April Mendoza

A Chemoattractant Role for NT-3 in Proprioceptive Axon Guidance

Neurotrophin-3 (NT-3) is required for proprioceptive neuron survival. Deletion of the proapoptotic gene Bax in NT-3 knockout mice rescues these neurons and allows for examination of their axon growth in the absence of NT-3 signaling. TrkC-positive peripheral and central axons from dorsal root ganglia follow proper trajectories and arrive in close proximity to their targets but fail to innervate them. Peripherally, muscle spindles are absent and TrkC-positive axons do not enter their target muscles. Centrally, proprioceptive axons branch in ectopic regions of the spinal cord, even crossing the midline. In vitro assays reveal chemoattractant effects of NT-3 on dorsal root ganglion axons. Our results show that survival factor NT-3 acts as a short-distance axon guidance molecule for muscle sensory afferents as they approach their proper targets.

Flagellin Treatment Prevents Increased Susceptibility to Systemic Bacterial Infection after Injury by Inhibiting Anti-Inflammatory IL-10+ IL-12- Neutrophil Polarization

Severe trauma renders patients susceptible to infection. In sepsis, defective bacterial clearance has been linked to specific deviations in the innate immune response. We hypothesized that innate immune modulations observed during sepsis also contribute to increased bacterial susceptibility after severe trauma. A well-established murine model of burn injury, used to replicate infection following trauma, showed that wound inoculation with P. aeruginosa quickly spreads systemically. The systemic IL-10/IL-12 axis was skewed after burn injury with infection as indicated by a significant elevation in serum IL-10 and polarization of neutrophils into an anti-inflammatory (“N2”; IL-10+ IL-12−) phenotype. Infection with an attenuated P. aeruginosa strain (ΔCyaB) was cleared better than the wildtype strain and was associated with an increased pro-inflammatory neutrophil (“N1”; IL-10−IL-12+) response in burn mice. This suggests that neutrophil polarization influences bacterial clearance after burn injury. Administration of a TLR5 agonist, flagellin, after burn injury restored the neutrophil response towards a N1 phenotype resulting in an increased clearance of wildtype P. aeruginosa after wound inoculation. This study details specific alterations in innate cell populations after burn injury that contribute to increased susceptibility to bacterial infection. In addition, for the first time, it identifies neutrophil polarization as a therapeutic target for the reversal of bacterial susceptibility after injury.

Radiation combined with thermal injury induces immature myeloid cells.

ABSTRACT The continued development of nuclear weapons and the potential for thermonuclear injury necessitates the further understanding of the immune consequences after radiation combined with injury (RCI). We hypothesized that sublethal ionization radiation exposure combined with a full-thickness thermal injury would result in the production of immature myeloid cells. Mice underwent either a full-thickness contact burn of 20% total body surface area or sham procedure followed by a single whole-body dose of 5-Gy radiation. Serum, spleen, and peripheral lymph nodes were harvested at 3 and 14 days after injury. Flow cytometry was performed to identify and characterize adaptive and innate cell compartments. Elevated proinflammatory and anti-inflammatory serum cytokines and profound leukopenia were observed after RCI. A population of cells with dual expression of the cell surface markers Gr-1 and CD11b were identified in all experimental groups, but were significantly elevated after burn alone and RCI at 14 days after injury. In contrast to the T-cell–suppressive nature of myeloid-derived suppressor cells found after trauma and sepsis, myeloid cells after RCI augmented T-cell proliferation and were associated with a weak but significant increase in interferon &ggr; and a decrease in interleukin 10. This is consistent with previous work in burn injury indicating that a myeloid-derived suppressor cell–like population increases innate immunity. Radiation combined injury results in the increase in distinct populations of Gr-1+CD11b+ cells within the secondary lymphoid organs, and we propose these immature inflammatory myeloid cells provide innate immunity to the severely injured and immunocompromised host.

Routine computed tomography after recent operative exploration for penetrating trauma: what injuries do we miss?

BACKGROUND Patients with penetrating trauma who cannot be stabilized undergo operative intervention without preoperative imaging. In such cases, postoperative imaging may reveal additional injuries not identified during the initial operative exploration. The purpose of this study is to explore the utility of postoperative CT imaging in the setting of penetrating trauma. METHODS This was a retrospective analysis of patients with penetrating trauma treated at an urban Level 1 trauma center between 2010 and 2015. Patients were included if they underwent an emergent laparotomy without preoperative imaging. Patients were excluded if they had prior imaging or concomitant blunt injury. For the purposes of this study, occult injury was defined as a CT scan finding not mentioned in the first operative report. Descriptive statistics were used to compare patient characteristics who had received imaging immediately postoperatively with those who had not. RESULTS During the 5-year study period, 328 patients who had a laparotomy for penetrating trauma over the study period, 225 patients met the inclusion criteria. Seventy-three (32%) patients underwent CT scanning immediately postoperatively with occult injuries identified in 38 (52%) patients. The most frequent occult injuries were orthopedic (20 of 43) and genitourinary (9 of 43). Importantly, 10 (26%) of the 38 patients required an intervention for these occult injuries. Those selected for immediate postoperative imaging were more likely to have sustained gunshot wounds and were significantly more severely injured (higher Injury Severity Score and longer length of hospital stay) when compared to patients who did not receive immediate imaging. CONCLUSION We recommend the use of immediate postoperative CT after emergent laparotomy especially when there is a high index of suspicion for spine or genitourinary injuries and in patients who have sustained ballistic penetrating injuries. LEVEL OF EVIDENCE Therapeutic/care management, level IV; diagnostic tests or criteria, level IV.

