Reduced mortality associated with pulmonary embolism response team consultation for intermediate and high-risk pulmonary embolism: a retrospective cohort study.

BACKGROUND: The management of acute pulmonary embolism (PE) has become increasingly complex with the expansion of advanced therapeutic options, resulting in the development and widespread adoption of multidisciplinary Pulmonary Embolism Response Teams (PERTs). Much of the literature evaluating the impact of PERTs has been limited by pre- postimplementation study design, leading to confounding by changes in global practice patterns over time, and has yielded mixed results. To address this ambiguity, we conducted a retrospective cohort study to evaluate the impact of the distinct exposures of PERT availability and direct PERT consultation. METHODS: At a single tertiary center, we conducted propensity-matched analyses of hospitalized patients with intermediate or high-risk PE. To assess the impact of PERT availability, we evaluated the changes in 30-day mortality, hospital length of stay (HLOS), time to therapeutic anticoagulation (TAC), in-hospital bleeding complications, and use of advanced therapies between the two years preceding and following PERT implementation. To evaluate the impact of direct PERT consultation, we conducted the same analyses in the post-PERT era, comparing patients who did and did not receive PERT consultation. RESULTS: Six hundred eighty four patients were included, of which 315 were pre-PERT patients. Of the 367 postPERT patients, 201 received PERT consultation. For patients who received PERT consultation, we observed a significant reduction in 30-day mortality (5% vs 20%, OR 0.38, p = 0.0024), HLOS. (-5.4 days, p < 0.001), TAC (-0.25 h, p = 0.041), and in-hospital bleeding (OR 0.28, p = 0.011). These differences were not observed evaluating the impact of PERT presence in pre-vs postimplementation eras. CONCLUSIONS: We observed a significant reduction in 30-day mortality, hospital LOS, TAC, and in-hospital bleeding complications for patients who received PERT consultation without an observed difference in these metrics when comparing the pre- vs post-implementation eras. This suggests the benefits stem from direct PERT involvement rather than the mere existence of PERT. Our data supports that PERT consultation may provide benefit to patients with acute intermediate or high-risk PE and can be achieved without a concomitant increase in advanced therapies.

Lung metabolomics after ischemic acute kidney injury reveals increased oxidative stress, altered energy production, and ATP depletion.

Acute kidney injury (AKI) is a complex disease associated with increased mortality that may be due to deleterious distant organ effects. AKI associated with respiratory complications, in particular, has a poor outcome. In murine models, AKI is characterized by increased circulating cytokines, lung chemokine upregulation, and neutrophilic infiltration, similar to other causes of indirect acute lung injury (ALI; e.g., sepsis). Many causes of lung inflammation are associated with a lung metabolic profile characterized by increased oxidative stress, a shift toward the use of other forms of energy production, and/or a depleted energy state. To our knowledge, there are no studies that have evaluated pulmonary energy production and metabolism after AKI. We hypothesized that based on the parallels between inflammatory acute lung injury and AKI-mediated lung injury, a similar metabolic profile would be observed. Lung metabolomics and ATP levels were assessed 4 h, 24 h, and 7 days after ischemic AKI in mice. Numerous novel findings regarding the effect of AKI on the lung were observed including 1) increased oxidative stress, 2) a shift toward alternate methods of energy production, and 3) depleted levels of ATP. The findings in this report bring to light novel characteristics of AKI-mediated lung injury and provide new leads into the mechanisms by which AKI in patients predisposes to pulmonary complications.

The effects of oxygenation on acute vasodilator challenge in pulmonary arterial hypertension.

