DUI histories in intoxicated injured bicyclists.

INTRODUCTION: It has been well documented that the use of alcohol correlates with injury risk, especially in DUI (driving under the influence) and DWI (driving while intoxicated). Consumption of alcohol in patients presenting with bicycle-related injuries is associated with greater injury severity, longer hospitalization, and higher health care costs. We hypothesized that intoxicated patients operating a bicycle with traumatic injuries have previous DUI or DWI convictions and had lost their privilege to drive a motor vehicle, resorted to bicycling, and had continued alcohol consumption despite negative previous consequences. METHODS: We retrospectively collected data on injured bicyclists older than 18 years with positive blood alcohol content levels treated from the period January 2009 to June 2014 at a large Level 1 urban trauma center. We then matched each patient by name and date of birth and were able to obtain public criminal records through the Superior Court of California for the local of county. RESULTS: A total of 149 injured bicyclists with positive blood alcohol levels were identified. Their average blood alcohol content was 236.0 mg/dL, and their average age was 41 years. Sixty-six (44.2%) of these patients had prior DUI/DWI convictions with suspension of driving privileges. Ninety-five patients in this group (63.8%) had no health insurance, and 51 patients (34.2%) tested positive for other drugs. Intoxicated bicyclists trended toward longer hospital length compared with nonintoxicated bicyclists (4.60 vs. 3.44 days; p = 0.07). Three (0.02%) of 149 patients were charged with bicycling while intoxicated. CONCLUSION: Intoxicated bicyclists involved in trauma are more likely to have a previous DUI/DWI, have other drug use, tend to have longer hospital stays, and are less likely to have insurance. Bicycle safety education and behavior modification targeting DUI/DWI offenders are warranted. In order to promote injury prevention, resources to increase awareness of this underestimated public health issue should be promoted. LEVEL OF EVIDENCE: Epidemiologic study, level III.

Generation of GFAP::GFP astrocyte reporter lines from human adult fibroblast-derived iPS cells using zinc-finger nuclease technology.

Astrocytes are instrumental to major brain functions, including metabolic support, extracellular ion regulation, the shaping of excitatory signaling events and maintenance of synaptic glutamate homeostasis. Astrocyte dysfunction contributes to numerous developmental, psychiatric and neurodegenerative disorders. The generation of adult human fibroblast-derived induced pluripotent stem cells (iPSCs) has provided novel opportunities to study mechanisms of astrocyte dysfunction in human-derived cells. To overcome the difficulties of cell type heterogeneity during the differentiation process from iPSCs to astroglial cells (iPS astrocytes), we generated homogenous populations of iPS astrocytes using zinc-finger nuclease (ZFN) technology. Enhanced green fluorescent protein (eGFP) driven by the astrocyte-specific glial fibrillary acidic protein (GFAP) promoter was inserted into the safe harbor adeno-associated virus integration site 1 (AAVS1) locus in disease and control-derived iPSCs. Astrocyte populations were enriched using Fluorescence Activated Cell Sorting (FACS) and after enrichment more than 99% of iPS astrocytes expressed mature astrocyte markers including GFAP, S100ß, NFIA and ALDH1L1. In addition, mature pure GFP-iPS astrocytes exhibited a well-described functional astrocytic activity in vitro characterized by neuron-dependent regulation of glutamate transporters to regulate extracellular glutamate concentrations. Engraftment of GFP-iPS astrocytes into rat spinal cord grey matter confirmed in vivo cell survival and continued astrocytic maturation. In conclusion, the generation of GFAP::GFP-iPS astrocytes provides a powerful in vitro and in vivo tool for studying astrocyte biology and astrocyte-driven disease pathogenesis and therapy.

RNA toxicity from the ALS/FTD C9ORF72 expansion is mitigated by antisense intervention.

A hexanucleotide GGGGCC repeat expansion in the noncoding region of the C9ORF72 gene is the most common genetic abnormality in familial and sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The function of the C9ORF72 protein is unknown, as is the mechanism by which the repeat expansion could cause disease. Induced pluripotent stem cell (iPSC)-differentiated neurons from C9ORF72 ALS patients revealed disease-specific (1) intranuclear GGGGCCexp RNA foci, (2) dysregulated gene expression, (3) sequestration of GGGGCCexp RNA binding protein ADARB2, and (4) susceptibility to excitotoxicity. These pathological and pathogenic characteristics were confirmed in ALS brain and were mitigated with antisense oligonucleotide (ASO) therapeutics to the C9ORF72 transcript or repeat expansion despite the presence of repeat-associated non-ATG translation (RAN) products. These data indicate a toxic RNA gain-of-function mechanism as a cause of C9ORF72 ALS and provide candidate antisense therapeutics and candidate human pharmacodynamic markers for therapy.

Computed tomography blush and splenic injury: does it always require angioembolization?

The implication of splenic contrast blush on computed tomography (CT) in blunt trauma patients and whether it is an indication for angioembolization (AE) remains controversial. Our objective was to determine whether CT blush and its subsequent treatment have any impact on outcomes in blunt trauma patients with low-grade splenic injuries. A retrospective review identified adult patients with splenic injury (American Association for the Surgery of Trauma grades 1 to 3) from blunt abdominal trauma who were evaluated with a CT scan over a 3.5-year period at a Level I trauma center. Patient groups analyzed included: observation patients with no CT blush (n = 110), observation patients with CT blush (n = 18), and AE patients with CT blush (n = 22). Patients with CT blush who were observed did not demonstrate significantly worse outcomes compared with the patients with no CT blush. Additionally, patients with CT blush who underwent AE did not show any significant improvement in outcomes compared with patients who were observed with CT blush. Our study suggests that CT blush does not predict worse outcomes for blunt trauma patients with low-grade splenic injury who underwent observation. Furthermore, AE does not seem to provide any advantage to this subset of patients.

