We came, we saw, we cannulated?

Introduction: Despite advances in management of patients with severe acute respiratory distress syndrome (ARDS), mortality due to ARDS still remains high. In patients with refractory gas-exchange abnormalities, extracorporeal membrane oxygenation (ECMO) is considered as salvage therapy that aims to decrease ventilator induced lung injury and provide lung rest. injury and provide lung rest. Methods: We conducted a retrospective study of patients diagnosed with ARDS from October 2010 to September 2012. The aim of the study was to describe the population of patients placed on ECMO for ARDS in our institution. All patients placed on ARDSnet protocol were identified in the electronic patient record. Demographic, laboratory and ventilator data was extracted. Specifically mode of ventilation, use of rescue modalities (which included inhaled epoprostenol, skeletal muscle paralytics and/or use of airway pressure release ventilation (APRV)), Murray score, Oxygenation Index (OI), Alveolar-arterial gradient (A-a) and PaO2/FiO2 ratio (P/F) were tabulated. Survival to hospital discharge was recorded. Results: We identified a total of 149 patients. Of these 87 were managed per ARDSnet protocol, 48 received rescue modalities, and 14 patients were placed on ECMO in addition to rescue therapy after a mean interval of 72 hours. Six of 14 patients were placed on veno-arterial ECMO and the rest on veno-venous ECMO. Table 1 shows the baseline characteristics of these patients. Table 2 depicts the etiology of ARDS among our patient population. Mortality was higher in the ARDS group treated with rescue modalities (other than ECMO) compared to the group placed on ECMO as additional rescue therapy (77% vs. 50%; p = 0.3243). The ECMO group had a survival advantage despite higher A-a gradient, PaO2/Fio2 ratio, Oxygenation Index and Murray Score in the ECMO group (Table 1). Conclusion: Patients with ARDS placed on ECMO had an absolute reduction in mortality of 27% when compared to other rescue modalities. However this did not reach statistical significance due to the small sample size. We believe that ECMO is an important rescue modality in the right clinical setting. Treating physicians should consider ECMO as a treatment modality for severe ARDS patients

Left ventricular thrombus found in a patient with ARDS and stress-induced cardiomyopathy requiring veno-arterial ECMO.

Presentation: 68 year-old male with a history of acute leukemia with complete remission after bone marrow transplant 4 months ago, coronary disease s/p LAD stents about 14 years ago with no chronic anti-platelet medication, and repeated episode of DVT despite appropriate anti-coagulation, presented with viral pneumonia (rhinovirus)

Heterologous Protein Expression Is Enhanced by Harmonizing the Codon Usage Frequencies of the Target Gene with those of the Expression Host

Synonymous codon replacement can change protein structure and function, indicating that protein structure depends on DNA sequence. During heterologous protein expression, low expression or formation of insoluble aggregates may be attributable to differences in synonymous codon usage between expression and natural hosts. This discordance may be particularly important during translation of the domain boundaries (link/end segments) that separate elements of higher ordered structure. Within such regions, ribosomal progression slows as the ribosome encounters clusters of infrequently used codons that preferentially encode a subset of amino acids. To replicate the modulation of such localized translation rates during heterologous expression, we used known relationships between codon usage frequencies and secondary protein structure to develop an algorithm (“codon harmonization”) for identifying regions of slowly translated mRNA that are putatively associated with link/end segments. It then recommends synonymous replacement codons having usage frequencies in the heterologous expression host that are less than or equal to the usage frequencies of native codons in the native expression host. For protein regions other than these putative link/end segments, it recommends synonymous substitutions with codons having usage frequencies matched as nearly as possible to the native expression system. Previous application of this algorithm facilitated E. coli expression, manufacture and testing of two Plasmodium falciparum vaccine candidates. Here we describe the algorithm in detail and apply it to E. coli expression of three additional P. falciparum proteins. Expression of the “recoded” genes exceeded that of the native genes by 4- to 1,000-fold, representing levels suitable for vaccine manufacture. The proteins were soluble and reacted with a variety of functional conformation-specific mAbs suggesting that they were folded properly and had assumed native conformation. Codon harmonization may further provide a general strategy for improving the expression of soluble functional proteins during heterologous expression in hosts other than E. coli