Identification of long-term calcium channel blocker (CCB) responders with acute vasodilator challenge is critical in the evaluation of patients with pulmonary arterial hypertension. Currently there is no standardized approach for use of supplemental oxygen during acute vasodilator challenge. In this retrospective analysis of patients identified as acute vasoresponders, treated with CCBs, all patients had hemodynamic measurements in three steps: (1) at baseline; (2) with 100% fractional inspired oxygen; and (3) with 100% fractional inspired oxygen plus inhaled nitric oxide (iNO). Those meeting the definition of acute vasoresponsiveness only after first normalizing for the effects of oxygen in step 2 were labeled "iNO Responders." Those who met the definition of acute vasoresponsiveness from a combination of the effects of 100% FiO2 and iNO were labeled "oxygen responders." Survival, hospitalization for decompensated right heart failure, duration of CCB monotherapy, and functional data were collected. iNO responders, when compared to oxygen responders, had superior survival (100% vs. 50.1% 5-year survival, respectively), fewer hospitalizations for acute decompensated right heart failure (0% vs. 30.4% at 1 year, respectively), longer duration of CCB monotherapy (80% vs. 52% at 1 year, respectively), and superior 6-min walk distance. Current guidelines for acute vasodilator testing do not standardize oxygen coadministration with iNO. This study demonstrates that adjusting for the effects of supplemental oxygen before assessing for acute vasoresponsiveness identifies a cohort with superior functional status, tolerance of CCB monotherapy, and survival while on long-term CCB therapy.

Disruption in glutathione metabolism and altered energy production in the liver and kidney after ischemic acute kidney injury in mice.

Acute kidney injury (AKI) is a systemic disease that affects energy metabolism in various remote organs in murine models of ischemic AKI. However, AKI-mediated effects in the liver have not been comprehensively assessed. After inducing ischemic AKI in 8-10-week-old, male C57BL/6 mice, mass spectrometry metabolomics revealed that the liver had the most distinct phenotype 24 h after AKI versus 4 h and 7 days. Follow up studies with in vivo [13C6]-glucose tracing on liver and kidney 24 h after AKI revealed 4 major findings: (1) increased flux through glycolysis and the tricarboxylic (TCA) cycle in both kidney and liver; (2) depleted hepatic glutathione levels and its intermediates despite unchanged level of reactive oxygen species, suggesting glutathione consumption exceeds production due to systemic oxidative stress after AKI; (3) hepatic ATP depletion despite unchanged rate of mitochondrial respiration, suggesting increased ATP consumption relative to production; (4) increased hepatic and renal urea cycle intermediates suggesting hypercatabolism and upregulation of the urea cycle independent of impaired renal clearance of nitrogenous waste. Taken together, this is the first study to describe the hepatic metabolome after ischemic AKI in a murine model and demonstrates that there is significant liver-kidney crosstalk after AKI.

Two-axis MEMS scanner with transfer-printed high-reflectivity, broadband monolithic silicon photonic crystal mirrors.

We present a two-axis electrostatic MEMS scanner with high-reflectivity monolithic single-crystal-silicon photonic crystal (PC) mirrors suitable for applications in harsh environments. The reflective surfaces of the MEMS scanner are transfer-printed PC mirrors with low polarization dependence, low angular dependence, and reflectivity over 85% in the wavelength range of 1490nm~1505nm and above 90% over the wavelength band of 1550~1570nm. In static mode, the scanner has total scan range of 10.2° on one rotation axis and 7.8° on the other. Dynamic operation on resonance increase the scan range to 21° at 608Hz around the outer rotation axis and 9.5° at 1.73kHz about the inner rotation axis.

Relationship Between a State-Directed Lockdown on Non-COVID-19-related ICU Admissions and Mortality in a Multicenter Colorado Healthcare System.

