Cardiothoracic operating room blood gas workflow performance improvement initiative.

OBJECTIVES: To evaluate the current workflow of blood gas ordering and testing in a cardiothoracic operating room to identify opportunities to streamline the process, using performance improvement methodologies. METHODS: Issues with specimen relabeling were identified that lead to delayed results and potential patient safety concerns. Blood gas specimen relabeling was evaluated for operating room cases from August 2018 to December 2022. An OpTime Epic Sidebar button for arterial blood gas and venous blood gas orders was created in January 2019 to streamline the ordering process so that laboratory barcode labels were then printed in the operating room and attached to the specimen, eliminating the need for relabeling by the technologists. RESULTS: This Epic Sidebar intervention led to a drastic improvement of appropriate labeling, which has been sustained. From March 2019 to January 2023, with our new workflow, over 95% of blood gas specimens arrived barcode labeled compared to less than 1% in the preintervention era. CONCLUSIONS: A multidisciplinary team with key stakeholders is important to address complex care issues. Performance improvement methodology is critical to develop interventions that hardwire the process. This intervention led to a sustained reduction in secondary relabeling of patient samples and improved timeliness of reporting of blood gas results.

Cessation of grazing causes biodiversity loss and homogenization of soil food webs.

There is widespread concern that cessation of grazing in historically grazed ecosystems is causing biotic homogenization and biodiversity loss. We used 12 montane grassland sites along an 800 km north-south gradient across the UK, to test whether cessation of grazing affects local α- and ß-diversity of below-ground food webs. We show cessation of grazing leads to strongly decreased α-diversity of most groups of soil microbes and fauna, particularly of relatively rare taxa. By contrast, the ß-diversity varied between groups of soil organisms. While most soil microbial communities exhibited increased homogenization after cessation of grazing, we observed decreased homogenization for soil fauna after cessation of grazing. Overall, our results indicate that exclusion of domesticated herbivores from historically grazed montane grasslands has far-ranging negative consequences for diversity of below-ground food webs. This underscores the importance of grazers for maintaining the diversity of below-ground communities, which play a central role in ecosystem functioning.

Methemoglobin as a marker of acute anemic stress in cardiac surgery.

Biological evidence supports plasma methemoglobin as a biomarker for anemia-induced tissue hypoxia. In this translational planned substudy of the multinational randomized controlled transfusion thresholds in cardiac surgery (TRICS-III) trial, which included adults undergoing cardiac surgery requiring cardiopulmonary bypass with a moderate-to-high risk of death, we investigated the relationship between perioperative hemoglobin concentration (Hb) and methemoglobin; and evaluated its association with postoperative outcomes. The primary endpoint was a composite of death, myocardial infarction, stroke, and severe acute kidney injury at 28 days. We observe weak non-linear associations between decreasing Hb and increasing methemoglobin, which were strongest in magnitude at the post-surgical time point. Increased levels of post-surgical methemoglobin were associated with a trend toward an elevated risk for stroke and exploratory neurological outcomes. Our generalizable study demonstrates post-surgical methemoglobin may be a marker of anemia-induced organ injury/dysfunction, and may have utility for guiding personalized approaches to anemia management. Clinicaltrials.gov registration NCT02042898.

The Impact of the COVID-19 Surge Response on Motivation Among Anesthesiology Residents and Fellows: A discussion of findings from semi-structured interviews at Montefiore Medical Center and educational takeaways.

