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Expansion duraplasty to reopen effaced subarachnoid space and improve spinal cord perfusion, autoregulation, and spinal pressure reactivity index (sPRX) has been advocated in patients with traumatic cervical spinal cord injury (tCSCI). We designed this study to identify candidates for expansion duraplasty, based on the absence of cerebrospinal fluid (CSF) interface around the spinal cord on magnetic resonance imaging (MRI), in the setting of otherwise adequate bony decompression. Over a 61-month period, 104 consecutive American Spinal Injury Association Impairment Scale (AIS) grades A-C patients with tCSCI had post-operative MRI to assess the adequacy of surgical decompression. Their mean age was 53.4 years, and 89% were male. Sixty-one patients had falls, 31 motor vehicle collisions, 11 sport injuries, and one an assault. The AIS grade was A in 56, B in 18, and C in 30 patients. Fifty-four patients had fracture dislocations; there was no evidence of skeletal injury in 50 patients. Mean intramedullary lesion length (IMLL) was 46.9 (standard deviation = 19.4) mm. Median time from injury to decompression was 17 h (interquartile range 15.2 h). After surgery, 94 patients had adequate decompression as judged by the presence of CSF anterior and posterior to the spinal cord, whereas 10 patients had effacement of the subarachnoid space at the injury epicenter. In two patients whose decompression was not definitive and post-operative MRI indicated inadequate decompression, expansion duraplasty was performed. Candidates for expansion duraplasty (i.e., those with inadequate decompression) were significantly younger (

Consensus is currently lacking in the optimal treatment for blunt traumatic cerebral venous sinus thrombosis (tCVST). Anticoagulation (AC) is used for treating spontaneous CVST, but its role in tCVST remains unclear.To investigate the characteristics and outcomes of patients treated with AC compared with patients managed conservatively.We retrospectively reviewed patients who presented to a Level 1 trauma center with acute skull fracture after blunt head trauma who underwent dedicated venous imaging.There were 137 of 424 patients (32.3%) presenting with skull fractures with tCVST on venous imaging. Among them, 82 (60%) were treated with AC while 55 (40%) were managed conservatively. Analysis of baseline characteristics demonstrated no significant difference in age, sex, admission Glasgow Coma Scale, admission Injury Severity Score, rates of associated intracranial hemorrhage, or neurosurgical interventions. New or worsening intracranial hemorrhage was seen in 7 patients treated with AC. Patients on AC had significantly lower mortality than non-AC (1% vs 15%; P = .003). There was no difference in the Glasgow Coma Scale or Glasgow Outcome Scale at last clinical follow-up. On follow-up venous imaging, patients treated with AC were more likely to experience full thrombus recanalization than non-AC (54% vs 32%; P = .012), and subsequent multiple regression analysis revealed that treatment with AC was a significant predictor of full thrombus recanalization (odds ratio, 5.18; CI, 1.60-16.81; P = .006).Treatment with AC for tCVST due to blunt head trauma may promote higher rates of complete thrombus recanalization when compared with conservative management.

Over the past four decades, there have been progressive changes in the epidemiology of traumatic spinal cord injury (tSCI). We assessed trends in demographic and injury-related variables in traumatic cervical spinal cord injury (tCSCI) patients over an 18-year period at a single Level I trauma center. We included all magnetic resonance imaging-confirmed tCSCI patients ≥15 years of age for years 2001-2018. Among 1420 patients, 78.3% were male with a mean age 51.5 years. Etiology included falls (46.9%), motor vehicle collisions (MVCs; 34.2%), and sports injuries (10.9%). Median American Spinal Injury Association (ASIA) Motor Score (AMS) was 44, complete tCSCI was noted in 29.6% of patients, fracture dislocations were noted in 44.7%, and median intramedullary lesion length (IMLL) was 30.8 mm (complete injuries 56.3 mm and incomplete injuries 27.4 mm). Over the study period, mean age and proportion of falls increased (

