Acute Limb Ischemia in a 26-Year-Old Man Presenting with an Idiopathic Thrombosed Popliteal Artery Aneurysm.

Popliteal artery aneurysms (PAAs) are the most common peripheral arterial aneurysms and develop almost exclusively (>90%) in men who have a history of tobacco abuse at an average age of 65 years. Most PAAs are caused by chronic inflammation secondary to atherosclerotic disease; other nondegenerative causes of PAAs include arterial trauma, infection, Behçet's disease, medial fibromuscular dysplasia, or popliteal artery entrapment. Few case reports have been published on idiopathic congenital PAAs. We report a case of a 26-year-old man who presented with progressive claudication and subsequent acute limb ischemia due to the thrombosis of a large idiopathic PAA. Our case demonstrates that the differential diagnosis of young adult or pediatric patients presenting with signs of acute limb ischemia or claudication should include a symptomatic PAA.

Novel Causative Variants in DYRK1A, KARS, and KAT6A Associated with Intellectual Disability and Additional Phenotypic Features.

Patients with unclear patterns of developmental and cognitive delay may go years without a definitive diagnosis despite extensive testing due to overlapping phenotypes of many genetic disorders. In this study, we identified causative variants in DYRK1A, KARS, or KAT6A in four individuals with global developmental delay and various findings including microcephaly and sensorineural hearing loss using whole exome sequencing. We present the cognitive, neurologic, and physical findings of four individuals to expand the clinical knowledge of possible features of the phenotypes of three rare genetic disorders. Through this process, we provide support for the use of whole exome sequencing in the setting of severe, intellectual disability or in those in whom a genetic disorder is suspected despite initial negative testing.

Non-alcoholic fatty liver disease phosphoproteomics: A functional piece of the precision puzzle.

BACKGROUND: Molecular signaling events associated with the necroinflammatory changes in nonalcoholic steatohepatitis (NASH) are not well understood. AIMS: To understand the molecular basis of NASH, we evaluated reversible phosphorylation events in hepatic tissue derived from Class III obese subjects by phosphoproteomic means with the aim of highlighting key regulatory pathways that distinguish NASH from non-alcoholic fatty liver disease (also known as simple steatosis; SS). MATERIALS & METHODS: Class III obese subjects undergoing bariatric surgery underwent liver biopsy (eight normal patients, eight with simple steatosis, and eight NASH patients). Our strategy was unbiased, comparing global differences in liver protein reversible phosphorylation events across the 24 subjects. RESULTS: Of the 3078 phosphorylation sites assigned (2465 phosphoserine, 445 phosphothreonine, 165 phosphotyrosine), 53 were altered by a factor of 2 among cohorts, and of those, 12 were significantly increased or decreased by ANOVA (P < 0.05). DISCUSSION: Statistical analyses of canonical signaling pathways identified carbohydrate metabolism and RNA post-transcriptional modification among the most over-represented networks. CONCLUSION: Collectively, these results raise the possibility of abnormalities in carbohydrate metabolism as an important trigger for the development of NASH, in parallel with already established abnormalities in lipid metabolism.

Recent Advances in Forward Surgical Team Training at the U.S. Army Trauma Training Department.

U.S. Army Forward Surgical Teams (FSTs) are elite, multidisciplinary units that are highly mobile, and rapidly deployable. The mission of the FST is to provide resuscitative and damage control surgery for stabilization of life-threatening injuries in austere environments. The Army Trauma Training Center began in 2001 at the University of Miami Ryder Trauma Center under the direction of COL T. E. Knuth, MC USA (Ret.), as a multimodality combination of lectures, laboratory exercises, and clinical experiences that provided the only predeployment mass casualty and clinical trauma training center for all FSTs. Each of the subsequent five directors has restructured the training based on dynamic feedback from trainees, current military needs, and on the rapid advances in combat casualty care. We have highlighted these evolutionary changes at the Army Trauma Training Center in previous reviews. Under the current director, LTC J. M. Seery, MC USA, there are new team-building exercises, mobile learning modules and simulators, and other alternative methods in the mass casualty exercise. This report summarizes the latest updates to the state of the art training since the last review.

Risk factors for venous thromboembolism after pediatric trauma.

BACKGROUND/PURPOSE: The purposes of this study were to identify independent predictors of venous thromboembolism (VTE), to evaluate the relative impact of adult VTE risk factors, and to identify a pediatric population at high-risk for VTE after trauma. METHODS: 1934 consecutive pediatric admissions (≤ 17 years) from 01/2000 to 12/2012 at a level 1 trauma center were reviewed. Logistic regression was used to identify predictors of VTE. RESULTS: Twenty-two patients (1.2%) developed a VTE, including 5% of those requiring orthopedic surgery, 14% of those with major vascular injury (MVI), and 36% of those with both. Most (84%) were diagnosed at the primary site of injury. 86% of those who developed a VTE were receiving thromboprophylaxis at the time of diagnosis. Independent predictors were age (odds ratio (OR): 1.59, 95% confidence interval (CI): 1.11-2.25), orthopedic surgery (OR: 8.10, CI: 3.10-21.39), transfusion (OR: 3.37, CI: 1.26-8.99), and MVI (OR: 15.43, CI: 5.70-41.76). When known risk factors for VTE in adults were adjusted, significant factors were age ≥ 13 years (OR: 9.16, CI: 1.08-77.89), indwelling central venous catheter (OR: 4.41, CI: 1.31-14.82), orthopedic surgery (OR: 6.80, CI: 2.47-18.74), and MVI (OR: 14.41, CI: 4.60-45.13). CONCLUSION: MVI and orthopedic surgery are synergistic predictors of pediatric VTE. Most children who developed a VTE were receiving thromboprophylaxis at the time of diagnosis.

