Trigger and Target for Fibrinogen Supplementation Using Thromboelastometry (ROTEM) in Patients Undergoing Open Thoraco-Abdominal Aortic Aneurysm Repair.

OBJECTIVE: To determine the relationship between the value of fibrinogen assessed by the FIBTEM clot amplitude at 10 minutes (A10 FIBTEM) measured on admission to the intensive care unit (ICU) and the amount of drainage output at 24 hours, to investigate whether the A10 FIBTEM predicts severe bleeding (SB), and to define A10 FIBTEM thresholds to prevent (trigger) and treat (target) severe bleeding by fibrinogen supplementation. METHODS: In a single centre, retrospective observational study, 166 patients underwent elective open thoraco-abdominal aortic aneurysm (TAAA) repair between March 2016 and January 2019. Exclusion criteria were emergency, congenital, or acquired coagulopathy, or administration of P2Y12 inhibitor antiplatelet agents in the five days before surgery. All patients were managed intra-operatively and post-operatively according to a rotational thromboelastometry driven transfusion protocol. The principal endpoint was a composite outcome, which included bleeding, large volume transfusion, and re-operation. RESULTS: FIBTEM clot amplitude after 10 minutes measured on ICU admission and post-operative bleeding at 24 hours showed an inverse linear relationship (R2 = .03; p = .026). Performance of A10 FIBTEM in predicting SB evaluated by Receiving Operating Curve analysis showed an area under the curve of 0.63 (95% CI 0.56 - 0.70; p = .026) with a best cutoff of 9 mm. An A10 FIBTEM of 3 mm was the cutoff associated with a positive predictive value of 50%, while an A10 FIBTEM of 9 mm showed a negative predictive value of 92%. On multivariable analysis, an A10 FIBTEM ≤ 3 mm remained independently associated with SB. CONCLUSION: The present investigation shows for the first time in a population undergoing open TAAA repair that an A10 FIBTEM ≤ 3mm on ICU admission is associated with post-operative severe bleeding. Trigger and target values for fibrinogen supplementation, based on A10 FIBTEM, have been provided. The transferability and reliability of these cutoff values require further study.

Prevalence, Characteristics, Risk Factors, and Outcomes of Invasively Ventilated COVID-19 Patients with Acute Kidney Injury and Renal Replacement Therapy.

BACKGROUND: There is no information on acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) among invasively ventilated coronavirus disease 2019 (COVID-19) patients in Western healthcare systems. OBJECTIVE: To study the prevalence, characteristics, risk factors and outcome of AKI and CRRT among invasively ventilated COVID-19 patients. METHODS: Observational study in a tertiary care hospital in Milan, Italy. RESULTS: Among 99 patients, 72 (75.0%) developed AKI and 17 (17.7%) received CRRT. Most of the patients developed stage 1 AKI (33 [45.8%]), while 15 (20.8%) developed stage 2 AKI and 24 (33.4%) a stage 3 AKI. Patients who developed AKI or needed CRRT at latest follow-up were older, and among CRRT treated patients a greater proportion had preexisting CKD. Hospital mortality was 38.9% for AKI and 52.9% for CRRT patients. CONCLUSIONS: Among invasively ventilated COVID-19 patients, AKI is very common and CRRT use is common. Both carry a high risk of in-hospital mortality.

On-Surface Decarboxylation Coupling Facilitated by Lock-to-Unlock Variation of Molecules upon the Reaction.

On-surface synthesis (OSS) involving relatively high energy barriers remains challenging due to a typical dilemma: firm molecular anchor is required to prevent molecular desorption upon the reaction, whereas sufficient lateral mobility is crucial for subsequent coupling and assembly. By locking the molecular precursors on the substrate then unlocking them during the reaction, we present a strategy to address this challenge. High-yield synthesis based on well-defined decarboxylation, intermediate transition, and hexamerization is demonstrated, resulting in an extended and ordered network exclusively composed of the newly synthesized macrocyclic compound. Thanks to the steric hindrance of its maleimide group, we attain a preferential selection of the coupling. This work unlocks a promising path to enrich the reaction types and improve the coupling selectivity hence the structual homogeneity of the final product for OSS.