To date, the description of the natural course of concurrent tethered cord syndrome with a low-lying conus medullaris and split cord malformation is lacking in the literature. We report a cohort of adult and pediatric patients with concurrent malformations and long-term follow-up. Patients with concurrent diagnoses of split cord malformation and tethered cord (radiographic evidence supporting clinical symptomatology) were identified between 2000 and 2020. Patients without sufficient documentation or at least 6-month follow-up were excluded. Nine patients were identified with an average of 8.9 years follow-up (range 2–31 years). The most common symptoms were radiating leg pain and lower extremity paresthesias, occurring in 44% of patients; and bladder/bowel dysfunction, worsening scoliosis, and acute motor deterioration were less common. Two patients were successfully treated conservatively for mild leg pain and paresthesias. For those who underwent surgery, all experienced symptomatic relief upon first follow-up. Two had late symptomatic recurrence; one 4 and 8 years after initial surgery; and the other, 11, 26, and 31 years after initial surgery. The rarity of concurrent split cord and tethered cord syndrome with a low-lying conus makes management difficult to formulate. This series supplements our knowledge of the long-term outcomes and lessons learned from the management of these patients. Approximately 25% of patients were managed conservatively and had symptomatic improvement. For surgically managed patients, with intractable pain or worsening neurological function, symptoms can still recur over a decade after intervention. Reoperation, however, can still be beneficial, can provide years of relief, and should be considered.

Valproate (VPA) has been used in the treatment of bipolar disorder since the 1990s. However, the therapeutic targets of VPA have remained elusive. Here we employ a preclinical model to identify the therapeutic targets of VPA. We find compounds that inhibit histone deacetylase proteins (HDACs) are effective in normalizing manic-like behavior, and that class I HDACs (e.g., HDAC1 and HDAC2) are most important in this response. Using an RNAi approach, we find that HDAC2, but not HDAC1, inhibition in the ventral tegmental area (VTA) is sufficient to normalize behavior. Furthermore, HDAC2 overexpression in the VTA prevents the actions of VPA. We used RNA sequencing in both mice and human induced pluripotent stem cells (iPSCs) derived from bipolar patients to further identify important molecular targets. Together, these studies identify HDAC2 and downstream targets for the development of novel therapeutics for bipolar mania.

Post-operative vision loss (POVL) can be a devastating complication of neurosurgical procedures and is unusual in the pediatric population. Mechanisms of POVL include direct optic nerve injury, vascular occlusion, or indirect malperfusion resultant from surgeries with substantial blood loss or fluid shifts, with prone positioning being a major risk factor for these events. Posterior ischemic optic neuropathy (PION) is a rare cause of POVL and is associated with a poor prognosis for recovery of visual function. We present a case of PION following a supine bifrontal craniotomy for a frontal epidural abscess secondary to pan-sinusitis in a pediatric patient. This is an unusual reported case in that no additional traditional risk factors were identified. We present clinical and radiographic findings, diagnostic considerations, treatment strategies, and a literature review. The patient was managed medically and recovered substantial vision in the affected eye.

In cervical traumatic spinal cord injury (TSCI), the therapeutic effect of timing of surgery on neurological recovery remains uncertain. Additionally, the relationship between extent of decompression, imaging biomarker evidence of injury severity, and outcome is incompletely understood. We investigated the effect of timing of decompression on long-term neurological outcome in patients with complete spinal cord decompression confirmed on postoperative magnetic resonance imaging (MRI). American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade conversion was determined in 72 AIS grades A, B, and C patients 6 months after confirmed decompression. Thirty-two patients underwent decompressive surgery ultra-early (< 12 h), 25 underwent decompressive surgery early (12–24 h), and 15 underwent decompressive surgery late (> 24–138.5 h) after injury. Age, gender, injury mechanism, intramedullary lesion length (IMLL) on MRI, admission ASIA motor score, and surgical technique were not statistically different among groups. Motor complete patients (p = 0.009) and those with fracture dislocations (p = 0.01) tended to be operated on earlier. Improvement of one grade or more was present in 55.6% of AIS grade A, 60.9% of AIS grade B, and 86.4% of AIS grade C patients. Admission AIS motor score (p = 0.0004) and pre-operative IMLL (p = 0.00001) were the strongest predictors of neurological outcome. AIS grade improvement occurred in 65.6%, 60%, and 80% of patients who underwent decompression ultra-early, early, and late, respectively (p = 0.424). Multiple regression analysis revealed that IMLL was the only significant variable predictive of AIS grade conversion to a better grade (odds ratio, 0.908; confidence interval [CI], 0.862–0.957; p

