Cureton, Elizabeth L. MD; Ereso, Alexander Q. MD; Dozier, Kristopher D. MD; Kwan, Rita O. MD, MPH; Sadjadi, Javid MD; Curran, Brian BS; Murphy, Jane E. PhD; Bhargava, Aditi PhD; Victorino, Gregory P. MD, FACS Author Information

BACKGROUND: Certain clinical environments, including military field hospitals or rural medical centers, lack readily available surgical subspecialists. We hypothesized that telementoring by a surgical sub-specialist using a robotic platform is feasible and can convey subspecialty knowledge and skill to a remotely located general surgeon.STUDY DESIGN: Eight general surgery residents evaluated the effect of remote surgical telementoring by performing 3 operative procedures, first unproctored and then again when teleproctored by a surgical subspecialist. The clinical scenarios consisted of a penetrating right ventricular injury requiring suture repair, an open tibial fracture requiring external fixation, and a traumatic subdural hematoma requiring craniectomy. A robotic platform consisting of a pan-and-tilt camera with laser pointer attached to an overhead surgical light with integrated audio allowed surgical subspecialists the ability to remotely teleproctor residents. Performance was evaluated using an Operative Performance Scale. Satisfaction surveys were given after performing the scenario unproctored and again after proctoring.RESULTS: Overall mean performance scores were superior in all scenarios when residents were proctored than when they were not (4.30 +/- 0.25 versus 2.43 +/- 0.20; p < 0.001). Mean performance scores for individual metrics, including tissue handling, instrument handling, speed of completion, and knowledge of anatomy, were all superior when residents were proctored (p < 0.001). Satisfaction surveys showed greater satisfaction and comfort among residents when proctored. Proctored residents believed the robotic platform facilitated learning and would be feasible if used clinically.CONCLUSIONS: This study supports the use of surgical teleproctoring in guiding remote general surgeons by a surgical subspecialist in the care of a wounded patient in need of an emergency subspecialty operation. (J Am Coll Surg 2010;211:400-411. (C) 2010 by the American College of Surgeons)

Kwan, Rita O. MD, MPH; Ereso, Alexander Q. MD; Cureton, Elizabeth MD; Dozier, Kristopher MD; Castro-Moure, Frederico MD, PhD; Patel, Atul MD; Sadjadi, Javid MD; Victorino, Gregory P. MD, FACS Author Information

Background: We have used single-contrast (intravenous contrast only) computed tomography (SCCT) for triaging hemodynamically stable patients with penetrating torso trauma. We hypothesized that SCCT safely determines the need for operative exploration. Furthermore, trauma surgeons without specialized training in body imaging can accurately apply this modality.Methods: We retrospectively reviewed the records of patients with penetrating torso injuries at a university-based urban trauma center to establish the accuracy of SCCT in determining the need for exploratory laparotomy. The scan was considered positive or negative with respect to the need for exploratory laparotomy as documented by the attending surgeon, who may have considered the read of the on call radiologist if available. In a separate study, four trauma surgeons independently reviewed 42 SCCT scans to establish whether the scans alone could be used to determine whether operative exploration was necessary.Results: Between 1997 and 2008, 306 hemodynamically stable patients with penetrating torso trauma were triaged by SCCT. Overall, SCCT predicted the need for laparotomy with 98% sensitivity and 90% specificity. The positive predictive value was 84% and the negative predictive value (NPV) was 99%. In the 222 patients with gunshot wounds, SCCT had 100% sensitivity and 100% NPV. In the 84 patients with stab wounds, SCCT had 92% sensitivity and 97% NPV. Trauma surgeon agreement in the retrospective review of 42 computed tomography scans was "nearly perfect": positive predictive value was 93% and NPV was 92% for determining the need for exploratory laparotomy surgery.Conclusions: SCCT is safe and effective for triaging hemodynamically stable patients with penetrating torso trauma. It successfully determined the need for operative intervention with appropriate clinical accuracy without the additional costs, morbidity, and delay of oral and rectal contrast. Trauma surgeons can reproducibly interpret SCCT with high-predictive accuracy as to whether patients with penetrating torso trauma require operative exploration.

