To probe the potential for enzymatic activity in unevolved amino acid sequence space, we created a combinatorial library of de novo 4-helix bundle proteins. This collection of novel proteins can be considered an ''artificial superfamily'' of helical bundles. The superfamily of 102-residue proteins was designed using binary patterning of polar and nonpolar residues, and expressed in Escherichia coli from a library of synthetic genes. Sequences from the library were screened for a range of biological functions including heme binding and peroxidase, esterase, and lipase activities. Proteins exhibiting these functions were purified and characterized biochemically. The majority of de novo proteins from this superfamily bound the heme cofactor, and a sizable fraction of the proteins showed activity significantly above background for at least one of the tested enzymatic activities. Moreover, several of the designed 4-helix bundles proteins showed activity in all of the assays, thereby demonstrating the functional promiscuity of unevolved proteins. These studies reveal that de novo proteins-which have neither been designed for function, nor subjected to evolutionary pressure (either in vivo or in vitro)-can provide rudimentary activities and serve as a ''feedstock'' for evolution.

Our results suggest that PEEP can be applied safely in patients with acute brain injury as it does not have a clinically significant effect on ICP or CPP. Further prospective studies are required to assess the safety of applying a lung protective ventilation strategy in brain-injured patients with lung injury.

Rationale: Neurocognitive outcome after out-of-hospital cardiac arrest (OHCA) is often poor, even when initial resuscitation succeeds. Lower tidal volumes (VTs) attenuate extrapulmonary organ injury in other disease states and are neuroprotective in preclinical models of critical illness.Objective: To evaluate the association between VT and neurocognitive outcome after OHCA.Methods: We performed a propensity-adjusted analysis of a twocenter retrospective cohort of patients experiencing OHCA who received mechanical ventilation for at least the first 48 hours of hospitalization. VT was calculated as the time-weighted average over the first 48 hours, in milliliters per kilogram of predicted body weight (PBW). The primary endpoint was favorable neurocognitive outcome (cerebral performance category of 1 or 2) at discharge.Measurements and Main Results: Of 256 included patients, 38% received time-weighted average VT greater than 8 ml/kg PBW during the first 48 hours. Lower VT was independently associated with favorable neurocognitive outcome in propensityadjusted analysis (odds ratio, 1.61; 95% confidence interval [CI], 1.13-2.28 per 1-ml/kg PBW decrease in VT; P = 0.008). This finding was robust to several sensitivity analyses. Lower VT also was associated with more ventilator-free days (b = 1.78; 95% CI, 0.39-3.16 per 1-ml/kg PBW decrease; P = 0.012) and shockfree days (b = 1.31; 95% CI, 0.10-2.51; P = 0.034). VT was not associated with hypercapnia (P = 1.00). Although the propensity score incorporated several biologically relevant covariates, only height, weight, and admitting hospital were independent predictors of VT less than or equal to 8 ml/kg PBW.Conclusions: Lower VT after OHCA is independently associated with favorable neurocognitive outcome, more ventilator-free days, and more shock-free days. These findings suggest a role for low-VT ventilation after cardiac arrest.

Increasing systolic blood pressure variability was associated with 30-day mortality and development of renal failure, with surgery phase-specific relationships observed. Further research is required to determine how to prospectively detect blood pressure variability and elucidate opportunities for intervention.

Objective: Postoperative pneumonia is one of the most common complications after cardiac surgery, entailing increased patient morbidity, mortality, and health care burden. The primary aim of this study was to assess whether preoperative chlorhexidine mouthwash is associated with reduced postoperative pneumonia after cardiac surgery.Methods: A comprehensive systematic search of NLM Pubmed, Embase, Scopus, and Cumulative Index of Nursing and Allied Health was executed to include the studies since inception to June 27, 2017, which assessed the effects of preoperative chlorhexidine gluconate mouthwash on postoperative pneumonia. Studies were identified by 2 independent reviewers, and data were extracted using a predefined protocol. Random effects models were run to obtain risk ratios with 95% confidence intervals. Quality of evidence was evaluated using Grading of Recommendations Assessment, Development and Evaluation criteria. Postoperative pneumonia after cardiac surgery was the primary outcome of the study.Results: Five studies including a cumulative of 2284 patients were included. A total of 1125 patients received preoperative chlorhexidine. Use of chlorhexidine gluconate was associated with reduced risk of postoperative pneumonia compared with the patients who did not receive it (risk ratio, 0.52; 95% confidence interval, 0.39-0.70; P<.001). No adverse effects from chlorhexidine gluconate mouthwash were reported by any of these studies.Conclusions: Among the patients receiving preoperative chlorhexidine mouthwash, the risk of postoperative pneumonia is reduced by approximately onehalf; its adoption in preoperative protocols could help improve patient outcomes.

