Propofol vs etomidate for induction prior to invasive mechanical ventilation in patients with acute myocardial infarction.

BACKGROUND: Patients with acute myocardial infarction (AMI) requiring invasive mechanical ventilation (IMV) have a high mortality. However, little is known regarding the impact of induction agents, used prior to IMV, on clinical outcomes in this population. We assessed for the association between induction agent and mortality in patients with AMI requiring IMV. METHODS: We compared clinical outcomes between those receiving propofol compared to etomidate for induction among adults with AMI between October 2015 and December 2019 using the Vizient® Clinical Data Base, a multicenter, US national database. We used inverse probability treatment weighting (IPTW) to assess for the association between induction agent and in-hospital mortality. RESULTS: We identified 5,147 patients, 1,386 (26.9%) of received propofol and 3,761 (73.1%) received etomidate for IMV induction. The mean (SD) age was 66.1 (12.4) years, 33.0% were women, and 51.6% and 39.8% presented with STEMI and cardiogenic shock, respectively. Patients in the propofol group were more likely to require preintubation vasoactive medication and mechanical circulatory support (both, P < .05). Utilization of propofol was associated with lower mortality compared to etomidate (32.3% vs 36.1%, P = .01). After propensity weighting, propofol use remained associated with lower mortality (weighted mean difference -4.7%; 95% confidence interval: -7.6% to -1.8%, P = .002). Total cost, ventilator days, and length of stay were higher in the propofol group (all, P < .001). CONCLUSIONS: Induction with propofol, compared with etomidate, was associated with lower mortality for patients with AMI requiring IMV. Randomized trials are needed to determine the optimal induction agent for this critically ill patient population.

Noninvasive Ventilation in the Cardiac Intensive Care Unit.

Over the last several decades, the cardiac intensive care unit (CICU) has seen an increase in the complexity of the patient population and etiologies requiring CICU admission. Currently, respiratory failure is the most common reason for admission to the contemporary CICU. As a result, noninvasive ventilation (NIV), including noninvasive positive-pressure ventilation and high-flow nasal cannula, has been increasingly utilized in the management of patients admitted to the CICU. In this review, we detail the different NIV modalities and summarize the evidence supporting their use in conditions frequently encountered in the CICU. We describe the unique pathophysiologic interactions between positive pressure ventilation and left and/or right ventricular dysfunction. Additionally, we discuss the evidence and strategies for utilization of NIV as a method to reduce extubation failure in patients who required invasive mechanical ventilation. Lastly, we examine unique considerations for managing respiratory failure in certain, high-risk patient populations such as those with right ventricular failure, severe valvular disease, and adult congenital heart disease. Overall, it is critical for clinicians who practice in the CICU to be experts with the application, risks, benefits, and modalities of NIV in cardiac patients with respiratory failure.

Tracheostomy in Patients with Acute Myocardial Infarction and Respiratory Failure.

OBJECTIVE: Patients with acute myocardial infarction (AMI) complicated by respiratory failure require antiplatelet regimens which often cannot be stopped and may increase bleeding from tracheostomy. However, there is limited available data on both the proportion of patients undergoing tracheostomy and the impact on antiplatelet regimens on outcomes. METHODS: Utilizing the Vizient® Clinical Data Base, we identified patients ≥18 years admitted from 2015 to 2019 with a primary diagnosis of AMI and requiring invasive mechanical ventilation (IMV). We assessed for the incidence of patients undergoing tracheostomy, outcomes stratified by the timing of tracheostomy (≤10 vs >10 days), and the association between dual antiplatelet therapy (DAPT) use and in-hospital mortality. RESULTS: We identified 26 435 patients presenting with AMI requiring IMV. The mean (SD) age was 66.8 (12.3) years and 33.4% were women. The incidence of tracheostomy was 6.0% (n = 1573), and the median IMV time to tracheostomy was 12 days, 55.6% of which underwent percutaneous and 44.4% underwent open tracheostomy. Over 90% (n = 1424) underwent tracheostomy (>10 days) and had a similar mortality when compared to early (≤10 days) tracheostomy (22.5% vs 22.8%, P = 0.94). On the day of tracheostomy, only 24.7% were given DAPT, which was associated with a lower mortality than those not on DAPT (17.4% vs 23.7%, P = 0.01). After multivariable adjustment, DAPT use on the day of tracheostomy remained associated with lower in-hospital mortality (odds ratio 0.68; 95% confidence interval: 0.49-0.94, P = 0.02). Tracheostomy complications were not different between groups (P > 0.05), but more patients in the DAPT group required post-tracheostomy blood transfusions (5.6% vs 2.7%, P = 0.01). CONCLUSION: Approximately 1 in 20 intubated AMI patients requires tracheostomy. The lack of DAPT interruption on the day of tracheostomy but not the timing of tracheostomy was associated with a lower in-hospital mortality. Our results suggest that DAPT should not be a barrier to tracheostomy for patients with AMI.