Subsurface-Carbon-Induced Local Charge of Copper for an On-Surface Displacement Reaction.

Transition-metal carbides have sparked unprecedented enthusiasm as high-performance catalysts in recent years. Still, the catalytic properties of copper carbide remain unexplored. By introducing subsurface carbon to Cu(111), a displacement reaction of a proton in a carboxyl acid group with a single Cu atom is demonstrated at the atomic scale and room temperature. Its occurrence is attributed to the C-doping-induced local charge of surface Cu atoms (up to +0.30 e/atom), which accelerates the rate of on-surface deprotonation via reduction of the corresponding energy barrier, thus enabling the instant displacement of a proton with a Cu atom when the molecules adsorb on the surface. This well-defined and robust Cuδ+ surface based on subsurface-carbon doping offers a novel catalytic platform for on-surface synthesis.

Tranexamic acid in open aortic aneurysm surgery: a randomised clinical trial.

BACKGROUND: Bleeding and transfusions affect mortality in aortic surgery. Although tranexamic acid significantly reduced bleeding in multiple settings, its role in major vascular surgery was never studied. The aim of this study was to determine if tranexamic acid reduces blood loss in open abdominal aortic aneurysm (AAA) surgery. METHODS: A total of 100 patients undergoing elective open AAA repair were randomised to receive tranexamic acid (a loading dose of 500 mg and a continuous infusion of 250 mg h-1) or placebo. The primary outcome was intraoperative blood loss, and the secondary outcomes were the number of patients receiving red blood cells, occurrence of thromboembolic events, and mortality. Data were analysed using the intention-to-treat principle. RESULTS: Fifty patients were randomised into each group. Median (inter-quartile range) intraoperative blood loss was 400 (300-1050) ml in the tranexamic acid group vs 500 (360-1000) ml in the placebo group (P=0.44). Transfusion rate was seven/50 (14%) in the tranexamic group vs 12/50 (24%) in the placebo group (P=0.20). No thrombosis was recorded. In a post hoc analysis, postoperative blood loss was reduced in the tranexamic group both at 4 h (60 [40-80] ml vs 100 [60-140] ml, P<0.001) and 24 h (180 [120-275] vs 275 [190-395] ml, P=0.003) after surgery. At 1 yr, three patients were dead, all in the placebo group (P=0.24) and all after 28 days. CONCLUSIONS: Tranexamic acid did not reduce intraoperative blood loss or blood transfusions in open AAA repair, although it may reduce postoperative blood loss without increasing adverse effects. CLINICAL TRIAL REGISTRATION: NCT02335359.

Editor's Choice - A Rotational Thromboelastometry Driven Transfusion Strategy Reduces Allogenic Blood Transfusion During Open Thoraco-abdominal Aortic Aneurysm Repair: A Propensity Score Matched Study.

OBJECTIVE: Open repair of thoraco-abdominal aortic aneurysm (TAAA) is a challenging procedure, associated with high rates of peri-operative bleeding and blood product transfusions. A large intra-operative volume transfusion has been associated with higher in hospital mortality and prolonged mechanical ventilation. A propensity score matched study was carried out to assess whether the introduction of a rotational thromboelastometry (ROTEM) based transfusion strategy reduces allogenic blood transfusion and affects morbidity in patients undergoing open TAAA repair. METHODS: All patients undergoing open TAAA repair at the San Raffaele Scientific Institute between 2009 and 2017 were included. Until 2016, a protocol based on estimated blood loss and conventional coagulation tests was used. After March 2016 a ROTEM guided transfusion protocol was developed and adopted. To account for selection bias, propensity score matching was performed. RESULTS: Five hundred and forty-seven consecutive patients were included. After propensity score matching, 77 patients in the ROTEM algorithm group were successfully matched with 77 patients in the standard algorithm group. Patients managed with ROTEM received fewer red blood cells units (3.5 [range 0-11] vs. 4 [range 0-17]; p = .026) and a lower volume of fresh frozen plasma (286 ± 496 vs. 2,050 ± 1,120; p < .001). In addition, fewer patients received fresh frozen plasma (35% vs. 97%; p < .001). Patients in the ROTEM group showed a significant decrease in the occurrence of pulmonary complications (44% vs. 83%; p = .01). Cost analysis showed a relevant reduction of per-patient expense after the introduction of ROTEM (€834 ± €577 vs. €1,285 ± €851; p < .001) CONCLUSION: A ROTEM guided transfusion strategy significantly limited the quantity of transfused blood products during open TAAA repair, improving clinical outcomes while reducing costs, allowing for better resource distribution in a setting where blood loss is relevant.

