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Item Open Access 2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline for Perioperative Cardiovascular Management for Noncardiac Surgery: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines(Circulation) Thompson, Annemarie; Fleischmann, Kirsten E; Smilowitz, Nathaniel R; de las Fuentes, Lisa; Mukherjee, Debabrata; Aggarwal, Niti R; Ahmad, Faraz S; Allen, Robert B; Altin, S Elissa; Auerbach, Andrew; Berger, Jeffrey S; Chow, Benjamin; Dakik, Habib A; Eisenstein, Eric L; Gerhard-Herman, Marie; Ghadimi, Kamrouz; Kachulis, Bessie; Leclerc, Jacinthe; Lee, Christopher S; Macaulay, Tracy E; Mates, Gail; Merli, Geno J; Parwani, Purvi; Poole, Jeanne E; Rich, Michael W; Ruetzler, Kurt; Stain, Steven C; Sweitzer, BobbieJean; Talbot, Amy W; Vallabhajosyula, Saraschandra; Whittle, John; Williams, Kim AllanAim: The “2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline for Perioperative Cardiovascular Management for Noncardiac Surgery” provides recommendations to guide clinicians in the perioperative cardiovascular evaluation and management of adult patients undergoing noncardiac surgery. Methods: A comprehensive literature search was conducted from August 2022 to March 2023 to identify clinical studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Structure: Recommendations from the “2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery” have been updated with new evidence consolidated to guide clinicians; clinicians should be advised this guideline supersedes the previously published 2014 guideline. In addition, evidence-based management strategies, including pharmacological therapies, perioperative monitoring, and devices, for cardiovascular disease and associated medical conditions, have been developed.Item Open Access 2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline for Perioperative Cardiovascular Management for Noncardiac Surgery: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.(Journal of the American College of Cardiology, 2024-09) Writing Committee Members; Thompson, Annemarie; Fleischmann, Kirsten E; Smilowitz, Nathaniel R; de Las Fuentes, Lisa; Mukherjee, Debabrata; Aggarwal, Niti R; Ahmad, Faraz S; Allen, Robert B; Altin, S Elissa; Auerbach, Andrew; Berger, Jeffrey S; Chow, Benjamin; Dakik, Habib A; Eisenstein, Eric L; Gerhard-Herman, Marie; Ghadimi, Kamrouz; Kachulis, Bessie; Leclerc, Jacinthe; Lee, Christopher S; Macaulay, Tracy E; Mates, Gail; Merli, Geno J; Parwani, Purvi; Poole, Jeanne E; Rich, Michael W; Ruetzler, Kurt; Stain, Steven C; Sweitzer, BobbieJean; Talbot, Amy W; Vallabhajosyula, Saraschandra; Whittle, John; Williams, Kim AllanAim
The "2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline for Perioperative Cardiovascular Management for Noncardiac Surgery" provides recommendations to guide clinicians in the perioperative cardiovascular evaluation and management of adult patients undergoing noncardiac surgery.Methods
A comprehensive literature search was conducted from August 2022 to March 2023 to identify clinical studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.Structure
Recommendations from the "2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery" have been updated with new evidence consolidated to guide clinicians; clinicians should be advised this guideline supersedes the previously published 2014 guideline. In addition, evidence-based management strategies, including pharmacological therapies, perioperative monitoring, and devices, for cardiovascular disease and associated medical conditions, have been developed.Item Open Access 3D TEE-Applications for Daily Practice (canceled)(2020-04-21) Cherry, AnneDiscussion of applications for 3D TEE in the Operating Room.Item Open Access 5-Hydroxymethylfurfural reduces skeletal muscle superoxide production and modifies force production in rats exposed to hypobaric hypoxia.(Physiological reports, 2023-07) Ciarlone, Geoffrey E; Swift, Joshua M; Williams, Brian T; Mahon, Richard T; Roney, Nicholas G; Yu, Tianzheng; Gasier, Heath GDecreased blood-tissue oxygenation at high altitude (HA) increases mitochondrial oxidant production and reduces exercise capacity. 