Improved adherence to hip fracture standards reduces mortality after hip fractures.

BACKGROUND: Hip fractures are increasing in incidence due to increasing life expectancy. Mortality continues to improve but it is important to explore which factors are responsible for driving improvements. METHODS: A cohort of hip fracture patients predating SARS-CoV-2 was examined to determine the predictors of adherence to the six Irish Hip Fracture Standards (IHFS) and the impact of adherence on short (30 day) and long term (1 year) mortality. Our primary aim was assess the impact of a single HFS and cumulative number of HFS on mortality after hip fracture. Our secondary aim was to determine the impact of the HFS which are intrinsically linked to specialist Geriatric care. RESULTS: Across 962 patients, over 5 years, the factors which were associated with adherence to HFS were female gender, increasing ASA grade and being nursed on an orthopaedic ward. Patients with increasing ASA were more likely to have met HFS 4-6 (Geriatrician review HFS4, bone health HFS5 & specialist falls assessment HFS6), less likely to have surgery within 48 h are more likely to develop a pressure ulcer. If the patient was not nursed on an orthopaedic ward all HFS were less likely to be met. At 30 days HFS 4-6 were associated with a statistically significant odds ratio (OR) of being alive, while at one year HFS 1 (admitted to an orthopaedic ward within 4 h), 5 and 6 were associated with a statistically significant OR of being alive. As increasing numbers of hip fracture standards were met patients were more likely to be alive at 30 days and one year. CONCLUSION: This study has identified that improved adherence to hip fracture standards are associated with improved mortality at 30 days and one year.

Trends in outcomes and resource utilization for acute myocardial infarction admissions during the COVID-19 pandemic.

During the early COVID-19 pandemic, resources were at times rationed, and as a result, cardiovascular outcomes may have suffered, however despite this, there is a paucity of national data specifically examining the relationship between COVID-19 and acute myocardial infarction (AMI). Some of the most robust previous cohort studies suggest the risk of AMI is increased in patients with COVID-19 infection, and disproportionately so in certain patient populations. To better define national trends in the associations between COVID-19 and AMI, this study aimed to examine demographics, outcomes, and health care utilization in hospitalizations for AMI with a codiagnosis of COVID-19 using a nationally representative database.

Effects of COVID-19 on heart failure admissions.

Despite significant investigation into the effects of COVID-19 on cardiovascular disease, there is a paucity of national data specifically examining its effects on heart failure (HF) hospitalizations. Previous cohort study data demonstrate worsened outcomes in HF patients with recent COVID-19 infection. To better understand this association, this study aimed to utilize a nationally representative database to examine demographics, outcomes, and health care utilization in hospitalizations for HF with a codiagnosis of COVID-19.

The Ccr4-Not complex regulates TORC1 signaling and mitochondrial metabolism by promoting vacuole V-ATPase activity.

The Ccr4-Not complex functions as an effector of multiple signaling pathways that control gene transcription and mRNA turnover. Consequently, Ccr4-Not contributes to a diverse array of processes, which includes a significant role in cell metabolism. Yet a mechanistic understanding of how it contributes to metabolism is lacking. Herein, we provide evidence that Ccr4-Not activates nutrient signaling through the essential target of rapamycin complex 1 (TORC1) pathway. Ccr4-Not disruption reduces global TORC1 signaling, and it also upregulates expression of the cell wall integrity (CWI) pathway terminal kinase Mpk1. Although CWI signaling represses TORC1 signaling, we find that Ccr4-Not loss inhibits TORC1 independently of CWI activation. Instead, we demonstrate that Ccr4-Not promotes the function of the vacuole V-ATPase, which interacts with the Gtr1 GTPase-containing EGO complex to stimulate TORC1 in response to nutrient sufficiency. Bypassing the V-ATPase requirement in TORC1 activation using a constitutively active Gtr1 mutant fully restores TORC1 signaling in Ccr4-Not deficient cells. Transcriptome analysis and functional studies revealed that loss of the Ccr4 subunit activates the TORC1 repressed retrograde signaling pathway to upregulate mitochondrial activity. Blocking this mitochondrial upregulation in Ccr4-Not deficient cells further represses TORC1 signaling, and it causes synergistic deficiencies in mitochondrial-dependent metabolism. These data support a model whereby Ccr4-Not loss impairs V-ATPase dependent TORC1 activation that forces cells to enhance mitochondrial metabolism to sustain a minimal level of TORC1 signaling necessary for cell growth and proliferation. Therefore, Ccr4-Not plays an integral role in nutrient signaling and cell metabolism by promoting V-ATPase dependent TORC1 activation.