A comparison of thoracic CT and abdominal CT for the identification of thoracic blunt trauma.

BACKGROUND: In light of current trends to limit radiation exposure and costs, as well as increased traffic safety, computed tomography (CT) may have decreasing value for evaluating patients with blunt trauma. The authors examined the utility of chest x-ray and abdominal CT for identifying clinically significant thoracic blunt trauma. METHODS: In this prospective study, findings on thoracic CT, abdominal CT, and chest x-ray from trauma patients were compared to assess injury prevalence and relevance to treatment outcomes. RESULTS: Four hundred forty-four patients were identified, of whom 76% had no findings. Occult findings had significantly lower Injury Severity Scores. All clinically relevant pneumothoraces and most other injuries could be identified without thoracic CT. Two of 3 aortic abnormalities were suspected from chest x-ray. CONCLUSIONS: Clinically significant injuries can be identified with abdominal CT and chest x-ray, safely allowing reductions in radiation exposure, hospital stays, and costs by limiting the use of thoracic CT.

Risk for contrast-induced nephropathy in elderly trauma patients.

The objective of this study was to determine if elderly trauma patients are at risk for contrast-induced nephropathy (CIN). A retrospective study was conducted identifying 362 patients 65 years and older in our Level I trauma center who received computerized tomography (CT) scans with intravenous contrast. CIN was defined as a 25 per cent increase in serum creatinine levels or a 0.5 mg/dL increase above baseline after CT. History of diabetes mellitus, hospital length of stay, intensive care unit length of stay, Injury Severity Score (ISS), and age were recorded. Eighteen per cent (21 of 118) of the patients had a peak in creatinine, 12 per cent (14 of 118) peaked and returned to baseline, and 6 per cent (7 of 118) peaked and stayed high. Pre-CT elevated creatinine, diabetes mellitus, increased hospital length of stay, ISS, and age show little association to CIN. The data suggest that CIN in elderly trauma patients is rare, regardless of history of diabetes mellitus, age, creatinine, high ISS, or result in higher length of stay. Therefore, there is little justification for the delay in diagnosis to assess a patient's renal susceptibility.

Ability of a chest X-ray and an abdominal computed tomography scan to identify traumatic thoracic injury.

OBJECTIVE: Our objective was to show that a chest X-ray (CXR) and an abdominal computed tomography (CT) scan are sufficient to identify most clinically significant thoracic injuries in trauma patients, rendering the thoracic CT scan useful in only a subset of patients. METHODS: A retrospective study identified thoracic injuries in 374 trauma patients evaluated with a CXR, a thoracic CT scan, and an abdominal CT scan. Injuries seen on the initial CXR versus those seen on a CT scan only (occult) were identified and assessed for clinical relevance. RESULTS: An abdominal CT scan identified 65% (15/23) of occult pneumothoraces, 100% (25/25) of occult hemothoraces, 64% (18/28) of occult pulmonary contusions, and 58% (18/31) of occult rib fractures. No occult pneumothoraces seen on the thoracic CT scan alone required tube thoracostomy. CONCLUSIONS: Our pilot study suggests that a CXR and an abdominal CT scan will identify most occult intrathoracic injuries. Reserving a thoracic CT scan for patients with an abnormal CXR or high-risk mechanism could safely reduce cost and radiation exposure while still diagnosing significant thoracic injuries.

Ciliary beating recovery in deficient human airway epithelial cells after lentivirus ex vivo gene therapy.

Primary Ciliary Dyskinesia is a heterogeneous genetic disease that is characterized by cilia dysfunction of the epithelial cells lining the respiratory tracts, resulting in recurrent respiratory tract infections. Despite lifelong physiological therapy and antibiotics, the lungs of affected patients are progressively destroyed, leading to respiratory insufficiency. Recessive mutations in Dynein Axonemal Intermediate chain type 1 (DNAI1) gene have been described in 10% of cases of Primary Ciliary Dyskinesia. Our goal was to restore normal ciliary beating in DNAI1-deficient human airway epithelial cells. A lentiviral vector based on Simian Immunodeficiency Virus pseudotyped with Vesicular Stomatitis Virus Glycoprotein was used to transduce cultured human airway epithelial cells with a cDNA of DNAI1 driven by the Elongation Factor 1 promoter. Transcription and translation of the transduced gene were tested by RT-PCR and western blot, respectively. Human airway epithelial cells that were DNAI1-deficient due to compound heterozygous mutations, and consequently had immotile cilia and no outer dynein arm, were transduced by the lentivirus. Cilia beating was recorded and electron microscopy of the cilia was performed. Transcription and translation of the transduced DNAI1 gene were detected in human cells treated with the lentivirus. In addition, immotile cilia recovered a normal beat and outer dynein arms reappeared. We demonstrated that it is possible to obtain a normalization of ciliary beat frequency of deficient human airway epithelial cells by using a lentivirus to transduce cells with the therapeutic gene. This preliminary step constitutes a conceptual proof that is indispensable in the perspective of Primary Ciliary Dyskinesia's in vivo gene therapy. This is the first time that recovery of cilia beating is demonstrated in this disease.