How I do it: Pedal access and pedal loop revascularization for patients with chronic limb-threatening ischemia.

An increasing proportion of patients with chronic limb-threatening ischemia are older and have multiple comorbidities, including diabetes and renal failure. For those who are not candidates for a surgical bypass, this set of patients presents a challenge to vascular surgeons and interventionalists owing to the complex below-the-knee and increasingly below-the-ankle disease pattern that can fail traditional approaches for endovascular intervention. Two techniques, the retrograde pedal access and the pedal-plantar loop technique, can be useful in these settings and in skilled hands can be used safely, with a high technical success rate. In patients with chronic limb-threatening ischemia who are not candidates for a single-segment saphenous vein bypass, the retrograde pedal access technique can be used not only in the setting of failed antegrade treatment, but also primarily when faced with a difficult groin or as an adjunct during a planned antegrade-retrograde intervention. The pedal plantar loop technique allows for retrograde access to tibial vessels without retrograde vessel puncture and additionally offers the ability to treat the pedal-plantar arch, which may have added benefit in wound healing. We describe the tips and tricks for these two techniques used in our limb salvage practice.

Lytic Therapy for Retained Traumatic Hemothorax: A Systematic Review and Meta-analysis.

BACKGROUND: Intrapleural lytic therapy has been established as an important modality of treatment for many pleural disorders, including hemothorax and empyema. Retained traumatic hemothorax is a common and understudied subset of pleural disease. The current standard of care for retained traumatic hemothorax is operative management. The use of lytic therapy for avoidance of operative intervention in the trauma population has not been well established. METHODS: Randomized controlled trials (RCTs) and non-RCTs reporting operative intervention following the use of intrapleural lytic treatment for retained traumatic hemothorax were identified in the literature. The primary outcome was avoidance of surgery following treatment with any lytic agent. Meta-analysis was performed to pool the results of those studies. Subgroup analysis by type of lytic therapy and analysis of length of stay were also performed. RESULTS: One RCT and nine non-RCTs including 162 patients were pooled in the analysis. Avoidance of surgery following treatment with any lytic agent was found to be 87% (95% CI, 81%-92%). Tissue plasminogen activator resulted in 83% operative avoidance (95% CI, 71%-94%), and other, non-tissue plasminogen activator lytic agents resulted in 87% operative avoidance (95% CI, 82%-93%). The average length of stay for patients undergoing lytic therapy was 14.88 days (95% CI, 12.88-16.88). CONCLUSIONS: Lytic therapy could reduce the need for operative intervention in trauma patients with retained traumatic hemothorax. RCTs are indicated to definitively evaluate the benefit of this approach.

Bone marrow stromal and vascular smooth muscle cells have chemosensory capacity via bitter taste receptor expression.

The ability of cells to detect changes in the microenvironment is important in cell signaling and responsiveness to environmental fluctuations. Our interest is in understanding how human bone marrow stromal-derived cells (MSC) and their relatives, vascular smooth muscle cells (VSMC), interact with their environment through novel receptors. We found, through a proteomics screen, that MSC express the bitter taste receptor, TAS2R46, a protein more typically localized to the taste bud. Expression was also confirmed in VSMCs. A prototypical bitter compound that binds to the bitter taste receptor class, denatonium, increased intracellular calcium release and decreased cAMP levels as well as increased the extracellular release of ATP in human MSC. Denatonium also bound and activated rodent VSMC with a change in morphology upon compound exposure. Finally, rodents given denatonium in vivo had a significant drop in blood pressure indicating a vasodilator response. This is the first description of chemosensory detection by MSC and VSMCs via a taste receptor. These data open a new avenue of research into discovering novel compounds that operate through taste receptors expressed by cells in the marrow and vascular microenvironments.

Single-quantum-dot-based DNA nanosensor.

Rapid and highly sensitive detection of DNA is critical in diagnosing genetic diseases. Conventional approaches often rely on cumbersome, semi-quantitative amplification of target DNA to improve detection sensitivity. In addition, most DNA detection systems (microarrays, for example), regardless of their need for target amplification, require separation of unhybridized DNA strands from hybridized stands immobilized on a solid substrate, and are thereby complicated by solution-surface binding kinetics. Here, we report an ultrasensitive nanosensor based on fluorescence resonance energy transfer (FRET) capable of detecting low concentrations of DNA in a separation-free format. This system uses quantum dots (QDs) linked to DNA probes to capture DNA targets. The target strand binds to a dye-labelled reporter strand thus forming a FRET donor-acceptor ensemble. The QD also functions as a concentrator that amplifies the target signal by confining several targets in a nanoscale domain. Unbound nanosensors produce near-zero background fluorescence, but on binding to even a small amount of target DNA (approximately 50 copies or less) they generate a very distinct FRET signal. A nanosensor-based oligonucleotide ligation assay has been demonstrated to successfully detect a point mutation typical of some ovarian tumours in clinical samples.