Joshua A. Marks

Multicenter evaluation of temporary intravascular shunt use in vascular trauma.

BACKGROUND The indications and outcomes associated with temporary intravascular shunting (TIVS) for vascular trauma in the civilian sector are poorly understood. The objective of this study was to perform a contemporary multicenter review of TIVS use and outcomes. METHODS Patients sustaining vascular trauma, requiring TIVS insertion (January 2005 to December 2013), were retrospectively identified at seven Level I trauma centers. Clinical demographics, operative details, and outcomes were abstracted. RESULTS A total of 213 injuries (2.7%; 94.8% arterial) requiring TIVS were identified in 7,385 patients with vascular injuries. Median age was 27.0 years (range, 4–89 years), 91.0% were male, Glasgow Coma Scale (GCS) score was 15.0 (interquartile range, 4.0), Injury Severity Score (ISS) was 16.0 (interquartile range, 15.0), 26.0% had an ISS of 25 or greater, and 71.1% had penetrating injuries. The most common mechanism was gunshot wound (62.7%), followed by auto versus pedestrian (11.4%) and motor vehicle collision (6.5%). Shunts were placed for damage control in 63.4%, staged repair for combined orthopedic and vascular injuries in 36.1%, and for insufficient surgeon skill set in 0.5%. The most common vessel shunted was the superficial femoral artery (23.9%), followed by popliteal artery (18.8%) and brachial artery (13.2%). An argyle shunt (81.2%) was the most common conduit, followed by Pruitt-Inahara (9.4%). Dwell time was less than 6 hours in 61.4%, 24 hours in 86.5%, 48 hours in 95.9%, with only 4.1% remaining in place for more than 48 hours. Of the patients, 81.6% survived to definitive repair, and 79.6% survived overall. Complications included shunt thrombosis (5.6%) and dislodgment (1.4%). There was no association between dwell time and shunt thrombosis. The use of a noncommercial shunt (chest tube/feeding tube) did not impact shunt thrombosis but was an independent risk factor for subsequent graft failure. The limb salvage rate was 96.3%. No deaths could be attributed to a shunt complication. CONCLUSION In the largest civilian TIVS experience insertion to date, both damage control and staged orthopedic vascular injuries were common indications for shunting. With an acceptable complication burden and no associated mortality attributed to this technique, shunting should be considered a viable treatment option. LEVEL OF EVIDENCE Therapeutic study, level V.

Similar effects of hypertonic saline and mannitol on the inflammation of the blood-brain barrier microcirculation after brain injury in a mouse model.

BACKGROUND There has been substantial debate regarding the efficacy of hypertonic saline (HTS) versus mannitol (MTL) in treating moderate and severe traumatic brain injury (TBI). HTS blunts polymorphonuclear neutrophil (PMN) and endothelial cell (EC) activation and reduces tissue edema after resuscitated shock in systemic microvascular beds. MTL also modulates PMN activation markers. It remains unknown if either of these osmotherapies exert similar anti-inflammatory effects along the blood-brain barrier (BBB). We hypothesized that HTS, as compared with MTL, would more greatly reduce PMN-EC interactions, thereby reducing BBB permeability and tissue edema after simulated TBI. METHODS CD1 male mice (25–30 g) underwent craniotomy and window placement for observation of in vivo PMN-EC interactions in pial venules using intravital video microscopy. TBI was simulated through local suffusion of the brain surface with interleukin 1&bgr; (100 ng/0.1 mL). Animals were randomized to receive a single, equiosmolar, intravenous dose of 20% MTL or 5% HTS after injury. Live microcirculatory footage was obtained every 15 minutes for 2 hours, after which fluorescent-labeled albumin was administered to assess microvascular permeability. PMN rolling and adhesion and macromolecular leakage were analyzed offline by a blinded observer and postmortem brain and lung edema assessed by wet-to-dry ratios. Student’s t test and Mann-Whitney U test determined significance (p ⩽ 0.05). RESULTS Neither osmotherapy resulted in significant differences in PMN rolling or adhesion; however, both trended higher in HTS. Similarly, vessel permeability did not differ between groups but also trended higher with HTS. In contrast, brain and lung edema was greater in MTL than HTS as compared with controls (p = 0.05). CONCLUSION MTL and HTS have indistinguishable effects on PMN-EC interactions in the brain after simulated TBI. Additional studies are needed to determine if either osmotherapy has more subtle effects on BBB PMN-EC interactions after injury exerting a potential clinical advantage.