Cureton, Elizabeth L. MD; Ereso, Alexander Q. MD; Kwan, Rita O. MD, MPH; Dozier, Kristopher C. MD; Sadjadi, Javid MD; Curran, Brian BS; Victorino, Gregory P. MD, FACS Author Information

Urocortin 1 (Ucn1) is a neuropeptide that regulates vascular tone and is implicated in both the vascular and immune cell-mediated responses to inflammation. The role of Ucn1 in regulating microvascular permeability has not been determined. We hypothesized that local Ucn1 release promotes microvascular permeability and that this effect augments the local gastrointestinal vascular response to lipopolysaccharide (LPS)-induced systemic inflammation. We measured hydraulic (L(p)) and macromolecule permeability in mesenteric venules. We show that a continuous infusion of 10(-7) m Ucn1 in a postcapillary venule increased L(p) 2-fold over baseline, as did LPS-induced inflammation. However, simultaneous infusion of Ucn1 and LPS markedly increased L(p) by 7-fold. After local knockdown of Ucn1 using RNA interference, infusion of Ucn1 with LPS resulted in return to 2-fold increase, confirming that Ucn1 synergistically augments hydraulic permeability during inflammation. LPS and Ucn1 treatment also resulted in increased numbers of interstitial microspheres, which colocalized with CD31(+) immune cells. Ucn1 activity is mediated through two receptor subtypes, CRH-R(1) and CRH-R(2). CRH-R(1) receptor blockade exacerbated, whereas CRH-R(2) receptor blockade decreased the LPS-induced increase in L(p). Finally, treatment with the c-JUN N-terminal kinase (JNK) antagonist SP600125 during infusion of LPS, but not Ucn1, decreased L(p). These findings suggest that Ucn1 increases microvascular permeability and acts synergistically with LPS to increase fluid and macromolecule losses during inflammation. Knockdown of endogenous Ucn1 during inflammation attenuates synergistic increases in L(p). Ucn1's effect on L(p) is partially mediated by the CRH-R(2) receptor and acts independently of the c-JUN N-terminal kinase signal transduction pathway.

Little is known regarding the effects of I/R on hydraulic permeability (Lp). We sought to compare the individual influences of hypoxia, ischemia, reoxygenation, and reperfusion on Lp. We hypothesized that (1) hypoxia increases Lp; (2) reoxygenation further increases Lp; (3) ischemia results in greater increases in Lp compared with hypoxia; (4) reperfusion causes additional increases in Lp compared with hypoxia, ischemia, and reoxygenation; and (5) xanthine oxidase (XO) and white blood cell adherence play important roles in hypoxia, ischemia, and reperfusion. Hydraulic permeability was measured by an in vivo microcannulation technique during hypoxia, reoxygenation, ischemia, and reperfusion in rat mesenteric postcapillary venules. Additional rats were fed a Tungsten-enriched diet to inhibit XO activity, and the studies were repeated. White blood cell adherence was also documented. Hypoxia and ischemia both increased Lp 2-fold from baseline levels (P < 0.001). Reoxygenation did not alter Lp compared with 15 min of hypoxia alone (P > 0.07). Reperfusion after hypoxia increased Lp 6-fold (P < 0.001). Reperfusion after ischemia also increased Lp 6-fold (P < 0.001). Inhibition of XO had no effect on the increase in Lp after both hypoxia and ischemia. However, inhibition of XO attenuated the 6-fold increase in Lp observed during reperfusion after both hypoxia and ischemia by approximately 50% (P < 0.001). White blood cell adherence increased during reperfusion but not hypoxia or ischemia. The complexity of I/R injury makes it a difficult clinical scenario to model for research. We have demonstrated in an in vivo model that hypoxia and ischemia increase Lp similarly, and that reperfusion has a profound deleterious effect on Lp. These changes in Lp seem to be XO and white blood cell dependent.

Background. The release of proinflammatory cytokines during inflammation disturbs the endothelial barrier and can initiate significant intravascular volume loss. Proinflammatory cytokines also induce the expression of anti-inflammatory mediators, such as lipoxin, which promote the resolution of inflammation. Our hypothesis is that lipoxin A(4) (LXA(4)) reverses the increased microvascular fluid leak observed during inflammatory conditions.Materials and Methods. Microvascular fluid leak (L-p) was measured in rat mesenteric venules using a micro-cannulation technique. L-p was measured under the following conditions: (1) LXA(4) (100 nM) alone (n = 5), (2) LXA(4) (100 nM) administered after endothelial hyperpermeability induced by a continuous perfusion of 10 nM platelet activating factor (PAF) (n = 5), (3) LXA(4) (100 nM) perfused after inflammation induced by a systemic bolus of 10 mg/kg lipopolysaccharide (LPS) (n = 5), and (4) LXA(4) (100 nM) perfused after LPS-induced inflammation during inhibition of c-Jun N-terminal kinase (n = 4).Results. LXA(4) alone slightly increased L-p from baseline (L-p-baseline = 1.05 +/- 0.03, L-p-LXA(4) = 1.55 +/- 0.04; P < 0.0001). PAF increased L-p 4-fold (L-p-baseline = 1.20 +/- 0.10, L-p-PAF = 4.49 +/- 0.95; P < 0.0001). LXA(4) administration after PAF decreased L-p 66% versus PAF alone (from 4.49 +/- 0.95 to 1.54 +/- 0.13; P = 0.0004). LPS-induced inflammation increased L-p over 2-fold (L-p-baseline = 1.05 +/- 0.03, L-p-LPS = 2.27 +/- 0.13; P < 0.0001). LXA(4) administration after LPS decreased L-p 42% versus LPS alone (from 2.27 +/- 0.13 to 1.31 +/- 0.05; P < 0.0001). The effect of c-Jun N-terminal kinase inhibition during LPS-induced inflammation attenuated the decrease in leak cause by LXA(4) by 51% (P = 0.0002).Conclusion. After either LPS or PAF, LXA(4) attenuated the intravascular volume loss caused by these inflammatory mediators. The activity of LXA(4) may be partly mediated by the c-Jun N-terminal kinase signaling pathway. These data support an anti-inflammatory role for LXA(4) and suggests a potential pharmacologic role for LXA(4) during inflammation. (C) 2009 Elsevier Inc. All rights reserved.