5-Hydroxymethylfurfural (5-HMF) is an antioxidant that increases hemoglobin's binding affinity for oxygen. For these reasons, we hypothesized that 5-HMF would improve muscle performance in rats exposed to a simulated HA of ~5500 m. A secondary objective was to measure mitochondrial activity and dynamic regulation of fission and fusion because they are linked processes impacted by HA. Fisher 344 rats received 5-HMF (40 mg/kg/day) or vehicle during exposure to sea level or HA for 72 h. Right ankle plantarflexor muscle function was measured pre- and post-exposure. Post-exposure measurements included arterial blood gas and complete blood count, flexor digitorum brevis myofiber superoxide production and mitochondrial membrane potential (ΔΨm), and mitochondrial dynamic regulation in the soleus muscle. HA reduced blood oxygenation, increased superoxide levels and lowered ΔΨm, responses that were accompanied by decreased peak isometric torque and force production at frequencies >75 Hz. 5-HMF increased isometric force production and lowered oxidant production at sea level. In HA exposed animals, 5-HMF prevented a decline in isometric force production at 75-125 Hz, prevented an increase in superoxide levels, further decreased ΔΨm, and increased mitochondrial fusion 2 protein expression. These results suggest that 5-HMF may prevent a decrease in hypoxic force production during submaximal isometric contractions by an antioxidant mechanism.Item Open Access A blinded randomized assessment of laser Doppler flowmetry efficacy in standardizing outcome from intraluminal filament MCAO in the rat.(Journal of neuroscience methods, 2015-02) Taninishi, Hideki; Jung, Jin Yong; Izutsu, Miwa; Wang, Zhengfeng; Sheng, Huaxin; Warner, David SBackground
Laser Doppler flowmetry (LDF) is widely used for estimating cerebral blood flow changes during intraluminal middle cerebral artery occlusion (MCAO). No investigation has systematically examined LDF efficacy in standardizing outcome. We examined MCAO histologic and behavioral outcome as a function of LDF measurement.Materials and methods
Rats were subjected to 90min MCAO by 4 surgeons having different levels of MCAO surgical experience. LDF was measured in all rats during ischemia. By random assignment, LDF values were (Assisted) or were not (Blinded) made available to each surgeon during MCAO (n=12-17 per group). Neurologic and histologic outcomes were measured 7 days post-MCAO. A second study examined LDF effects on 1-day post-MCAO outcome.Results
Pooled across surgeons, intra-ischemic %LDF change (P=0.12), neurologic scores (Assisted vs. Blinded=14±6 vs. 13±7, P=0.61, mean±standard deviation) and cerebral infarct volume (162±63mm(3)vs. 143±86mm(3), P=0.24) were not different between groups. Only for one surgeon (novice) did LDF use alter infarct volume (145±28mm(3)vs. 98±61mm(3), P=0.03). LDF use decreased infarct volume coefficient of variation (COV) by 35% (P=0.02), but had no effect on neurologic score COV.Comparison with existing methods
We compared intraluminal MCAO outcome as a function of LDF use.Conclusions
LDF measurement altered neither neurologic nor histologic MCAO outcome. LDF did not decrease neurologic deficit COV, but did decrease infarct volume COV. LDF may allow use of fewer animals if infarct volume is the primary dependent variable, but is unlikely to impact requisite sample sizes if neurologic function is of primary interest.Item Open Access A blood-based biomarker panel to risk-stratify mild traumatic brain injury.(PloS one, 2017-01) Sharma, Richa; Rosenberg, Alexandra; Bennett, Ellen R; Laskowitz, Daniel T; Acheson, Shawn KMild traumatic brain injury (TBI) accounts for the vast majority of the nearly two million brain injuries suffered in the United States each year. Mild TBI is commonly classified as complicated (radiographic evidence of intracranial injury) or uncomplicated (radiographically negative). Such a distinction is important because it helps to determine the need for further neuroimaging, potential admission, or neurosurgical intervention. Unfortunately, imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) are costly and not without some risk. The purpose of this study was to screen 87 serum biomarkers to identify a select panel of biomarkers that would predict the presence of intracranial injury as determined by initial brain CT. Serum was collected from 110 patients who sustained a mild TBI within 24 hours of blood draw. Two models were created. In the broad inclusive model, 72kDa type IV collagenase (MMP-2), C-reactive protein (CRP), creatine kinase B type (CKBB), fatty acid binding protein-heart (hFABP), granulocyte-macrophage colony-stimulating factor (GM-CSF) and malondialdehyde modified low density lipoprotein (MDA-LDL) significantly predicted injury visualized on CT, yielding an overall c-statistic of 0.975 and a negative predictive value (NPV) of 98.6. In the parsimonious model, MMP-2, CRP, and CKBB type significantly predicted injury visualized on CT, yielding an overall c-statistic of 0.964 and a negative predictive value (NPV) of 97.2. These results suggest that a serum based biomarker panel can accurately differentiate patients with complicated mild TBI from those with uncomplicated mild TBI. Such a panel could be useful to guide early triage decisions, including the need for further evaluation or admission, especially in those environments in which resources are limited.Item Open Access A Breaking Bad News Exercise to Assess Student Competence Prior to Graduation(MedEdPORTAL, 2015-02-20) Clay, Alison; Ross, Elizabeth; Knudsen, Nancy; Chudgar, Saumil; Engle, Deborah; Grochowski, ColleenItem Open Access A cross-sectional survey study of United States residency program directors' perceptions of parental leave and pregnancy among anesthesiology trainees.