The therapeutic significance of timing of decompression in acute traumatic central cord syndrome (ATCCS) caused by spinal stenosis remains unsettled. We retrospectively examined a homogenous cohort of patients with ATCCS and magnetic resonance imaging (MRI) evidence of post-treatment spinal cord decompression to determine whether timing of decompression played a significant role in American Spinal Injury Association (ASIA) motor score (AMS) 6 months following trauma. We used the t test, analysis of variance, Pearson correlation coefficient, and multiple regression for statistical analysis. During a 19-year period, 101 patients with ATCCS, admission ASIA Impairment Scale (AIS) grades C and D, and an admission AMS of ≤95 were surgically decompressed. Twenty-four of 101 patients had an AIS grade C injury. Eighty-two patients were males, the mean age of patients was 57.9 years, and 69 patients had had a fall. AMS at admission was 68.3 (standard deviation [SD] 23.4); upper extremities (UE) 28.6 (SD 14.7), and lower extremities (LE) 41.0 (SD 12.7). AMS at the latest follow-up was 93.1 (SD 12.8), UE 45.4 (SD 7.6), and LE 47.9 (SD 6.6). Mean number of stenotic segments was 2.8, mean canal compromise was 38.6% (SD 8.7%), and mean intramedullary lesion length (IMLL) was 23 mm (SD 11). Thirty-six of 101 patients had decompression within 24 h, 38 patients had decompression between 25 and 72 h, and 27 patients had decompression >72 h after injury. Demographics, etiology, AMS, AIS grade, morphometry, lesion length, surgical technique, steroid protocol, and follow-up AMS were not statistically different between groups treated at different times. We analyzed the effect size of timing of decompression categorically and in a continuous fashion. There was no significant effect of the timing of decompression on follow-up AMS. Only AMS at admission determined AMS at follow-up (coefficient = 0.31; 95% confidence interval [CI]:0.21; p = 0.001). We conclude that timing of decompression in ATCCS caused by spinal stenosis has little bearing on ultimate AMS at follow-up.

Objective Hemorrhagic contusion in cervical spinal cord injury (CSCI) is poorly understood. We investigated hemorrhagic expansion in patients with CSCI with an assigned elevated mean arterial pressure (MAP) goal of >85 mm Hg. The change in hemorrhagic area and long-term follow-up data ≥6 months after injury was studied. Methods A retrospective review was performed from 2005 to 2016 to identify patients with motor complete CSCI with 2 cervical magnetic resonance imaging (MRI) scans within 7 days of injury showing evidence of hemorrhagic contusion and assigned a MAP goal of >85 mm Hg for 7 days. T2-weighted MRI was used to calculate the hemorrhagic surface area in the sagittal plane. A calculated MAP was recorded for each blood pressure measure between the initial and follow-up MRI scans. The American Spinal Injury Association impairment scale (AIS) and American Spinal Injury Association motor scores were recorded at the final follow-up examination at ≥6 months. Results A total of 193 patients were identified. The mean change in the hemorrhagic area was 24.0 mm2. Of the 193 patients, the AIS grade was A for 114 and B for 79 patients. Multiple logistic regression analysis demonstrated that the MAP and systolic blood pressure were nonsignificant predictors of hemorrhagic contusion expansion. An increased hemorrhagic contusion area on the follow-up MRI scan was associated with a reduced odds of AIS improvement of ≥1 and ≥2 points (odds ratio, 0.97; 95% confidence interval, 0.87–0.97; P = 0.028; and odds ratio, 0.92; 95% confidence interval, 0.99–1.13; P = 0.008, respectively) at the final ≥6-month follow-up examination. Conclusion The present study investigated the clinical safety of elevated MAP goals for patients with CSCI and hemorrhagic contusion. Elevated MAPs did not significantly increase the risk of hemorrhagic expansion in those with CSCI. We have also reported the use of hemorrhagic contusion size as a potential radiographic biomarker for neurological outcomes.

