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.

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.

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.

Long-Distance Distribution of Atom-Photon Entanglement at Telecom Wavelength.

Entanglement between stationary quantum memories and photonic channels is the essential resource for future quantum networks. Together with entanglement distillation, it will enable efficient distribution of quantum states. We report on the generation and observation of entanglement between a ^{87}Rb atom and a photon at telecom wavelength transmitted through up to 20 km of optical fiber. For this purpose, we use polarization-preserving quantum frequency conversion to transform the wavelength of a photon entangled with the atomic spin state from 780 nm to the telecom S band at 1522 nm. We achieve an unprecedented external device conversion efficiency of 57% and observe an entanglement fidelity between the atom and telecom photon of ≥78.5±0.9% after transmission through 20 km of optical fiber, mainly limited by decoherence of the atomic state. This result is an important milestone on the road to distribute quantum information on a large scale.

The posttraumatic activation of CD4+ T regulatory cells is modulated by TNFR2- and TLR4-dependent pathways, but not by IL-10.

Platelets modulate the immune system following injury by interacting with CD4+ T regulatory cells (CD4+ Tregs). The underlying mechanisms remain unsolved. We hypothesize paracrine interactions via Tumor necrosis factor-alpha (TNFα)-, Toll like receptor-4 (TLR4)-, and Interleukin-10 (IL-10). In the murine burn injury model, CD4+ Treg activation pathways were selectively addressed using TNFR2-, TLR4- and IL-10-deficient mice. The CD4+ Treg signalling molecule PKC-θ was analyzed using phospho-flow cytometry to detect rapid cell activation. Thromboelastometry (ROTEM®) was used to assess platelet activation. Injury induced significant early activation of CD4+ Tregs, disruption of TNFR2 and TLR4 activation pathways resulted in lower activity. The disruption of IL-10 crosstalk had no significant impact. Selective disruption of paracrine interactions is associated with changes in posttraumatic hemostasis parameters. TNFR2- and TLR4-dependent pathways modulate the activation of CD4+ Tregs following trauma. In contrast, we did not observe a role of IL-10 in the posttraumatic activation of CD4+ Tregs. ONE SENTENCE SUMMARY: TLR4- and TNFR2-dependent mechanisms, but not IL-10-dependent pathways, modulate the anti-inflammatory response of CD4+ Tregs following trauma.

Pre-operative evaluation of adults undergoing elective noncardiac surgery: Updated guideline from the European Society of Anaesthesiology.

: The purpose of this update of the European Society of Anaesthesiology (ESA) guidelines on the pre-operative evaluation of the adult undergoing noncardiac surgery is to present recommendations based on the available relevant clinical evidence. Well performed randomised studies on the topic are limited and therefore many recommendations rely to a large extent on expert opinion and may need to be adapted specifically to the healthcare systems of individual countries. This article aims to provide an overview of current knowledge on the subject with an assessment of the quality of the evidence in order to allow anaesthesiologists all over Europe to integrate - wherever possible - this knowledge into daily patient care. The Guidelines Committee of the ESA formed a task force comprising members of the previous task force, members of ESA scientific subcommittees and an open call for volunteers was made to all individual active members of the ESA and national societies. Electronic databases were searched from July 2010 (end of the literature search of the previous ESA guidelines on pre-operative evaluation) to May 2016 without language restrictions. A total of 34 066 abtracts were screened from which 2536 were included for further analysis. Relevant systematic reviews with meta-analyses, randomised controlled trials, cohort studies, case-control studies and cross-sectional surveys were selected. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to assess the level of evidence and to grade recommendations. The final draft guideline was posted on the ESA website for 4 weeks and the link was sent to all ESA members, individual or national (thus including most European national anaesthesia societies). Comments were collated and the guidelines amended as appropriate. When the final draft was complete, the Guidelines Committee and ESA Board ratified the guidelines.

Coherence and entanglement preservation of frequency-converted heralded single photons.