Background: The American Board of Medical Specialties definition of medical professionalism cites the need to acquire, maintain, and advance a value system serving the patients' and public's interests above self-interests.4 Medical professionalism is a one of the core physician competencies assessed by both the ACGME training program evaluation and the ABA certification process. However, a growing concern for the decline of professionalism and altruism in medicine resulted in increased publications on the matter, citing various potential sources for the issue. Methods: All residents and fellows (Focus Group 1) of the Anesthesiology Department of Montefiore Medical Center in Bronx, NY were invited to participate in a semi-structured interview via Zoom, held on two separate dates. A separate invitation was sent to the faculty of the department (Focus Group 2), held on one date. During the interview, guiding questions were provided by the 4 interviews to facilitate discussion. The interviewers, all members of the anesthesia faculty, took notes as the interviews progressed. The notes were reviewed for common themes as well as supporting and contradicting quotations. Results: A total of 23 residents and fellows and a total of 25 faculty members within the Anesthesiology department at Montefiore Medical Center were interviewed. Amongst the findings, common discussions concerned motivating and demotivating factors contributing to the professionalism and altruism exhibited by the residents and fellows when caring for critical COVID-19 patients during the height of the pandemic. It was widely regarded that patient improvement, community and team support, as well as intrinsic desire to help greatly motivated the team while continuous patient deterioration, uncertainty in staffing and treatment, and concerns for personal and family safety were sources of discouragement. Overall, faculty perceived an increased demonstration of altruism amongst residents and fellows. The statements made by the residents and fellows during their interviews supported this observation. Conclusions: The actions of the Montefiore Anesthesiology residents and fellows demonstrated that altruism and professionalism were readily available amongst physicians. Increased levels of empathy and responsibility contributed to a demonstration of professionalism that challenges previous views of a perceived decline of these attributes in the medical field. The findings of this study stress the importance of creating a curriculum and exercise that stress empathy-based care and altruism in order to improve resident satisfaction and decrease feelings of burnout. Additionally, curriculum additions to facilitate professionalism are proposed.

Loss of Independent Living in Patients Undergoing Transcatheter or Surgical Aortic Valve Replacement: A Retrospective Cohort Study.

BACKGROUND: The recommendation for transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) in patients 65 to 80 years of age is equivocal, leaving patients with a difficult decision. We evaluated whether TAVR compared to SAVR is associated with reduced odds for loss of independent living in patients ≤65, 66 to 79, and ≥80 years of age. Further, we explored mechanisms of the association of TAVR and adverse discharge. METHODS: Adult patients undergoing TAVR or SAVR within a large academic medical system who lived independently before the procedure were included. A multivariable logistic regression model, adjusting for a priori defined confounders including patient demographics, preoperative comorbidities, and a risk score for adverse discharge after cardiac surgery, was used to assess the primary association. We tested the interaction of patient age with the association between aortic valve replacement (AVR) procedure and loss of independent living. We further assessed whether the primary association was mediated (ie, percentage of the association that can be attributed to the mediator) by the procedural duration as prespecified mediator. RESULTS: A total of 1751 patients (age median [quartiles; min-max], 76 [67, 84; 23-100]; sex, 56% female) were included. A total of 27% (222/812) of these patients undergoing SAVR and 20% (188/939) undergoing TAVR lost the ability to live independently. In our cohort, TAVR was associated with reduced odds for loss of independent living compared to SAVR (adjusted odds ratio [OR adj ] 0.19 [95% confidence interval {CI}, 0.14-0.26]; P < .001). This association was attenuated in patients ≤65 years of age (OR adj 0.63 [0.26-1.56]; P = .32) and between 66 and 79 years of age (OR adj 0.23 [0.15-0.35]; P < .001), and magnified in patients ≥80 years of age (OR adj 0.16 [0.10-0.25]; P < .001; P -for-interaction = .004). Among those >65 years of age, a shorter procedural duration mediated 50% (95% CI, 28-76; P < .001) of the beneficial association of TAVR and independent living. CONCLUSIONS: Patients >65 years of age undergoing TAVR compared to SAVR had reduced odds for loss of independent living. This association was partly mediated by shorter procedural duration. No association between AVR approach and the primary end point was found in patients ≤65 years of age.

A prospective observational study evaluating the use of remote patient monitoring in ED discharged COVID-19 patients in NYC.