Effect of 4 weeks of plyometric training in the pre-competitive period on volleyball athletes' performance.

We aimed to evaluate the effect of 4 weeks of plyometric training (PT), performed in the pre-competitive period, on the vertical jump performance of professional volleyball athletes. We recruited 17 professional female volleyball players (age: 19 ± 3 years; weight: 67.2 ± 5.50 kg; height: 1.81 ± 0.22 m; body fat: 14.4 ± 2.12%; squat 1RM test: 75.5 ± 7.82 kg; training time experience: 6.2 ± 3.4 years) to participate in four weeks of training and assessments. They were divided into an experimental group (EG = 9) and a control group (CG = 8). Both groups were submitted to friendly matches, technical, tactical and resistance training (4 weeks/˜9 sessions per week), and internal load monitoring was carried out. The EG performed PT twice a week. At the beginning and end of the four weeks, jump tests were performed. The main findings are: 1) PT when incorporated into the pre-competitive period can induce greater improvements in jumping performance (EG = 28.93 ± 3.24 cm to 31.67 ± 3.39 cm; CG = 27.91 ± 4.64 cm to 28.97 ± 4.58 cm; when comparing the percentage delta, we found a difference between groups with ES of 1.04 and P = 0.02); 2) this result is observed when the training load is similar between groups and increases over the weeks, respecting the linear progression principle. Therefore, including plyometric training in the preparatory period for volleyball, with low monotony and training strain increment, is an effective strategy for further CMJ performance improvement.

Trends in transcatheter and surgical aortic valve replacement in the United States, 2008-2018.

We conducted a retrospective study using the NIS database from 2008 to 2018 to examine the most contemporary national hospitalization trends of transcatheter (TAVR) and surgical (SAVR) aortic valve replacement regarding volume, patient and hospital demographics and economics, resource utilization, total cost of stay, and in-hospital mortality. We demonstrate that TAVR procedures have been performed on a slow by steadily diversifying patient population while volume has grown significantly, while in-hospital mortality, length of stay, discharge home, and costs have improved, whereas these metrics have generally remained stable for SAVR. These trends will likely drive continued TAVR adoption, greatly expanding the overall aortic stenosis patient population eligible for AVR.

Trends in Heart Failure Hospitalizations in the US from 2008 to 2018.

BACKGROUND: Heart failure (HF) is a major driver of health care costs in the United States and is increasing in prevalence. There is a paucity of contemporary data examining trends among hospitalizations for HF that specifically compare HF with reduced or preserved ejection fraction (HFrEF or HFpEF, respectively). METHODS AND RESULTS: Using the National Inpatient Sample, we identified 11,692,995 hospitalizations due to HF. Hospitalizations increased from 1,060,540 in 2008 to 1,270,360 in 2018. Over time, the median age of patients hospitalized because of HF decreased from 76.0 to 73.0 years (P < 0.001). There were increases in the proportions of Black patients (18.4% in 2008 to 21.2% in 2018) and of Hispanic patients (7.1% in 2008 to 9.0% in 2018; P < 0.001, all). Over the study period, we saw an increase in comorbid diabetes, sleep apnea and obesity (P < 0.001, all) in the entire cohort with HF as well as in the HFrEF and HFpEF subgroups. Persons admitted because of HFpEF were more likely to be white and older compared to admissions because of HFrEF and also had lower costs. Inpatient mortality decreased from 2008 to 2018 for overall HF (3.3% to 2.6%) and HFpEF (2.4% to 2.1%; P < 0.001, all) but was stable for HFrEF (2.8%, both years). Hospital costs, adjusted for inflation, decreased in all 3 groups across the study period, whereas length of stay was relatively stable over time for all groups. CONCLUSIONS: The volume of patients hospitalized due to HF has increased over time and across subgroups of ejection fraction. The demographics of HF, HFrEF and HFpEF have become more diverse over time, and hospital inpatient costs have decreased, regardless of HF type. Inpatient mortality rates improved for overall HF and HFpEF admissions but remained stable for HFrEF admissions.

