RetroBioCat Database: A Platform for Collaborative Curation and Automated Meta-Analysis of Biocatalysis Data.

Despite the increasing use of biocatalysis for organic synthesis, there are currently no databases that adequately capture synthetic biotransformations. The lack of a biocatalysis database prevents accelerating biocatalyst characterization efforts from being leveraged to quickly identify candidate enzymes for reactions or cascades, slowing their development. The RetroBioCat Database (available at retrobiocat.com) addresses this gap by capturing information on synthetic biotransformations and providing an analysis platform that allows biocatalysis data to be searched and explored through a range of highly interactive data visualization tools. This database makes it simple to explore available enzymes, their substrate scopes, and how characterized enzymes are related to each other and the wider sequence space. Data entry is facilitated through an openly accessible curation platform, featuring automated tools to accelerate the process. The RetroBioCat Database democratizes biocatalysis knowledge and has the potential to accelerate biocatalytic reaction development, making it a valuable resource for the community.

Biocatalytic Cascades toward Iminosugar Scaffolds Reveal Promiscuous Activity of Shikimate Dehydrogenases.

Iminosugar scaffolds are highly sought-after pharmaceutical targets, but their chemical synthesis is lengthy and can suffer from poor scalability and purification. Here we report protecting-group-free chemoenzymatic and biocatalytic cascades to synthesize iminosugars from sugar-derived aminopolyols in two steps. Using galactose oxidase variant F2 followed by a chemical or enzymatic reduction provided an efficient one-pot route to these targets, with product formation >70%. Key to success of this strategy was the application of genome mining, which identified bacterial shikimate dehydrogenases as promiscuous iminosugar reductases. The cell-free protocols allowed for isolation of highly polar iminosugar products from biotransformations in a single step through development of a gradient-elution cation exchange purification. The two-step pathway provides a short synthetic route that can be used as a cell-free platform for broader iminosugar synthesis.

Three-Component Stereoselective Enzymatic Synthesis of Amino-Diols and Amino-Polyols.

Amino-polyols represent attractive chemical building blocks but can be challenging to synthesize because of the high density of asymmetric functionalities and the need for extensive protecting-group strategies. Here we present a three-component strategy for the stereoselective enzymatic synthesis of amino-diols and amino-polyols using a diverse set of prochiral aldehydes, hydroxy ketones, and amines as starting materials. We were able to combine biocatalytic aldol reactions, using variants of d-fructose-6-phosphate aldolase (FSA), with reductive aminations catalyzed by IRED-259, identified from a metagenomic library. A two-step process, without the need for intermediate isolation, was developed to avoid cross-reactivity of the carbonyl components. Stereoselective formation of the 2R,3R,4R enantiomers of amino-polyols was observed and confirmed by X-ray crystallography.

Are biomechanics during gait associated with the structural disease onset and progression of lower limb osteoarthritis? A systematic review and meta-analysis.

OBJECTIVE: To evaluate if gait biomechanics are associated with increased risk of structurally diagnosed disease onset or progression of lower limb osteoarthritis (OA). METHOD: A systematic review of Medline and Embase was conducted from inception to July 2021. Two reviewers independently screened records, extracted data and assessed risk of bias. Included studies reported gait biomechanics at baseline, and either structural imaging or joint replacement occurrence in the lower limb at follow-up. The primary outcome was the Odds Ratio (OR) (95% confidence interval (CI)) of the association between biomechanics and structural OA outcomes with data pooled for meta-analysis. RESULTS: Twenty-three studies reporting 25 different biomechanical metrics and 11 OA imaging outcomes were included (quality scores ranged 12-20/21). Twenty studies investigated knee OA progression; three studies investigated knee OA onset. Two studies investigated hip OA progression. 91% of studies reported a significant association between at least one biomechanical variable and OA onset or progression. There was an association between frontal plane biomechanics with medial tibiofemoral and hip OA progression and sagittal plane biomechanics with patellofemoral OA progression. Meta-analyses demonstrated increased odds of medial tibiofemoral OA progression with greater baseline peak knee adduction moment (KAM) (OR: 1.88 [95%CI: 1.08, 3.29]) and varus thrust presence (OR: 1.97 [95%CI: 1.32, 2.96]). CONCLUSION: Evidence suggests that certain gait biomechanics are associated with an increased odds of OA onset and progression in the knee, and progression in the hip. REGISTRATION NUMBER: PROSPERO CRD42019133920.

