Soluble Glycoprotein VI Predicts Abdominal Aortic Aneurysm Growth Rate and is a Novel Therapeutic Target.

A common feature in patients with abdominal aortic aneurysms (AAA) is the formation of a nonocclusive intraluminal thrombus (ILT) in regions of aortic dilation. Platelets are known to maintain hemostasis and propagate thrombosis through several redundant activation mechanisms, yet the role of platelet activation in the pathogenesis of AAA associated ILT is still poorly understood. Thus, we sought to investigate how platelet activation impacts the pathogenesis of AAA. Using RNA-sequencing, we identify that the platelet-associated transcripts are significantly enriched in the ILT compared to the adjacent aneurysm wall and healthy control aortas. We found that the platelet specific receptor glycoprotein VI (GPVI) is among the top enriched genes in AAA ILT and is increased on the platelet surface of AAA patients. Examination of a specific indicator of platelet activity, soluble GPVI (sGPVI), in two independent AAA patient cohorts is highly predictive of a AAA diagnosis and associates more strongly with aneurysm growth rate when compared to D-dimer in humans. Finally, intervention with the anti-GPVI antibody (JAQ1) in mice with established aneurysms blunted the progression of AAA in two independent mouse models. In conclusion, we show that levels of sGPVI in humans can predict a diagnosis of AAA and AAA growth rate, which may be critical in the identification of high-risk patients. We also identify GPVI as a novel platelet-specific AAA therapeutic target, with minimal risk of adverse bleeding complications, where none currently exist.

Glycoprotein VI is Critical for the Detection and Progression of Abdominal Aortic Aneurysms.

A common feature in patients with abdominal aortic aneurysms (AAA) is the formation of a nonocclusive intraluminal thrombus (ILT) in regions of aortic dilation. Platelets are known to maintain hemostasis and propagate thrombosis through several redundant activation mechanisms, yet the role of platelet activation in the pathogenesis of AAA associated ILT is still poorly understood. Thus, we sought to investigate how platelet activation impacts the pathogenesis of AAA. Using RNA-sequencing, we identify that the platelet-associated transcripts are significantly enriched in the ILT compared to the adjacent aneurysm wall and healthy control aortas. We found that the platelet specific receptor glycoprotein VI (GPVI) is among the top enriched genes in AAA ILT and is increased on the platelet surface of AAA patients. Examination of a specific indicator of platelet activity, soluble GPVI (sGPVI), in two independent AAA patient cohorts is highly predictive of a AAA diagnosis and associates more strongly with aneurysm growth rate when compared to D-dimer in humans. Finally, intervention with the anti-GPVI antibody (J) in mice with established aneurysms blunted the progression of AAA in two independent mouse models. In conclusion, we show that levels of sGPVI in humans can predict a diagnosis of AAA and AAA growth rate, which may be critical in the identification of high-risk patients. We also identify GPVI as a novel platelet-specific AAA therapeutic target, with minimal risk of adverse bleeding complications, where none currently exist. KEY POINTS: Soluble glycoprotein VI, which is a platelet-derived blood biomarker, predicts a diagnosis of AAA, with high sensitivity and specificity in distinguishing patients with fast from slow-growing AAA.Blockade of glycoprotein VI in mice with established aneurysms reduces AAA progression and mortality, indicating therapeutic potential.

Endocutter Staple Height Auto-Adjusts to Tissue Thickness.