Staffing models in the cardiac intensive care unit.

PURPOSE OF REVIEW: The modern cardiac intensive care unit (CICU) has evolved into a high-intensity unit that cares for critically ill patients. Despite this transformation, changes to the staffing model and organizational structure in these specialized units have only recently begun to meet these challenges. We describe the most recent evidence which will inform future CICU staffing models. RECENT FINDINGS: In the United States, the majority of CICUs are open as opposed to closed units, yet recent data suggests that transition to a closed staffing model is associated with a decrease in mortality. These reductions in mortality in closed CICUs are most pronounced in the most critically ill populations, such as patients with mechanical circulatory support, cardiac arrest, and respiratory failure. In addition, one study has shown that transition to a cardiac intensivist staffed CICU was associated with a reduction in mortality. Finally, multidisciplinary and protocolized teams imbedded within the CICU, specifically 'shock teams,' have recently been developed and may reduce mortality in this particularly sick patient population. SUMMARY: Although the preponderance of data suggests improved outcomes with a closed, intensivist staffed CICU model, future multicenter studies are needed to better define the ideal staffing models for the contemporary CICU.

Trends in Therapy and Outcomes Associated With Respiratory Failure in Patients Admitted to the Cardiac Intensive Care Unit.

PURPOSE: To describe the epidemiology, outcomes, and temporal trends of respiratory failure in the cardiac intensive care unit (CICU). MATERIALS AND METHODS: Retrospective cohort analysis of 2,986 unique Mayo Clinic CICU patients from 2007 to 2018 with respiratory failure. Temporal trends were analyzed, along with hospital and 1-year mortality. Multivariable logistic regression was used to determine adjusted hospital mortality trends. RESULTS: The prevalence of respiratory failure in the CICU increased from 15% to 38% during the study period (P < 0.001 for trend). Among patients with respiratory failure, the utilization of invasive ventilation decreased and noninvasive ventilation modalities increased over time. Hospital mortality and 1-year mortality were 24% and 54%, respectively, with variation according to the type of respiratory support (highest among patients receiving invasive ventilation alone: 35% and 46%, respectively). Hospital mortality was highest among patients with concomitant cardiac arrest and/or shock (52% for patients with both). Hospital mortality decreased in the overall population from 35% to 25% (P < 0.001 for trend), but was unchanged among patients receiving positive-pressure ventilation. CONCLUSIONS: The prevalence of respiratory failure in CICU more than doubled during the last decade. The use of noninvasive respiratory support increased, while overall mortality declined over time. Cardiac arrest and shock accounted for the majority of deaths. Further research is needed to optimize the outcomes of high-risk CICU patients with respiratory failure.

Evaluation of plasma nucleosome concentrations in dogs with a variety of common cancers and in healthy dogs.

BACKGROUND: Cell free DNA, in the form of nucleosomes, is released into circulation during apoptosis and necrosis in a variety of diseases. They are small fragments of chromosomes that are composed of DNA wrapped around a histone core made of four duplicate histone proteins forming an octamer. The nucleosome compartment is a relatively uninvestigated area of circulating tumor biomarkers in dogs. The objectives of this study were to quantify and better characterize nucleosome concentrations in 528 dogs with various common malignancies and compare them to 134 healthy dogs. RESULTS: The sensitivity of increased circulating nucleosome concentrations for the detection of cancer in all dogs was 49.8% with a specificity of 97% with an area under the curve of 68.74%. The top 4 malignancies detected by the test included lymphoma, hemangiosarcoma, histiocytic sarcoma and malignant melanoma. The malignancies least likely to be detected were soft tissue sarcomas, osteosarcoma and mast cell tumors. CONCLUSIONS: A variety of tumor types may cause increased nucleosome concentrations in dogs. Tumors of hematopoietic origin are most likely to cause elevations and local tumors such as soft tissue sarcomas are least likely to cause elevations in plasma nucleosome concentrations.