(Canadian journal of anaesthesia = Journal canadien d'anesthesie, 2021-06-22) Sharpe, Emily E; Ku, Cindy; Malinzak, Elizabeth B; Kraus, Molly B; Chandrabose, Rekha; Hartlage, Sarah EH; Hanson, Andrew C; Schulte, Phillip J; Pearson, Amy CSPurpose
Little is known about program directors' knowledge, attitudes, and beliefs regarding parental leave policies in anesthesiology training. This study sought to understand program director perceptions about the effects of pregnancy and parental leave on resident training, skills, and productivity.Methods
An online 43-question survey was developed to evaluate United States anesthesiology program directors' perceptions of parental leave policies. The survey included questions regarding demographics, anesthesiology program characteristics, parental leave policies, call coverage, and the perceived effects of parental leave on resident performance. Data were collected by Qualtrics (Qualtrics, Provo, UT, USA).Results
Fifty-six of 145 (39%) anesthesiology program directors completed the survey. Forty-eight of 54 (89%) program directors had a female resident take maternity leave in the past three years. When asked how parental leave affects residents' futures, 24/50 (48%) program directors felt it delayed board certification and 28/50 (56%) thought it affected fellowship opportunities. Program directors were split on their perceived impact of becoming a parent on a trainee's work. Yet, when compared with male trainees, program directors perceived that becoming a parent negatively affected female trainees' timeliness, technical skills, scholarly activities, procedural volume, and standardized test scores and affected training experience of co-residents. Program directors perceived no difference in impact on female trainees' dedication to patients and clinical performance.Conclusions
Program directors perceived that becoming a parent negatively affects the work performance of female but not male trainees. These negative perceptions could impact evaluations and future plans of female residents.Item Open Access A few of our favorite unconfirmed ideas.(Crit Care, 2015) Marini, John J; Gattinoni, Luciano; Ince, Can; Kozek-Langenecker, Sibylle; Mehta, Ravindra L; Pichard, Claude; Westphal, Martin; Wischmeyer, Paul; Vincent, Jean-LouisMedical practice is rooted in our dependence on the best available evidence from incremental scientific experimentation and rigorous clinical trials. Progress toward determining the true worth of ongoing practice or suggested innovations can be glacially slow when we insist on following the stepwise scientific pathway, and a prevailing but imperfect paradigm often proves difficult to challenge. Yet most experienced clinicians and clinical scientists harbor strong thoughts about how care could or should be improved, even if the existing evidence base is thin or lacking. One of our Future of Critical Care Medicine conference sessions encouraged sharing of novel ideas, each presented with what the speaker considers a defensible rationale. Our intent was to stimulate insightful thinking and free interchange, and perhaps to point in new directions toward lines of innovative theory and improved care of the critically ill. In what follows, a brief background outlines the rationale for each novel and deliberately provocative unconfirmed idea endorsed by the presenter.Item Open Access A genetic polymorphism that is associated with mitochondrial energy metabolism increases risk of fibromyalgia.(Pain, 2020-07-10) van Tilburg, Miranda AL; Parisien, Marc; Boles, Richard G; Drury, Gillian L; Smith-Voudouris, Julian; Verma, Vivek; Khoury, Samar; Chabot-Doré, Anne-Julie; Nackley, Andrea G; Smith, Shad B; Whitehead, William E; Zolnoun, Denniz A; Slade, Gary D; Tchivileva, Inna; Maixner, William; Diatchenko, LudaAlterations in cellular energy metabolism have been implicated in chronic pain, suggesting a role for mitochondrial DNA. Previous studies reported associations of a limited number of mitochondrial DNA polymorphisms with specific pain conditions. In this study, we examined the full mitochondrial genomes of people with a variety of chronic pain conditions. A discovery cohort consisting of 609 participants either with or without a complex