OBJECTIVES: We investigated whether continuous remote patient monitoring (RPM) could significantly reduce return Emergency Department (ED) revisits among coronavirus disease 2019 (COVID-19) patients discharged from the emergency Department. MATERIALS AND METHODS: A prospective observational study was conducted from a total of 2833 COVID-19 diagnosed patients who presented to the Montefiore Medical Center ED between September 2020-March 2021. Study patients were remotely monitored through a digital platform that was supervised 24/7 by licensed healthcare professionals. Age and time-period matched controls were randomly sampled through retrospective review. The primary outcome was ED revisit rates among the two groups. RESULTS: In our study, 150 patients enrolled in the RPM program and 150 controls were sampled for a total of 300 patients. Overall, 59.1% of the patients identified as Hispanic/Latino. The RPM group had higher body mass index (BMI) (29 (25-35) vs. 27 (25-31) p-value 0.020) and rates of hypertension (50.7% (76) vs. 35.8% (54) p-value 0.009). There were no statistically significant differences in rates of ED revisit between the RPM group (8% (12)) and control group (9.3% (14)) (OR: 0.863; 95% CI:0.413-1. 803; p- 0.695). DISCUSSION AND CONCLUSION: Our study explored the impact of continuous monitoring versus intermittent monitoring for reducing ED revisits in a largely underrepresented population of the Bronx. Our study demonstrated that continuous remote patient monitoring showed no significant difference in preventing ED revisits compared to non-standardized intermittent monitoring. However, potential other acute care settings where RPM may be useful for identifying high-risk patients for early interventions warrant further study.

Nitrogen and phosphorus fertilization consistently favor pathogenic over mutualistic fungi in grassland soils.

Ecosystems across the globe receive elevated inputs of nutrients, but the consequences of this for soil fungal guilds that mediate key ecosystem functions remain unclear. We find that nitrogen and phosphorus addition to 25 grasslands distributed across four continents promotes the relative abundance of fungal pathogens, suppresses mutualists, but does not affect saprotrophs. Structural equation models suggest that responses are often indirect and primarily mediated by nutrient-induced shifts in plant communities. Nutrient addition also reduces co-occurrences within and among fungal guilds, which could have important consequences for belowground interactions. Focusing only on plots that received no nutrient addition, soil properties influence pathogen abundance globally, whereas plant community characteristics influence mutualists, and climate influence saprotrophs. We show consistent, guild-level responses that enhance our ability to predict shifts in soil function related to anthropogenic eutrophication, which can have longer-term consequences for plant communities.

On-admission anemia predicts mortality in COVID-19 patients: A single center, retrospective cohort study.

OBJECTIVES: We investigated the impact of anemia based on admission hemoglobin (Hb) level as a prognostic risk factor for severe outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS: A single-center, retrospective cohort study was conducted from a random sample of 733 adult patients (age ≥ 18 years) obtained from a total of 4356 laboratory confirmed SARS-CoV-2 cases who presented to the Emergency Department of Montefiore Medical Center between March-June 2020. The primary outcome was a composite endpoint of in-hospital severe outcomes of COVID-19. A secondary outcome was in-hospital all-cause mortality. RESULTS: Among the 733 patients included in our final analysis, 438 patients (59.8%) presented with anemia. 105 patients (14.3%) had mild, and 333 patients (45.5%) had moderate-severe anemia. Overall, 437 patients (59.6%) had a composite endpoint of severe outcomes. On-admission anemia was an independent risk factor for all-cause mortality, (Odds Ratio 1.52, 95% CI [1.01-2.30], p = 0.046) but not for composite severe outcomes. However, moderate-severe anemia (Hb < 11 g/dL) on admission was independently associated with both severe outcomes (OR1.53, 95% CI [1.05-2.23], p = 0.028) and mortality (OR 1.67, 95% CI [1.09-2.56], p = 0.019) during hospitalization. CONCLUSION: Anemia on admission was independently associated with increased odds of all-cause mortality in patients hospitalized with COVID-19. Furthermore, moderate-severe anemia (Hb <11 g/dL) was an independent risk factor for severe COVID-19 outcomes. Moving forward, COVID-19 patient management and risk stratification may benefit from addressing anemia on admission.

How Oncologists Perceive the Availability and Quality of Information Generated From Patient-Reported Outcomes (PROs).

