially associated with cardiometabolic phenotype and aerobic capacity.

Entangling single atoms over 33 km telecom fibre.

Quantum networks promise to provide the infrastructure for many disruptive applications, such as efficient long-distance quantum communication and distributed quantum computing1,2. Central to these networks is the ability to distribute entanglement between distant nodes using photonic channels. Initially developed for quantum teleportation3,4 and loophole-free tests of Bell's inequality5,6, recently, entanglement distribution has also been achieved over telecom fibres and analysed retrospectively7,8. Yet, to fully use entanglement over long-distance quantum network links it is mandatory to know it is available at the nodes before the entangled state decays. Here we demonstrate heralded entanglement between two independently trapped single rubidium atoms generated over fibre links with a length up to 33 km. For this, we generate atom-photon entanglement in two nodes located in buildings 400 m line-of-sight apart and to overcome high-attenuation losses in the fibres convert the photons to telecom wavelength using polarization-preserving quantum frequency conversion9. The long fibres guide the photons to a Bell-state measurement setup in which a successful photonic projection measurement heralds the entanglement of the atoms10. Our results show the feasibility of entanglement distribution over telecom fibre links useful, for example, for device-independent quantum key distribution11-13 and quantum repeater protocols. The presented work represents an important step towards the realization of large-scale quantum network links.

On-the-Job Safety During Enlarging an Intensive Care Unit for the COVID-19 Pandemic: Team-Based Approach with Low Infection Rate of the Staff.

OBJECTIVE: Healthcare workers had a 7.4-fold risk of severe coronavirus disease-19 than non-essential employees in the United Kingdom during the first phase of the pandemic. In this study, we describe interdisciplinary measures for increasing on-the-job safety used during the first phase of the pandemic in an Italian hospital. METHODS: We converted an intensive care/intermediate care unit into a fully equipped 16-bed intensive care unit with adjustments for infection control and on-the-job safety within 4 days. We compared our actions with a recently published concept on team management in the pandemic and described the implementation of each issue. It was our principal goal in this completely unknown emergency to guarantee safety for both staff and patients. We defined independent pathways for staff, patients, material, and waste. Clear procedures were defined for protecting the employees and for creating a working environment that minimizes mistakes despite challenging conditions. RESULTS: From March 7 to April 29, we treated 34 mechanically ventilated patients in our intensive care unit with a mean bed occupancy rate of 62%. The team worked in the upgraded intensive care unit with an increased perception of safety. After cessation of the first wave of the pandemic, we tested the department's entire staff for antibodies against severe acute respiratory syndrome coronavirus 2. Totally 2 of 122 (1.6%) team members developed anti-severe acute respiratory syndrome coronavirus 2 immunoglobulin-G antibodies during the intensive care unit's running time. CONCLUSION: The successful implementation of theoretical concepts on team management into clinical practice was crucial for staff safety and on-the-job safety during the pandemic.

Patient Characteristics, Procedural Characteristics, and Outcomes in Patients Having Lead Extraction in a High-Volume Center.

The rate of transvenous lead extraction (TLE) is increasing, with an increasing rate of complex devices being implanted. TLE is now a routine part of cardiac device management and up-to-date data on the safety and efficacy of TLE with modern tools and techniques is essential to management decisions regarding noninfectious indications for lead extraction. We present a contemporary, prospective review of TLE at our high-volume cardiac center. All patients who underwent TLE from June 2016 to June 2019 were enrolled in our local database, and baseline clinical data, procedural information, and outcome data were collected. In total, 561 leads were explanted (n = 153) or extracted (n = 408) from 341 patients over the study period. Patients were predominantly male (71%), with a mean age of 65 ± 17 years. The most common indication for lead removal was lead failure (45.2%, n = 154), followed by infection of the pocket or device (29.3%, n = 100). In total, complete success was achieved in 96.4% (n = 541) leads, clinical success in a further 2.1% (n = 12), and failure only in 1.4% (n = 8). There was an overall complication rate of 0.9% (3/341) for major complications and 1.5% (5/341) for minor complications. There were no deaths. In conclusion, our data suggest that there are ongoing improvements in the safety profile and success rates of lead extraction undertaken by experienced operators. The major complication rate now is <1%.

A prospective case-control validation of procalcitonin as a biomarker diagnosing pacemaker and implantable cardioverter-defibrillator pocket infection.