persistent pain conditions (CPPCs) was examined. Mitochondrial DNA was subjected to deep sequencing for identification of rare mutations, common variants, haplogroups, and heteroplasmy associated with 5 CPPCs: episodic migraine, irritable bowel syndrome, fibromyalgia, vulvar vestibulitis, or temporomandibular disorders. The strongest association found was the presence of the C allele at the single nucleotide polymorphism m.2352T>C (rs28358579) that significantly increased the risk for fibromyalgia (odds ratio [OR] = 4.6, P = 4.3 × 10). This relationship was even stronger in women (OR = 5.1, P = 2.8 × 10), and m.2352T>C was associated with all other CPPCs in a consistent risk-increasing fashion. This finding was replicated in another cohort (OR = 4.3, P = 2.6 × 10) of the Orofacial Pain: Prospective Evaluation and Risk Assessment study consisting of 1754 female participants. To gain insight into the cellular consequences of the associated genetic variability, we conducted an assay testing metabolic reprogramming in human cell lines with defined genotypes. The minor allele C was associated with decreased mitochondrial membrane potential under conditions where oxidative phosphorylation is required, indicating a role of oxidative phosphorylation in pathophysiology of chronic pain. Our results suggest that cellular energy metabolism, modulated by m.2352T>C, contributes to fibromyalgia and possibly other chronic pain conditions.Item Open Access A genome-wide association study of variants associated with acquisition of Staphylococcus aureus bacteremia in a healthcare setting.(BMC Infect Dis, 2014-02-13) Nelson, Charlotte L; Pelak, Kimberly; Podgoreanu, Mihai V; Ahn, Sun Hee; Scott, William K; Allen, Andrew S; Cowell, Lindsay G; Rude, Thomas H; Zhang, Yurong; Tong, Amy; Ruffin, Felicia; Sharma-Kuinkel, Batu K; Fowler, Vance GBACKGROUND: Humans vary in their susceptibility to acquiring Staphylococcus aureus infection, and research suggests that there is a genetic basis for this variability. Several recent genome-wide association studies (GWAS) have identified variants that may affect susceptibility to infectious diseases, demonstrating the potential value of GWAS in this arena. METHODS: We conducted a GWAS to identify common variants associated with acquisition of S. aureus bacteremia (SAB) resulting from healthcare contact. We performed a logistic regression analysis to compare patients with healthcare contact who developed SAB (361 cases) to patients with healthcare contact in the same hospital who did not develop SAB (699 controls), testing 542,410 SNPs and adjusting for age (by decade), sex, and 6 significant principal components from our EIGENSTRAT analysis. Additionally, we evaluated the joint effect of the host and pathogen genomes in association with severity of SAB infection via logistic regression, including an interaction of host SNP with bacterial genotype, and adjusting for age (by decade), sex, the 6 significant principal components, and dialysis status. Bonferroni corrections were applied in both analyses to control for multiple comparisons. RESULTS: Ours is the first study that has attempted to evaluate the entire human genome for variants potentially involved in the acquisition or severity of SAB. Although this study identified no common variant of large effect size to have genome-wide significance for association with either the risk of acquiring SAB or severity of SAB, the variant (rs2043436) most significantly associated with severity of infection is located in a biologically plausible candidate gene (CDON, a member of the immunoglobulin family) and may warrant further study. CONCLUSIONS: The genetic architecture underlying SAB is likely to be complex. Future investigations using larger samples, narrowed phenotypes, and advances in both genotyping and analytical methodologies will be important tools for identifying causative variants for this common and serious cause of healthcare-associated infection.Item Open Access A nationwide survey of intravenous antimicrobial use in intensive care units in Japan.