We report on quantum frequency conversion of near-infrared photons from a wave-length of 854 nm to the telecommunication O-band at 1310 nm with 8 % overall conversion efficiency. Entangled photon pairs at 854 nm are generated via type-II spontaneous parametric down conversion. One photon is mixed with a strong pump field in a nonlinear ridge waveguide for its conversion to 1310 nm. We demonstrate preservation of first and second order coherence of the photons in the conversion process. Based on this we infer the coherence function of the two-photon state and compare it with the actual measured one. This measurement demonstrates preservation of time-energy entanglement of the pair. With 88 % visibility we violate a Bell inequality.

Highly efficient heralded single-photon source for telecom wavelengths based on a PPLN waveguide.

We present the realization of a highly efficient photon pair source based on spontaneous parametric downconversion (SPDC) in a periodically poled lithium niobate (PPLN) ridge waveguide. The source is suitable for long distance quantum communication applications as the photon pairs are located at the centers of the telecommunication O- and C- band at 1312 nm and 1557 nm. The high efficiency is confirmed by a conversion efficiency of 4 × 10-6 - which is to our knowledge among the highest conversion efficiencies reported so far - and a heralding efficiency of 64.1 ± 2.1%. The heralded single-photon properties are confirmed by the measurement of the photon statistics with a Click/No-Click method as well as the heralded g(2)-function. A minimum value for g(2)(0) of 0.001 ± 0.0003 indicating clear antibunching has been observed.

Low-noise quantum frequency down-conversion of indistinguishable photons.

We present experimental results on quantum frequency down-conversion of indistinguishable single photons emitted by an InAs/GaAs quantum dot at 904 nm to the telecom C-band at 1557 nm. Hong-Ou-Mandel (HOM) interference measurements are shown prior to and after the down-conversion step. We perform Monte-Carlo simulations of the HOM experiments taking into account the time delays of the different interferometers used and the signal-to-background ratio and further estimate the impact of spectral diffusion on the degree of indistinguishability. By that we conclude that the down-conversion step does not introduce any loss of HOM interference visibility. A noise-free conversion-process along with a high conversion-efficiency (> 30 %) emphasize that our scheme is a promising candidate for an efficient source of indistinguishable single photons at telecom wavelengths.

Identification of ELF3 as an early transcriptional regulator of human urothelium.

Despite major advances in high-throughput and computational modelling techniques, understanding of the mechanisms regulating tissue specification and differentiation in higher eukaryotes, particularly man, remains limited. Microarray technology has been explored exhaustively in recent years and several standard approaches have been established to analyse the resultant datasets on a genome-wide scale. Gene expression time series offer a valuable opportunity to define temporal hierarchies and gain insight into the regulatory relationships of biological processes. However, unless datasets are exactly synchronous, time points cannot be compared directly. Here we present a data-driven analysis of regulatory elements from a microarray time series that tracked the differentiation of non-immortalised normal human urothelial (NHU) cells grown in culture. The datasets were obtained by harvesting differentiating and control cultures from finite bladder- and ureter-derived NHU cell lines at different time points using two previously validated, independent differentiation-inducing protocols. Due to the asynchronous nature of the data, a novel ranking analysis approach was adopted whereby we compared changes in the amplitude of experiment and control time series to identify common regulatory elements. Our approach offers a simple, fast and effective ranking method for genes that can be applied to other time series. The analysis identified ELF3 as a candidate transcriptional regulator involved in human urothelial cytodifferentiation. Differentiation-associated expression of ELF3 was confirmed in cell culture experiments and by immunohistochemical demonstration in situ. The importance of ELF3 in urothelial differentiation was verified by knockdown in NHU cells, which led to reduced expression of FOXA1 and GRHL3 transcription factors in response to PPARγ activation. The consequences of this were seen in the repressed expression of late/terminal differentiation-associated uroplakin 3a gene expression and in the compromised development and regeneration of urothelial barrier function.