BACKGROUND: The diagnosis of device infections, especially pocket infections, is challenging and relies primarily on clinical presentation. The prospective DIRT (Device associated Infections Role of new diagnostic Tools) study identified procalcitonin (PCT) as the most promising biomarker among other 14 biomarkers to aid the diagnosis of pocket infection. It also identified an optimized cut-off value of 0.05 ng/ml for a localized generator pocket infection. AIMS: The present study aims to validate the proposed PCT cut-off value of 0.05 ng/ml for the diagnosis of pocket infection in an independent cohort. METHODS: We prospectively enrolled 81 patients with pocket infections and 81 controls matched for age and renal function presenting for elective device exchange or lead revision. Patients with concomitant infectious or inflammatory diseases, end-stage renal failure, current active malignancy, or receiving immunosuppressive therapy were excluded. RESULTS: An elevated PCT over 0.05 ng/ml was found in 68% (n = 55) of pocket infections and 24% (n = 19) of controls, corresponding to a sensitivity of 68% and a specificity of 77% for diagnosing a pocket infection. In receiver operating characteristic (ROC) analysis, PCT showed an area under the curve of 0.75 (95% confidence interval, 0.68-0.83; P < 0.001). Sensitivity remained high with antibiotic pretreatment (65% compared to 69% without pretreatment) and in cases with minimal inflammatory signs (67% compared to 70% with extensive inflammation). CONCLUSION: Our study validates the cut-off value of 0.05 ng/ml PCT for diagnosis of a pocket infection, even in patients pre-treated with antibiotics or with minimal clinical signs of inflammation.

BNT162b2 vaccination enhances interferon-JAK-STAT-regulated antiviral programs in COVID-19 patients infected with the SARS-CoV-2 Beta variant.

Background: SARS-CoV-2 infection activates interferon-controlled signaling pathways and elicits a wide spectrum of immune responses and clinical manifestations in human patients. Methods: Here, we investigate the impact of prior vaccination on the innate immune response of hospitalized COVID-19 patients infected with the SARS-CoV-2 Beta variant through RNA sequencing of peripheral blood immune cells. Four patients had received the first dose of BNT162b2 about 11 days prior to the onset of COVID-19 symptoms and five patients were unvaccinated. Patients had received dexamethasone treatment. Immune transcriptomes were obtained at days 7-13, 20-32 and 42-60 after first symptomology. Results: RNA-seq reveals an enhanced JAK-STAT-mediated immune transcriptome response at day 10 in vaccinated patients as compared to unvaccinated ones. This increase subsides by day 35. Expression of the gene encoding the antiviral protein oligoadenylate synthetase (OAS) 1, which is inversely correlated with disease severity, and other key antiviral proteins increases in the vaccinated group. We also investigate the immune transcriptome in naïve individuals receiving their first dose of BNT162b2 and identify a gene signature shared with the vaccinated COVID-19 patients. Conclusions: Our study demonstrates that RNA-seq can be used to monitor molecular immune responses elicited by the BNT162b2 vaccine, both in naïve individuals and in COVID-19 patients, and it provides a biomarker-based approach to systems vaccinology.

Platelets differentially modulate CD4+ Treg activation via GPIIa/IIIb-, fibrinogen-, and PAR4-dependent pathways.

CD4+FoxP3+ regulatory T cells (CD4+ Tregs) are known to dampen inflammation following severe trauma. Platelets were shown to augment their posttraumatic activation in burn injury, but the exact mechanisms remain unclear. We hypothesized that platelet activation mechanisms via GPIIb/IIIa, fibrinogen, and PAR4 have an immunological effect and modulate CD4+ Treg activation early after trauma. Therefore, C57Bl/6 N mice were injected with tirofiban (GPIIb/IIIa inhibition), ancrod (fibrinogen splitting enzyme), or tcY-NH2 (selective PAR4 antagonist peptide) before inducing a third-degree burn injury of 25% of the total body surface area. Changes in coagulation, and local and systemic CD4+ Treg activity were assessed via rotational thromboelastometry (ROTEM®) and phospho-flow cytometry 1 h post intervention. The inhibition of GPIIb/IIIa and fibrinogen locally led to a higher basic activity of CD4+ Tregs compared to non-inhibited animals. In contrast, PAR4 disruption on platelets locally led to an increased posttraumatic activation of CD4+ Tregs. Fibrinogen led to complete elimination of coagulation, whereas GPIIb/IIIa or PAR4 inhibition did not. GPIIb/IIIa receptor and fibrinogen inhibition increase CD4+ Tregs activity independently of trauma. Both are crucial for thrombus formation. We suggest platelets trapped in thrombi are unable to interact with CD4+ Tregs but augment their activity when circulating freely. In contrast, PAR4 seems to reduce CD4+ Treg activation following trauma. In summary, GPIIb/IIIa-, PAR4-, and fibrinogen-dependent pathways in platelets modulate CD4+ Treg baseline activity, independently from their hemostatic functionality. PAR4-dependent pathways modulate the posttraumatic interplay of platelets and CD4+ Tregs.

