Considerations for instituting pediatric pulmonary embolism response teams: A tool kit.

The incidence of pediatric pulmonary embolism (PE) has increased by 200 % in the last decade, but at a single center, it is still infrequent. Given the unique epidemiologic features of pediatric PE, diagnosis is often delayed, and the management is empiric, based on individual physician experience or preference. Thus, there is a strong need for center-specific uniform management of pediatric PE patients. In adults, the development of pulmonary embolism response teams (PERTs) or PE critical care pathways has shortened the time to diagnosis and the initiation of definitive management. Evidence to support an improvement in PE outcomes after the development of PERTs does not exist in children. Nonetheless, we have summarized the practical practice guidelines that physicians and institutions can adopt to establish their institutional PERTs or critical pathways. We also provide strategies for resource-challenged institutions for partnering with centers with expertise in the management of pediatric PE.

Beneficial Effects of Dietary Flaxseed on Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD), a significant cause of chronic liver disease, presents a considerable public health concern. Despite this, there is currently no treatment available. This study aimed to investigate dietary flaxseed in the JCR:LA-corpulent rat strain model of NAFLD. Both obese male and female rats were studied along with their lean counterparts after 12 weeks of ingestion of a control diet, or control diet with flaxseed, or high fat, high sucrose (HFHS), or HFHS plus flaxseed. Obese rats showed higher liver weight and increased levels of cholesterol, triglyceride, and saturated fatty acid, which were further elevated in rats on the HFHS diet. The HFHS diet induced a significant two-fold elevation in the plasma levels of both aspartate aminotransferase and alanine aminotransferase in the obese male and female rats. Including flaxseed in the HFHS diet significantly lowered liver weight, depressed the plasma levels of both enzymes in the obese male rats, and reduced hepatic cholesterol and triglyceride content as well as improving the fatty acid profile. In summary, including flaxseed in the diet of male and female obese rats led to an improved lipid composition in the liver and significantly reduced biomarkers of tissue injury despite consuming a HFHS chow.

Preoperative Workup of Patients With Excessive Central Airway Collapse: Does Stent Evaluation Serve a Role?

BACKGROUND: Tracheobronchoplasty (TBP) is a definitive anatomic intervention for patients with severe symptomatic expiratory central airway collapse. Although stent evaluations have been described for surgical workup, current literature does not address if improvement during stent evaluation is sustained after TBP. We compared health-related quality of life (HRQOL) and functional status responses after airway stenting to those post-TBP. METHODS: A retrospective review was performed in patients with severe expiratory central airway collapse who underwent stent evaluation followed by TBP from January 2004 to December 2019. Baseline, poststent, 3- and 12-month postoperative HRQOL scores, and functional status were analyzed with statistical tests as appropriate. RESULTS: One hundred twenty patients underwent a stent evaluation and TBP. Baseline and stent evaluation measurements were compared with statistically and clinically significant differences in the Cough Quality-of-life Questionnaire (CQLQ) (55 vs. 68, P <0.01), Modified Medical Research Council (mMRC) 0 to 2 (90% vs. 47%, P <0.01), 6-minute walk test (6MWT) (1301 ft vs. 1138 ft, P <0.01). Improvements in the HRQOL and functional status were maintained from stent evaluation to 3 months postoperatively [CQLQ 55 vs. 54, P =0.63; mMRC 0 to 2 (87% vs. 84%), P =0.39; 6MWT 1350 ft vs. 1314 ft, P =0.33], and 12 months postoperatively [CQLQ 54 vs. 54, P =0.91; mMRC 0 to 2 (95% vs. 86%), P =0.74; 6MWT 1409 ft vs. 1328 ft, P =0.13]. The magnitude of change between the data was not significantly different between the stent evaluation, 3-, and 12 months postoperative. Predicted forced expiratory volume in 1-second measurements at baseline, after stent placement, 3 months, and 12 months post-TBP were 74%, 79%, 73%, and 73%, respectively, and not clinically significant. CONCLUSIONS: Improvement after stent evaluation and the magnitude of improvement may be predictive of postoperative outcomes up to 1 year after surgery.

Considerations for choosing an optimal animal model of cardiovascular disease.