(International journal of antimicrobial agents, 2018-04) Ohnuma, Tetsu; Hayashi, Yoshiro; Yamashita, Kazuto; Marquess, John; Lefor, Alan Kawarai; Sanui, Masamitsu; Japanese Survey of AntimiCRobial Use in ICU PatienTs (JSCRIPT) investigatorsAlthough most patients in the intensive care unit (ICU) receive antibiotics, little is known about patterns of antibiotic use in ICUs in Japan. The objective of this study was to evaluate the pattern of antibiotic use in ICUs. A nationwide one-day cross-sectional surveillance of antibiotic use in the ICU was conducted three times between January 2011 and December 2011. All patients aged at least16 years were included. Data from 52 ICUs and 1148 patients were reviewed. There were 1028 prescriptions for intravenous antibiotics. Of 1148 patients, 834 (73%) received at least one intravenous antibiotic, and 575 had at least one known site of infection. Respiratory and intra-abdominal infections were the two most common types. Of 1028 prescriptions, 331 (34%) were for surgical or medical prophylaxis. Excluding prophylaxis, carbapenems were the most commonly prescribed agent. Infectious disease consultations, pre- and post-prescription antimicrobial stewardship, and ICU-dedicated antibiograms were available in 44%, 52%, 77%, and 21% of the ICUs, respectively. In logistic regression analysis adjusting for patient characteristics, treatment in a university hospital (adjusted odds ratio, 1.72; 95% CI, 1.05-2.84; P = 0.033) and an open ICU (adjusted odds ratio, 2.30; 95% CI, 1.02-5.17; P = 0.044) were significantly associated with greater likelihood of carbapenem use. An increase in the number of closed ICUs and more intensive care specialists may reduce carbapenem use in Japanese ICUs. Large-scale epidemiological studies of antimicrobial resistance in the ICU are needed.Item Open Access A new SOD mimic, Mn(III) ortho N-butoxyethylpyridylporphyrin, combines superb potency and lipophilicity with low toxicity.(Free radical biology & medicine, 2012-05) Rajic, Zrinka; Tovmasyan, Artak; Spasojevic, Ivan; Sheng, Huaxin; Lu, Miaomiao; Li, Alice M; Gralla, Edith B; Warner, David S; Benov, Ludmil; Batinic-Haberle, InesThe Mn porphyrins of k(cat)(O(2)(.-)) as high as that of a superoxide dismutase enzyme and of optimized lipophilicity have already been synthesized. Their exceptional in vivo potency is at least in part due to their ability to mimic the site and location of mitochondrial superoxide dismutase, MnSOD. MnTnHex-2-PyP(5+) is the most studied among lipophilic Mn porphyrins. It is of remarkable efficacy in animal models of oxidative stress injuries and particularly in central nervous system diseases. However, when used at high single and multiple doses it becomes toxic. The toxicity of MnTnHex-2-PyP(5+) has been in part attributed to its micellar properties, i.e., the presence of polar cationic nitrogens and hydrophobic alkyl chains. The replacement of a CH(2) group by an oxygen atom in each of the four alkyl chains was meant to disrupt the porphyrin micellar character. When such modification occurs at the end of long alkyl chains, the oxygens become heavily solvated, which leads to a significant drop in the lipophilicity of porphyrin. However, when the oxygen atoms are buried deeper within the long heptyl chains, their excessive solvation is precluded and the lipophilicity preserved. The presence of oxygens and the high lipophilicity bestow the exceptional chemical and physical properties to Mn(III) meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin, MnTnBuOE-2-PyP(5+). The high SOD-like activity is preserved and even enhanced: log k(cat)(O(2)(.-))=7.83 vs 7.48 and 7.65 for MnTnHex-2-PyP(5+) and MnTnHep-2-PyP(5+), respectively. MnTnBuOE-2-PyP(5+) was tested in an O(2)(.-) -specific in vivo assay, aerobic growth of SOD-deficient yeast, Saccharomyces cerevisiae, where it was fully protective in the range of 5-30 μM. MnTnHep-2-PyP(5+) was already toxic at 5 μM, and MnTnHex-2-PyP(5+) became toxic at 30 μM. In a mouse toxicity study, MnTnBuOE-2-PyP(5+) was several-fold less toxic than either MnTnHex-2-PyP(5+) or MnTnHep-2-PyP(5+).Item Open Access A prospective comparison of a noninvasive cardiac output monitor versus esophageal doppler monitor for goal-directed fluid therapy in colorectal surgery patients(Anesthesia and Analgesia, 2014-01-01) Waldron, Nathan H; Miller, Timothy E; Thacker, Julie K; Manchester, Amy K; White, William D; Nardiello, John; Elgasim, Magdi A; Moon, Richard E; Gan, Tong JCopyright © 2014 International Anesthesia Research Society.BACKGROUND: Goal-directed fluid therapy (GDFT) is associated with improved outcomes after surgery. The esophageal Doppler monitor (EDM) is widely used, but has several limitations. The NICOM, a completely noninvasive cardiac output monitor (Cheetah Medical), may be appropriate for guiding GDFT. No prospective studies have compared the NICOM and the EDM. We hypothesized that the NICOM is not significantly different from the EDM for monitoring during GDFT. METHODS: One hundred adult patients undergoing elective colorectal surgery participated in this study. Patients in phase I (n = 50) had intraoperative GDFT guided by the EDM while the NICOM was connected, and patients in phase II (n = 50) had intraoperative GDFT guided by the NICOM while the EDM was connected. Each patient's stroke volume was optimized using 250- mL colloid boluses. Agreement between the