Military field hospitals and rural medical centers may lack surgical subspecialists. Robotic technology can enable proctoring of remotely located general surgeons by subspecialists. Our objective compared three proctoring platforms: (1) 6-degree-of-freedom (DOF) computer input devices controlling a camera and laser pointer mounted on robotic arms, (2) a computer mouse controlling a pan-tilt-zoom (PTZ) camera and robotic laser scanner, and (3) a computer pen/tablet controlling a PTZ-camera and robotic laser scanner. Our hypothesis was that a pen/tablet or mouse platform would be superior to the 6-DOF-input device platform. Five surgeons used each platform by simulating the creation of operative incisions. Qualitative (instrument handling, time, motion, spatial awareness) and quantitative performance (accuracy, speed) was assessed on a five-point scale. Each surgeon completed a satisfaction survey. Both mouse and pen/tablet had higher mean performance scores than the 6-DOF-input device in all quantitative (6-DOF = 1.7 +/- 0.8, mouse = 4.3 +/- 0.2, pen = 4.1 +/- 0.6; p < 0.001) and qualitative measures (6-DOF = 1.7 +/- 0.2, mouse = 4.8 +/- 0.0, pen = 4.6 +/- 0.1; p < 0.001). Handling, motion, and instrument awareness were superior with the mouse and pen/tablet versus 6-DOF-input devices (p < 0.0001). Speed and accuracy were also superior using the mouse or pen/tablet versus 6-DOF-input devices (p < 0.0001). Surgeons completed tasks faster using the mouse versus pen/tablet (p = 0.02). Satisfaction surveys revealed a preference for the mouse. This study demonstrates the superiority of a mouse or pen/tablet controlling a PTZ-camera and robotic laser scanner for remote surgical teleproctoring versus 6-DOF-input devices controlling a camera and laser pointer. Either a mouse or pen/tablet platform allows subspecialists to proctor remotely located surgeons.

Introduction: Lipoxins are eicosanoids generated within the vascular lumen during inflammation and ischemia-reperfusion injury. During sepsis and shock, inflammatory cytokines initiate events that can lead to a significant loss of intravascular volume. Proinflammatory cytokines also induce the expression of anti-inflammatory mediators, such as lipoxins, which promote the resolution phase of inflammation. Several studies have supported the actions of lipoxins as “endogenous brakes” in the inflammatory process. Our hypothesis is that lipoxins reverse the increased microvascular fluid leak during inflammation. The purposes of this study are: 1) to determine the effect of lipoxin (LXA4) on microvascular fluid leak, 2) to determine the effect of platelet activating factor (PAF)- and lipopolysaccharide (LPS)-induced inflammation on microvascular fluid leak, and 3) to determine if lipoxin reverses the increase in microvascular fluid leak that is associated with PAF- and LPS-induced inflammation. Methods: Microvascular fluid leak (Lp) was measured in rat mesenteric venules using a micro-cannulation technique. Upon initial cannulation of the venule, baseline Lp was first measured. The following conditions were studied: 1) LXA4 alone: LXA4’s effect on microvascular fluid leak was obtained during continuous perfusion of 100 nM LXA4 and Lp was measured every 5 min (n=3), 2) PAF- and LPS-induced inflammation: inflammation was induced by a continuous perfusion of PAF (10 nM) (n=5) or LPS administered as a systemic bolus (10 mg/kg) followed by a continuous perfusion of LPS (0.5 mg/kg) (n=5) and Lp measured every 5 min, and 3) during administration of LXA4 after either PAF or LPS. Changes in Lp were measured during continuous administration of LXA4 after PAF (n=4) and after LPS-induced (n=3) inflammation. Results: Continuous administration of LXA4 minimally increased Lp from baseline (from 1.05 ± 0.02 to 1.59 ± 0.05; p<0.001). Changes in Lp were transient and reached baseline after ten minutes. PAF-induced inflammation maximally increased Lp fourfold by 10 minutes (from 1.20 ± 0.10 to 4.49 ± 0.74; p<0.0001). LPS-induced inflammation increased Lp by 55% (1.20 ± 0.10 to 2.27 ± 0.13; p<0.002). Administration of LXA4 after PAF-induced inflammation decreased Lp 73% from PAF alone (from 4.49 ± 0.74 to 1.43 ± 0.07; p<0.01) (figure 1). Administration of LXA4 after LPS-induced inflammation decreased Lp 41% from LPS alone (from 2.27 ± 0.09 to 1.34 ± 0.06; p<0.02). Conclusion: This study supports a role for lipoxins as an anti-inflammatory mediator in the mesenteric microvasculature during inflammation. Administered alone, LXA4 minimally increases microvascular fluid leak. However, in the presence of either LPS-induced or PAF-induced inflammation, LXA4 minimized the loss of intravascular volume associated with these circumstances. A pharmacologic role for LXA4 during inflammation may have therapeutic potential for surgeons in the management of patients during shock.