The mortality inflection point for age and acute cervical spinal cord injury.

BACKGROUND Acute cervical spinal cord injury (cSCI) is associated with significant morbidity and mortality. Vertebral level and American Spinal Injury Association (ASIA) score influence both hospital course and ultimate outcome. While controlling for these variables, we describe the effect of age on cSCI-related pneumonia and mortality. METHODS All patients treated at our regional spinal cord injury center with an acute cSCI during a 5-year period (2005-2009) were reviewed retrospectively. Patient demographics, injury level, ASIA score, length of stay (LOS), radiologic, laboratory, and microbiology data were reviewed. Pneumonia was defined as an infiltrate on chest X-ray along with two of the following: leukocytosis, fever greater than 101°F, or positive bronchial alveolar lavage cultures; all occurring within the same 24-hour period. RESULTS There were 244 cSCI during the study period. In-hospital mortality was significantly higher for those older than 75 years (40.5% vs. 4.0%, p < 0.0001). Pneumonia rates were not significantly different between age groups. In all age groups, high ASIA scores (A and B) were associated with increased pneumonia (61.9% vs. 17.4%, p < 0.0001) and mortality (16.7% vs. 3.5%, p = 0.002). Similarly, patients with higher cervical injury levels (C4 and above) had a higher incidence of pneumonia (39.5% vs. 25.9%, p < 0.05) and a trend toward higher mortality. CONCLUSIONS Age was associated with an increase in mortality among patients with an acute cSCI. Injury level and ASIA score contributed significantly to overall pneumonia rate and mortality at all ages; however, pneumonia did not correlate directly with mortality in this population. Other factors play a role in the mortality associated with geriatric spinal cord-injured patients, including end-of-life decision making; these need to be investigated further in future studies.

Lower extremity vascular stenting for a post-traumatic pseudoaneurysm in a young trauma patient

Endovascular treatment of post-traumatic pseudoaneurysms has become a viable, less invasive option when compared to open repair. Due to the relative youth of this technology, studies have yet to be concluded on the long-term patency of stent grafts in this population. For this reason, concern exists with endovascular stent placement in the young trauma patient. In this study, we present a case and review the literature on a post-traumatic pseudoaneurysm of the posterior tibial artery in a 19-year-old man treated with an endovascular stent.

Enoxaparin ameliorates post-traumatic brain injury edema and neurologic recovery, reducing cerebral leukocyte endothelial interactions and vessel permeability in vivo.

BACKGROUND Traumatic brain injury (TBI) confers a high risk of venous thrombosis, but early prevention with heparinoids is often withheld, fearing cerebral hematoma expansion. Yet, studies have shown heparinoids not only to be safe but also to limit brain edema and contusion size after TBI. Human TBI data also suggest faster radiologic and clinical neurologic recovery with earlier heparinoid administration. We hypothesized that enoxaparin (ENX) after TBI blunts in vivo leukocyte (LEU) mobilization to injured brain and cerebral edema, while improving neurologic recovery without increasing the size of the cerebral hemorrhagic contusion. METHODS CD1 male mice underwent either TBI by controlled cortical impact (CCI, 1-mm depth, 6 m/s) or sham craniotomy. ENX (1 mg/kg) or vehicle (VEH, 0.9% saline, 1 mL/kg) was administered at 2, 8, 14, 23, and 32 hours after TBI. At 48 hours, intravital microscopy was used to visualize live LEUs interacting with endothelium and microvascular leakage of fluorescein isothiocyanate–albumin. Neurologic function (Neurological Severity Score, NSS), activated clotting time, hemorrhagic contusion size, as well as brain and lung wet-to-dry ratios were evaluated post mortem. Analysis of variance with Bonferroni correction was used for statistical comparisons between groups. RESULTS Compared with VEH, ENX significantly reduced in vivo LEU rolling on endothelium (72.7 ± 28.3 LEU/100 &mgr;m/min vs. 30.6 ± 18.3 LEU/100 &mgr;m/min, p = 0.02) and cerebrovascular albumin leakage (34.5% ± 8.1% vs. 23.8% ± 5.5%, p = 0.047). CCI significantly increased ipsilateral cerebral hemisphere edema, but ENX treatment reduced post-CCI edema to near control levels (81.5% ± 1.5% vs. 77.6% ± 0.6%, p < 0.01). Compared with VEH, ENX reduced body weight loss at 24 hours (8.7% ± 1.2% vs. 5.8% ± 1.1%, p < 0.01) and improved NSS at 24 hours (14.5 ± 0.5 vs. 16.2 ± 0.4, p < 0.01) and 48 hours (15.1 ± 0.4 vs. 16.7 ± 0.5, p < 0.01) after injury. There were no significant differences in activated clotting time, hemorrhagic contusion size, and lung water content between the groups. CONCLUSION ENX reduces LEU recruitment to injured brain, diminishing visible microvascular permeability and edema. ENX may also accelerate neurologic recovery without increasing cerebral contusion size. Further study in humans is necessary to determine safety, appropriate dosage, and timing of ENX administration early after TBI.