BACKGROUND: Despite increased incorporation of patient-reported outcome (PRO) measures into clinical trials, information generated from PROs remains largely absent from drug labeling and electronic health records, giving rise to concerns that such information is not adequately informing clinical practice. OBJECTIVE: To evaluate oncologists' perceptions concerning the availability and quality of information generated from PRO measures. Additionally, to identify whether an association exists between perceptions of availability and attitudes concerning quality. METHOD: An online, 11-item questionnaire was developed to capture clinician perspectives on the availability and use of PRO data to inform practice. The survey also asked respondents to rate information on the basis of 4 quality metrics: "usefulness," "interpretability," "accessibility," and "scientific rigor." RESULTS: Responses were received from 298 of 1301 invitations sent (22.9% response rate). Perceptions regarding the availability of PRO information differed widely among respondents and did not appear to be linked to practice setting. Ratings of PRO quality were generally consistent, with average ratings for the 4 quality metrics between "satisfactory" and "good." A relationship was observed between ratings of PRO data quality and perceptions of the availability. CONCLUSION: Oncologists' attitudes toward the quality of information generated from PRO measures are favorable but not enthusiastic. These attitudes may improve as the availability of PRO data increases, given the association we observed between oncologists' ratings of the quality of PRO information and their perceptions of its availability.

High-resolution temporal profiling of the human gut microbiome reveals consistent and cascading alterations in response to dietary glycans.

BACKGROUND: Dietary glycans, widely used as food ingredients and not directly digested by humans, are of intense interest for their beneficial roles in human health through shaping the microbiome. Characterizing the consistency and temporal responses of the gut microbiome to glycans is critical for rationally developing and deploying these compounds as therapeutics. METHODS: We investigated the effect of two chemically distinct glycans (fructooligosaccharides and polydextrose) through three clinical studies conducted with 80 healthy volunteers. Stool samples, collected at dense temporal resolution (~ 4 times per week over 10 weeks) and analyzed using shotgun metagenomic sequencing, enabled detailed characterization of participants' microbiomes. For analyzing the microbiome time-series data, we developed MC-TIMME2 (Microbial Counts Trajectories Infinite Mixture Model Engine 2.0), a purpose-built computational tool based on nonparametric Bayesian methods that infer temporal patterns induced by perturbations and groups of microbes sharing these patterns. RESULTS: Overall microbiome structure as well as individual taxa showed rapid, consistent, and durable alterations across participants, regardless of compound dose or the order in which glycans were consumed. Significant changes also occurred in the abundances of microbial carbohydrate utilization genes in response to polydextrose, but not in response to fructooligosaccharides. Using MC-TIMME2, we produced detailed, high-resolution temporal maps of the microbiota in response to glycans within and across microbiomes. CONCLUSIONS: Our findings indicate that dietary glycans cause reproducible, dynamic, and differential alterations to the community structure of the human microbiome.

A Randomized Double-Blind Placebo-Controlled First-In-Human Phase 1 Trial of TransCon PTH in Healthy Adults.