BACKGROUND: Surgeon choice of the appropriate staple height has been cited as a factor in the mechanical integrity of a staple line. However, tissue measured at the industry standard 8 g/mm2 is usually thicker than the formed staple height of the staples that hold it together. This means that the pressure that the staples apply must be greater than 8g/mm2. Additionally, formed staple heights in tissue may be different than formed staple heights of the same cartridge type when fired without tissue. This means that there is likely a compressive limit to the individual staples deployed by the stapling system. The purpose of this study is to establish the degree to which staple heights of endocutter staples auto-adjust to tissue and the compressive limit to tissue that this infers. MATERIALS AND METHODS: Excised gastric remnants from laparoscopic sleeve gastrectomy were measured for tissue thickness at different external pressures. An optimized experimental staple line was then created in parallel to the clinical staple line. The doubly-stapled gastric sliver then underwent computed tomography with solid modeling software to measure staple heights. RESULTS: Staple heights fired in gastric tissue were significantly different than industry labelled and control staple heights. Clinical staple heights were significantly shorter than measured tissue thickness at 8 g/mm2. Staple height more closely approximated tissue thickness under 15 g/mm2 of pressure, rather than the 8 g/mm2 loading pressure used by industry for tissue thickness range labelling. CONCLUSIONS: Staples deployed in human gastric tissue are taller than commercial labelling. The closed staple height corresponds to tissue thickness under 15g/mm2 of pressure, not the labelled staple height. These results demonstrate that staple heights from modern endocutter staplers adjust to tissue, approximating a maximum compressive force just above 15g/mm2.

Efficacy of Noninvasive Technologies in Triaging Traumatic Brain Injury and Correlating With Intracranial Pressure: A Prospective Study.

BACKGROUND: There is interest in methods of measuring noninvasive intracranial pressure (ICP), including pupillometry, ultrasonographic transcranial Doppler (TCD), and optic nerve sheath diameter (ONSD), for diagnosing traumatic brain injury (TBI) in limited resource environments. Whether these technologies have diagnostic agreement is unknown. We hypothesized that ONSD, pupillometry, and TCD could both distinguish severe TBI and correlate with ICP. METHODS: A prospective study of 135 patients was conducted at a level 1 trauma center. Four test groups were established: nontrauma patients with ICP monitoring, trauma patients without TBI, trauma patients with mild TBI, and trauma patients with severe TBI with ICP monitoring. All patients underwent daily measurements of ONSD, pupillometry, and TCD with both CX50 Sonosite and the Spencer ST3 Yi Pencil probe. RESULTS: ONSD differed significantly in patients with severe TBI compared with patients with mild and no TBI, but did not correlate with ICP. Pupillometric constriction velocity, dilation velocity, and percent change in pupil diameter were significantly different in patients with severe TBI, but also did not correlate with ICP. TCD did not differ among TBI severities, but middle cerebral artery peak systolic velocity, middle cerebral artery flow velocity, and carotid flow velocity correlated with ICP. CONCLUSIONS: This is a novel study of four noninvasive tests to screen for severity of TBI and measure ICP. Our analysis indicates that no single device can do both. However, ONSD and pupillometry may be used as a supplementary screening tool for severe TBI, whereas TCD could be used to estimate and follow ICP in patients with severe TBI.

Assessment of a novel stapler performance for laparoscopic sleeve gastrectomy.

BACKGROUND: Optimal stapler selection during laparoscopic sleeve gastrectomy requires careful balance between tissue compression, hemostasis, and mechanical integrity. Junctions along a staple line can further increase the risks of technical or mechanical staple line failures. The aim of this study was to compare two commonly utilized laparoscopic linear gastrointestinal staplers (Ethicon, Medtronic) with a novel linear stapler (Titan) designed to perform a sleeve gastrectomy with a single stapler firing. METHODS: Excised gastric remnants from laparoscopic sleeve gastrectomy were utilized and tissue thickness was measured from fundus to antrum. An optimized experimental staple line was then created. The greater curve remnant was insufflated to determine the staple line burst pressure and location. The doubly stapled (clinical and experimental) gastric specimen underwent staple analysis for junctional location, malformation, and height. RESULTS: The Titan stapler withstood a significantly higher burst pressure than both Ethicon and Medtronic linear cutting staplers. While the Medtronic and Ethicon staplers had a similar percentage of staples in junctions, the Titan stapler has no junctions. In considering the formation of all staples outside of junctions, the Medtronic and Titan staplers had no difference in percentage of malformed staples, while the Ethicon stapler had a significantly higher percentage. Additionally, there were no differences in mismatch between staple height and tissue thickness between experimental groups. CONCLUSIONS: The Titan stapler conveys the mechanical benefits of higher burst pressure with the advantage of single load functionality. This single staple load eliminates staple line junctions without sacrificing the integrity of staple formation.