monitors was assessed, and patient outcomes (postoperative pain, nausea, and return of bowel function), complications (renal, pulmonary, infectious, and wound complications), and length of hospital stay (LOS) were compared. RESULTS: Using a 10% increase in stroke volume after fluid challenge, agreement between monitors was 60% at 5 minutes, 61% at 10 minutes, and 66% at 15 minutes, with no significant systematic disagreement (McNemar P > 0.05) at any time point. The EDM had significantly more missing data than the NICOM. No clinically significant differences were found in total LOS or other outcomes. The mean LOS was 6.56 ± 4.32 days in phase I and 6.07 ± 2.85 days in phase II, and 95% confidence limits for the difference were -0.96 to +1.95 days (P = 0.5016). CONCLUSIONS: The NICOM performs similarly to the EDM in guiding GDFT, with no clinically significant differences in outcomes, and offers increased ease of use as well as fewer missing data points. The NICOM may be a viable alternative monitor to guide GDFT.Item Open Access A randomized trial of supplemental parenteral nutrition in underweight and overweight critically ill patients: the TOP-UP pilot trial.(Crit Care, 2017-06-09) Wischmeyer, Paul E; Hasselmann, Michel; Kummerlen, Christine; Kozar, Rosemary; Kutsogiannis, Demetrios James; Karvellas, Constantine J; Besecker, Beth; Evans, David K; Preiser, Jean-Charles; Gramlich, Leah; Jeejeebhoy, Khursheed; Dhaliwal, Rupinder; Jiang, Xuran; Day, Andrew G; Heyland, Daren KBACKGROUND: Nutrition guidelines recommendations differ on the use of parenteral nutrition (PN), and existing clinical trial data are inconclusive. Our recent observational data show that amounts of energy/protein received early in the intensive care unit (ICU) affect patient mortality, particularly for inadequate nutrition intake in patients with body mass indices (BMIs) of <25 or >35. Thus, we hypothesized increased nutrition delivery via supplemental PN (SPN) + enteral nutrition (EN) to underweight and obese ICU patients would improve 60-day survival and quality of life (QoL) versus usual care (EN alone). METHODS: In this multicenter, randomized, controlled pilot trial completed in 11 centers across four countries, adult ICU patients with acute respiratory failure expected to require mechanical ventilation for >72 hours and with a BMI of <25 or ≥35 were randomized to receive EN alone or SPN + EN to reach 100% of their prescribed nutrition goal for 7 days after randomization. The primary aim of this pilot trial was to achieve a 30% improvement in nutrition delivery. RESULTS: In total, 125 patients were enrolled. Over the first 7 post-randomization ICU days, patients in the SPN + EN arm had a 26% increase in delivered calories and protein, whereas patients in the EN-alone arm had a 22% increase (both p < 0.001). Surgical ICU patients received poorer EN nutrition delivery and had a significantly greater increase in calorie and protein delivery when receiving SPN versus medical ICU patients. SPN proved feasible to deliver with our prescribed protocol. In this pilot trial, no significant outcome differences were observed between groups, including no difference in infection risk. Potential, although statistically insignificant, trends of reduced hospital mortality and improved discharge functional outcomes and QoL outcomes in the SPN + EN group versus the EN-alone group were observed. CONCLUSIONS: Provision of SPN + EN significantly increased calorie/protein delivery over the first week of ICU residence versus EN alone. This was achieved with no increased infection risk. Given feasibility and consistent encouraging trends in hospital mortality, QoL, and functional endpoints, a full-scale trial of SPN powered to assess these clinical outcome endpoints in high-nutritional-risk ICU patients is indicated-potentially focusing on the more poorly EN-fed surgical ICU setting. TRIAL REGISTRATION: NCT01206166.Item Open Access A Randomized, Placebo-Controlled, Phase II Trial of Intravenous Allogeneic Non-HLA Matched, Unrelated Donor, Cord Blood Infusion for Ischemic Stroke.