The posttraumatic response of CD4+ regulatory T cells is modulated by direct cell-cell contact via CD40L- and P-selectin-dependent pathways.

CD4+ FoxP3+ regulatory T cells (CD4+ Tregs) are important for the posttraumatic anti-inflammatory host response. As described previously, platelets are able to modulate CD4+ Treg activity in a reciprocally activating interaction following injury. The underlying mechanisms of the posttraumatic interaction between platelets and CD4+ Tregs remain unclear. We investigated the potential influence of CD40L and P-selectin, molecules known to be involved in direct cell contact of these cell types. In a murine burn injury model, the potential interaction pathways were addressed using CD40L- and P-selectin-deficient mice. Draining lymph nodes were harvested following trauma (1 h) and following a sham procedure. Early rapid activation of CD4+ Tregs was assessed by phospho-flow cytometry (signaling molecules (p)PKC-δ and (p)ZAP-70). Platelet function was analyzed performing rotational thromboelastometry (ROTEM). We hypothesized that disruption of the direct cell-cell contact via CD40L and P-selectin would affect posttraumatic activation of CD4+ Tregs and influence the hemostatic function of platelets. Indeed, while injury induced early activation of CD4+ Tregs in wild-type mice (ZAP-70: p = 0.13, pZAP-70: p < 0.05, PKC-δ: p < 0.05, pPKC-δ: p < 0.05), disruption of CD40L-dependent interaction (ZAP-70: p = 0.57, pZAP-70: p = 0.68, PKC-δ: p = 0.68, pPKC-δ: p = 0.9) or P-selectin-dependent interaction (ZAP-70: p = 0.78, pZAP-70: p = 0.58, PKC-δ: p = 0.81, pPKC-δ: p = 0.73) resulted in reduced posttraumatic activation. Furthermore, hemostatic function was impaired towards hypocoagulability in either deficiency. Our results suggest that the posttraumatic activation of CD4+ Tregs and hemostatic function of platelets are affected by direct cell-cell-signaling via CD40L and P-selectin.

Perioperative Hypothermia-A Narrative Review.

Unintentional hypothermia (core temperature < 36 °C) is a common side effect in patients undergoing surgery. Several patient-centred and external factors, e.g., drugs, comorbidities, trauma, environmental temperature, type of anaesthesia, as well as extent and duration of surgery, influence core temperature. Perioperative hypothermia has negative effects on coagulation, blood loss and transfusion requirements, metabolization of drugs, surgical site infections, and discharge from the post-anaesthesia care unit. Therefore, active temperature management is required in the pre-, intra-, and postoperative period to diminish the risks of perioperative hypothermia. Temperature measurement should be done with accurate and continuous probes. Perioperative temperature management includes a bundle of warming tools adapted to individual needs and local circumstances. Warming blankets and mattresses as well as the administration of properly warmed infusions via dedicated devices are important for this purpose. Temperature management should follow checklists and be individualized to the patient's requirements and the local possibilities.

Impact of BNT162b First Vaccination on the Immune Transcriptome of Elderly Patients Infected with the B.1.351 SARS-CoV-2 Variant.

Fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) energize the COVID-19 pandemic. The B.1.351 variant carrying the escape mutation E484K in the receptor binding domain is of particular concern due to reduced immunological protection following vaccination. Protection can manifest as early as 10 days following immunization with full protection two weeks following the second dose, but the course is not well-characterized for variants. Here, we investigated the immune transcriptome of six elderly individuals (average age 82 yr.) from an old people’s home, who contracted B.1.351, with four having received the first dose of BNT162b eight to 11 days prior to the onset of COVID-19 symptoms. The patients were hospitalized and received dexamethasone treatment. Immune transcriptomes were established from PBMCs approximately 10 and 35 days after the onset of COVID-19 symptomology. RNA-seq revealed a more intensive immune response in vaccinated patients as compared to unvaccinated ones. Specifically, transcription factors linked to the JAK/STAT pathway, interferon stimulated genes, and genes associated with innate antiviral immunity and COVID-19-SARS-CoV-2 infection were highly enriched in vaccinated patients. This rendered the transcriptomes of the older vaccinated group significantly different than older unvaccinated individuals infected at the same institution and more similar to the immune response of younger unvaccinated individuals (ages 48-62) following B.1.351 infection. All individuals in this study whether vaccinated or not were hospitalized due to B.1.351 infection and one vaccinated patient died illustrating that although an enhanced immune response was documented infection it was insufficient to protect from disease. This highlights the need for maintaining physical distancing and prevention measures throughout the time course of vaccination in older adults.