The decision to use the optimal animal model to mimic the various types of cardiovascular disease is a critical one for a basic scientist. Clinical cardiovascular disease can be complex and presents itself as atherosclerosis, hypertension, ischemia/reperfusion injury, myocardial infarcts, and cardiomyopathies, amongst others. This may be further complicated by the simultaneous presence of two or more cardiovascular lesions (for example, atherosclerosis and hypertension) and co-morbidities (i.e., diabetes, infectious disease, obesity, etc). This variety and merging of disease states creates an unusually difficult situation for the researcher who needs to identify the optimal animal model that is available to best represent all of the characteristics of the clinical cardiovascular disease. The present manuscript reviews the characteristics of the various animal models of cardiovascular disease available today, their advantages and disadvantages, with the goal to allow the reader access to the most recent data available for optimal choices prior to the initiation of the study. The animal species that can be chosen, the methods of generating these models of cardiovascular disease, as well as the specific cardiovascular lesions involved in each of these models are reviewed. A particular focus on the JCR:LA-cp rat as a model of cardiovascular disease is discussed.

Cardiomyocyte and endothelial cells play distinct roles in the tumour necrosis factor (TNF)-dependent atrial responses and increased atrial fibrillation vulnerability induced by endurance exercise training in mice.

AIMS: Endurance exercise is associated with an increased risk of atrial fibrillation (AF). We previously established that adverse atrial remodelling and AF susceptibility induced by intense exercise in mice require the mechanosensitive and pro-inflammatory cytokine tumour necrosis factor (TNF). The cellular and mechanistic basis for these TNF-mediated effects is unknown. METHODS AND RESULTS: We studied the impact of Tnf excision, in either atrial cardiomyocytes or endothelial cells (using Cre-recombinase expression controlled by Nppa or Tie2 promoters, respectively), on the cardiac responses to six weeks of intense swim exercise training. TNF ablation, in either cell type, had no impact on the changes in heart rate, autonomic tone, or left ventricular structure and function induced by exercise training. Tnf excision in atrial cardiomyocytes did, however, prevent atrial hypertrophy, fibrosis, and macrophage infiltration as well as conduction slowing and increased AF susceptibility arising from exercise training. In contrast, endothelial-specific excision only reduced the training-induced atrial hypertrophy. Consistent with these cell-specific effects of Tnf excision, inducing TNF loss from atrial cardiomyocytes prevented activation of p38MAPKinase, a strain-dependent downstream mediator of TNF signalling, without affecting the atrial stretch as assessed by atrial pressures induced by exercise. Despite TNF's established role in innate immune responses and inflammation, neither acute nor chronic exercise training caused measurable NLRP3 inflammasome activation. CONCLUSIONS: Our findings demonstrate that adverse atrial remodelling and AF vulnerability induced by intense exercise require TNF in atrial cardiomyocytes whereas the impact of endothelial-derived TNF is limited to hypertrophy modulation. The implications of the cell autonomous effects of TNF and crosstalk between cells in the atria are discussed.

Tracheobronchoplasty yields long-term anatomy, function, and quality of life improvement for patients with severe excessive central airway collapse.

OBJECTIVES: This study examines the long-term anatomic and clinical effects of tracheobronchoplasty in severe excessive central airway collapse. METHODS: Included patients underwent tracheobronchoplasty for excessive central airway collapse (2002-2016). The cross-sectional area of main airways on dynamic airway computed tomography was measured before and after tracheobronchoplasty. Expiratory collapse was calculated as the difference between inspiratory and expiratory cross-sectional area divided by inspiratory cross-sectional area ×100. The primary outcome was improvement in the percentage of expiratory collapse in years 1, 2, and 5 post-tracheobronchoplasty. Secondary outcomes included mean response profile for the 6-minute walk test, Cough-Specific Quality of Life Questionnaire, Karnofsky Performance Status score, and St George Respiratory Questionnaire. Repeated-measures analysis of variance was used for statistical analyses. RESULTS: The cohort included 61 patients with complete radiological follow-up at years 1, 2, and 5 post-tracheobronchoplasty. A significant linear decrease in the percentage of expiratory collapsibility of the central airways after tracheobronchoplasty was present. Anatomic repair durability was preserved 5 years after tracheobronchoplasty, with decrease in percentage of expiratory airway collapse up to 40% and 30% at years 1 and 2, respectively. The St George Respiratory Questionnaire (74.7 vs 41.8%, P < .001) and Cough-Specific Quality of Life Questionnaire (78 vs 47, P < .001) demonstrated significant improvement at year 5 compared with baseline. Similar results were observed in the 6-minute walk test (1079 vs 1268 ft, P < .001) and Karnofsky score (57 vs 82, P < .001). CONCLUSIONS: Tracheobronchoplasty has durable effects on airway anatomy, functional status, and quality of life in carefully selected patients with severe excessive central airway collapse.