Does enoxaparin interfere with HMGB1 signaling after TBI? A potential mechanism for reduced cerebral edema and neurologic recovery.

BACKGROUND Enoxaparin (ENX) has been shown to reduce cerebral edema and improve neurologic recovery after traumatic brain injury (TBI), through blunting of cerebral leukocyte (LEU) recruitment. High mobility group box 1 (HMGB1) protein may induce inflammation through LEU activation. We hypothesized that ENX after TBI reduces LEU-mediated edema through blockade of HMGB1 signaling. METHODS Twenty-three CD1 mice underwent severe TBI by controlled cortical impact and were randomized to one of four groups receiving either monoclonal antibody against HMGB1 (MAb) or isotype (Iso) and either ENX (1 mg/kg) or normal saline (NS): NS + Iso (n = 5), NS + MAb (n = 6), ENX + Iso (n = 6), ENX + MAb (n = 6). ENX or NS was administered 2, 8, 14, 23 and 32 hours after TBI. MAb or Iso (25 &mgr;g) was administered 2 hours after TBI. At 48 hours, cerebral intravital microscopy served to visualize live LEU interacting with endothelium and microvascular fluorescein isothiocyanate–albumin leakage. The Neurological Severity Score (NSS) graded neurologic recovery; wet-to-dry ratios determined cerebral/lung edema. Analysis of variance with Bonferroni correction was used for statistical analyses. RESULTS ENX and MAb similarly reduced in vivo pial LEU rolling without demonstrating additive effect. In vivo albumin leakage was greatest in vehicle-treated animals but decreased by 25% with either MAb or ENX but by 50% when both were combined. Controlled cortical impact–induced cerebral wet-to-dry ratios were reduced by MAb or ENX without additive effect. Postinjury lung water was reduced by ENX but not by MAb. Neurologic recovery at 24 hours and 48 hours was similarly improved with ENX, MAb, or both treatments combined. CONCLUSION Mirroring ENX, HMGB1 signaling blockade reduces LEU recruitment, cerebrovascular permeability, and cerebral edema following TBI. ENX further reduced lung edema indicating a multifaceted effect beyond HMGB1 blockade. Further study is needed to determine how ENX may play a role in blunting HMGB1 signaling in brain injury patients.

In vivo leukocyte-mediated brain microcirculatory inflammation: a comparison of osmotherapies and progesterone in severe traumatic brain injury

BACKGROUND Mannitol, hypertonic saline, and progesterone may blunt leukocyte recruitment after traumatic brain injury (TBI). We hypothesized that progesterone reduces pericontusional recruitment of leukocytes to a greater extent than either osmotherapy a day after TBI. METHODS CD1 mice underwent controlled cortical impact and were treated with osmotherapy (mannitol and hypertonic saline) or progesterone. Thirty-two hours after TBI, live pial microscopy was used to evaluate leukocyte-endothelial interactions and immunohistochemistry was used for the detection of pericontusional tissue polymorphonuclear neutrophils. Neurologic recovery was assessed before sacrifice. RESULTS Mannitol resulted in the lowest in vivo leukocyte recruitment compared with progesterone (795 ± 282 vs 1,636 ± 434 LEU/100 μm/minutes, P < .05). Mannitol also displayed lower tissue accumulation of leukocytes as compared with progesterone (5.7 ± 1.7 vs 15.2 ± .1 LEU/mm(2), P = .03). However, progesterone resulted in better neurologic recovery than either osmotherapy. CONCLUSIONS Leukocyte recruitment to injured brain is lowest with mannitol administration. How different agents alter progression of secondary brain injury will require further evaluation in humans.