Mobile meditation for improving quality of life, anxiety and depression among surgical residents and faculty.

BACKGROUND: Burnout, anxiety and depression are commonly reported among surgical residents and faculty members. Resident training programmes are encouraged to implement structured wellness initiatives, to address emotional stress. METHODS: Thirty otolaryngology residents and faculty members were invited to participate in this prospective pilot trial. Participants were randomised to either the intervention group, which involved completing 10 mobile meditation sessions, or the control group. Outcomes were measured with the Generalized Anxiety Disorder scale-7, Patient Health Questionnaire and Professional Quality of Life scale. RESULTS: Nineteen participants completed the study. Participants in the intervention group had a significantly greater mean change in Generalized Anxiety Disorder scale-7 score (-2.7 ± 3.335 vs 0.33 ± 1.225; p = 0.04). There was no significant difference in average change in Patient Health Questionnaire-9 scores or Professional Quality of Life scale sub-scores between the intervention and control groups. CONCLUSION: Short meditation sessions can significantly improve anxiety in surgical residents and faculty members, and they offer a simple, attainable and effective wellness intervention.

Boomers and Generation Z on campus: Expectations, goals, and experiences.

Compared to the other Anglo-American democracies, when they start job searches, Canadian post-secondary graduates likely confront more competition from similarly educated youth, and experience a relatively high unemployment rate. In addition, should they find work, there is no guarantee for graduates that it will be in their area of specialization. There is an added possibility that employment will be precarious. By comparison, in the mid-sixties, labour market conditions were more accommodating to university graduates. Are these different labour market conditions consistent with students' expectations, goals, and campus experiences prior to graduation? An answer to this question was found through a comparison of those entering Glendon College, York University, in 1963, and in 2013. The examination was based on surveys students completed in 1963, 1967, 2013, and 2017. Data from these sources was. supplemented by information obtained through interviews with students, archival materials, and by analyzing the contents of the student newspaper. Overall, the expectations of Glendon students in the 1960s, and 50 years later, were in keeping with respective favourable and unfavorable labour market conditions. For students' experiences this was not the case. Despite considerable changes in the labour market, the way in which students experienced their time on campus was comparable in the two eras.

Lorsqu'ils se lancent dans la recherche d'un emploi, les diplômés canadiens de niveau postsecondaire sont susceptibles d'être confrontés à une plus grande concurrence de la part de jeunes ayant un niveau d'éducation similaire, et connaissent un taux de chômage relativement élevé. De plus, s'ils trouvent du travail, rien ne garantit que ce sera dans leur domaine de spécialisation. Il est également possible que l'emploi soit précaire. En comparaison, au milieu des années 60, les conditions du marché du travail étaient plus favorables aux diplômés universitaires. Ces différentes conditions du marché du travail correspondent-elles aux attentes, aux objectifs et aux expériences des étudiants sur le campus avant l'obtention du diplôme ? Une réponse à cette question a été trouvée en comparant les étudiants entrés au Glendon College de l'Université York en 1963 et en 2013. L'examen s'est appuyé sur les enquêtes auxquelles les étudiants ont répondu en 1963, 1967, 2013 et 2017, et a été complété par des informations obtenues lors d'entretiens avec des étudiants, des documents d'archives et par l'analyse du contenu du journal étudiant. Dans l'ensemble, les attentes des étudiants de Glendon dans les années 1960, et cinquante ans plus tard, correspondaient aux conditions favorables et défavorables respectives du marché du travail. En ce qui concerne les expériences des étudiants, ce n'était pas le cas. Malgré des changements considérables sur le marché du travail, la manière dont les étudiants ont vécu leur séjour sur le campus était comparable aux deux époques.

Improved Constraints on Primordial Gravitational Waves using Planck, WMAP, and BICEP/Keck Observations through the 2018 Observing Season.

