Colorimetric capnography to ensure correct nasogastric tube position

Purpose

We evaluate a procedure, combining colorimetric capnography with epigastric auscultation, to ensure nasogastric (NG) feeding tube correct position without any radiograph.

Methods

We first evaluated the accuracy of colorimetric capnography in detecting tracheal positioning in a control group of 100 mechanically ventilated patients. The procedure was thereafter evaluated in a study group including patients requiring an NG tube. The NG tube was first inserted 30 cm and connected to a colorimetric capnograph (first step). If the capnograph did not detect carbon dioxide, insertion was completed to a total distance of 50 cm. An epigastric auscultation after air insufflation and a second capnography (second step) were performed. A radiograph evaluated correct tube position.

Results

In the control group, colorimetric capnograph sensitivity to detect tracheal placement was 100%. In the study group, negative predictive value of first-step capnography to rule out tracheobronchial insertion was 100%. The association of a first-step negative capnography with a positive epigastric auscultation correctly identified all but one gastric insertions, yielding a sensitivity of 98.5% (95% confidence interval, 95.7-100). The positive predictive value of this association to detect gastric placement was 100%.

Conclusion

Colorimetric capnography combined with epigastric auscultation is safe and accurate in ensuring correct gastric tube insertion.     

At-risk but viable myocardium in a large animal model of non ST-segment elevation acute coronary syndrome: cardiovascular magnetic resonance with ex vivo validation

Background

Patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) have varying degrees of salvageable myocardium at risk of irreversible injury. We hypothesized that a novel model of NSTE-ACS produces acute myocardial injury, measured by increased T2 cardiovascular magnetic resonance (CMR), without significant necrosis by late gadolinium enhancement (LGE).

Methods

In a canine model, partial coronary stenosis was created and electrodes placed on the epicardium. Myocardial T2, an indicator of at-risk myocardium, was measured pre- and post-tachycardic pacing.

Results

Serum troponin-I (TnI) was not detectable in unoperated sham animals but averaged 1.97 ± 0.72 ng/mL in model animals. Coronary stenosis and pacing produced significantly higher T2 in the affected vs. the remote myocardium (53.2 ± 4.9 vs. 43.6 ± 2.8 ms, p < 0.01) with no evident injury by LGE. Microscopy revealed no significant irreversible cellular injury. Relative respiration rate (RRR) of affected vs. remote myocardial tissue was significantly lower in model vs. sham animals (0.72 ± 0.07 vs. 1.04 ± 0.07, p < 0.001). Lower RRR corresponded to higher final TnI levels (R² = 0.83, p = 0.004) and changes in CaMKIID and mitochondrial gene expression.

Conclusions

A large animal NSTE-ACS model with mild TnI elevation and without ST elevation, similar to the human syndrome, demonstrates signs of acute myocardial injury by T2-CMR without significant irreversible damage. Reduced tissue respiration and associated adaptations of critical metabolic pathways correspond to increased myocardial injury by serum biomarkers in this model. T2-CMR as a biomarker of at-risk but salvageable myocardium warrants further consideration in preclinical and clinical studies of NSTE-ACS.     

Review of Recently Approved Alternatives to Anticoagulation with Warfarin for Emergency Clinicians

Background

Dabigatran and rivaroxaban are novel anticoagulants that have been approved for the prevention of thromboembolic events in atrial fibrillation. These medications are attractive to both patients and clinicians, as, unlike warfarin, they do not require laboratory monitoring or dietary restrictions. However, they carry bleeding risks similar to that of warfarin and are without a reliable reversal agent.

Objectives

The objectives of this article are to 1) summarize the pivotal trials leading to the U.S. Food and Drug Administration approvals of dabigatran (Pradaxa; Boehringer Ingelheim, Ridgefield, CT) and rivaroxaban (Xarelto; Janssen Pharmaceuticals, Inc., Titusville, NJ); 2) present the limited data available regarding the management of bleeding patients on these agents; and 3) provide suggestions to guide emergency providers given the limited data.

Discussion

Dabigatran and rivaroxaban were approved based on large, non-inferiority trials comparing the new agents to warfarin with stroke or systemic embolism as the primary outcome. Traditional coagulation studies cannot be used to determine the degree of anti-coagulation produced by these agents. Fresh frozen plasma is unlikely to be effective in patients on these drugs who are acutely bleeding. Prothrombin complex concentrate can be considered in patients on rivaroxaban. Dabigatran is renally cleared, so dabigatran could be removed by hemodialysis. Theoretically, DDAVP (Sanofi-Aventis U.S. LLC, Bridgewater, NJ), aminocaproic acid, tranexamic acid, or recombinant activated factor VII could also be used in an attempt to control bleeding.

Conclusion

There is a need for assays for the degree of anticoagulation produced by drugs such as dabigatran and rivaroxaban. Additionally, studies are needed to evaluate reversal agents that could be effective in the setting of acute bleeding.     

Correlation of the Tei index with invasive measurements of ventricular function in a porcine model.