The diurnal regulation of dopamine is important for normal physiology and diseases such as addiction. Here we find a novel role for the CLOCK protein to antagonize CREB-mediated transcriptional activity at the tyrosine hydroxylase (TH) promoter, which is mediated by the interaction with the metabolic sensing protein, Sirtuin 1 (SIRT1). Additionally, we demonstrate that the transcriptional activity of TH is modulated by the cellular redox state, and daily rhythms of redox balance in the ventral tegmental area (VTA), along with TH transcription, are highly disrupted following chronic cocaine administration. Furthermore, CLOCK and SIRT1 are important for regulating cocaine reward and dopaminergic (DAergic) activity, with interesting differences depending on whether DAergic activity is in a heightened state and if there is a functional CLOCK protein. Taken together, we find that rhythms in cellular metabolism and circadian proteins work together to regulate dopamine synthesis and the reward value for drugs of abuse.

Background: There is an information gap in literature regarding postoperative outcome of total knee arthroplasty (TKA)in patients with hardware in-situ from the previous knee surgery. The present study aims to evaluate impact of retainedhardware on short-term outcome of TKA patients.Methods: Perioperative radiographs of patients who had undergone TKA between 2007 and 2012 were reviewedand patients in whom partial or complete retention of hardware was evident after TKA were included. These patientswere matched in 1 to 2 ratio based on age (+/- 2 years), gender, surgeon and year of surgery to a group of patientsthat underwent primary TKA without hardware in the affected knee. The average follow up of these patients was 43.45(range 12-155.2) months. Complication rates were compared between the two groups using statistical tests that tookinto account the matched data structure.Results: We included a total of 55 cases and 110 controls. The incidence of complications was higher, although notall statistically significant, in the case group. Only mechanical complications were significantly different in the casesgroup (5.5% versus 0%, P=0.01). Time to event analysis using the mixed-effects Cox model didn’t show a statisticallysignificant difference between two groups for various outcomes.Conclusion: Presence of retained hardware around the knee may predispose the patient to a higher rate ofcomplications particularly mechanical complications of the implant after TKA. Further studies are required to investigateimpact of retained hardware around the knee in patients undergoing TKA.

OBJECTIVEThe authors sought to evaluate whether a sustained systemic inflammatory response was associated with shunt-dependent hydrocephalus following aneurysmal subarachnoid hemorrhage.METHODSA retrospective analysis of 193 consecutive patients with aneurysmal subarachnoid hemorrhage was performed. Management of hydrocephalus followed a stepwise algorithm to determine the need for external CSF drainage and subsequent shunt placement. Systemic inflammatory response syndrome (SIRS) data were collected for all patients during the first 7 days of hospitalization. Patients who met the SIRS criteria every day for the first 7 days of hospitalization were considered as having a sustained SIRS. Univariate and multivariate regression analyses were used to determine predictors of shunt dependence.RESULTSSixteen percent of patients required shunt placement. Sustained SIRS was observed in 35% of shunt-dependent patients compared to 14% in non–shunt-dependent patients (p = 0.004). On multivariate logistic regression, female sex (OR 0.35, 95% CI 0.142–0.885), moderate to severe vasospasm (OR 3.78, 95% CI 1.333–10.745), acute hydrocephalus (OR 21.39, 95% CI 2.260–202.417), and sustained SIRS (OR 2.94, 95% CI 1.125–7.689) were significantly associated with shunt dependence after aneurysmal subarachnoid hemorrhage. Receiver operating characteristic analysis revealed an area under the curve of 0.83 for the final regression model.CONCLUSIONSSustained SIRS was a predictor of shunt-dependent hydrocephalus following aneurysmal subarachnoid hemorrhage even after adjustment for potential confounding variables in a multivariate logistic regression model.