We present results from an analysis of all data taken by the BICEP2, Keck Array, and BICEP3 CMB polarization experiments up to and including the 2018 observing season. We add additional Keck Array observations at 220 GHz and BICEP3 observations at 95 GHz to the previous 95/150/220 GHz dataset. The Q/U maps now reach depths of 2.8, 2.8, and 8.8 µK_{CMB} arcmin at 95, 150, and 220 GHz, respectively, over an effective area of ≈600 square degrees at 95 GHz and ≈400 square degrees at 150 and 220 GHz. The 220 GHz maps now achieve a signal-to-noise ratio on polarized dust emission exceeding that of Planck at 353 GHz. We take auto- and cross-spectra between these maps and publicly available WMAP and Planck maps at frequencies from 23 to 353 GHz and evaluate the joint likelihood of the spectra versus a multicomponent model of lensed ΛCDM+r+dust+synchrotron+noise. The foreground model has seven parameters, and no longer requires a prior on the frequency spectral index of the dust emission taken from measurements on other regions of the sky. This model is an adequate description of the data at the current noise levels. The likelihood analysis yields the constraint r_{0.05}<0.036 at 95% confidence. Running maximum likelihood search on simulations we obtain unbiased results and find that σ(r)=0.009. These are the strongest constraints to date on primordial gravitational waves.

Optimal timing and technique for endoscopic management of dysphagia in pediatric aerodigestive patients.

INTRODUCTION: The best strategy to manage an interarytenoid defect [Type 1 laryngeal cleft (LC-1) or deep interarytenoid groove (DIG)] in pediatric aerodigestive patients with dysphagia remains uncertain. This study compared benefit of interarytenoid augmentation (IAA) to suture repair or clinical observation alone in pediatric patients. METHODS: A 3-year retrospective, single-center analysis of children with dysphagia undergoing endoscopic airway evaluation was performed. Physician preference guided treatment plan: suture repair with CO2 laser, IAA (carboxy methylcellulose or calcium hydroxyapatite), or observation. Primary outcome was improved post-operative diet. Significance was assumed at p < 0.05. RESULTS: 449 patients underwent diagnostic endoscopy. Mean age (±SD) at procedure was 21 ± 13 months, with nearly one fourth (28 %) of children ≤ 12 months. Eighty (18 %) had either an LC-1 (n = 55) or DIG (n = 25). Of these, 35 (42 %) underwent suture repair, 22 (28 %) IAA, and 23 (30 %) observation only. Aspiration improved overall in the interventional groups compared to observational controls (58 % vs. 9 %, p < 0.05), with no change in benefit observed by age of intervention. IAA was as effective as suture repair (59 % vs 55 %, p = 0.46). In patients with only a DIG, IAA intervention alone significantly improved swallow function (66.6 % vs. 0 %, p < 0.05). CONCLUSION: In pediatric aerodigestive patients with dysphagia, 18 % of children have an addressable lesion. IAA or suture repair similarly improves dietary advancement. IAA improves swallow function in patients with DIG. These findings support a novel protocol to intervene in dysphagia patients with LC-1 or DIG via IAA at the initial operative evaluation.

Development of Continuous Flow Systems to Access Secondary Amines Through Previously Incompatible Biocatalytic Cascades*.

A key aim of biocatalysis is to mimic the ability of eukaryotic cells to carry out multistep cascades in a controlled and selective way. As biocatalytic cascades get more complex, reactions become unattainable under typical batch conditions. Here a number of continuous flow systems were used to overcome batch incompatibility, thus allowing for successful biocatalytic cascades. As proof-of-principle, reactive carbonyl intermediates were generated in situ using alcohol oxidases, then passed directly to a series of packed-bed modules containing different aminating biocatalysts which accordingly produced a range of structurally distinct amines. The method was expanded to employ a batch incompatible sequential amination cascade via an oxidase/transaminase/imine reductase sequence, introducing different amine reagents at each step without cross-reactivity. The combined approaches allowed for the biocatalytic synthesis of the natural product 4O-methylnorbelladine.

Systemic medication requirement in post-surgical patients with eosinophilic chronic rhinosinusitis.

