Veno-arteriovenous (V-AV) ECMO configuration: A single-center experience.

BACKGROUND: With increasing extracorporeal membrane oxygenation (ECMO) utilization over the last decade, clinicians have developed "hybrid" configurations to meet complex perfusion requirements. In the setting of differential hypoxemia, a veno-arteriovenous (V-AV) configuration provides oxygenated cardiac preload and hemodynamic support to satisfy physiologic demands. We aim to further characterize the patient population, indications, and outcomes associated with this hybrid configuration. METHODS: We retrospectively reviewed all adult patients placed on V-AV ECMO at our institution from June 2016 to December 2019. Through a review of the electronic medical records, data describing demographic features, comorbidities, and ECMO-specific information were analyzed systematically. RESULTS: 14 patients were placed on V-AV ECMO during the study period. Our cohort was 79% male with a median age of 54 and BMI of 30.3. These patients had a median SOFA-0 score of 15 and SAVE score of -12. Patients were treated with ECMO support for a median of 144.1 (IQR 98.5 - 183.1) hours, consisting of 0.2 (IQR 0 - 17.7) hours of VA and 92.4 (IQR 53.7 - 115.1) hours of V-AV followed by 67.4 (IQR 20.3 - 96.6) hours of VV support. Of these 14 patients, 11 survived to decannulation (79%) and 9 survived to hospital discharge (64%). CONCLUSION: ECMO patients with recovering left ventricular function and persistent gas exchange abnormalities are at risk for developing differential hypoxemia. We describe an approach to utilizing V-AV configuration when the likelihood of differential hypoxemia is extremely high, with a survival rate that compares favorably to Extracorporeal Life Support Organization statistics and published case series.

Thoracolumbar Evaluation in the Low-Risk Trauma Patient: A Pilot Study Towards Development of a Clinical Decision Rule to Avoid Unnecessary Imaging in the Emergency Department.

BACKGROUND: Thoracolumbar (TL) injury is a common finding in the severely injured multi-trauma patient. However, the incidence and pattern of TL injury in patients with milder trauma is unclear. OBJECTIVE: The aim of this study was to collect and analyze evidence for the development of a clinical decision rule (CDR) to evaluate the TL spine in patients with non-severe blunt trauma and avoid dedicated imaging in low-risk cases. METHODS: Adult patients with blunt trauma who presented to a major academic center (May 2016 to October 2017) and received dedicated imaging of the TL spine were included. Exclusion criteria consisted of any coexisting condition preventing the acquisition of history or examination. The primary endpoint is TL spine injury requiring orthopedic evaluation, bracing/orthosis, or surgery. Preliminary CDR derivation was performed with recursive partitioning. RESULTS: Of 4612 patients screened, 1049 (22.7%) met inclusion criteria. Thirty-six (3.4%) patients were found to have TL spine injury, of which 88.9% received spinal bracing, orthosis, or surgery. Absence of midline tenderness conveyed the highest negative predictive value, followed by a non-severe mechanism of injury, lack of neurologic examination findings, and age < 65 years. No patients in this cohort with these four findings had a TL spine injury. CONCLUSIONS: In certain lower-risk blunt trauma patients < 65 years of age, focused examination combined with mechanism of injury may be highly sensitive (100%) to rule out TL injury without the need for dedicated imaging. However, validation is necessary, given multiple study limitations. Potential instrument to screen for TL injury in minor trauma: TL injury is unlikely if all four of the following are present: 1) no midline back tenderness or deformity, 2) no focal neurologic signs or symptoms or altered mentation, 3) age < 65 years; and 4) lack of severe mechanism of injury, for example, fall greater than standing, motor-vehicle collision with rollover/ejection/pedestrian or unenclosed vehicle, and assault with a weapon.

Targeting miRNA by tunable small molecule binders: peptidic aminosugar mediated interference in miR-21 biogenesis reverts epithelial to mesenchymal transition.

Epithelial to mesenchymal transition (EMT) is a process in which epithelial cells lose cell polarity and cell-cell adhesion and gain migratory and invasive properties to become mesenchymal cells that are very vital for development, wound healing and stem cell behavior and contribute pathologically to fibrosis and cancer progression. miR21, a potent regulator of the tumor suppressor gene PTEN, can be silenced to reverse EMT, thereby providing an attractive target for abrogating the malignant behavior of breast cancer. Here, we report the design, synthesis and binding of a peptidic-aminoglycoside (PA) based chemical library against pre-miR21 that led to the identification of a group of small molecules that bind to pre-miR21 with high affinities and antagonize miR-21 maturation and function, thereby reversing EMT. The approach described here offers a promising miRNA targeting platform where such aminosugar conjugates can be similarly used to target other oncogenic miRNAs. Minor changes in the amino acid sequence allow us to tailor the binding effectiveness and downstream biological effects, thus making this approach a potentially tunable method of regulation of miRNA function.