Malignant Melanoma Presenting as Obstructive Jaundice Secondary to Metastasis to the Ampulla of Vater

CONTEXT Malignant melanoma commonly metastasizes to the small intestine where it can cause pain, bleeding, and obstruction. However, jaundice from metastatic melanoma is relatively uncommon. CASE REPORT A case of known malignant melanoma presenting as new onset obstructive jaundice as a result of a rarely reported metastasis to the ampulla of Vater. CONCLUSION Multidisciplinary management of patients with metastatic melanoma is essential.

Unfractionated heparin after TBI reduces in vivo cerebrovascular inflammation, brain edema and accelerates cognitive recovery.

BACKGROUND Severe traumatic brain injury (TBI) may increase the risk of venous thromboembolic complications; however, early prevention with heparinoids is often withheld for its anticoagulant effect. New evidence suggests low molecular weight heparin reduces cerebral edema and improves neurological recovery after stroke and TBI, through blunting of cerebral leukocyte (LEU) recruitment. It remains unknown if unfractionated heparin (UFH) similarly affects brain inflammation and neurological recovery post-TBI. We hypothesized that UFH after TBI reduces cerebral edema by reducing LEU-mediated inflammation and improves neurological recovery. METHODS CD1 male mice underwent either TBI by controlled cortical impact (CCI) or sham craniotomy. UFH (75 U/kg or 225 U/kg) or vehicle (VEH, 0.9% saline) was administered 2, 11, 20, 27, and 34 hours after TBI. At 48 hours, pial intravital microscopy through a craniotomy was used to visualize live brain LEUs interacting with endothelium and microvascular fluorescein isothiocyanate–albumin leakage. Neurologic function (Garcia Neurological Test, GNT) and body weight loss ratios were evaluated 24 and 48 hours after TBI. Cerebral and lung wet-to-dry ratios were evaluated post mortem. ANOVA with Bonferroni correction was used to determine significance (p < 0.05). RESULTS Compared to positive controls (CCI), both UFH doses reduced post-TBI in vivo LEU rolling on endothelium, concurrent cerebrovascular albumin leakage, and ipsilateral cerebral water content after TBI. Additionally, only low dose UFH (75 U/kg) improved GNT at both 24 and 48 hours after TBI. High dose UFH (225 U/kg) significantly increased body weight loss above sham at 48 hours. Differences in lung water content and blood pressure between groups were not significant. CONCLUSIONS UFH after TBI reduces LEU recruitment, microvascular permeability, and brain edema to injured brain. Lower UFH doses concurrently improve neurological recovery whereas higher UFH may worsen functional recovery. Further study is needed to determine if this is caused by increased bleeding from injured brain with higher UFH doses.

Hypertonic saline resuscitation of hemorrhagic shock does not decrease in vivo neutrophil interactions with endothelium in the blood-brain microcirculation.

BACKGROUND Resuscitation of hemorrhagic shock with isotonic crystalloids has been shown to activate polymorphonuclear neutrophils (PMNs). Although hypertonic saline (HTS) can reduce PMN activation and interactions with endothelial cells (EC) in systemic microvascular beds, no data exist demonstrating that the same occurs in the unique blood-brain barrier microcirculation. We hypothesized that resuscitation of hemorrhagic shock with HTS would blunt brain in vivo PMN-EC interactions. METHODS Wistar rats (250-350 g) underwent craniotomy and placement of a window for live intravital viewing of pial vessels. Twenty animals were bled to a mean arterial pressure of 30 mm Hg to 35 mm Hg for 1 hour and resuscitated with shed blood and either 5% HTS (6 mL/kg) or Ringers lactate (RL) (2× shed blood volume). Circulating rhodamine-6G-labeled PMN in pial venules were captured by videomicroscopy at baseline (preshock), end of the shock period, after resuscitation, and every 15 minutes to 30 minutes for 2 hours. Hemodynamics and arterial gases were monitored. Off-line footage analysis allowed comparisons of PMN-EC interactions between groups. RESULTS Animals in both groups developed significant metabolic acidosis (p < 0.01) after hemorrhage, but postresuscitation blood pressures were similar at all time points. Crystalloid resuscitation volumes were 10× greater in RL than HTS animals (p < 0.001). For all time points, we did not observe the expected reduction in PMN rolling and adhesion in HTS animals, instead noted trends of consistently lower interactions in RL counterparts. CONCLUSIONS In contradistinction to studies evaluating the systemic microcirculation, HTS may activate PMN-EC crosstalk in the blood-brain microcirculation. Further studies are needed to analyze whether this effect is due to the unique nature of the blood-brain interface.