BACKGROUND: Eosinophilic chronic rhinosinusitis (eCRS) is contemporarily managed by surgical creation of a 'neo-sinus' cavity and corticosteroid irrigations. While most patients gain control of their disease with this approach, similar to preventive inhaler therapy in asthma, some patients need systemic therapies. This study aimed to define those patients needing ongoing systemic therapy for eCRS. METHODS: Consecutive adult patients (>18 years) who were seen at a tertiary referral clinic, diagnosed as eCRS and underwent endoscopic sinus surgery were included. Patients were followed up for a minimum of 12 months. All patients had a simple neo- sinus cavity surgically created and used initially a once daily topical corticosteroid irrigation maintenance therapy. Patients who re- quired long term systemic oral corticosteroids and/or biologic therapy were compared to those who remained on topical control. RESULTS: 222 patients with eCRS were assessed (follow-up 2.76 years). Long term systemic therapy was required in 5.4% of pa- tients. Receiver operating curve analysis predicted local treatment failure at an eosinophil count cut-off level 0.455x109/L. Asthma, atopy and aspirin sensitivity also predicted long term systemic therapy. There were no associations with nasal polyposis or revi- sion surgery. Multivariate logistic regression showed elevated blood eosinophil count >0.455 x109/L was 9.27 times more likely to require for systemic medication. CONCLUSION: Pre-operative blood eosinophil count >0.45 x109/L was associated with failure of local therapy following contem- porary management of eCRS. The quantitative value of serum eosinophilia may be a useful predictor of disease progression and those patients in need of systemic therapies, such as biologic agents.

Improvised Field Expedient Method for Renal Replacement Therapy in a Porcine Model of Acute Kidney Injury.

OBJECTIVE: Dialysis patients may not have access to conventional renal replacement therapy (RRT) following disasters. We hypothesized that improvised renal replacement therapy (ImpRRT) would be comparable to continuous renal replacement therapy (CRRT) in a porcine acute kidney injury model. METHODS: Following bilateral nephrectomies and 2 hours of caudal aortic occlusion, 12 pigs were randomized to 4 hours of ImpRRT or CRRT. In the ImpRRT group, blood was circulated through a dialysis filter using a rapid infuser to collect the ultrafiltrate. Improvised replacement fluid, made with stock solutions, was infused pre-pump. In the CRRT group, commercial replacement fluid was used. During RRT, animals received isotonic crystalloids and norepinephrine. RESULTS: There were no differences in serum creatinine, calcium, magnesium, or phosphorus concentrations. While there was a difference between groups in serum potassium concentration over time (P < 0.001), significance was lost in pairwise comparison at specific time points. Replacement fluids or ultrafiltrate flows did not differ between groups. There were no differences in lactate concentration, isotonic crystalloid requirement, or norepinephrine doses. No difference was found in electrolyte concentrations between the commercial and improvised replacement solutions. CONCLUSION: The ImpRRT system achieved similar performance to CRRT and may represent a potential option for temporary RRT following disasters.

Development of Continuous Flow Systems to Access Secondary Amines Through Previously Incompatible Biocatalytic Cascades.

A key aim of biocatalysis is to mimic the ability of eukaryotic cells to carry out multistep cascades in a controlled and selective way. As biocatalytic cascades get more complex, reactions become unattainable under typical batch conditions. Here a number of continuous flow systems were used to overcome batch incompatibility, thus allowing for successful biocatalytic cascades. As proof-of-principle, reactive carbonyl intermediates were generated in situ using alcohol oxidases, then passed directly to a series of packed-bed modules containing different aminating biocatalysts which accordingly produced a range of structurally distinct amines. The method was expanded to employ a batch incompatible sequential amination cascade via an oxidase/transaminase/imine reductase sequence, introducing different amine reagents at each step without cross-reactivity. The combined approaches allowed for the biocatalytic synthesis of the natural product 4O-methylnorbelladine.

Does the pediatric hemodynamic cliff exist in response to hemorrhagic shock?