TransCon PTH is a sustained-release, essentially inactive prodrug transiently bound to an inert carrier, designed to release PTH(1-34), and in development for hypoparathyroidism (HP). This phase 1, randomized, placebo-controlled, single and multiple ascending dose (SAD and MAD, respectively) trial evaluated safety, tolerability, pharmacodynamics (PD), and pharmacokinetics (PK) of TransCon PTH in healthy adults. SAD and MAD cohorts consisted of 10 subjects (eight active, two placebo) who received up to seven single or six multiple ascending doses of TransCon PTH, respectively. TransCon PTH doses ranged from 3.5 to 124 µg PTH(1-34) for the SAD cohorts and 3.5 to 24 µg PTH(1-34)/day for the MAD cohorts. The primary PK endpoint was Free PTH. The PD endpoints included albumin adjusted serum calcium (sCa), fractional excretion of calcium (FECa), intact endogenous PTH(1-84), bone turnover markers, renal tubular maximum reabsorption of phosphate/glomerular filtration rate (TMP/GFR), serum phosphate (sP) and magnesium, and 1,25 dihydroxyvitamin D. TransCon PTH was generally well tolerated; there were no drug-related serious adverse events (SAEs), and all AEs were transient in nature. Free PTH demonstrated an effective half-life of approximately 60 hours and a dose-dependent, sustained exposure with an infusion-like profile within the calculated physiologic range for active PTH at steady-state. Albumin-adjusted sCa demonstrated a dose-dependent, sustained response with complete control of FECa despite modest hypercalcemia at higher doses. Renal tubular maximum reabsorption of phosphate/glomerular filtration rate (TMP/GFR) showed a dose-dependent decrease, resulting in a dose-dependent decrease in sP. TransCon PTH administered daily for 10 days showed no increase in the osteoblastic bone formation markers, serum bone-specific alkaline phosphatase (BSAP) or P1NP, or the osteoclastic bone resorption marker, urine NTx, but modestly and transiently increased the osteoclast marker, serum CTx. These phase 1 data support TransCon PTH as a daily replacement therapy for HP providing physiological levels of PTH 24 hours per day and advancement into phase 2 clinical development. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Reasons for article retraction in anesthesiology: a comprehensive analysis.

BACKGROUND: Increasing awareness of scientific misconduct has prompted various fields of medicine, including orthopedic surgery, neurosurgery, and dentistry to characterize the reasons for article retraction. The purpose of this review was to evaluate the reasons for and the rate of article retraction in the field of anesthesia within the last 30 years. METHODS: Based on a reproducible search strategy, two independent reviewers searched MEDLINE, EMBASE, and the Retraction Watch website to identify retracted anesthesiology articles. Extracted data included: author names, year of publication, year of the retracted article, journal name, journal five-year impact factor, research type (clinical, basic science, or review), reason for article retraction, number of citations, and presence of a watermark indicating article retraction. RESULTS: Three hundred and fifty articles were included for data extraction. Reasons for article retraction could be grouped into six broad categories. The most common reason for retraction was fraud (data fabrication or manipulation), which accounted for nearly half (49.4%) of all retractions, followed by lack of appropriate ethical approval (28%). Other reasons for retraction included publication issues (e.g., duplicate publications), plagiarism, and studies with methodologic or other non-fraud data issues. Four authors were associated with most of the retracted articles (59%). The majority (69%) of publications utilized a watermark on the original article to indicate that the article was retracted. Journal Citation Reports journal impact factors ranged from 0.9 to 48.1 (median [interquartile range (IQR)], 3.6 [2.5-4.0]), and the most cited article was referenced 197 times (median [IQR], 13 [5-26]). Most retracted articles (66%) were cited at least once by other journal articles after having been withdrawn. CONCLUSIONS: Most retracted articles in anesthesiology literature were retracted because of research misconduct. Limited information is available in the retraction notices, unless explicitly stated, so it is challenging to distinguish between an honest error and research misconduct. Therefore, a standardized reporting process with structured retraction notices is desired.

Hybrid Coronary Revascularization - Current State of the Art.

Hybrid coronary revascularization (HCR) seeks to combine the benefit of surgical and nonsurgical techniques for optimum management for selective patients with multivessel obstructive coronary artery disease. The goal of HCR is to combine the benefit of surgical anastomosis of the left internal mammary artery to the left anterior descending coronary artery (LAD) graft along with stenting of non-LAD lesions with percutaneous coronary intervention (PCI). HCR usually involves the use of minimally invasive surgical techniques like robotically assisted coronary artery bypass graft (CABG), with the objective to produce a rapid recovery in the postoperative period, lower complications, and decreased length of stay in the hospital. In this review the authors seek to define the role of HCR in current practice including patient selection, techniques, logistics, outcome data and the challenges it faces in comparison to conventional CABG and PCI.

A randomized, double-blinded trial comparing the effectiveness of tranexamic acid and epsilon-aminocaproic acid in reducing bleeding and transfusion in cardiac surgery.