Stent Evaluation for Expiratory Central Airway Collapse: Does the Type of Stent Really Matter?

BACKGROUND: Careful selection of patients with expiratory central airway collapse (ECAC) that may benefit from tracheobronchoplasty (TBP) can be aided by a short-term airway stent evaluation. This can be performed with either silicone Y-stents (SYSs) or uncovered self-expanding metallic airway-stents (USEMAS). No direct comparison has been made between these 2 stent types. METHODS: This was a small retrospective review of consecutive patients that underwent a stent evaluation. A propensity score was used to match patients in the USEMAS and SYS groups. Outcomes included complications, changes in the health-related quality-of-life (HR-QoL), and changes in exercise capacity. Baseline measurements were compared with those obtained during stent evaluation and after TBP. RESULTS: Forty-two patients with severe ECAC underwent USEMAS placement, while 18 patients had an SYS placed. Propensity score matching resulted in 13 matched SYS and USEMAS pairs. The SYS group had an increased rate of mucus plugging (38.5% vs. 0%, P <0.047). Although not statically significant, a clinical improvement was observed in HR-QoL and exercise capacity in the USEMAS group during stent placement. In patients who underwent TBP, both USEMAS and SYS groups had a statistically significant change in the Modified Medical Research Council Dyspnea Scale during stent evaluation and after TBP. CONCLUSION: In patients with severe ECAC, short-term evaluation with airway stents appears to be safe and improves respiratory symptoms, HR-QoL, and exercise capacity. The use of USEMAS led to a lower complication rate, a greater improvement in HR-QoL and exercise capacity, and appeared to better predict how the patients would respond to TBP.

Pleural Disease in Acute COVID-19 Pneumonia: A Single Center Retrospective Cohort Study.

BACKGROUND: Pleural diseases encompass pleural effusion and pneumothorax (PTX), both of which were uncommon in coronavirus disease of 2019 (COVID-19). We aimed to describe the frequency, characteristics, and main outcomes of these conditions in patients with COVID-19 pneumonia. METHODS: We performed a retrospective cohort analysis of inpatients with COVID-19 pneumonia between January 1, 2020 and January 1, 2022, at Beth Israel Deaconess Medical Center in Boston, Massachusetts. RESULTS: Among 4419 inpatients with COVID-19 pneumonia, 109 (2.5%) had concurrent pleural disease. Ninety-four (2.1%) had pleural effusion (50% seen on admission) and 15 (0.3%) had PTX, both with higher rates of underlying conditions such as heart failure, liver disease, kidney disease, and malignancy. A total of 28 (30%) pleural effusions were drained resulting in 32% being exudative, 43% pseudoexudative, and 25% transudative. Regarding PTX, 5 (33%) were spontaneous and 10 (67%) were due to barotrauma while on mechanical ventilation. We found that the presence of underlying lung disease was not associated with an increased risk of developing PTX. In addition, patients with pleural disease had a higher incidence of severe or critical illness as represented by intensive care unit admission and intubation, longer hospital and intensive care unit stay, and a higher mortality rate as compared with patients without the pleural disease. CONCLUSION: Pleural effusions and pneumothoraces are infrequent findings in patients admitted due to COVID-19 pneumonia, worsened outcomes in these patients likely reflect an interplay between the severity of inflammation and parenchymal injury due to COVID-19 disease and underlying comorbidities.

Transcriptomic Signatures of End-Stage Human Dilated Cardiomyopathy Hearts with and without Left Ventricular Assist Device Support.