BACKGROUND: The paradigm that children maintain normal blood pressure during hemorrhagic shock until 30%-45% hemorrhage is widely accepted. There are minimal data supporting when decompensation occurs and how a child's vasculature compensates up to that point. We aimed to observe the arterial response to hemorrhage and when mean arterial pressure (MAP) decreased from baseline in pediatric swine. METHODS: Piglets were hemorrhaged in 20% increments of their total blood volume to 60%. MAP and angiograms of the thoracic aorta (TA) and abdominal arteries were obtained. Percent change in area of the vessels from baseline was calculated. RESULTS: Piglets (n = 8) had a differential vasoconstriction starting at 20% hemorrhage (celiac artery 36.3% [31.4-44.6] vs TA 16.7% [10.7-19.1] p = 0.0012). At 40% hemorrhage, the differential vasoconstriction favored shunting blood away from the abdominal visceral branches to the TA (celiac artery 54.7% [36.9-60.6] vs TA 29.5% [23.9-36.2] p = 0.0056 superior mesenteric artery 46.7% [43.9-68.6] vs TA 29.5% [23.9-36.2] p = 0.0100). This was exacerbated at 60% hemorrhage. MAP decreased from baseline at 20% hemorrhage (66.4 ±â€¯6.0 mmHg vs 41.4 ±â€¯10.4 mmHg, p < 0.0001), and worsened at 40% and 60% hemorrhage. CONCLUSION: In piglets, a differential vasocontriction shunting blood proximally occurred in response to hemorrhage. This did not maintain normal MAP at 20%, 40% or 60% hemorrhage. LEVEL OF EVIDENCE: Level II.

Automated Partial Versus Complete Resuscitative Endovascular Balloon Occlusion of the Aorta for the Management of Hemorrhagic Shock in a Pig Model of Polytrauma: a Randomized Controlled Pilot Study.

INTRODUCTION: Endovascular variable aortic control (EVAC) is an automated partial resuscitative endovascular balloon occlusion of the aorta (REBOA) platform designed to mitigate the deleterious effects of complete REBOA. Long-term experiments are needed to assess potential benefits. The feasibility of a 24-hour experiment in a complex large animal trauma model remains unknown. MATERIALS AND METHODS: Anesthetized swine were subjected to controlled hemorrhage, blunt thoracic trauma, and tibial fractures. Animals were then randomized (N = 3/group) to control (No balloon support), 90 minutes of complete supraceliac REBOA, or 10 minutes of supraceliac REBOA followed by 80 minutes of EVAC. One hundred ten minutes after injury, animals were resuscitated with shed blood, the REBOA catheter was removed. Automated critical care under general anesthesia was maintained for 24 hours. RESULTS: Animals in the control and EVAC groups survived to the end of the experiment. Animals in the REBOA group survived for 120, 130, and 660 minutes, respectively. Animals in the EVAC group displayed similar mean arterial pressure and plasma lactate concentration as the control group by the end of the experiment. Histologic analysis suggested myocardial injury in the REBOA group when compared with controls. CONCLUSIONS: This study demonstrates the feasibility of intermediate-term experiments in a complex swine model of polytrauma with 90 minutes of REBOA. EVAC may be associated with improved survival at 24 hours when compared with complete REBOA. EVAC resulted in normalized physiology after 24 hours, suggesting that prolonged partial occlusion is possible. Longer studies evaluating partial REBOA strategies are needed.

Zone 3 REBOA does not provide hemodynamic benefits during nontraumatic cardiac arrest.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) may be a novel intervention to improve cardiopulmonary resuscitation (CPR) quality during cardiac arrest. Zone 1 supraceliac aortic occlusion improves coronary and cerebral blood flow. It is unknown if Zone 3 occlusion distal to the renal arteries offers a similar physiologic benefit while maintaining blood flow to organs above the point of occlusion. METHODS: Fifteen swine were anesthetized, instrumented, and placed into ventricular fibrillation. Mechanical CPR was immediately initiated. After 5 min of CPR, Zone 1 REBOA, Zone 3 REBOA, or no intervention (control) was initiated. Hemodynamic variables were continuously recorded for 30 min. RESULTS: There were no significant differences between groups before REBOA deployment. Once REBOA was deployed, Zone 1 animals had statistically greater diastolic blood pressure compared to control (median [IQR]: 19.9 mmHg [9.5-20.5] vs 3.9 mmHg [2.4-4.8], p = .006). There were no differences in diastolic blood pressure between Zone 1 and Zone 3 (8.6 mmHg [5.1-13.1], p = .10) or between Zone 3 and control (p = .10). There were no significant differences in systolic blood pressure, cerebral blood flow, or time to return of spontaneous circulation (ROSC) between groups. CONCLUSION: In our swine model of cardiac arrest, Zone 1 REBOA improved diastolic blood pressure when compared to control. Zone 3 does not offer a hemodynamic benefit when compared to no occlusion. Unlike prior studies, immediate use of REBOA after arrest did not result in an increase in ROSC rate, suggesting REBOA may be more beneficial in patients with prolonged no-flow time. INSTITUTIONAL PROTOCOL NUMBER: FDG20180024A.