Temperature-controlled Laminar Airflow (TLA) in symptomatic severe asthma - a post hoc analysis of severe exacerbations, quality of life and health economics.

PURPOSE: Uncontrolled severe asthma constitutes a major economic burden to society. Add-ons to standard inhaled treatments include inexpensive oral corticosteroids and expensive biologics. Nocturnal treatment with Temperature-controlled Laminar Airflow (TLA; Airsonett®) could be an effective, safe and cheaper alternative. The potential of TLA in reducing severe asthma exacerbations was addressed in a recent randomised placebo-controlled trial (RCT) in patients with severe asthma (Global Initiative for Asthma (GINA) step 4/5), but the results were inconclusive. We re-analysed the RCT with severe exacerbations stratified by the level of baseline asthma symptoms and Quality of Life. METHODS: More uncontrolled patients, defined by Asthma Control Questionnaire 7 (ACQ7) > 3, EuroQoL 5-Dimension Questionnaire Visual Analogue Scale (EQ5D-VAS) ≤ 65 and Asthma Quality of Life Questionnaire (AQLQ) ≤ 4 were selected for re-analysis. The rates of severe asthma exacerbations, changes in QoL and health-economics were analysed and compared between TLA and placebo. RESULTS: The study population included 226 patients (113 TLA / 113 placebo.) The rates of severe asthma exacerbations were reduced by 33, 31 and 25% (p = 0.083, 0.073, 0.180) for TLA compared to placebo, dependent on selected control measures (ACQ7, EQ5D-VAS, AQLQ, respectively). For patients with less control defined by AQLQ≤4, the difference in mean AQLQ0-12M between TLA and placebo was 0.31, 0.33, 0.26 (p = 0.085, 0.034, 0.150), dependent on selected covariate (AQLQ, EQ5D-VAS, ACQ7, respectively). For patients with poor control defined by ACQ7 > 3, the difference in EQ5D-5 L utility scores between TLA and placebo was significant at 9 and 12 months with a cost-effective ICER. The results from the original study did not demonstrate these differences. CONCLUSION: This post hoc analysis demonstrated an effect of TLA over placebo on severe exacerbations, asthma control and health economics in a subgroup of patients with more symptomatic severe allergic asthma. The results are consistent with the present recommendations for TLA. However, these differences were not demonstrated in the full study. Several explanations for the different outcomes have been outlined, which should be addressed in future studies. FUNDING: NIHR Health Technology Assessment Programme and Portsmouth Hospitals NHS Trust.

Electronic health record risk score provides earlier prognostication of clinical outcomes in patients admitted to the cardiac intensive care unit.

In this observational study, we compared the prognostic ability of an electronic health record (EHR)-derived risk score, the Rothman Index (RI), automatically derived on admission, to the first 24-hour Sequential Organ Failure Assessment (SOFA) score for outcome prediction in the modern cardiac intensive care unit (CICU). We found that while the 24-hour SOFA score provided modestly superior discrimination for both in-hospital and CICU mortality, the RI upon CICU admission had better calibration for both outcomes. Given the ubiquitous nature of EHR utilization in the United States, the RI may become an important tool to rapidly risk stratify CICU patients within the ICU and improve resource allocation.

Association between Respiratory Failure and Clinical Outcomes in Patients with Acute Heart Failure: Analysis of 5 Pooled Clinical Trials.

BACKGROUND: Despite a temporal increase in respiratory failure in patients hospitalized with acute heart failure (HF), clinical trials have largely not reported the incidence or associated clinical outcomes for patients requiring mechanical ventilation. METHODS AND RESULTS: After pooling 5 acute HF clinical trials, we used multivariable logistic regression adjusted for demographics, comorbidities, examinations, and laboratory findings to assess associations between mechanical ventilation and clinical outcomes. Among the 8296 patients, 210 (2.5%) required mechanical ventilation. Age, sex, smoking history, baseline ejection fraction, HF etiology, and the proportion of patients randomized to treatment or placebo in the original clinical trial were similar between groups (all, P > 0.05). Baseline diabetes mellitus was more common in the mechanical ventilation group (P = 0.02), but other comorbidities, including chronic lung disease, were otherwise similar (all P > 0.05). HF rehospitalization at 30 days (12.7% vs 6.6%, P < 0.001) and all-cause 60-day mortality (33.3% vs 6.1%, P < 0.001) was higher among patients requiring mechanical ventilation. After multivariable adjustment, mechanical ventilation use was associated with an increased 30-day HF rehospitalization (odds ratio 2.03; 95% confidence interval, 1.29-3.21, P = 0.002), 30-day mortality (odds ratio 10.40; 95% confidence interval, 7.22-14.98, P < 0.001), and 60-day mortality (odds ratio 7.68; 95% confidence interval, 5.50-10.74, P < 0.001). The influence of mechanical ventilation did not differ by HF etiology or baseline ejection fraction (both, interaction P > 0.20). CONCLUSIONS: Respiratory failure during an index hospitalization for acute HF was associated with increased rehospitalization and all-cause mortality. The development of respiratory failure during an acute HF admission identifies a particularly vulnerable population, which should be identified for closer monitoring.