(Stem cells translational medicine, 2024-02) Laskowitz, Daniel T; Troy, Jesse; Poehlein, Emily; Bennett, Ellen R; Shpall, Elizabeth J; Wingard, John R; Freed, Brian; Belagaje, Samir R; Khanna, Anna; Jones, William; Volpi, John J; Marrotte, Eric; Kurtzberg, JoanneStroke remains a leading cause of death and disability in the US, and time-limited reperfusion strategies remain the only approved treatment options. To address this unmet clinical need, we conducted a phase II randomized clinical trial to determine whether intravenous infusion of banked, non-HLA matched unrelated donor umbilical cord blood (UCB) improved functional outcome after stroke. Participants were randomized 2:1 to UCB or placebo within strata of National Institutes of Health Stroke Scale Score (NIHSS) and study center. Study product was infused 3-10 days following index stroke. The primary endpoint was change in modified Rankin Scale (mRS) from baseline to day 90. Key secondary outcomes included functional independence, NIHSS, the Barthel Index, and assessment of adverse events. The trial was terminated early due to slow accrual and logistical concerns associated with the COVID-19 pandemic, and a total of 73 of a planned 100 participants were included in primary analyses. The median (range) of the change in mRS was 1 point (-2, 3) in UCB and 1 point (-1,4) in Placebo (P = 0.72). A shift analysis comparing the mRS at day 90 utilizing proportional odds modeling showed a common odds ratio of 0.9 (95% CI: 0.4, 2.3) after adjustment for baseline NIHSS and randomization strata. The distribution of adverse events was similar between arms. Although this study did not suggest any safety concerns related to UCB in ischemic stroke, we did not show a clinical benefit in the reduced sample size evaluated.Item Open Access A robotics platform for automated batch fabrication of high density, microfluidics-based DNA microarrays, with applications to single cell, multiplex assays of secreted proteins.(The Review of scientific instruments, 2011-09) Ahmad, Habib; Sutherland, Alex; Shin, Young Shik; Hwang, Kiwook; Qin, Lidong; Krom, Russell-John; Heath, James RMicrofluidics flow-patterning has been utilized for the construction of chip-scale miniaturized DNA and protein barcode arrays. Such arrays have been used for specific clinical and fundamental investigations in which many proteins are assayed from single cells or other small sample sizes. However, flow-patterned arrays are hand-prepared, and so are impractical for broad applications. We describe an integrated robotics/microfluidics platform for the automated preparation of such arrays, and we apply it to the batch fabrication of up to eighteen chips of flow-patterned DNA barcodes. The resulting substrates are comparable in quality with hand-made arrays and exhibit excellent substrate-to-substrate consistency. We demonstrate the utility and reproducibility of robotics-patterned barcodes by utilizing two flow-patterned chips for highly parallel assays of a panel of secreted proteins from single macrophage cells.Item Open Access A Study of Practice Behavior for Endotracheal Intubation Site for Children With Congenital Heart Disease Undergoing Surgery: Impact of Endotracheal Intubation Site on Perioperative Outcomes-An Analysis of the Society of Thoracic Surgeons Congenital Cardiac Anesthesia Society Database.(Anesthesia and analgesia, 2018-09-05) Greene, Nathaniel H; Jooste, Edmund H; Thibault, Dylan P; Wallace, Amelia S; Wang, Alice; Vener, David F; Matsouaka, Roland A; Jacobs, Marshall L; Jacobs, Jeffrey P; Hill, Kevin D; Ames, Warwick AIn adults undergoing cardiopulmonary bypass surgery, oral intubation is typically preferred over nasal intubation due to reduced risk of sinusitis and infection. In children, nasal intubation is more common and sometimes preferred due to perceived benefits of less postoperative sedation and a lower risk for accidental extubation. This study sought to describe the practice of nasal intubation in the pediatric population undergoing cardiopulmonary bypass surgery and assess the risks/benefits of a nasal route against an oral one.Patients <18 years of age in the Society of Thoracic Surgeons Congenital Heart Surgery Database between January 2010 and December 2015 were included. Patients with a preoperative endotracheal tube, tracheostomy, or known airway anomalies were excluded. Multivariable modeling was used to assess the association between route of tracheal intubation and a composite measure of infection risk (wound infection, mediastinitis, septicemia, pneumonia, and endocarditis). Covariates were included to adjust for important patient characteristics (eg, weight, age, comorbidities), case complexity, and center effects. Secondary outcomes included length of intubation, hospital length of stay, and airway complications including accidental extubations. We also performed a subanalysis in children <12 months of age in high-volume centers (>100 cases/y) examining how infection risk may change with age at the time of surgery.Nasal intubation was used in 41% of operations in neonates, 38% in infants, 15% in school-aged children, and 2% in adolescents. Nasal intubation appeared protective for accidental extubation only in neonates (P = .02). Multivariable analysis in infants and neonates showed that the nasal route of intubation was not associated with the infection composite (relative risk [RR], 0.84; 95% CI, 0.59-1.18) or a shorter length of stay (RR, 0.992; 95% CI, 0.947-1.039), but was associated with a shorter intubation length (RR, 0.929; 95% CI, 0.869-0.992). Restricting to high-volume centers showed a significant interaction between age and intubation route with a risk change for infection occurring between approximately 6-12 months of age (P = .003).While older children undergoing nasal intubation trend similar to the adult population with an increased risk of infection, nasal intubation in neonates and infants does not appear to carry a similar risk. Nasal intubation in neonates and infants may also be associated with a shorter intubation length but not a shorter length of stay. Prospective studies are required to better understand these complex associations.Item Open Access A Systematic Approach to Perioperative Smoking Cessation(Techniques in Orthopaedics, 2020-01-01) Davis, JM; Thomas, LC; Dirkes, JEH; Aronson, S© 2020 Wolters Kluwer Health, Inc. All rights reserved. Background:There is compelling evidence that smoking leads to poor postoperative outcomes including increased incidence of wound infection, respiratory infection, sepsis, cardiac arrest, and mortality. There is also compelling evidence that smoking cessation before surgery leads to improved outcomes. A recent meta-analysis found that brief smoking interventions may be insufficient to change postoperative outcomes. However, more intensive evidence-based smoking cessation interventions do improve postoperative outcomes and lead to long-term smoking abstinence. From a healthcare perspective, this raises a question of how to best provide effective perioperative smoking cessation treatment to a population.Methods:Duke University Health System recently developed a systematic approach to perioperative smoking cessation. In this report, we outline evidence-based principles for perioperative smoking cessation and describe initial results from a perioperative smoking cessation program.Results:In the first 100 days of the Duke Perioperative Smoking Cessation Program, we received 420 referrals. Participants had a mean pack-year history of 50.3 (packs/day×years smoking; SD 32.5), a mean Fagerström Test for Nicotine Dependence score of 4.5 (SD 2.5), and a mean expired breath carbon monoxide of 11.8 (SD 7.5) parts per million. Mean days from initial perioperative smoking cessation visit to surgery was 21.4 (SD 22.3).Discussion:This model of perioperative smoking cessation is in the early stages of development; however, evidence-based perioperative smoking cessation services can be effective across a health system.Item Open Access A systematic review and consensus definitions for standardised end-points in perioperative medicine: pulmonary complications.(British journal of anaesthesia, 2018-05) Abbott, TEF; Fowler, AJ; Pelosi, P; Gama de Abreu, M; Møller, AM; Canet, J; Creagh-Brown, B; Mythen, M; Gin, T; Lalu, MM; Futier, E; Grocott, MP; Schultz, MJ; Pearse, RM; StEP-COMPAC GroupThere is a need for robust, clearly defined, patient-relevant outcome measures for use in randomised trials in perioperative medicine. Our objective was to establish standard outcome measures for postoperative pulmonary complications research.A systematic literature search was conducted using MEDLINE, Web of Science, SciELO, and the Korean Journal Database. Definitions were extracted from included manuscripts. We then conducted a three-stage Delphi consensus process to select the optimal outcome measures in terms of methodological quality and overall suitability for perioperative trials.From 2358 records, the full texts of 81 manuscripts were retrieved, of which 45 met the inclusion criteria. We identified three main categories of outcome measure specific to perioperative pulmonary outcomes: (i) composite outcome measures of multiple pulmonary outcomes (27 definitions); (ii) pneumonia (12 definitions); and (iii) respiratory failure (six definitions). These were rated by the group according to suitability for routine use. The majority of definitions were given a low score, and many were imprecise, difficult to apply consistently, or both, in large patient populations. A small number of highly rated definitions were identified as appropriate for widespread use. The group then recommended four outcome measures for future use, including one new definition.A large number of postoperative pulmonary outcome measures have been used, but most are poorly defined. Our four recommended outcome measures include a new definition of postoperative pulmonary complications, incorporating an assessment of severity. These definitions will meet the needs of most clinical effectiveness trials of treatments to improve postoperative pulmonary outcomes.