OBJECTIVEThe Pipeline embolization device (PED) has become a valuable tool in the treatment of cerebral aneurysms. Although failures with PED treatment have been reported, the characteristics and course of these aneurysms remain a topic of uncertainty.METHODSElectronic medical records and imaging studies were reviewed for all patients treated with the PED between July 2010 and March 2015 to identify characteristics of patients and aneurysms with residual filling after PED treatment.RESULTSOf 316 cases treated at a single institution, 281 patients had a long-term follow-up. A total of 52 (16.4%) aneurysms with residual filling were identified and constituted the study population. The mean patient age in this population was 58.8 years. The mean aneurysm size was 10.1 mm ± 7.15 mm. Twelve aneurysms were fusiform (23%). Of the aneurysms with residual filling, there were 20 carotid ophthalmic (CO) aneurysms (20% of all CO aneurysms treated), 10 other paraclinoid aneurysms (16.4% of all paraclinoid aneurysms), 7 posterior communicating artery (PCoA) aneurysms (21.9% of all PCoA aneurysms), 7 cavernous internal carotid artery (ICA) aneurysms (14.9% of all cavernous ICA aneurysms), 4 vertebrobasilar (VB) junction aneurysms (14.8% of all VB junction aneurysms), and 3 middle cerebral artery (MCA) aneurysms (25% of all MCA aneurysms). Eleven patients underwent placement of more than one PED (21.2%), with a mean number of devices of 1.28 per case. Eight of 12 aneurysms were previously treated with a stent (15.4%). Nineteen patients underwent re-treatment (36.5%); the 33 patients who did not undergo re-treatment (63.5%) were monitored by angiography or noninvasive imaging. In multivariate analysis, age older than 65 years (OR 2.65, 95% CI 1.33–5.28; p = 0.05), prior stent placement across the target aneurysm (OR 2.94, 95% CI 1.15–7.51; p = 0.02), aneurysm location in the distal anterior circulation (MCA, PCoA, and anterior choroidal artery: OR 2.72, 95% CI 1.19–6.18; p = 0.017), and longer follow-up duration (OR 1.06, 95% CI 1.03–1.09; p < 0.001) were associated with incomplete aneurysm occlusion.CONCLUSIONSWhile the PED can allow for treatment of large, broad-necked aneurysms with high efficacy, treatment failures do occur (16.4%). Aneurysm size, shape, and previous treatment may influence treatment outcome.

Introduction Studies show that patients who spend more than 2 hours in the emergency department (ED) report more dissatisfaction with their visits. To remedy this situation, several EDs have implemented programs that insert a medical provider into triage. The objective of this study was to determine whether a Physician Assistant (PA) and Combat Medic performing triage care during peak hours could increase patient throughput. Methods This study is a comparative analysis. We implemented an Emergency Department Provider Level Triage Team (PLTT) that consisted of 1 Emergency Medicine Physician Assistant and 1 Combat Medic to intervene in patient care in the ED at Womack Army Medical Center (WAMC), Fort Bragg, North Carolina, USA. Three days of 12 hours shifts were selected during the peak hours of the ED and compared to the same period on days that did not have the intervention. Only patients categorized with an Emergency Severity Index of 2 or 3 were selected and compared. No additional medical, nursing and medic staff were used. This study was approved by the WAMC Institutional Review Board. Results In total, there were 241 cases during the trial period and 231 controls. Median times were significantly reduced (p=Conclusion The implementation of the PLTT model in our ED was associated with reduced time to healthcare provider assessment, decreased overall ED length of stay, and improved patient satisfaction.

We report a case of a previously healthy 17-year-old male with a history of cigarette smoking, who presented with acute development of respiratory distress. Computed tomography demonstrated cystic pulmonary changes. A lung biopsy confirmed Langerhans cell histiocytosis (LCH). The definitive diagnosis was isolated pulmonary LCH, a disorder that is infrequently found in adults, and rarely in children. We know of only one other case of a previously healthy adolescent cigarette smoker who developed isolated pulmonary LCH. The etiology of pulmonary LCH is unknown, but smoking has been considered as a risk factor.

This paper reports two experiments concerned with the form of the linear function relating memory span to pronunciation rate. Experiment 1 asked whether the intercept of the equation is attributable to an interaction between modality, word-length, and serial position. The results lead us to reject this possibility. Experiment 2 examined the shape of the span function for visual presentation of lists read aloud or silently. The results show that the intercept of the span function disappears for silent presentation but not for aloud presentation. The results are discussed in terms of a balance between two opposing effects of word-length.

Adoptive immunotherapy is hampered by poor lymphocyte localization in tumors. The polarized, adhesive phenotype of activated lymphocytes may contribute to this problem by making the cells prone to trapping and damage in pulmonary microvasculature. We found that transient inhibition of T cell polarization prior to i.v. infusion reduces trapping and improves tumor localization. Activated T cells were rendered nonpolar and nonadhesive by treatment with myosin light-chain kinase inhibitor ML-7. Polarity, adhesiveness, and motility recovered by 6 h after treatment, cytotoxicity, and proliferation by 24 h. ErbB2-specific T cells were infused i.v. into mice bearing ErbB2-expressing mammary tumors. ML-7 pre-treatment reduced T cell arrest in lungs by a factor of eight, improved tumor localization by 4-fold, and increased lymph node homing. Although this improvement alone proved insufficient to alter outcome in an immunotherapy experiment, this study indicates that cytoskeletal modification is a promising strategy for altering the trafficking of infused lymphocytes.