Objectives: To compare the effectiveness of epsilon aminocaproic acid (EACA) to tranexamic acid (TA) in reducing blood loss and transfusion requirements in patients undergone cardiac surgery under cardiopulmonary bypass. Design: Randomized, double blinded study. Outcome variables collected included; baseline demographic characteristics, type of surgery, amount of 24 hour chest tube drainage, amount of 24 hour blood products administered, 30 day mortality and morbidity and length of stay. We analyzed the data using parametric and non-parametric tests as appropriate. Setting: Single center tertiary-care university hospital setting. Participants: 114 patients who had undergone cardiac surgery under cardiopulmonary bypass. Interventions: Standard dose of intra-operative EACA or TA was compared in patients undergone cardiac surgery under cardiopulmonary bypass. Results: There was no statistically significant difference between groups when analyzing chest tube drainage. However, there was a significant difference in the administration of any transfusion (PRBC's, FFP, platelets) intra-operatively to 24 hours postoperatively, with less transfusion in patients receiving EACA compared to TA (25% vs. 44.8%, respectively P = 0.027). Additionally, there was no significant difference in terms of adverse events during the one month follow up period. Conclusion: The findings of this study suggest that EACA and TA have similar effects on chest tube drainage but EACA is associated with fewer transfusions in CABG alone surgeries. Our results suggest that EACA can be used in a similar fashion to TA which may result in a cost and morbidity advantage.

Validation Study of the Transfusion Risk and Clinical Knowledge (TRACK) Tool in Cardiac Surgery Patients: A Retrospective Analysis.

OBJECTIVE: The Transfusion Risk and Clinical Knowledge (TRACK) scoring system has been developed for predicting perioperative blood transfusions. However, the TRACK score needs to be validated externally in the US population. The primary objective of this study is to validate TRACK at the authors' institution. DESIGN: This study was a single-center retrospective analysis. SETTING: Operating room and intensive care units of academic medical center. PARTICIPANTS: Adult cardiac surgery patients. INTERVENTIONS: The authors retrospectively queried all cardiac surgeries at the authors' institution between 2010 and 2015 from the Society of Thoracic Surgeons database. The TRACK scores were determined for all patients. The authors used receiver operating characteristic (ROC) curves to assess the discriminatory power of TRACK in predicting any perioperative, intraoperative, and postoperative transfusions. The maximum Youden's index was used to determine optimal cutoff scores for predicting perioperative transfusions. MEASUREMENTS AND MAIN RESULTS: The authors analyzed 2,776 cardiac surgery patients with 51.8% transfused perioperatively. The average TRACK score (mean ± standard deviation) in transfused versus non-transfused patients was 12.4 ± 7.2 versus 6.1 ± 5.4, respectively (p < 0.001). The area under the ROC curve was 0.768 (95% confidence interval 0.800-0.835, p < 0.001) for any perioperative transfusion. Optimal sensitivity (67%) and specificity (73%) for predicting any perioperative transfusions was achieved with a TRACK score cutoff of greater than or equal to 22 of 32. CONCLUSION: This study demonstrates the validity of the TRACK score in predicting blood perioperative transfusions in cardiac surgery patients at the authors' institution. This study supports the external validity of TRACK and adds to its clinical utility by establishing cutoff scores for identifying patients at high risk of transfusion.

Continuous-Flow Left Ventricular Assist Device Survival Improves With Multidisciplinary Approach.

