Can time to healing in pediatric blunt splenic injury be predicted?

BACKGROUND: Current consensus guidelines do not recommend routine follow-up imaging for blunt splenic injury (BSI) in children. However, repeat imaging is recommended based on persistent symptoms. Wide variation of practice continues to exist among surgeons. By defining the natural evolution of BSI, we sought to identify patients at higher risk for delayed healing who could benefit from outpatient imaging. METHODS: A retrospective review of all children with BSI at a Level 1 Pediatric Trauma Center was completed. Grade of injury, hospital course, laboratory values and follow-up imaging results were obtained. Injured spleens were classified as 'healed', 'healing' (with echogenic scar), or 'non-healing' with persistence of parenchymal abnormalities. RESULTS: Between 2000 and 2014, 222 patients with BSI were identified. Seven patients (3%) underwent immediate splenectomy. Packed red blood cell transfusion was required in 13 (6%) of the 222 patients, and 3 (2%) of 145 with isolated splenic injuries. Seventy-one percent of patients underwent additional imaging 2-74 weeks post-injury. A receiver operating characteristics (ROC) curve was used to establish the relationship between sensitivity and specificity of capturing non-healing spleens over time. Optimal timing for post-injury imaging for grades I-II was 7-8 weeks; healing of higher-grade injuries could not accurately be predicted. CONCLUSIONS: If return to full physical activity, in particular contact sports, is contingent upon documented healing of the splenic parenchyma after blunt trauma in the pediatric population, follow-up imaging for low-grade injuries is best obtained around 7-8 weeks. No such recommendations can be made for high-grade splenic injuries, as the exact time to healing cannot be predicted based on initial data. LEVEL OF EVIDENCE: IV. Diagnostic test.

Inhibition of Integrin VLA-3 and Tetraspanin CD151 Protects Against Neutrophil-Mediated Endothelial Damage.

BACKGROUND: The recruitment of neutrophils to sites of localized injury or infection is initiated by changes on the surface of endothelial cells located in proximity to tissue damage. Inflammatory mediators, such as TNF-α, increase surface expression of adhesive ligands and receptors on the endothelial surface to which neutrophils tether and adhere. Neutrophils then transit through the activated endothelium to reach sites of tissue injury with little lasting vascular injury. However, in cases of sepsis, the interaction of endothelial cells with highly activated neutrophils can cause damage vascular damage. The identification of molecules that are essential for neutrophil diapedesis may reveal targets of therapeutic opportunity for preservation of endothelial function in the presence of critical illness. We tested the hypothesis that inhibition of neutrophil ß1 integrin Very Late Antigen-3 (VLA-3; α3ß1) and/or inhibition of the Tetraspanin (TM4) family member CD151 would protect against neutrophil-mediated loss of endothelial function. METHODS: Blood was obtained from septic patients or healthy donors. Neutrophils were purified and aliquots were treated with/without proinflammatory molecules. Confluent Human Umbilical Vascular Endothelial Cells (HUVECs) were activated with tumor necrosis factor (TNF-α). Electric Cell Impedance Sensing (ECIS) was used to determine monolayer resistance over time after the addition of neutrophils that were treated with blocking antibodies against VLA-3 and/or CD151 or isotype controls. Groups (depending on relevancy) were analyzed by Mann-Whitney test, Wilcoxon test, or repeated measures one-way analysis of variance (ANOVA). RESULTS: Neutrophils from septic patients and neutrophils activated ex vivo reduced endothelial monolayer resistance to a greater extent than neutrophils from healthy donors. Antibody blockade of VLA-3 and/or CD151 significantly reduced activation-associated endothelial damage. Similar findings were demonstrated on fibronectin, collagen I, collagen IV and laminin suggesting that neutrophil surface VLA-3 and CD151 are responsible for endothelial damage regardless of substrata and are likely to be operative in all bodily tissues. CONCLUSION: This report identifies VLA-3 and CD151, on the activated human neutrophil that are responsible for damage to endothelial function. Targeting these molecules in vivo may demonstrate preservation of organ function during critical illness.

Proximity to the Diaphragm Predicts the Presence of Rhabdomyomatous Dysplasia in Congenital Pulmonary Airway Malformations.