BACKGROUND Overexpression of p53 in head and neck carcinoma cells has demonstrated tumor growth suppression using in vitro and in vivo models. The effects of exogenous overexpression of wild-type p53 on human papilloma virus (HPV)–immortalized and carcinogen transformed oral keratinocytes were determined. METHODS The p53 gene was overexpressed in IHGK (immortalized human gingival keratinocyte), IHGKN [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, (NNK)]-carcinogen transformed keratinocytes, and two head and neck squamous carcinoma (HNSCC) cell lines, HN30 and HN12. The transfection efficiency, growth suppression, and inhibition of the cell cycle along with the induction of apoptosis were measured. RESULTS Transfections with adenoviruses were more efficient for IHGK cells than for IHGKN, HN12, and HN30 cells. Inhibition of proliferation in all cell lines was proportional to the viral particle to cell (VPC) ratios. IHGK cells were more sensitive to p53 than IHGKN cells. HN12 cells were more suppressed than HN30 cells. HN12 were the most suppressed at 72 hours whereas HN30 cells were most suppressed at 24 hours. Expression of exogenous p53-induced G1 cell cycle arrest and p21 expression as VPC ratios increased in IHGK and IHGKN cell lines. Apoptosis also was induced in these cells by p53 as VPC increased. IHGK cells were more sensitive to p53-induced growth inhibition, cell cycle regulation, p21 expression and apoptosis than IHGKN cells. HN12 (mutated p53) cells were more sensitive to p53 overexpression than HN30 (wild-type p53) cells. Gene transfer and expression of exogenous p53 by using Ad-p53 demonstrates suppressive effects on HPV immortalized and carcinogen transformed oral keratinocytes. CONCLUSIONS Cell cycle regulation by gene transfer is feasible in immortalized oral keratinocytes. Carcinogen transformed cells are less susceptible to the effects of p53 overexpression. Expression of exogenous p53 through p53 gene transfer can suppress HPV immortalization and carcinogen transformation in oral keratinocytes. The sensitivity of HNSCC cell lines to p53-induced cell cycle regulation and apoptosis is variable and dependent on the cell line and duration of exposure. In vitro results using p53 gene transfer must be validated in clinical studies with patients at risk for HNSCC. Cancer 2002;94:159–66. © 2002 American Cancer Society.

Previous studies demonstrated a decrease in fluorescence intensity as tissue temperature increased. In vitro samples were increased from room temperature and in vivo canine liver from body temperature. This study investigated variations in fluorescence intensity with temperatures starting at 14°C and compared in vivo and in vitro results for consistency.A fiber optic-based noninvasive system was used to characterize the temperature effect on tissue fluorescence in hamster dorsal skin in vivo, and in sclera and cornea of enucleated pig eyes in vitro. As tissue was allowed to progress through the temperature range of 14-42°C, the spectra of auto-fluorescence with respect to temperature was sampled every 1-2 minutes. A pulsed nitrogen laser was used to excite fluorescence through a fiber optic probe with a source-detector aperture separation of 370 µm.Fluorescence intensity decreased as temperature increased from 14 to 42°C in a phantom containing Rhodamine B dye. Results from both in vivo and in vitro tissue followed the same trend of decreasing intensity as tissue temperature increased from 14°C. Spectral intensity lineshape changed around 450 nm due to absorption from tissue.Cooling a tissue increased fluorescence intensity of skin in vivo, in all experiments. In vitro results were consistent with in vivo measurements.