Cureton, Elizabeth L. MD; Ereso, Alexander Q. MD; Sadjadi, Javid MD; Curran, Brian BS; Cottrell, Graeme S. PhD; Bhargava, Aditi PhD; Bunnett, Nigel W. PhD; Victorino, Gregory P. MD, FACS Author Information

Introduction: Resolvins are omega-3 fatty acid derivatives associated with the resolution phase of inflammation and have been shown to protect against colitis and peritonitis. Lipopolysaccharide (LPS) and platelet-activating factor (PAF) are major inflammatory mediators that are associated with gastrointestinal infection, peritonitis and sepsis. Our hypothesis was that resolvin (RvE1) reverses the increase in microvascular fluid leak that occurs during inflammation. The purposes of this study are: 1) to determine the effect of RvE1 on microvascular fluid leak, 2) to determine the effect of LPS-induced and PAF-induced inflammation on microvascular fluid leak, and 3) to determine if RvE1 reverses the increase in microvascular fluid leak induced by LPS- and PAF-induced inflammation. Methods: A micro-cannulation technique was used to determine microvascular fluid leak or hydraulic permeability (Lp) in rat mesenteric venules. Upon initial cannulation of the study venule, baseline Lp measurements were obtained. Then Lp was measured during the following conditions: 1) RvE1 alone: RvE1 (100 nM) was continuously perfused and Lp measured every 5 minutes (n=3), 2) LPS-induced and PAF-induced inflammation: LPS was given as a systemic bolus (10 mg/kg) followed by a continuous LPS perfusion (0.5 mg/ml) and Lp measured every 5 minutes (n=5), and PAF (10 nM) was perfused continuously and Lp measured every 5 minutes (n=4), and 3) RvE1 treatment after LPS-induced and PAF-induced inflammation: after inflammation was induced by LPS or PAF as above, RvE1 (100 nM) was administered as a continuous perfusion and Lp measured every 5 minutes (n=3 each). Results: There was a small initial increase in Lp due to RvE1 alone (from 1.02 ± 0.007 to 1.23 ± 0.06, p<0.004), but by 10 minutes Lp had returned to baseline. LPS-induced inflammation increased Lp two-fold (1.20 ± 0.13 to 2.27 ± 0.13; p<0.002). PAF-induced inflammation increased Lp four-fold (from 1.20 ± 0.13 to 4.49 ± 0.95, p<0.001). Compared with LPS alone, treatment with RvE1 after LPS-induced inflammation decreased Lp by 44% (from 2.27 ± 0.13 to 1.13 ± 0.03, p<0.004). Compared to PAF alone, treatment with RvE1 after PAF-induced inflammation decreased Lp by 42% (from 4.94 ± 0.95 to 2.86 ± 0.28). Units for Lp are cm-sec /cm-H2O x10−7. Conclusions: Resolvins are endogenously released anti-inflammatory mediators that are upregulated during the resolution phase of inflammation and have been shown to protect against colitis and peritonitis. We found that resolvin reversed the microvascular fluid leak that occurs during LPS- and PAF-induced inflammation. Resolvin may be useful therapeutically for the management of microvascular fluid loss associated with inflammation and shock due to gastrointestinal infections and peritonitis.

Cripps, Michael W. MD; Ereso, Alexander Q. MD; Victorino, Gregory P. MD, FACS; Harken, Alden H. MD, FACS; Soupene, Eric PhD; Kuypers, Frans PhD Author Information