Surveillance and Early Management of Deep Vein Thrombosis Decreases Rate of Pulmonary Embolism in High-Risk Trauma Patients.

BACKGROUND: Venous duplex ultrasound (VDU) is the modality of choice for surveillance of venous thromboembolism (VTE), but there is controversy about its appropriate implementation as a screening method. We hypothesize that VDU surveillance in trauma patients at high risk for VTE decreases the rate of pulmonary embolism (PE). STUDY DESIGN: One thousand two hundred and eighty-two trauma ICU admissions were screened with Greenfield's Risk Assessment Profile from August 2011 to September 2014. Four hundred and two patients were identified as high risk for VTE (Risk Assessment Profile ≥10). Those who received weekly VDU to evaluate for deep vein thrombosis (n = 259 [64%]) were compared with those who did not (n = 143 [36%]). Parametric data are reported as mean ± SD and nonparametric data are reported as median (interquartile range). Statistical significance was determined at an α level of 0.05. RESULTS: The overall study population was 47 ± 19 years old and 75% were male, 78% of injuries were blunt mechanism, Injury Severity Score was 28 ± 13, Risk Assessment Profile was 14 ± 4, and mortality was 14.3%. Deep vein thrombosis rate was 11.6% (n = 30) in the surveillance group vs 2.1% (n = 3) in the non-surveillance group (p < 0.001). Deep vein thromboses detected in the surveillance group were managed with systemic anticoagulation (43%) or with IVC filter placement (57%). In the surveillance group, the PE rate was 1.9% (n = 5) vs 7.0% (n = 10) in the non-surveillance group (p = 0.014). CONCLUSIONS: Trauma patients at high risk for VTE and who received VDU surveillance and early management of deep vein thrombosis have decreased rates of pulmonary embolism.

Causes of death differ between elderly and adult falls.

BACKGROUND: As the population ages, mortality from falls will soon exceed that from all other forms of injury. Tremendous resources are focused on this problem, but how these patients die is unclear. To fill this gap, we tested the hypothesis that falls among the elderly are related to patient, rather than to injury factors when compared with falls among younger adults. METHODS: From January 2002 to December 2012, 7,293 fall admissions were reviewed. Data are reported as mean ± SD if normally distributed or median (interquartile range) if not. RESULTS: In 2002 to 2007, 25% of all falls were in elderly patients (≥65 years), but in 2008 to 2012, this proportion increased to 30% (p < 0.001). When comparing adult (n = 5,216) with elderly (n = 2,077) admissions, characteristics were as follow: Injury Severity Score (ISS) of 8 (4-13) versus 9 (5-17), length of stay (in days) of 3 (1-7) versus 6 (2-11), and mortality of 3.8% versus 13.7% (all p < 0.001). After controlling for variables associated with mortality using multiple logistic regression, elderly age was the strongest independent predictor of mortality (odds ratio, 8.18; confidence interval, 4.88-13.71). When comparing adult (n = 198) with elderly (n = 285) fatalities, ground-level falls occurred in 31% versus 91%, ISS was 27 (25-41) versus 25 (16-36), and length of stay (in days) was 2 (0-6) versus 4 (1-11) (all p < 0.001). Death occurred directly from fall in 82% versus 63%, from complications in 10% versus 20%, and from a fatal event preceding the fall in 8% vs. 17% (all p < 0.001). CONCLUSION: The proportion of fall admissions in the elderly is growing in this trauma system. Elderly age is the strongest independent predictor of mortality following a fall. In those who die, death is less likely a direct effect of the fall. LEVEL OF EVIDENCE: Epidemiologic study, level III.

Coagulation Profile Changes Due to Thromboprophylaxis and Platelets in Trauma Patients at High-Risk for Venous Thromboembolism.