Left ventricular assist device (LVAD) use in patients with dilated cardiomyopathy (DCM) can lead to a differential response in the LV and right ventricle (RV), and RV failure remains the most common complication post-LVAD insertion. We assessed transcriptomic signatures in end-stage DCM, and evaluated changes in gene expression (mRNA) and regulation (microRNA/miRNA) following LVAD. LV and RV free-wall tissues were collected from end-stage DCM hearts with (n = 8) and without LVAD (n = 8). Non-failing control tissues were collected from donated hearts (n = 6). Gene expression (for mRNAs/miRNAs) was determined using microarrays. Our results demonstrate that immune response, oxygen homeostasis, and cellular physiological processes were the most enriched pathways among differentially expressed genes in both ventricles of end-stage DCM hearts. LV genes involved in circadian rhythm, muscle contraction, cellular hypertrophy, and extracellular matrix (ECM) remodelling were differentially expressed. In the RV, genes related to the apelin signalling pathway were affected. Following LVAD use, immune response genes improved in both ventricles; oxygen homeostasis and ECM remodelling genes improved in the LV and, four miRNAs normalized. We conclude that LVAD reduced the expression and induced additional transcriptomic changes of various mRNAs and miRNAs as an integral component of the reverse ventricular remodelling in a chamber-specific manner.

Ion: Technology and Techniques for Shape-sensing Robotic-assisted Bronchoscopy.

PURPOSE: This report describes the Ion Endoluminal System (Intuitive Surgical, Inc, Sunnyvale, CA) and practices for safe and effective use in patients with small peripheral pulmonary nodules (PPNs). DESCRIPTION: This shape-sensing robotic-assisted bronchoscopy system allows airway visualization and navigation to reach and biopsy small PPNs through a stable platform. The system provides 3-dimensional mapping and visualization of the airways, a flexible and fully articulating 3.5-mm (outer diameter) catheter, a peripheral vision probe, and system-specific biopsy needles. EVALUATION: The Ion Endoluminal System was evaluated in an ongoing prospective, multicenter trial including 241 patients with 270 PPNs (largest mean cardinal measurement, 18.8 ± 6.5 mm). Mean time to register and navigate decreased from 10 minutes in the first 10 cases to 7 minutes in the subsequent cases. Asymptomatic pneumothorax occurred in 8 patients (3.3%), 1 (0.4%) with pigtail catheter placement. Two patients (0.8%) experienced airway bleeding; both cases of bleeding resolved within 5 minutes of tamponade. CONCLUSIONS: The Ion Endoluminal System's unique shape-sensing technology can be leveraged to facilitate localization and sampling of PPNs and potentially improve diagnostic accuracy.

Obese Patients Undergoing Tracheobronchoplasty Have Excellent Outcomes.

BACKGROUND: Tracheobronchoplasty (TBP) is the gold-standard treatment for severe symptomatic excessive central airway collapse; however outcomes among obese patients are unknown. METHODS: A retrospective, single-center analysis was conducted on consecutive patients undergoing TBP for severe symptomatic excessive central airway collapse from 2003 to 2020. Demographics, comorbidities, functional status, and perioperative complications were collected. Functional status was assessed with a 6-minute walk test (6MWT). Health-related quality of life (HRQOL) was assessed with the St George's Respiratory Questionnaire (SGRQ), Cough-specific Quality of Life Questionnaire, and modified Medical Research Council dyspnea scale (mMRC) at baseline and postoperatively. Wilcoxon rank-sum and χ2 tests were used to compare outcomes between groups. A mixed-effects regression model compared 6MWT and HRQOL over time. RESULTS: One hundred three patients underwent TBP with complete follow-up data. Thirty-four patients (33%) were obese (body mass index ≥ 35 kg/m2). Baseline demographics were similar between obese and nonobese groups, but obese patients had worse preoperative SGRQ and mMRC scores. Overall complication rates were similar (52.9% vs 43.5%, P = .36). At 3 months there was no significant difference in SGRQ, Cough-specific Quality of Life Questionnaire, or 6MWT scores; however mMRC scores were higher in obese patients (P = .04). At 12 months there was no significant difference in SGRQ, Cough-specific Quality of Life Questionnaire, mMRC, or 6MWT scores. Correcting for age, sex, and Charlson Comorbidity Index a mixed-effects regression model demonstrated obesity was not an independent predictor for lower 6MWT scores or HRQOL. CONCLUSIONS: Obese patients achieve similar improvement in HRQOL and functional capacity with comparable morbidity after TBP as nonobese patients. Obesity should not preclude patients with severe symptomatic excessive central airway collapse from TBP.