BooleSim: an interactive Boolean network simulator.

SUMMARY: BooleSim (Boolean network simulator) is an open-source in-browser tool for simulation and manipulation of Boolean networks. It was developed mainly during Google's Summer of Code 2012 and uses the biographer project for network visualization. It can be used specifically for the modeling of gene regulatory or signal transduction networks. AVAILABILITY AND IMPLEMENTATION: BooleSim is free software and can be downloaded from GitHub (https://github.com/matthiasbock/BooleSim). Online version available at http://rumo.biologie.hu-berlin.de/boolesim/.

The impact of preoperative testing for blood glucose concentration and haemoglobin A1c on mortality, changes in management and complications in noncardiac elective surgery: a systematic review.

BACKGROUND: The risks associated with surgery are elevated in patients with diabetes mellitus. For this reason, preoperative diagnostics frequently include the measurement of blood glucose and haemoglobin A1c (HbA1c), but it is unclear whether these tests contribute to improved perioperative or postoperative outcomes. OBJECTIVES: This systematic review aimed to evaluate the evidence that preoperative testing for blood glucose and HbA1c might influence the following outcome parameters: changes in clinical management; mortality; and the incidence of perioperative and postoperative complications in patients undergoing elective, noncardiac surgery. DESIGN: We performed a systematic search of the literature from January 2001 to March 2013, thus updating a review carried out by the National Institute for Health and Clinical Excellence (NICE) up to the year 2001. ELIGIBILITY CRITERIA: Controlled studies including cohort and case-control studies with a population of at least 60 patients were eligible. RESULTS: The search retrieved 1346 records (including hand-search). Twenty-two studies met all inclusion criteria and were included in the review. Fifteen cohort and two case-control studies evaluated the effectiveness of preoperative blood glucose testing and nine studies the effectiveness of testing HbA1c. Four of the included studies evaluated both tests. There were no data derived from high-quality studies supporting routine preoperative testing for blood glucose or HbA1c in otherwise healthy adult patients undergoing elective noncardiac surgery. Only in vascular and orthopaedic surgery may screening identify patients at an increased risk. CONCLUSION: Preoperative blood glucose testing and testing for HbA1c is not required in nondiabetic patients unless there are clinical sings arousing suspicion. Patients scheduled for vascular and orthopaedic surgery carry an elevated risk justifying preoperative testing for blood glucose or HbA1c as a screening tool.

[OR management - Checklists for OR-design for OR-managers - results of a workshop]. / OP-Management - OP-Designchecklisten für OP-Manager - Ergebnisse eines Workshops.

The construction of an operating room (OR) suite represents an important intermediate- and long term investment. The planning process starts with the quantitative estimation of the procedures to be carried out which defines the operative capacity for the life time of the facility. This permits the calculation of the number of ORs and the definition of the resources for the recovery room, the intermediate care and intensive care unit.The projectors should integrate the new facility into workflow, workload and logistics of the entire hospital. The simulation flow of patients and accompanying persons and of the routes of the personnel is helpful for this purpose. Separating structures for outpatients from those for inpatients and avoiding de-centralized rooms helps designing an efficient and safe OR suite.The design of the single ORs should be flexible to permit changes or technical innovations during their use period. Mobile equipment is preferable to permanently installed devices. We consider an expanse of at least 45 m(2) for any location adequate for general ORs. The space requirements are elevated for hybrid ORs and rooms dedicated for robotic surgery.The design of the suite should separate the flow of personnel, patients and logistics. Surgical instruments and their logistics should be standardized. Dedicated locations for a simultaneous preparation of the instrumentation tables permit parallel processing. Thus an adequate capacity of preparation rooms and storage rooms is necessary. Dressing rooms, rest rooms, showers and lounges are important for the working conditions and should be planned in an adequate size and number.

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.

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.

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.

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.

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.

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.

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.