Impact of BNT162b first vaccination on the immune transcriptome of elderly patients infected with the B.1.351 SARS-CoV-2 variant.

Fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) energize the COVID-19 pandemic. The B.1.351 variant carrying the escape mutation E484K in the receptor binding domain is of particular concern due to reduced immunological protection following vaccination. Protection can manifest as early as 10 days following immunization with full protection two weeks following the second dose, but the course is not well-characterized for variants. Here, we investigated the immune transcriptome of six elderly individuals (average age 82 yr.) from an old people's home, who contracted B.1.351, with four having received the first dose of BNT162b eight to 11 days prior to the onset of COVID-19 symptoms. The patients were hospitalized and received dexamethasone treatment. Immune transcriptomes were established from PBMCs approximately 10 and 35 days after the onset of COVID-19 symptomology. RNA-seq revealed a more intensive immune response in vaccinated patients as compared to unvaccinated ones. Specifically, transcription factors linked to the JAK/STAT pathway, interferon stimulated genes, and genes associated with innate antiviral immunity and COVID-19-SARS-CoV-2 infection were highly enriched in vaccinated patients. This rendered the transcriptomes of the older vaccinated group significantly different than older unvaccinated individuals infected at the same institution and more similar to the immune response of younger unvaccinated individuals (age range 48-62) following B.1.351 infection. All individuals in this study whether vaccinated or not were hospitalized due to B.1.351 infection and one vaccinated patient died illustrating that although an enhanced immune response was documented infection it was insufficient to protect from disease. This highlights the need for maintaining physical distancing and prevention measures throughout the time course of vaccination in older adults.

Case Report: Prevention of Rhabdomyolysis-Associated Acute Kidney Injury by Extracorporeal Blood Purification With Cytosorb®.

Acute kidney injury (AKI) is a severe complication of rhabdomyolysis. The pathophysiology of rhabdomyolysis-associated AKI is complex, but myoglobin related damage plays a major role. Extracorporeal removal of myoglobin is therefore an appealing target to prevent AKI, however, attempts to remove myoglobin with standard dialysis membranes have so far been disappointing. Here we report the case of a 12-year-old boy with severe trauma-related rhabdomyolysis where we successfully utilized continuous renal replacement therapy in combination with Cytosorb® to eliminate myoglobin and prevent AKI. The early use of extracorporeal myoglobin removal with Cytosorb® after severe rhabdomyolysis might be an option and should be further investigated as a tool to prevent the development of AKI.

Lung Ultrasound and Respiratory Pathophysiology in Mechanically Ventilated COVID-19 Patients-an Observational Trial.

The relationship between respiratory system mechanics, lung ultrasound (LUS) abnormalities, and mortality in mechanically ventilated patients with COVID-19-associated respiratory failure is unknown. We assessed the pattern of respiratory mechanics and LUS, their changes over time, and the differences between survivors and non-survivors. We additionally analyzed the relationship between LUS findings and the severity of gas exchange impairment and interleukin 6 (IL-6). This was a two-center retrospective, observational trial carried out in the intensive care units of the hospitals of Bolzano and Merano, Italy, from March 15 to April 20, 2020. We enrolled 41 consecutive patients. Seven patients (17%, 95% CI 8.5-31.3%) died. Mean compliance of the respiratory system on ICU admission was 41.6 (± 18.8) ml/mbar (42.5 (± 19.6) for survivors, 38.0 (± 16.3) for deceased, p = 0.605). Non-survivors had a significantly lower compliance over time, decreasing from day 14 after symptom onset, compared with survivors (p = 0.008). Mean LUS score on admission was 11.2 (± 3.7) and survivors had lower LUS scores on admission than non-survivors (10.5 (± 3.6), 13.9 (2.8), respectively, t test, p = 0.029). LUS score correlated with IL-6 concentrations (r = 0.52, p = 0.001) and arterial pCO2 (r = 0.30, p = 0.033) and was inversely correlated with oxygenation (r = - 0.34, p = 0.001). No correlation was found between LUS and respiratory system compliance (r = - 0.02, p = 0.299). Non-survivors from COVID-19-associated respiratory failure had a significant decrease in compliance after day 14 of symptom onset. Compliance did not correlate with the degree of abnormalities found in LUS, but LUS score correlated with oxygenation, pCO2, and IL-6.