Colorado issued a month long statewide lockdown on March 26, 2020, during the initial surge of the COVID-19 pandemic. The impact of this mandate on non-COVID-19 ICU admission rates and outcomes is unclear. DESIGN: We performed a retrospective analysis of all medical ICU admissions in the University of Colorado Health System in four predefined periods: 1) prepandemic (2 mo prior to lockdown period 1); 2) mandated lockdown from March 26 to April 26, 2020 (period 2); 3) between surges (period 3); and 4) nonmandated lockdown surge (between November 1, 2020, and March 31, 2021, period 4). SETTING: Nonsurgical ICU admissions at the University of Colorado Health Systems, including 10 hospitals throughout Colorado. SUBJECTS: All ICU admissions in four predefined time periods. MEASUREMENTS AND MAIN RESULTS: We included 13,787 patients who were admitted during the four study periods. The 28-day mortality rates for non-COVID-19 ICU admissions following index ICU admission were 13.6%, 18.0%, 13.5%, and 16.0% across periods 1-4, respectively. However, the increased odds in non-COVID-19 ICU mortality during the mandated lockdown period relative to prepandemic 1 (odds ratio [OR], 1.39; 95% CI, 1.11-1.72; p = 0.0.04) was attenuated and nonsignificant after adjustment for demographics, comorbidities, diagnosis flags, and severity (OR, 1.15; 95% CI, 0.89-1.48; p = 0.27). Similar results were found in time-to-event analyses. The most common diagnosis in each time period was acute respiratory failure (ARF), and we found it to have increased during lockdown (p < 0.001), whereas sepsis admissions increased during and decreased after lockdown (p = 0.004). Admissions for alcohol withdrawal syndrome (AWS) increased during lockdown and 6 months afterwards (p = 0.005). CONCLUSIONS: For non-COVID-19-related ICU admissions, mortality rate was similar before, during, and after Colorado's month long lockdown after confounder adjustment, including typical ICU admission flags. Primary admission diagnoses shifted throughout the predefined study periods with more admissions for severe critical diagnoses (i.e., ARF, sepsis, AWS) occurring during the mandated lockdown and nonmandated lockdown periods compared with the prepandemic and between surge period. This would suggest that the perceived increase in mortality during the lockdown for non-COVID-19 ICU admissions may be related to a shift inpatient demographics.

Acute Kidney Injury and Acute Respiratory Distress Syndrome.

Acute kidney injury (AKI) complicates approximately a third of all acute respiratory distress syndrome (ARDS) cases, and the combination of the two drastically worsens prognosis. Recent advances in ARDS supportive care have led to improved outcomes; however, much less is known on how to prevent and support patients with AKI and ARDS together. Understanding the dynamic relationship between the kidneys and lungs is crucial for the practicing intensivist to prevent injury. This article summarizes key concepts for the critical care physician managing a patient with ARDS complicated by AKI. Also provided is a discussion of AKI in the COVID-19 era.

Longitudinal Associations of Fitness and Obesity in Young Adulthood With Right Ventricular Function and Pulmonary Artery Systolic Pressure in Middle Age: The CARDIA Study.

Background Low cardiorespiratory fitness (CRF) and obesity are risk factors for heart failure but their associations with right ventricular (RV) systolic function and pulmonary artery systolic pressure (PASP) are not well understood. Methods and Results Participants in the CARDIA (Coronary Artery Risk Development in Young Adults) study who underwent maximal treadmill testing at baseline and had a follow-up echocardiographic examination at year 25 were included. A subset of participants had repeat CRF and body mass index (BMI) assessment at year 20. The associations of baseline and changes in CRF and BMI on follow-up (baseline to year 20) with RV systolic function parameters (tricuspid annular plane systolic excursion, RV Doppler systolic velocity of the lateral tricuspid annulus), and PASP were assessed using multivariable-adjusted linear regression models. The study included 3433 participants. In adjusted analysis, higher baseline BMI but not CRF was significantly associated with higher PASP. Among RV systolic function parameters, higher baseline CRF and BMI were significantly associated with higher tricuspid annular plane systolic excursion and RV systolic velocity of the lateral tricuspid annulus. In the subgroup of participants with follow-up assessment of CRF or BMI at year 20, less decline in CRF was associated with higher RV systolic velocity of the lateral tricuspid annulus and lower PASP, while greater increase in BMI was significantly associated with higher PASP in middle age. Conclusions Higher CRF in young adulthood and less decline in CRF over time are each significantly associated with better RV systolic function. Higher baseline BMI and greater age-related increases in BMI are each significantly associated with higher PASP in middle age. These findings provide insights into possible mechanisms through which low fitness and obesity may contribute toward risk of heart failure.