Epidural Analgesia in Open Thoraco-abdominal Aortic Aneurysm Repair.

OBJECTIVE: Epidural analgesia improves pain control and outcomes of abdominal aortic aneurysm procedures, while the effect of thoracic epidural analgesia on thoraco-abdominal aortic aneurysm (TAAA) repair is unknown. The aim of the study was to evaluate thoracic epidural analgesia effects in patients undergoing open TAAA repair in terms of pain control and clinically relevant outcomes. METHODS: This was a retrospective study of a prospectively collected database. Patients undergoing open TAAA repair between January 2009 and December 2016. RESULTS: Four hundred and fifty-nine consecutive patients were included. Thoracic epidural analgesia was used in 409 (89%) of cases. On multivariable analysis, patients who received thoracic epidural analgesia experienced reduced post-operative pain (odds ratio [OR] 0.003, 95% confidence interval [CI] 0.0007-0.009; p < .001), a lower rate of acute kidney injury (AKI; OR 0.39, 95% CI 0.21-0.71 [p = .002]), atrial fibrillation (OR 0.47, 95% CI 0.23-0.95; p = .04), acute myocardial infarction (AMI; OR 0.189, 95% CI 0.05-0.64; p = .008), and paraplegia (OR 0.31, 95% CI 0.157-0.615; p = .001) compared with the conventional analgesia (CA) group. After propensity score matching, 43 patients in the CA group were compared with 43 in thoracic epidural analgesia group. On case match analysis thoracic epidural analgesia showed a significant reduction in post-operative pain (p < .001) and no differences in the incidence of AKI, atrial fibrillation, AMI, and paraplegia. In the thoracic epidural analgesia group there were no epidural haematomas. CONCLUSION: Thoracic epidural analgesia was effective in reducing post-operative pain with no effect on major post-operative complications. The use of thoracic epidural analgesia, if not contraindicated, might be considered in clinical practice, even in patients undergoing open TAAA repair. Whether a better post-operative management enhances patient's recovery in this setting remains to be tested.

Bicomponent Supramolecular Architectures at the Vacuum-Solid Interface.

This review aims at giving the readers the basic concepts needed to understand two-dimensional bimolecular organizations at the vacuum-solid interface. The first part describes and analyzes molecules-molecules and molecules-substrates interactions. The current limitations and needs in the understanding of these forces are also detailed. Then, a critical analysis of the past and recent advances in the field is presented by discussing most of the key papers describing bicomponents self-assembly on solid surface in an ultrahigh vacuum environment. These sections are organized by considering decreasing molecule-molecule interaction strengths (i.e. starting from strong directional multiple H bonds up to weaker nondirectional bonds taking into account the increasing fundamental role played by the surface). Finally, we conclude with some research directions (predicting self-assembly, multi-components systems, and nonmetallic surfaces) and potential applications (porous networks and organic surfaces).

Maleimides Designed for Self-Assembly and Reactivity on Graphene.

Two new maleimide derivatives have been synthesized, prone to self-assemble and react with graphene as dienophiles. Both compounds bear a long alkyl chain on the carbon-carbon double bond position 3. The maleimide 1 bears a second alkyl chain at the nitrogen, while in compound 2, three maleimide functionalities are linked to a triethynylbenzene core.

Extending on-surface synthesis from 2D to 3D by cycloaddition with C60.