Esmolol reduces myocardial injury induced by resuscitative endovascular balloon occlusion of the aorta (REBOA) in a porcine model of hemorrhagic shock.

PURPOSE: Resuscitative endovascular balloon occlusion of the aorta (REBOA) causes myocardial injury from increased aortic afterload and supraphysiologic cardiac output. However, pharmacologic methods to attenuate high cardiac output and reduce myocardial injury have not been explored. We hypothesized that the use of esmolol during REBOA would reduce myocardial injury. METHODS: Ten pigs were anesthetized and instrumented. Following 25% total blood volume hemorrhage, animals underwent 45 min of supraceliac (zone 1) REBOA with or without titration of esmolol to maintain heart rate between 80 and 100 beats per minute. Following the REBOA interventions, animals underwent 275 min of standardized critical care. RESULTS: During REBOA, heart rate was significantly lower in the esmolol group compared to control animals (100 [88 - 112] vs 193 [172 - 203] beats/minute, respectively, p < 0.001) and the average mean arterial pressure (MAP) was lower in the esmolol group (88.0 [80.3-94.9] vs 135.1 [131.7-140.4] mmHg, respectively, p = 0.01). During the critical care phase, there were no differences in heart rate or MAP between groups. Animals in the intervention group received 237.9 [218.7-266.5] µg/kg of esmolol. There was a significant increase from baseline in serum troponins for the control group (p = 0.006) and significantly more subendocardial hemorrhage compared to animals treated with esmolol (3 [3 - 3] and 0 [0 - 0], p = 0.009, respectively). CONCLUSION: In our porcine model of hemorrhagic shock, zone 1 REBOA was associated with myocardial injury. Pharmacologic heart rate titration with esmolol during occlusion may mitigate the deleterious effects of REBOA on the heart.

Synthesis of protected 3-aminopiperidine and 3-aminoazepane derivatives using enzyme cascades.

Multi-enzyme cascades utilising variants of galactose oxidase and imine reductase led to the successful conversion of N-Cbz-protected l-ornithinol and l-lysinol to l-3-N-Cbz-aminopiperidine and l-3-N-Cbz-aminoazepane respectively, in up to 54% isolated yield. Streamlining the reactions into one-pot prevented potential racemisation of key labile intermediates and led to products with high enantiopurity.

Reperfusion repercussions: A review of the metabolic derangements following resuscitative endovascular balloon occlusion of the aorta.

BACKGROUND: Current resuscitative endovascular balloon occlusion of the aorta (REBOA) literature focuses on improving outcomes through careful patient selection, diligent catheter placement, and expeditious definitive hemorrhage control. However, the detection and treatment of post-REBOA ischemia-reperfusion injury (IRI) remains an area for potential improvement. Herein, we provide a review of the metabolic derangements that we have encountered while managing post-REBOA IRI in past swine experiments. We also provide data-driven clinical recommendations to facilitate resuscitation post-REBOA deflation that may be translatable to humans. METHODS: We retrospectively reviewed the laboratory data from 25 swine across three varying hemorrhagic shock models that were subjected to complete REBOA of either 45 minutes, 60 minutes, or 90 minutes. In each model the balloon was deflated gradually following definitive hemorrhage control. Animals were then subjected to whole blood transfusion and critical care with frequent electrolyte monitoring and treatment of derangements as necessary. RESULTS: Plasma lactate peaked and pH nadired long after balloon deflation in all swine in the 45-minute, 60-minute, and 90-minute occlusion models (onset of peak lactate, 32.9 ± 6.35 minutes, 38.8 ± 10.55 minutes, and 49.5 ± 6.5 minutes; pH nadir, 4.3 ± 0.72 minutes, 26.9 ± 12.32 minutes, and 42 ± 7.45 minutes after balloon deflation in the 45-, 60-, and 90-minute occlusion models, respectively). All models displayed persistent hypoglycemia for more than an hour following reperfusion (92.1 ± 105.5 minutes, 125 ± 114.9 minutes, and 96 ± 97.8 minutes after balloon deflation in the 45-, 60-, and 90-minute occlusion groups, respectively). Hypocalcemia and hyperkalemia occurred in all three groups, with some animals requiring treatment more than an hour after reperfusion. CONCLUSION: Metabolic derangements resulting from REBOA use are common and may worsen long after reperfusion despite resuscitation. Vigilance is required to detect and proactively manage REBOA-associated IRI. Maintaining a readily available "deflation kit" of pharmacological agents needed to treat common post-REBOA electrolyte abnormalities may facilitate management. LEVEL OF EVIDENCE: Level V.