A 62-Year-Old Woman With Diffuse Myalgias, Fatigue, and Shortness of Breath.

CASE PRESENTATION: A 62-year-old woman with a history of partially treated Graves disease and hypertension presented with approximately 3 weeks of worsening fatigue, lower extremity myalgias, and shortness of breath. Her medical history included a thyroid radiofrequency ablation several years earlier. Following the ablation, she was found to have some residual thyroid activity, negating the need for therapy. She was lost to follow-up after months of normal thyroid-stimulating hormone values. On this presentation, the patient was noted to be in atrial fibrillation with a rapid ventricular rate, and although she presented alert and oriented initially, she developed progressive inattentiveness and confusion while in the ED. The patient was transferred to the medical ICU for further management of her rapid heart rate and progressive delirium.

Effect of Exercise and Pharmacological Interventions on Visceral Adiposity: A Systematic Review and Meta-analysis of Long-term Randomized Controlled Trials.

OBJECTIVE: To assess the effectiveness of exercise and pharmacotherapy interventions in reducing visceral adipose tissue (VAT). PATIENTS AND METHODS: A systematic search of Ovid MEDLINE, Scopus, Web of Science, Cochrane Library, ClinicalTrials.gov, New York Academy of Science Grey Literature Report, and OpenGrey was combined with hand searches of existing literature. A total of 2515 titles and abstracts were reviewed. Only randomized controlled trials evaluating the effectiveness of monitored exercise or pharmacological interventions in reducing VAT by using computed tomography or magnetic resonance imaging during a sustained intervention period (≥6 months) were included. Data were independently extracted by reviewers according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and assessed for quality and risk of bias. Separate analyses for each intervention were performed using random effect models, with pooled estimates of the change in VAT area (in centimeters squared) from baseline to follow-up reported as standardized mean difference (SMD; with 95% CI). RESULTS: A total of 3602 participants from 17 randomized controlled trials were included in the final analysis. Both exercise and pharmacological interventions were associated with significant reductions in VAT: small reduction with pharmacological interventions (SMD, -0.27; 95% CI, -0.47 to -0.07; P=.02) and more substantial reductions with exercise interventions (SMD, -0.54; 95% CI, -0.63 to -0.46; P<.001). The mean absolute VAT reduction was greater in pharmacological trials than in exercise trials. Meta-regression exhibited a linear correlation between VAT and weight loss (R2=0.52 for exercise and R2=0.88 for pharmacological interventions), but VAT reduction relative to weight loss differed by intervention type. CONCLUSION: Exercise interventions resulted in greater reduction in VAT relative to weight loss than did pharmacological interventions. A preferential reduction in VAT may be clinically meaningful when monitoring success of interventions because weight loss alone may underestimate benefits.

Relative Impairments in Hemodynamic Exercise Reserve Parameters in Heart Failure With Preserved Ejection Fraction: A Study-Level Pooled Analysis.

OBJECTIVES: The aim of this study was to compare the relative impairment in different exercise hemodynamic reserve parameters in patients with heart failure with preserved ejection fraction (HFpEF) and control patients using a study-level meta-analysis. BACKGROUND: A cardinal manifestation of chronic HFpEF is severely decreased exercise capacity. Developing effective therapies for exercise intolerance in HFpEF requires optimal understanding of the factors underlying exercise intolerance. METHODS: Data were included from 17 unique cohorts that measured peak oxygen uptake and hemodynamic or echocardiographic parameters during exercise in patients with HFpEF and control subjects in this meta-analysis. Standardized mean differences (SMDs) in the exercise reserve (exercise - resting) measures of hemodynamic or echocardiographic parameters between the HFpEF and control groups were pooled in a random-effects meta-analysis. RESULTS: The pooled analysis included 910 patients with HFpEF and 476 control subjects. In pooled analysis, patients with HFpEF had significantly lower peak oxygen uptake (SMD: -2.13; 95% confidence interval [CI]: -2.68 to -1.57). Among hemodynamic exercise reserve parameters, the largest impairment was observed in chronotropic response reserve (change in heart rate from rest to peak exercise; SMD: -1.87; 95% CI: -2.44 to -1.29), followed by exaggerated increase in pulmonary capillary wedge pressure with exercise (SMD: 1.78; 95% CI: 1.46 to 2.09). Significant abnormalities were also observed in the arteriovenous oxygen difference reserve and stroke volume reserve between the HFpEF and control groups. CONCLUSIONS: The most consistent and severe hemodynamic reserve abnormalities observed in patients with HFpEF were impairment in chronotropic reserve and exaggerated increase in pulmonary capillary wedge pressure with exercise. These may be important targets for therapeutic strategies to improve exercise tolerance in patients with HFpEF.