As an efficient molecular engineering approach, on-surface synthesis (OSS) defines a special opportunity to investigate intermolecular coupling at the sub-molecular level and has delivered many appealing polymers. So far, all OSS is based on the lateral covalent bonding of molecular precursors within a single molecular layer; extending OSS from two to three dimensions is yet to be realized. Herein, we address this challenge by cycloaddition between C60 and an aromatic compound. The C60 layer is assembled on the well-defined molecular network, allowing appropriate molecular orbital hybridization. Upon thermal activation, covalent coupling perpendicular to the surface via [4 + 2] cycloaddition between C60 and the phenyl ring of the molecule is realized; the resultant adduct shows frozen orientation and distinct sub-molecular feature at room temperature and further enables lateral covalent bonding via [2 + 2] cycloaddition. This work unlocks an unconventional route for bottom-up precise synthesis of three-dimensional covalently-bonded organic architectures/devices on surfaces.

Dexmedetomidine versus remifentanil for sedation under monitored anesthetic care in complex endovascular aortic aneurysm repair: a single center experience with mid-term follow-up.

BACKGROUND: Sedation protocols in patients undergoing complex endovascular aortic aneurysm repair are not fully investigated. The aim of this study was to compare a dexmedetomidine (DEX) based sedation protocol with a remifentanil-based sedation protocol. METHODS: Seventy-nine consecutive patients undergoing complex endovascular aortic repair were enrolled and retrospectively analyzed. Forty-two received 0.03 mg/kg midazolam intravenous bolus with remifentanil (0.075-0.1 µg/kg/min for 10 minutes followed by continuous infusion 0.050-0.25 µg/kg/min) and 37 DEX (1 µg/kg over 10 minutes and continuous infusion 0.50-0.75 µg/kg/hour) to achieve an Observer Assessment of Alertness/Sedation Scale (OAAS) ≤4, a Richmond Agitation/Sedation Scale (RASS) ≤-2 and a Visual Analogic Scale (VAS) <4. The primary endpoint was patients' satisfaction. Secondary endpoints included assessment of sedation and pain, the incidence of perioperative hemodynamic or gas exchange imbalance, and 36 month-mortality. RESULTS: Remifentanil group showed a higher satisfaction rate than DEX (P<0.001). Patients on DEX were more sedated than remifentanil according to OAAS (3 [2-3] vs. 4 [3-4]; P=0.001) and RASS (-2[-3/-2] vs. -2[-2/-2]; P=0.001) with no difference in VAS (2 [1-3] vs. 2 [1-3]; P=0.41). DEX provides reliable sedation with lower patient's satisfaction. A higher number of patients were discharged from the recovery room on vasopressors in the DEX group compare with the remifentanil group (5 vs. 0; P=0.045, respectively). The two groups showed a non-significant difference in the survival rate at 36-month (DEX 67% vs. remifentanil 73%; (P=0.90). CONCLUSIONS: In this setting remifentanil provides reliable sedation with higher patient's satisfaction and less hemodynamic effect than DEX.

Long-range ordered and atomic-scale control of graphene hybridization by photocycloaddition.

Chemical reactions that convert sp2 to sp3 hybridization have been demonstrated to be a fascinating yet challenging route to functionalize graphene. So far it has not been possible to precisely control the reaction sites nor their lateral order at the atomic/molecular scale. The application prospects have been limited for reactions that require long soaking, heating, electric pulses or probe-tip press. Here we demonstrate a spatially selective photocycloaddition reaction of a two-dimensional molecular network with defect-free basal plane of single-layer graphene. Directly visualized at the submolecular level, the cycloaddition is triggered by ultraviolet irradiation in ultrahigh vacuum, requiring no aid of the graphene Moiré pattern. The reaction involves both [2+2] and [2+4] cycloadditions, with the reaction sites aligned into a two-dimensional extended and well-ordered array, inducing a bandgap for the reacted graphene layer. This work provides a solid base for designing and engineering graphene-based optoelectronic and microelectronic devices.

Covalent Functionalization by Cycloaddition Reactions of Pristine Defect-Free Graphene.