BACKGROUND: The Doppler myocardial performance (Tei) index has been reported to be clinically useful in assessing left ventricular systolic and diastolic function in both adults and children. However, there are limited data to compare the Tei index with invasive measurements of ventricular function. We used a porcine model to directly correlate the Tei index with invasive indices of systolic and diastolic function. METHODS: Pressure volume loops were obtained from 10 pigs (32-45 kg). A micromanometer and a conductance catheter were placed in the left ventricle to record pressure and volume, respectively. A flow probe was placed around the ascending aorta to record cardiac output. Baseline pressure volume loops were generated during preload reduction through caval occlusion. Epicardial echocardiograms were performed just before the caval occlusion. Invasive indices including preload recruitable stroke work, ventricular stiffness constant, and cardiac output were assessed, as were noninvasive echocardiographic indices including Tei index and ejection fraction. An ischemic insult, ventricular fibrillation, was induced to alter ventricular function. After cardioversion and 40 minutes of reperfusion, echocardiographic and invasive measurements were repeated. RESULTS: There was a statistically significant inverse relationship between the percent change in Tei and the percent change in preload recruitable stroke work after ventricular fibrillation (r = -0.70, P =.02), although the correlation between the actual values of Tei and preload recruitable stroke work were not statistically significant. There was a statistically significant inverse relationship between the percent change in Tei and the percent change in cardiac output (r = -0.65, P =.03). There was a direct correlation between the value of Tei and the ventricular stiffness constant at baseline (r = 0.63, P <.05). As anticipated, the value of Tei was inversely related to ejection fraction by epicardial echocardiogram at baseline (r = -0.85, P <.001). The percent change in Tei was inversely related to the percent change in ejection fraction as well (r = -0.69, P <.05). CONCLUSIONS: This animal model is one of the first studies to demonstrate a direct correlation between the Tei index and systolic and diastolic invasive measurements of ventricular function. This supports the clinical use of this index as a measure of global ventricular function.     

Bioactive acylphloroglucinols from Hypericum densiflorum

Three acylphloroglucinol derivatives have been isolated from the hexane and acetone extracts of the aerial parts of Hypericum densiflorum Pursch. The compounds were characterized by NMR spectroscopy and mass spectrometry and identified as 4‐geranyloxy‐2,6‐dihydroxybenzophenone (1), 4‐geranyloxy‐1‐(2‐methylpropanoyl)‐ phloroglucinol (2) and 4‐geranyloxy‐1‐(2‐methylbutanoyl)‐phloroglucinol (3). Compounds 1–3 were evaluated for in vitro cell proliferation inhibitory activity against human breast (MCF‐7), lung (NCI H460), CNS (SF‐268), stomach (AGS) and colon (HCT‐116) tumor cell lines; antibacterial activity against methicillin‐resistant Staphylococcus aureus (MRSA); inhibition of cyclooxygenase (COX‐1 and ‐2) enzymes; and antioxidant activity in the lipid peroxidation (LPO) assay. All three compounds showed moderate to strong antitumor, antibacterial, antioxidant and inhibition of COX‐2 activities. Also, this is the first reported occurrence of compound 3 in the Hypericum genus. Copyright © 2009 John Wiley & Sons, Ltd.     

ZRSR1 co-operates with ZRSR2 in regulating splicing of U12-type introns in murine hematopoietic cells

Recurrent loss-of-function mutations of spliceosome gene, ZRSR2, occur in myelodysplastic syndromes (MDS). Mutation/loss of ZRSR2 in human myeloid cells primarily causes impaired splicing of the U12-type introns. In order to further investigate the role of this splice factor in RNA splicing and hematopoietic development, we generated mice lacking ZRSR2. Unexpectedly, Zrsr2-deficient mice developed normal hematopoiesis with no abnormalities in myeloid differentiation evident in either young or ≥1-year old knockout mice. Repopulation ability of Zrsr2-deficient hematopoietic stem cells was also unaffected in both competitive and non-competitive reconstitution assays. Myeloid progenitors lacking ZRSR2 exhibited mis-splicing of U12-type introns, however, this phenotype was moderate compared to the ZRSR2-deficient human cells. Our investigations revealed that a closely related homolog, Zrsr1, expressed in the murine hematopoietic cells, but not in human cells contributes to splicing of U12-type introns. Depletion of Zrsr1 in Zrsr2 KO myeloid cells exacerbated retention of the U12-type introns, thus highlighting a collective role of ZRSR1 and ZRSR2 in murine U12-spliceosome. We also demonstrate that aberrant retention of U12-type introns of MAPK9 and MAPK14 leads to their reduced protein expression. Overall, our findings highlight that both ZRSR1 and ZRSR2 are functional components of the murine U12-spliceosome, and depletion of both proteins is required to accurately model ZRSR2-mutant MDS in mice.     

Real-World Treatment Patterns and Clinical Effectiveness of Palbociclib Plus an Aromatase Inhibitor as First-Line Therapy in Advanced/Metastatic Breast Cancer: Analysis from the US Syapse Learning Health Network

This retrospective single-arm study assessed real-world treatment patterns and clinical outcomes in patients with hormone receptor—positive/human epidermal growth factor receptor 2—negative (HR+/HER2−) advanced/metastatic breast cancer (A/MBC) who received palbociclib plus an aromatase inhibitor as first-line therapy in US community health systems. Using electronic health records from the Syapse Learning Health Network, 242 patients were identified as having received first-line palbociclib plus an aromatase inhibitor between 3 February 2015, and 31 July 2019 (data cutoff 1 February 2020) resulting in a minimum potential 6-month follow-up period. In total, 56.6% of patients had de novo A/MBC at initial breast cancer diagnosis, 50.8% had bone-only disease, and 32.2% had visceral disease. Median follow-up was 22.4 months. Disease progression (26.4%) and intolerance/toxicity (14.9%) were the main reasons for treatment discontinuation. The median (95% CI) real-world progression-free survival was 31.7 (27.9—not estimable (NE)) months and 2-year estimated overall survival (OS) rate was 78.0%. In total, 25.6% of patients died; however, OS data are limited by the small population size and insufficient follow-up time. These real-world effectiveness outcomes complement findings from other real-world studies and randomized controlled trials and support palbociclib plus an aromatase inhibitor as first-line therapy for HR+/HER2− A/MBC.