INTRODUCTION: Rhabdomyomatous dysplasia (RD) is a pathologic finding in CPAMs that was incorrectly attributed to their malignant potential. The increasing recognition of extrathoracic (intradiaphragmatic and intraabdominal) congenital pulmonary airway malformations (CPAMs) offers a clue to the origin of RD. We hypothesize that the presence of RD is related to the CPAM's anatomic location. MATERIALS AND METHODS: Retrospective review was performed of all children who underwent resection of a CPAM during a 10-year period. The age at the time of operation, location of the CPAM, and pathologic findings were collected. Peridiaphragmatic location was defined as within the inferior pulmonary ligament, deep to the diaphragmatic portion of the parietal pleura ("intradiaphragmatic") or adjacent to the abdominal side of the diaphragm. Statistical analysis was performed using Fisher's exact test for 2 × 2 tables. RESULTS: Twenty-six patients with CPAM were identified. Preoperative imaging was performed by computed tomography (CT) scan (16/26), ultrasound (5/26), magnetic resonance imaging (MRI) (1/26), and chest radiograph (4/26). The median age at resection was 15 months. Of these, 16 were pure cystic adenomatoid malformations, 4 were extralobar sequestrations, 4 were intralobar sequestrations, and 2 were bronchogenic cysts. Nine lesions were peridiaphragmatic with four being intradiaphragmatic (44%). Eight of the nine resected peridiaphragmatic lesions contained histologic evidence of rhabdomyomatous changes (89%, confidence interval [CI] 52-99%). None of the other lesions contained RD (CI 0-19%, p < 0.001). CONCLUSION: RD was seen exclusively, and in virtually all peridiaphragmatic CPAMs. While the exact significance of RD remains unclear, it may represent incorporation of striated muscle tissue associated with the developing diaphragm.

Leukadherin-1 ameliorates endothelial barrier damage mediated by neutrophils from critically ill patients.

BACKGROUND: Multi-organ failure occurs during critical illness and is mediated in part by destructive neutrophil-to-endothelial interactions. The ß2 integrin receptor, CR3 (complement receptor 3; Mac-1; CD11b/CD18), which binds endothelial intercellular adhesion molecule-1 (ICAM-1), plays a key role in promoting the adhesion of activated neutrophils to inflamed endothelia which, when prolonged and excessive, can cause vascular damage. Leukadherin-1 (LA-1) is a small molecule allosteric activator of CR3 and has been shown to promote adhesion of blood neutrophils to inflamed endothelium and restrict tissue infiltration. Therefore, LA-1 offers a novel mechanism of anti-inflammatory action by activation, rather than inhibition, of the neutrophil CR3 integrin. However, whether promotion of neutrophil-to-endothelial interaction by this novel therapeutic is of benefit or detriment to endothelial barrier function is not known. METHODS: Critically ill septic and trauma patients were prospectively enrolled from the surgical and the trauma ICU. Blood was collected from these patients and healthy volunteers. Neutrophils were isolated by dextran sedimentation and adhered to TNF-α (tumor necrosis factor-α)-activated human umbilical vein endothelial (HUVEC) monolayers in the presence or absence of fMLP (formylmethionine-leucine-phenylalanine) and/or LA-1. Electric cell-substrate impedance sensing (ECIS) and exposure of underlying collagen were used to quantify endothelial barrier function and permeability. RESULTS: Neutrophils from critically ill trauma and septic patients caused similar degrees of endothelial barrier disruption which exceeded that caused by cells obtained from healthy controls both kinetically and quantitatively. LA-1 protected barrier function in the absence and presence of fMLP which served as a secondary stimulant to cause maximal loss of barrier function. LA-1 protection was also observed by quantifying collagen exposure underlying endothelial cells challenged with fMLP-stimulated neutrophils. LA-1 treatment resulted in decreased migration dynamics of neutrophils crawling on an endothelial monolayer with reduced speed (µm/s = 0.25 ± 0.01 vs. 0.06 ± 0.01, p < 0.05), path length (µm = 199.5 ± 14.3 vs. 42.1 ± 13.0, p < 0.05), and displacement (µm = 65.2 ± 4.7 vs. 10.4 ± 1.3; p < 0.05). CONCLUSION: Neutrophils from patients with trauma or sepsis cause endothelial barrier disruption to a similar extent relative to each other. The CR3 agonist LA-1 protects endothelial barrier function from damage caused by neutrophils obtained from both populations of critically ill patients even when exposed to secondary stimulation.

Early Predictors of Abscess Development after Perforated Pediatric Appendicitis.