We hypothesize there are coagulation profile changes associated both with initiation of thromboporphylaxis (TPX) and with change in platelet levels in trauma patients at high-risk for venous thromboembolism (VTE). A total of 1203 trauma intensive care unit patients were screened with a VTE risk assessment profile. In all, 302 high-risk patients (risk assessment profile score ≥ 10) were consented for weekly thromboelastography. TPX was initiated between initial and follow-up thromboelastography. Seventy-four patients were analyzed. Upon admission, 87 per cent were hypercoagulable, and 81 per cent remained hypercoagulable by Day 7 (P = 0.504). TPX was initiated 3.4 ± 1.4 days after admission; 68 per cent received unfractionated heparin and 32 per cent received low-molecular-weight heparin. The VTE rate was 18 per cent, length of stay 38 (25-37) days, and mortality of 17.6 per cent. In all, 76 per cent had a rapid clotting time at admission versus 39 per cent at Day 7 (P < 0.001); correcting from 7.75 (6.45-8.90) minutes to 10.45 (7.90-15.25) minutes (P < 0.001). At admission, 41 per cent had an elevated maximum clot formation (MCF) and 85 per cent had at Day 7 (P < 0.001); increasing from 61(55-65) mm to 75(69-80) mm (P < 0.001). Platelets positively correlated with MCF at admission (r = 0.308, R(2) = 0.095, P = 0.008) and at Day 7 (r = 0.516, R(2) = 0.266, P < 0.001). Change in platelet levels correlated with change in MCF (r = 0.332, R(2) = 0.110, P = 0.005). In conclusion, hypercoagulability persists despite the use of TPX. Although clotting time normalizes, MCF increases in correlation with platelet levels. As platelet function is a dominant contributor to sustained trauma-evoked hypercoagulability, antiplatelet therapy may be indicated in the management of severely injured trauma patients.

Risk of pulmonary embolism with repair or ligation of major venous injury following penetrating trauma.

BACKGROUND: There are many benefits of repair over ligation of major venous injuries (MVIs) following penetrating trauma, but the risk of pulmonary embolism (PE) is not well defined. We hypothesized that rates of PE are comparable between repair and ligation of MVI. METHODS: All penetrating trauma patients with MVI requiring an operation from 2003 to 2012 (n = 158) were retrospectively reviewed. Propensity scores were based on a logistic regression model using patient and injury characteristics. A 1:1 fixed ratio nearest neighbor matching was performed to compare outcomes of the repair and ligation cohorts. Data are reported as mean ± SD if parametric, or median (interquartile range) if not, and compared using a t test, Mann-Whitney U-test, χ2, or Fisher's exact test, as appropriate. RESULTS: The population was 89% male, age 32 ± 12 years, 74% gunshot wound, Injury Severity Score of 19 ± 13, length of stay of 9 (18) days, 3.8% PE, and a mortality of 21.5%. Repair was performed in 37% (n = 59), ligation was performed in 60% (n = 94), and 3% required both. With ligation versus repair, ligation patients were generally more critically injured; 48-hour survival was 78% versus 93% (p = 0.0083), initial Glasgow Coma Scale (GCS) score was 12 ± 5 versus 14 ± 3 (p = 0.003), initial base excess was -9 ± 8 versus -5 ± 5 mEq/L (p = 0.003), more packed red blood cells were transfused (12 (14) U vs. 9 (12) U; p = 0.032), and major arterial injury was more likely (86% vs. 42%, p < 0.001), but the PE rate was identical (5.9%) in propensity-matched cohorts. In those who developed a PE, all were receiving standard thromboprophylaxis. CONCLUSION: Following penetrating trauma, the risk of PE between repair and ligation of MVI is comparable. LEVEL OF EVIDENCE: Epidemiologic study, level III.

Altered cortical GABAA receptor composition, physiology, and endocytosis in a mouse model of a human genetic absence epilepsy syndrome.

Patients with generalized epilepsy exhibit cerebral cortical disinhibition. Likewise, mutations in the inhibitory ligand-gated ion channels, GABAA receptors (GABAARs), cause generalized epilepsy syndromes in humans. Recently, we demonstrated that heterozygous knock-out (Hetα1KO) of the human epilepsy gene, the GABAAR α1 subunit, produced absence epilepsy in mice. Here, we determined the effects of Hetα1KO on the expression and physiology of GABAARs in the mouse cortex. We found that Hetα1KO caused modest reductions in the total and surface expression of the ß2 subunit but did not alter ß1 or ß3 subunit expression, results consistent with a small reduction of GABAARs. Cortices partially compensated for Hetα1KO by increasing the fraction of residual α1 subunit on the cell surface and by increasing total and surface expression of α3, but not α2, subunits. Co-immunoprecipitation experiments revealed that Hetα1KO increased the fraction of α1 subunits, and decreased the fraction of α3 subunits, that associated in hybrid α1α3ßγ receptors. Patch clamp electrophysiology studies showed that Hetα1KO layer VI cortical neurons exhibited reduced inhibitory postsynaptic current peak amplitudes, prolonged current rise and decay times, and altered responses to benzodiazepine agonists. Finally, application of inhibitors of dynamin-mediated endocytosis revealed that Hetα1KO reduced base-line GABAAR endocytosis, an effect that probably contributes to the observed changes in GABAAR expression. These findings demonstrate that Hetα1KO exerts two principle disinhibitory effects on cortical GABAAR-mediated inhibitory neurotransmission: 1) a modest reduction of GABAAR number and 2) a partial compensation with GABAAR isoforms that possess physiological properties different from those of the otherwise predominant α1ßγ GABAARs.