BACKGROUND: Continuous-flow left ventricular assist devices have revolutionized the management of advanced heart failure. Device complications continue to limit survival, but enhanced management strategies have shown promise. This study compared outcomes for HeartMate II recipients before and after implementation of a multidisciplinary continuous support heart team (HTMCS) strategy. METHODS: Between January 2012 and December 2016, 124 consecutive patients underwent primary HeartMate II implantation at our institution. In January 2015, we instituted a HTMCS approach consisting of (1) daily simultaneous cardiology/cardiac surgery/critical care/pharmacy/coordinator rounds, (2) pharmacist-directed anticoagulation, (3) speed optimization echocardiogram before discharge, (4) comprehensive device thrombosis screening and early intervention, (5) blood pressure clinic with pulsatility-adjusted goals, (6) early follow-up after discharge and individual long-term coordinator/cardiologist assignment, and (7) systematic basic/advanced/expert training and credentialing of ancillary in-hospital providers. All patients completed 1-year of follow-up. RESULTS: Demographic characteristics for pre-HTMCS (n = 71) and HTMCS (n = 53) groups, including age (55.8 ± 12.1 versus 52.5 ± 14.1 years, p = not significant), percentage of men (77.5% versus 71.7%, p = not significant), and Interagency Registry for Mechanically Assisted Circulatory Support class 3 (84.5% versus 83.0%, p = not significant), were comparable. One-year survival was 74.6% versus 100% for the pre-HTMCS and HTMCS groups, respectively (p = 0.0002). One-year survival free of serious adverse events (reoperation to replace device or disabling stroke) was 70.4% versus 84.9% for the pre-HTMCS and HTMCS groups, respectively (p = 0.059). Event per patient-year rates for disabling stroke (0.15 versus 0, p = 0.019), gastrointestinal bleeding (0.87 versus 0.51, p = 0.11), and driveline infection (0.24 versus 0.10, p = 0.18) were lower for the HTMCS group, whereas pump thrombosis requiring device exchange was higher (0.09 versus 0.18, p = 0.14). CONCLUSIONS: Implementing a comprehensive multidisciplinary approach substantially improved outcomes for recipients of continuous-flow left ventricular assist devices.

Comprehensive characterization of ureagenesis in the spfash mouse, a model of human ornithine transcarbamylase deficiency, reveals age-dependency of ammonia detoxification.

The most common ureagenesis defect is X-linked ornithine transcarbamylase (OTC) deficiency which is a main target for novel therapeutic interventions. The spf ash mouse model carries a variant (c.386G>A, p.Arg129His) that is also found in patients. Male spf ash mice have a mild biochemical phenotype with low OTC activity (5%-10% of wild-type), resulting in elevated urinary orotic acid but no hyperammonemia. We recently established a dried blood spot method for in vivo quantification of ureagenesis by Gas chromatography-mass spectrometry (GC-MS) using stable isotopes. Here, we applied this assay to wild-type and spf ash mice to assess ureagenesis at different ages. Unexpectedly, we found an age-dependency with a higher capacity for ammonia detoxification in young mice after weaning. A parallel pattern was observed for carbamoylphosphate synthetase 1 and OTC enzyme expression and activities, which may act as pacemaker of this ammonia detoxification pathway. Moreover, high ureagenesis in younger mice was accompanied by elevated periportal expression of hepatic glutamine synthetase, another main enzyme required for ammonia detoxification. These observations led us to perform a more extensive analysis of the spf ash mouse in comparison to the wild-type, including characterization of the corresponding metabolites, enzyme activities in the liver and plasma and the gut microbiota. In conclusion, the comprehensive enzymatic and metabolic analysis of ureagenesis performed in the presented depth was only possible in animals. Our findings suggest such analyses being essential when using the mouse as a model and revealed age-dependent activity of ammonia detoxification.

Preparing for a Fellowship in Adult Cardiothoracic Anesthesiology: Resources and Approaches for the Anesthesiology Trainee.

Adult cardiothoracic anesthesiology (ACTA) is a competitive fellowship. Despite increases in both the number of programs offering cardiothoracic fellowships and the number of residents applying each year, there is little direction or advice for prospective candidates. This review aims to educate anesthesiology residents who are hoping to pursue cardiothoracic anesthesiology, by examining a brief history of the advanced perioperative echocardiography qualification, the credentialing goals of ACTA fellowships, and the current status of ACTA fellowships. The second part of the review covers the ACTA fellowship application and aims to assist the candidate in navigating this process. The review examines the qualifications that fellowship programs look for in a candidate, including a discussion on professional behavior, and what an applicant can look for in a program. Finally, there is a brief discussion on post-match preparation.