To develop and assess impact of a focused review of International Trauma Life Support (ITLS) and combat casualty care with hands-on procedure training for U.S. Army medics deploying to Iraq.The setting was a U.S. Army Medical Department Center and School and Camp Eagle, Iraq. Investigators developed and implemented a command-approved prospective educational intervention with a post hoc survey. Subjects completed a three-day course with simulator and live-tissue procedure laboratories. At deployment's end, medics were surveyed for experience, confidence, and preparedness in treating various casualty severity levels. Investigators used two-tailed t-test with unequal variance for continuous data and chi-square for categorical data.Twenty-nine medics deployed. Eight completed the experimental program. Twenty-one of 25 (84%) available medics completed the survey including six of the eight (75%) experimental medics. The experimental group reported significantly greater levels of preparedness and confidence treating "minimal," "delayed," and "immediate" casualties at arrival in Iraq. These differences dissipated progressively over the time course of the deployment.This experimental program increased combat medic confidence and perceived level of preparedness in treating several patient severity levels. Further research is warranted to determine if the experimental intervention objectively improves patient care quality and translates into lives saved early in deployment.

Study objective We describe outcomes for battle casualties receiving initial treatment at a US Army consolidated battalion aid station augmented with emergency medicine practitioners, advanced medic treatment protocols, and active medical direction. Battalion aid stations are mobile facilities integral to combat units, providing initial phases of advanced trauma life support and then evacuation. The setting was a forward base in central Iraq, with units engaged in urban combat operations. Methods This was a retrospective observational study. Rates of battle casualties, mechanism, evacuations, and outcome were calculated. Corresponding Iraqi theater-wide US casualty rates were also calculated for indirect comparison. Results The study population consisted of 1.1% of the total US military population in the Iraqi theater. Data were available for all battle casualties. The study facility's battle casualty rate was 22.2%. The case fatality rate was 7.14%, and the out-of-theater evacuation rate was 27%. Analysis of evacuated patients revealed a study average Injury Severity Score of 10 (95% confidence interval [CI] 8 to 12). Concurrent theater aggregate US casualty rates are provided for contextual reference and include battle casualty rate of 6.7%, case fatality rate of 10.45%, out-of-theater evacuation rate of 18%, and average out-of-theater evacuation casualty Injury Severity Score of 10 (95% CI 9.5 to 10.5). Conclusion The study battalion aid station experienced high casualty and evacuation rates while also demonstrating relatively low case fatality rates. A relatively high proportion of patients were evacuated out of the combat zone, reflecting both the battle casualty rate and number of patients surviving. Future effort should focus on improving out-of-hospital combat casualty data collection and prospective validation of emergency medicine–based out-of-hospital battlefield care and medical direction.

Objective To identify activity and biological mechanisms of intratumoral (IT) docetaxel on head and neck squamous cell carcinoma (HNSCC). Methods Docetaxel IT therapy was tested in xenograft models of 2 HNSCC lines, HN30 and HN12. The overall and disease-free survival rates, tumor growth, and toxic effects were measured. The pharmacokinetic profiles of docetaxel in plasma and tumor were compared after IT and intravenous (IV) administration. Comparisons between common and supradoses of docetaxel with regard to expression of regulators in the cell cycle, apoptosis, and signal transduction pathways were determined using Western blot analysis. Results In the HN30 and HN12 xenograft models, IT docetaxel improved overall as well as disease-free survival and reversed tumor growth. The only toxic effects noted were local (alopecia and skin breakdown). Skin breakdown resolved in all cases. At equivalent dosing levels, IT docetaxel achieved a 26-fold higher peak tumor concentration and 24-fold longer tumor exposure than IV treatment. Furthermore, limited plasma exposure was noted with IT docetaxel. Supradose levels of docetaxel produced distinct protein expression patterns for regulators of the cell cycle (cyclins A and B, p21, and p27), apoptosis (cleaved caspase-3 and cleaved PARP), and signal transduction (EGFR, pEGFR, pc-Jun, and pERK) in HNSCC, which supports a distinctive mechanism of action for supradose docetaxel levels. Since levels of cleaved caspase-3 and PARP, markers of apoptosis, were only elevated with lower doses, the observed cell death at supradose levels was probably due to necrosis. Conclusions Injections of IT docetaxel at usual and supradoses are associated with a pharmacokinetic profile and biological mechanism distinct from those observed with usual IV doses. It is calculated that IT therapy in men will increase peak concentrations of docetaxel in tumors by 1000-fold over the conventional IV dose used clinically. These preclinical results support further testing of IT docetaxel in HNSCC.