Reference Intervals for and the Effects of Sample Handling and Sex on Rotational Thromboelastometry in Healthy Adult Pigs.

Accurate assessment of coagulation in porcine studies is essential. We sought to establish normal values for porcine rotational thromboelastometry (ROTEM) according to the American Society for Veterinary Clinical Pathology guidelines and to assess the effects of various preanalytical parameters on those measurements. Healthy Yorkshire-cross pigs (n = 81; 46 males and 35 females) were anesthetized. By using a 18-gauge needle attached to a vacuum phlebotomy tube, blood was acquired from the cranial vena cava. Tubes were filled in the following order: evacuation clot tube, EDTA tube, heparin tube, and 2 citrate tubes. The citrate tubes were randomly assigned to 30 min with or without constant agitation on a rocker. The following parameters were reported according to the manufacturer's recommendations: clotting time, clot formation time, α, (tangent to the clot formation curve when the clot firmness is 20 mm), clot firmness after 10 and 20 min, maximal clot firmness, maximum lysis, and lysis indexes at 30 and 45 min. Reference intervals were reported as mean ± 2 SD (parametric distribution) or 2.5th and 97.5th percentile of the population's results (nonparametric distribution). The effects of sex, sampling order, and agitation on ROTEM results were analyzed through linear regression. Neither sex nor sample agitation influenced any of the ROTEM parameters. Combined reference intervals were established for each ROTEM parameter by pooling data from the nonagitated tubes for both male and female pigs. This study is the first to establish ROTEM reference intervals from a large number of male and female adult Yorkshire-cross pigs and to provide a detailed description of preanalytical sample processing.

Resuscitative endovascular balloon occlusion of the aorta in a pediatric swine model: Is 60 minutes too long?

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is recommended in adults with a noncompressible torso hemorrhage with occlusion times of less than 60 minutes. The tolerable duration in children is unknown. We used a pediatric swine controlled hemorrhage model to evaluate the physiologic effects of 30 minutes and 60 minutes of REBOA. METHODS: Pediatric swine weighing 20 kg to 30 kg underwent a splenectomy and a controlled 60% total blood volume hemorrhage over 30 minutes, followed by either zone 1 REBOA for 30 minutes (30R) or 60 minutes (60R). Swine were then resuscitated with shed blood and received critical care for 240 minutes. RESULTS: During critical care, the 30R group's (n = 3) pH, bicarbonate, base excess, and lactate were no different than baseline, while at the end of critical care, these variables continued to differ from baseline in the 60R group (n = 5) and were worsening (7.4 vs. 7.2, p < 0.001, 30.4 mmol/L vs. 18.4 mmol/L, p < 0.0001, 5.6 mmol/L vs. -8.5 mmol/L, p < 0.0001, 2.4 mmol/L vs. 5.7 mmol/L, p < 0.001, respectively). Compared with baseline, end creatinine and creatinine kinase were elevated in 60R swine (1.0 mg/dL vs. 1.7 mg/dL, p < 0.01 and 335.4 U/L vs. 961.0 U/L, p < 0.001, respectively), but not 30R swine (0.9 mg/dL vs. 1.2 mg/dL, p = 0.06 and 423.7 U/L vs. 769.5 U/L, p = 0.15, respectively). There was no difference in survival time between the 30R and 60R pediatric swine, p = 0.99. CONCLUSION: The physiologic effects of 30 minutes of zone 1 REBOA in pediatric swine mostly resolved during the subsequent 4 hours of critical care, whereas the effects of 60 minutes of REBOA persisted and worsened after 4 hours of critical care. Sixty minutes of zone 1 REBOA may create an irreversible physiologic insult in a pediatric population.