BACKGROUND: Approximately one-third of children with appendicitis present with advanced disease or perforation. Whereas this increases the risk for post-operative complications and re-admission, it is not yet possible to predict early on who will develop an abdominal abscess. We sought to identify specific risk factors for this complication, in an attempt to streamline post-operative care. PATIENTS AND METHODS: We reviewed the records of all cases of perforated appendicitis over a 12-month period at a tertiary children's hospital. All patients who developed an abscess despite treatment minimum of seven days of antibiotic therapy were identified. Patients who presented or were re-admitted with an abscess were excluded from analysis. Records were reviewed for demographics, laboratory results, progression of oral intake, and vital signs. RESULTS: Of 273 patients with appendicitis, we identified 59 cases of perforated appendicitis. Fifteen patients were excluded. Eight of the remaining 44 patients (18.2%) developed an abscess during their initial admission. Their mean length of stay was longer than that of patients without an abscess (13.4 ± 7.1 vs. 6.9 ± 1.9 d, p < 0.0001). Gender, leukocytosis, or diarrhea at presentation, maximum temperature on post-operative day 3, and maximum heart rate on post-operative day 3 were not statistically different. Diet progression was different between the two groups: none of the 21 patients who were tolerating a regular diet by post-operative day 3 developed an abscess, compared with 8 of the 23 patients who were not yet eating a regular diet on post-operative day 3 (p < 0.01). Late leukocytosis also correlated with the presence of an abscess: 7 of the 8 patients with an abscess had persistent leukocytosis at days 5 through 7, compared with 3 of 31 patients without abscess (p < 0.05). An ultrasound was obtained for these 3 patients and proved normal. CONCLUSIONS: Tolerating a regular diet three days after appendectomy for perforated appendicitis decreased the likelihood of a post-operative abscess. No other parameter was predictive of this complication early in the post-operative period. If confirmed in a larger prospective study, this finding may help decrease the length of stay for low-risk patients, and identify abscesses in high-risk patients in a timely fashion.

Do Patients with Pre-Existing Psychiatric Illness Have an Increased Risk of Infection after Injury?

BACKGROUND: Trauma remains a leading cause of death and long term-morbidity. We have shown that patients who sustain traumatic injuries are at increased risk for the development of infectious complications. Psychiatric illnesses (PIs) are also noted to occur frequently among the general population. The presence of a PI has been shown to be a risk factor for the development of infections. Despite the prevalence of both traumatic injuries and psychiatric diseases, there are little data relating the impact of PI on the outcome of patients with trauma. We hypothesize that the presence of a PI will be associated with an increased risk of an infection developing after injury. PATIENTS AND METHODS: This is a five year retrospective chart review of all admitted patients with trauma age 18 years and older. Patients with and without a major psychiatric illness were compared. Demographic data, mechanism of injury and Injury Severity Score (ISS) were reviewed. Co-morbidities included diabetes mellitus, obesity, pre-injury steroid use, and International Classification of Diseases, 9th edition, based psychiatric illness. All infections were diagnosed by microbiologic criteria (urinary tract infection [UTI], ventilator-associated pneumonia) or Centers for Disease Control and Prevention criteria for clinically evident infections (surgical site infection). RESULTS: Of the 11,147 admitted trauma patients, 14.5% had a pre-injury PI diagnosis. The PI patients were older (61.5 ± 0.5 vs. 54.3; p < 0.001), more often female (56% vs. 39.1%; p < 0.001), and had no difference in blunt mechanism rates (88.4% vs. 89.9%; p = 0.06) or median ISS (9 vs. 9; p = 0.06). There was no difference between PI and non-PI patients in pre-injury diabetes mellitus (13.4% vs. 12.7%; p = 0.4), steroid use (2.5% vs. 1.9%; p = 0.1), but patients with PI were more likely to be obese (15.7% vs. 13.6%; p = 0.03). Patients with PI were more likely to have an infection develop (10.4% vs. 7.5%; p < 0.001). The most common infection in both groups was UTI (6.9% vs. 4.2%; p < 0.001). Compared with non-PI patients, adjusting for age, gender, ISS, diabetes mellitus, and obesity, patients with PI were more likely to have an infection develop (odds ratio 1.3, 95% confidence interval = 1.1-1.5) Conclusions: Patients with an underlying PI are at increased risk of having a UTI after traumatic injury. This study identifies a previously unknown independent risk factor for UTIs in patients with trauma. This stresses the need for increased awareness and attention to this vulnerable population.