The Impact of Depression on Outcomes in Patients With Heart Failure and Reduced Ejection Fraction Treated in the GUIDE-IT Trial.

BACKGROUND: It remains unclear why depression is associated with adverse outcomes in patients with heart failure (HF). We examine the relationship between depression and clinical outcomes among patients with HF with reduced ejection fraction managed with guideline-directed medical therapy (GDMT). METHODS AND RESULTS: Using the GUIDE-IT trial, 894 patients with HF with reduced ejection fraction were stratified according to a history of depression, and Cox proportional hazards regression modeling was used to examine the association with outcomes. There were 140 patients (16%) in the overall cohort who had depression. They tended to be female (29% vs 46%, P < .001) and White (67% vs 53%, P = .002). There were no differences in GDMT rates at baseline or at 90 days; nor were there differences in target doses of these therapies achieved at 90 days (NS, all). amino-terminal pro-B-type natriuretic peptide levels at all time points were similar between the cohorts (P > .05, all). After adjustment, depression was associated with all-cause hospitalizations (hazard ratio, 1.42, 95% confidence interval 1.11-1.81, P < .01), cardiovascular death (hazard ratio, 1.69, 95% confidence interval 1.07-2.68, P = .025), and all-cause mortality (hazard ratio, 1.54, 95% confidence interval 1.03-2.32, P = .039). CONCLUSIONS: Depression impacts clinical outcomes in HF regardless of GDMT intensity and amino-terminal pro-B-type natriuretic peptide levels. This finding underscores the need for a focus on mental health in parallel to achievement of optimal GDMT in these patients. TRIAL REGISTRATION: NCT01685840, https://clinicaltrials.gov/ct2/show/NCT01685840.

Evaluation of chickens infected with a recombinant virulent NDV clone expressing chicken IL4.

BACKGROUND: There is evidence that chicken IL4 (chIL4) functions similarly to its mammalian analogue by enhancing type 2 T helper (Th2) humoral immunity and promoting protection against parasitic infections; however, no studies have been performed to assess the effect of chIL4 on the pathogenesis of Newcastle disease (ND). To assess the role of chIL4 in velogenic NDV pathogenesis we created a vNDV infectious clone expressing chIL4. We hypothesized that co-expression of chIL4 during virus replication would result in decreased inflammation caused by the Th1 response and thereby increasing survival to challenge with vNDV. METHODS: To evaluate the effect of chIL4 during early infection with velogenic Newcastle disease virus (NDV) in chickens, recombinant NDV clones expressing either chIL4 (rZJ1-IL4) or a control expressing green fluorescent protein (rZJ1-GFP) were created by inserting an expression cassette in an intergenic region of the NDV genome. The pathogenesis of rZJ1-IL4 was assessed in 4-week-old specific pathogen free chickens. The extent of virus replication was evaluated by titration in mucosal secretions and immunohistochemistry in multiple tissues. Expression of chIL4 was confirmed in tissues using immunohistochemistry. RESULTS: Infection of birds with the rZJ1-IL4 resulted in successful viral replication in vivo and in vitro and generation of the chIL4 in tissues. All birds were clinically normal 2 DPI, with one bird in each group showing conjunctival swelling and enlarged spleens grossly. At 5 DPI, moderate or severe depression was observed in birds infected with rZJ1-GFP or rZJ1-IL4, respectively. Neurological signs and thymic atrophy were observed in one bird infected with rZJ1-IL4. Grossly, conjunctival swelling, mottled spleen and proventricular hemorrhages were observed at 5 DPI in one bird from each group. At 5 DPI, severe necrosis in the spleen, bursa and cecal tonsils were observed in birds infected with rZJ1-GFP, along with minimal evidence of chIL4 expression. In contrast, splenic atrophy, and moderate necrosis in the bursa and cecal tonsils were observed in birds infected with rZJ1-IL4. In addition, chIL4 signal was found in all tissues of rZJ1-IL4 birds at 5DPI. CONCLUSIONS: The production of chIL4 by a recombinant NDV strain resulted in the activation of the positive feedback loop associated with IL4 production. Insertion of chIL4 into NDV may decrease necrosis to lymphoid organs while increasing the severity of lymphoid atrophy and prolonged disease. However, with a low number of birds it is difficult to determine whether these results are significant to disease outcome.