BackgroundPost-resuscitation hemodynamic instability following out-of-hospital cardiac arrest (OHCA) may occur from myocardial dysfunction underlying cardiogenic shock and/or inflammation-mediated distributive shock. Distinguishing the predominant shock subtype with widely available clinical metrics may have prognostic and therapeutic value.MethodsA two-hospital cohort was assembled of patients in shock following OHCA. Left ventricular ejection fraction (LVEF) was assessed via echocardiography or cardiac ventriculography within 1 day post arrest and used to delineate shock physiology. The study evaluated whether higher LVEF, indicating distributive-predominant shock physiology, was associated with neurocognitive outcome (primary endpoint), survival, and duration of multiple organ failures. The study also investigated whether volume resuscitation exhibited a subtype-specific association with outcome.ResultsOf 162 patients with post-resuscitation shock, 48% had normal LVEF (> 40%), consistent with distributive shock physiology. Higher LVEF was associated with less favorable neurocognitive outcome (OR 0.74, 95% CI 0.58–0.94 per 10% increase in LVEF; p = 0.01). Higher LVEF also was associated with worse survival (OR 0.81, 95% CI 0.67–0.97; p = 0.02) and fewer organ failure-free days (β = – 0.67, 95% CI – 1.28 to − 0.06; p = 0.03). Only 51% of patients received a volume challenge of at least 30 ml/kg body weight in the first 6 h post arrest, and the volume received did not differ by LVEF. Greater volume resuscitation in the first 6 h post arrest was associated with favorable neurocognitive outcome (OR 1.59, 95% CI 0.99–2.55 per liter; p = 0.03) and survival (OR 1.44, 95% CI 1.02–2.04; p = 0.02) among patients with normal LVEF but not low LVEF.ConclusionsIn post-resuscitation shock, higher LVEF—indicating distributive shock physiology—was associated with less favorable neurocognitive outcome, fewer days without organ failure, and higher mortality. Greater early volume resuscitation was associated with more favorable neurocognitive outcome and survival in patients with this shock subtype. Additional studies with repeated measures of complementary hemodynamic parameters are warranted to validate the clinical utility for subtyping post-resuscitation shock.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-2078-x) contains supplementary material, which is available to authorized users.

O perative management of axillosubclavian artery injuries is a challenge because of its location and the vital structures surrounding it. The subclavian artery is located in the transition zone between the thorax, neck, and upper extremity. It is protected by the structures of the thoracic outlet. Vital structures that are in proximity include the subclavian vein, vertebral artery, carotid artery, brachial plexus, aerodigestive tract, and sympathetic nerve chain. Because of this, open operative access to the artery is difficult, time-consuming, and often requires multiple incisions, including but not limited to sternotomy, anterolateral thoracotomy, "trap door" thoracotomy, and supraclavicular and infraclavicular incisions with claviculectomy. For all these reasons, open operative repair is highly morbid. Overall, patients with an isolated axillosubclavian arterial injury that reach the hospital have a mortality rate that ranges from 4.7% to 39%. [1][2][3][4][5] Endovascular repair of the axillosubclavian artery was first described in the 1990s in hemodynamically stable patients. [6][7][8] As surgeons became more facile in endovascular surgery and the technology evolved, the efficiency of this approach improved, and in the 2010s, endovascular repair of axillosubclavian injuries in hemodynamically unstable patients started to be described. 9 The endovascular approach eliminates the need for complex incisions, the risk of injury to surrounding vital structures, and the need to dissect in a bleeding and often distorted surgical field. Thus, the morbidity of the operation is much less given that large complex incisions do not need to be made, there is much lower blood loss, and less operative time is needed. 10 In a small retrospective study comparing endovascular versus open repair of subclavian or axillary artery injuries, endovascular repair was associated with lower in-hospital mortality and surgical site infections, with a trend toward lower rates of sepsis. 11 However, when vessels are injured, and especially transected, it can be challenging to get a wire across the injury. We have developed a step-wise endovascular approach using some previously developed techniques and a novel technique, which together can be used to cross any traumatic lesions, including partial and complete transections. The three techniques that make up this approach are as follows:

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