Relationship of Cardiorespiratory Fitness and Adiposity With Left Ventricular Strain in Middle-Age Adults (from the Dallas Heart Study).

Low cardiorespiratory fitness (CRF) and obesity are significant risk factors for heart failure (HF). However, given the inverse association between CRF and obesity, the independent contributions of low CRF and adiposity toward HF risk are not well established. We evaluated the association of CRF and measures of adiposity with left ventricular (LV) peak systolic strain-a subclinical measure of LV dysfunction-among the Dallas Heart Study phase II participants without cardiovascular disease who had CRF estimated using a submaximal treadmill test and LV systolic circumferential strain assessment by tissue-tagged cardiac magnetic resonance imaging. Peak midwall systolic circumferential strain (Ecc) was determined by harmonic phase imaging. Associations of CRF and adiposity measures with Ecc were determined using adjusted linear regression analysis. A total of 1,617 participants were included in the analysis. After adjustment for baseline risk factors, higher waist circumference (WC) and lower CRF were associated with higher Ecc (WC: ß = 0.07; p = 0.01; CRF: ß = -0.17; p = < 0.0001), whereas % body fat and body mass index were not associated with Ecc. The relationship between WC and Ecc was attenuated completely after additional adjustment for CRF. In contrast, the association between CRF and Ecc did not attenuate after additional adjustment for WC and other measures of LV structure and function (ß = -0.18; p = < 0.0001). Taken together, our study findings suggest that lower CRF, but not measures of adiposity, is associated with greater impairment in LV strain independent of LV mass and ejection fraction.

Determinants of Racial/Ethnic Differences in Cardiorespiratory Fitness (from the Dallas Heart Study).

Previous studies have demonstrated ethnic/racial differences in cardiorespiratory fitness (CRF). However, the relative contributions of body mass index (BMI), lifestyle behaviors, socioeconomic status (SES), cardiovascular (CV) risk factors, and cardiac function to these differences in CRF are unclear. In this study, we included 2,617 Dallas Heart Study participants (58.6% women, 48.6% black; 15.7% Hispanic) without CV disease who underwent estimation of CRF using a submaximal exercise test. We constructed multivariable-adjusted linear regression models to determine the association between race/ethnicity and CRF, which was defined as peak oxygen uptake (ml/kg/min). Black participants had the lowest CRF (blacks: 26.3 ± 10.2; whites: 29.0 ± 9.8; Hispanics: 29.1 ± 10.0 ml/kg/min). In multivariate analysis, both black and Hispanic participants had lower CRF after adjustment for age and gender (blacks: Std ß = -0.15; p value ≤0.0001, Hispanics: Std ß = -0.05, p value = 0.01; ref group: whites). However, this association was considerably attenuated for black (Std ß = -0.04, p value = 0.03) and no longer significant for Hispanic ethnicity (p value = 0.56) after additional adjustment for BMI, lifestyle factors, SES, and CV risk factors. Additional adjustment for stroke volume did not substantially change the association between black race/ethnicity and CRF (Std ß = -0.06, p value = 0.01). In conclusion, BMI, lifestyle, SES, and traditional risk factor burden are important determinants of ethnicity-based differences in CRF.