Based on a low-temperature scanning tunneling microscopy study, we present a direct visualization of a cycloaddition reaction performed for some specific fluorinated maleimide molecules deposited on graphene. Up to now, it was widely admitted that such a cycloaddition reaction can not happen without pre-existing defects. However, our study shows that the cycloaddition reaction can be carried out on a defect-free basal graphene plane at room temperature. In the course of covalently grafting the molecules to graphene, the sp2 conjugation of carbon atoms was broken, and local sp3 bonds were created. The grafted molecules perturbed the graphene lattice, generating a standing-wave pattern with an anisotropy which was attributed to a (1,2) cycloaddition, as revealed by T-matrix approximation calculations. DFT calculations showed that while both (1,4) and (1,2) cycloadditions were possible on free-standing graphene, only the (1,2) cycloaddition could be obtained for graphene on SiC(0001). Globally averaging spectroscopic techniques, XPS and ARPES, were used to determine the modification in the elemental composition of the samples induced by the reaction, indicating an opening of an electronic gap in graphene.

Traumatic subarachnoid hemorrhage on the computerized tomography scan obtained at admission: a multicenter assessment of the accuracy of diagnosis and the potential impact on patient outcome.

OBJECT: The goal of this study was fourfold: 1) to determine the incidence of traumatic subarachnoid hemorrhage (tSAH) in patients with traumatic brain injury (TBI); 2) to verify agreement in the diagnosis of tSAH in a multicenter study; 3) to assess the incidence of tSAH on the outcome of the patient; and 4) to establish whether tSAH itself leads to an unfavorable outcome or whether it is a sign of major brain trauma associated with severe posttraumatic lesions. METHODS: Computerized tomography (CT) scans obtained in 169 head-injured patients on admission to 12 Italian intensive care units during a 3-month period were examined. The scans were collected for neuroradiological review and were used for the analysis together with data from a multicenter database (Neurolink). A review committee found a high incidence of tSAH (61%) in patients with TBI and a moderate agreement among centers (K = 0.57). Significant associations were observed between the presence and grading of tSAH and patient outcomes, and between the presence of tSAH and the severity of the CT findings. Logistic regression analysis showed that the presence of tSAH and its grading alone do not assume statistical significance in the prediction of unfavorable outcome. CONCLUSIONS: Traumatic SAH frequently occurs in patients with TBI, but it is difficult to detect and grade. Traumatic SAH is associated with more severe CT findings and a worse patient outcome.

Sedation for children with metachromatic leukodystrophy undergoing MRI.

BACKGROUND: Metachromatic leukodystrophy (MLD) is a lysosomal storage disease with infantile and juvenile onset with a poor prognosis and magnetic resonance imaging (MRI) plays a fundamental role in its diagnosis. Procedural sedation is needed to carry out MRI on children. Very few case reports have been published on anesthesia or sedation for MLD patients. METHODS: We prospectively studied 18 MLD patients undergoing sedation for brain MRI. Twenty consecutive similar-aged ASA I children undergoing MRI during the same time span for suspected seizures and exhibiting no MRI brain alteration healthy (HLT) patients were also studied for comparison. In patients up to 3 years of age (T_MLD and T_HLT groups), sedation was induced with thiopental 5 mg x kg(-1) i.v. and further 2.5 mg x kg(-1) i.v. rescue boluses were given if the sedation level was inadequate. In patients over 3 years of age (P_MLD and P_HLT groups), sedation was induced with propofol 1-1.5 mg x kg(-1) i.v. and maintained with 0.1-0.15 mg x kg(-1) x min(-1) continuous i.v. infusion, which was increased if the sedation level was inadequate. We recorded complications, if any, caused by sedation (hypoxia, vomiting, bradycardia, other major arrhythmias, convulsions, MRI artifact movements with increasing sedation, prolonged recovery). RESULTS: No sedation complications occurred. The mean dose of thiopental required to warrant patient immobility was 0.227 +/- 0.053 mg x kg(-1) x min(-1) of procedure in T_MLD patients and 0.119 +/- 0.061 mg x kg(-1) x min(-1) of procedure in T_HLT patients (difference not significant). The mean dose of propofol required for immobility was 0.119 +/- 0.054 mg x kg(-1) x min(-1) of procedure in T_MLD patients and 0.115 +/- 0.043 mg x kg(-1) x min(-1) of procedure in T_HLT patients (difference not significant). CONCLUSIONS: Our protocol for sedation in the MRI setting proved safe and effective in children with MLD, who do not require different doses of sedatives compared with healthy children.