Cannabis use disorder among atrial fibrillation admissions, 2008-2018.

BACKGROUND: Despite changes inthe legality of cannabis use and the increasing prevalence of cannabis use disorder (CUD), there is little data investigating the association between CUD and inpatient atrial fibrillation (AF) hospitalizations. METHODS: Using the National Inpatient Sample, we identified Atrial Fibrillation (AF) hospitalizations with and without a codiagnosis of CUD using International Classification of Diseases diagnosis codes and compared demographics, socioeconomics, comorbidities, outcomes, and trends between cohorts. RESULTS: Between 2008 and 2018, we identified 5,155,789 admissions for AF of which 31,768 (0.6%) had a codiagnosis of CUD. The proportion of admissions with a history of CUD increased from 0.3% in 2008 to 1.0% in 2018 (p < .001). Hospital discharges of patients with CUD were significantly younger (53 vs. 72 years, p < .001), had a higher proportion of black race (CUD: 26.6% vs. 8.0%, p < .001), and had a higher proportion of income in the lowest income quartile than without a codiagnosis of CUD (CUD: 40.5% vs. 26.2%, p < .001). CONCLUSIONS: CUD is increasingly prevalent among AF hospitalizations, particularly among young patients. Codiagnosis of CUD in AF hospitalizations is also more common in underserved patients. As a result, it is important for future research to examine and understand the impact of CUD on this population, particularly in the light of changing legislation surrounding the legality of cannabis.

Factors that affect heat production in lactating Jersey cows.

Heat production (HP) represents a major energy cost in lactating dairy cows. Better understanding of factors that affect HP will improve our understanding of energy metabolism. Our objective was to derive models to explain variation in HP of lactating Jersey cows. Individual animal-period data from 9 studies (n = 293) were used. The data set included cows with a wide range (min to max) in days in milk (44-410) and milk yield (7.8-43.0 kg/d). Diets included corn silage as the predominate forage source, but diets varied (min to max on DM basis) in crude protein (CP; 15.2-19.5%), neutral detergent fiber (NDF; 35.5-43.0%), starch (16.2-31.1%), and crude fat (2.2 to 6.4%) contents. Average HP was (mean ± standard deviation) 22.1 ± 2.86 Mcal/d, or 28.1 ± 3.70% of gross energy intake. Eight models were fit to explain variation in HP: (1) dry matter intake (DMI; INT); (2) milk fat, protein, and lactose yield (MILKCOMP); (3) INT and milk yield (INT+MY); (4) INT and MILKCOMP/DMI (INT+MILKCOMP); (5) mass of digested NDF, CP, and starch (DIG); (6) INT and digested energy (INT+DE); (7) INT and NDF, CP, and starch digestibility (INT+DIG); or (8) INT+MILKCOMP model plus urinary N excretion (INT+MILKCOMP+UN). For all HP models, metabolic body weight was included. All models were derived via a backward elimination approach and included the random effects of study, cow, and period within block within study. The INT models adequately explained variation in HP with a nonrandom effect-adjusted concordance correlation coefficient of 0.84. Similar adjusted concordance correlation coefficients (0.79-0.85) were observed for other HP models. The HP associated with milk protein yield and supply of digestible protein was greater than other milk production and nutrient digestibility variables. The HP associated with urinary N excretion was 5.32. Overall, HP can be adequately predicted from metabolic body weight and DMI. Milk component yield, nutrient digestibility, or urinary N excretion explained similar variation as DMI. Coefficients for milk protein and protein digestion suggest that digestion and metabolism of protein and synthesis of milk protein contribute substantially to HP of a dairy cow.