Analysis of two methods of isometric muscle contractions during the anti-G straining maneuver

This study investigated the difference in Mean Arterial Pressure (MAP) and Cardiac Output (CO) between two methods of isometric muscle contractions during the Anti-G Straining Maneuver (AGSM). 12 subjects (ages 18 to 38 yrs, height 176.8 +/- 7.4 cm, body mass 78.8 +/- 15.6 kg, percent body fat 14.3 +/- 6.6%) participated in the study. The study was a one-way within-subject design with test conditions counterbalanced. Two methods of isometric muscle contractions lasting 30 seconds each were assessed; an isometric push contraction and an isometric muscle tensing contraction. The dependent parameters were MAP and CO. The average MAP during the push contraction was 123 mmHg, SD +/- 11 and for tense was 118 mmHg, SD +/- 8. CO was 7.6 L/min, SD +/- 1.6 for push and 7.9 L/min, SD +/- 2.0 for tense method. Dependent t-tests revealed t(11) = 1.517, p = 0.157 for MAP and t(11) = 0.875, p = 0.400 for CO. This study demonstrated that the two methods of isometric muscle contractions were not statistically different with regards to MAP and CO. Therefore, both forms of isometric contractions may be potentially useful when performing the muscle contraction portion of the AGSM

Poor Positive Predictive Value of McConnell’s Sign on Transthoracic Echocardiography for the Diagnosis of Acute Pulmonary Embolism

Abstract: Background: Acute pulmonary embolism (PE) is a life-threatening condition. Making a definitive diagnosis with radiologic studies may delay therapy or be unsafe for the patient. Echocardiography is readily available and can suggest PE by demonstrating right ventricular (RV) dysfunction. McConnell’s sign on echocardiogram (ECHO-CG) (RV dysfunction with characteristic sparing of the apex) has been reported to have high sensitivity and specificity for the diagnosis of acute PE. It is hypothesized that McConnell’s sign on ECHO-CG in patients hospitalized with suspected acute PE would have a high positive predictive value (PPV). Methods: Data, from 2005 to 2010, were retrospectively collected on all patients with an ECHO-CG interpreted as revealing McConnell’s sign, who had undergone another diagnostic study (computed tomography pulmonary angiography, ventilation-perfusion scan, upper or lower extremity Doppler ultrasound, or autopsy) for venous thromboembolic disease (VTE). The PPV on transthoracic ECHO-CG was calculated for the diagnostic accuracy of McConnell’s sign in all patients. To minimize the potential for ECHO-CG reader bias of patients already confirmed to have had a PE by another modality, the PPV was then recalculated only on the patients in whom the ECHO-GM was the first diagnostic study. Results: Seventy-three patients had findings of McConnell’s sign on ECHO-CG. The PPV of McConnell’s sign on ECHO-CG was 57% (CI, 45%–67%). Of the 37 patients who underwent an ECHO-CG in the first study for suspected acute PE, 15 patients had VTE confirmed; the PPV in this subset was only 40% (CI, 24%–56%). There were 20 patient deaths overall; of these, only 9 of the patients were confirmed to have VTE. Conclusion: We concluded that the presence of McConnell’s sign has a relatively poor PPV for the diagnosis of acute PE and should not be used in isolation when making a diagnosis of PE in patients

The Brain, Seizures and Epilepsy Throughout Life: Understanding a Moving Target

The human brain is a tremendously complex and still enigmatic three-dimensional structure, composed of countless interconnected neurons and glia. The temporal evolution of the brain throughout life provides a fourth dimension, one that influences every element of the brain's function in health and disease. This temporal evolution contributes to the probability of seizure generation and to the type and the nature of these seizures. The age-specific properties of the brain also influence the consequences of seizures on neuronal structure and behavior. These, in turn, govern epileptic activity and cognitive and emotional functions, contributing to the diverse consequences of seizures and epilepsy throughout life