Variation of Opioid Prescribing Patterns among Patients undergoing Similar Surgery on the Same Acute Care Surgery Service of the Same Institution: Time for Standardization?

Background Diversion of unused prescription opioids is a major contributor to the current United States opioid epidemic. We aimed to study the variation of opioid prescribing in emergency surgery. Methods Between October 2016 and March 2017, all patients undergoing laparoscopic appendectomy, laparoscopic cholecystectomy, or inguinal hernia repair in the acute care surgery service of 1 academic center were included. For each patient, we systematically reviewed the electronic medical record and the prescribing pharmacy platform to identify: (1) history of opioid abuse, (2) opioid intake 3 months preoperatively, (3) number of opioid pills prescribed, (4) prescription of nonopioid pain medications (eg, acetaminophen, ibuprofen), and (5) the need for opioid prescription refills. The mean and range of opioid pills prescribed, as well as their oral morphine equivalent, were calculated. Results A total of 255 patients were included (43.5% laparoscopic appendectomy, 44.3% laparoscopic cholecystectomy, and 12.1% inguinal hernia repair). The mean age was 47.5 years, 52.1% were female, 11.4% had a history of opioid use, and 92.5% received opioid prescriptions upon hospital discharge. Only 70.9% of patients were instructed to use nonopioid pain medications. The mean and range of opioid pills prescribed were 17.4; 0–56 (laparoscopic appendectomy), 17.1; 0–75 (laparoscopic cholecystectomy), and 20.9; 0–50 (inguinal hernia repair), while the range of prescribed oral morphine equivalent was 0–600 mg for laparoscopic appendectomy/laparoscopic cholecystectomy and 0–375 mg for inguinal hernia repair. No patients required any opioid medication refills. Conclusion Even within the same surgical service, wide variation of opioid prescription was observed. Guidelines that standardize pain management may help prevent opioid overprescribing.

High-risk mechanism of injury: A new indication for screening for blunt cerebrovascular injury?

Blunt cerebrovascular injury is a rare but catastrophic injury. Screening for blunt cerebrovascular injury after high-impact mechanism remains ill-defined but several associated lesions have been identified as high risk for concomitant blunt cerebrovascular injury and are used to prompt further investigation for early identification and intervention. We describe a case of a large cerebral infarction caused by a high cervical internal carotid dissection after a motorcycle collision. Upon presentation, the patient had a Glasgow coma scale of 14 and an open pelvic fracture, which was immediately addressed in the operating room. His subsequent imaging revealed a nasal fracture, bilateral rib fractures, bilateral pubic rami fractures and left acetabular fracture without evidence of traumatic brain injury, cervical spine injury or extensive facial fractures. After 48 h, he displayed a depressed sensorium and an abnormal pupillary exam. He was diagnosed by computed tomography angiogram with a carotid dissection resulting in a large infarct of the right hemisphere with herniation requiring emergent craniectomy. This case suggests screening for blunt cerebrovascular injury beyond the current recommendations especially in patients with high-impact mechanism.

Innate immune cell recovery is positively regulated by NLRP12 during emergency hematopoiesis

With enhanced concerns of terrorist attacks, dual exposure to radiation and thermal combined injury (RCI) has become a real threat with devastating immunosuppression. NLRP12, a member of the NOD-like receptor family, is expressed in myeloid and bone marrow cells and was implicated as a checkpoint regulator of inflammatory cytokines, as well as an inflammasome activator. We show that NLRP12 has a profound impact on hematopoietic recovery during RCI by serving as a checkpoint of TNF signaling and preventing hematopoietic apoptosis. Using a mouse model of RCI, increased NLRP12 expression was detected in target tissues. Nlrp12−/− mice exhibited significantly greater mortality, an inability to fight bacterial infection, heightened levels of proinflammatory cytokines, overt granulocyte/monocyte progenitor cell apoptosis, and failure to reconstitute peripheral myeloid populations. Anti-TNF Ab administration improved peripheral immune recovery. These data suggest that NLRP12 is essential for survival after RCI by regulating myelopoiesis and immune reconstitution.

The Worldwide Approach to Vision Zero: Implementing Road Safety Strategies to Eliminate Traffic-Related Fatalities

Purpose of ReviewThis review describes the principle of Vision Zero in traffic safety and its adoption into the worldwide community. The Vision Zero policy seeks to reduce fatalities and serious injuries from road traffic accidents to zero. This review aims to show how this philosophy has affected policies and prevention strategies throughout the world.Recent FindingsThe Vision Zero policy has been adopted throughout Europe as well as Australia. It has recently been adopted in the USA in many major cities with preliminary encouraging results.SummaryThis article defines the Vision Zero model and demonstrates how multiple countries have implemented and adapted the vision. We review its origins in Sweden with its eventual adoption within Europe, the UK, and Australia and its recent acceptance by several cities within the USA. We reflect on shortcomings, challenges, and its future directions.