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PURPOSE The Idaho State University Physician Assistant (PA) program was one of the first PA programs in the country to incorporate medication-assisted treatment (MAT) into its curriculum. This manuscript documents the impact of the course. METHODS In the spring and summer of 2018, 61 students and 12 local providers enrolled in an elective MAT course developed by Idaho State University. All completed the training. At the end of the course, only the students submitted reflective essays. RESULTS A review and coding of the essays indicated that MAT education increased knowledge about addiction and resulted in self-reported decreases in negative attitudes towards people with addictions. CONCLUSION PA programs can support communities' increased capacity to offer MAT. A widely available course appears to result in important gains in both knowledge and attitude.

Background Antibiotic therapy has been proposed as an alternative to surgery for the treatment of appendicitis. Methods We conducted a pragmatic, nonblinded, noninferiority, randomized trial comparing antibiotic therapy (10-day course) with appendectomy in patients with appendicitis at 25 U.S. centers. The primary outcome was 30-day health status, as assessed with the European Quality of Life-5 Dimensions (EQ-5D) questionnaire (scores range from 0 to 1, with higher scores indicating better health status; noninferiority margin, 0.05 points). Secondary outcomes included appendectomy in the antibiotics group and complications through 90 days; analyses were prespecified in subgroups defined according to the presence or absence of an appendicolith. Results In total, 1552 adults (414 with an appendicolith) underwent randomization; 776 were assigned to receive antibiotics (47% of whom were not hospitalized for the index treatment) and 776 to undergo appendectomy (96% of whom underwent a laparoscopic procedure). Antibiotics were noninferior to appendectomy on the basis of 30-day EQ-5D scores (mean difference, 0.01 points; 95% confidence interval [CI], -0.001 to 0.03). In the antibiotics group, 29% had undergone appendectomy by 90 days, including 41% of those with an appendicolith and 25% of those without an appendicolith. Complications were more common in the antibiotics group than in the appendectomy group (8.1 vs. 3.5 per 100 participants; rate ratio, 2.28; 95% CI, 1.30 to 3.98); the higher rate in the antibiotics group could be attributed to those with an appendicolith (20.2 vs. 3.6 per 100 participants; rate ratio, 5.69; 95% CI, 2.11 to 15.38) and not to those without an appendicolith (3.7 vs. 3.5 per 100 participants; rate ratio, 1.05; 95% CI, 0.45 to 2.43). The rate of serious adverse events was 4.0 per 100 participants in the antibiotics group and 3.0 per 100 participants in the appendectomy group (rate ratio, 1.29; 95% CI, 0.67 to 2.50). Conclusions For the treatment of appendicitis, antibiotics were noninferior to appendectomy on the basis of results of a standard health-status measure. In the antibiotics group, nearly 3 in 10 participants had undergone appendectomy by 90 days. Participants with an appendicolith were at a higher risk for appendectomy and for complications than those without an appendicolith. (Funded by the Patient-Centered Outcomes Research Institute; CODA ClinicalTrials.gov number, NCT02800785.).

Increased task-related blood oxygen level dependent (BOLD) activation is commonly observed in functional magnetic resonance imaging (fMRI) studies of moderate/severe traumatic brain injury (msTBI), but the functional relevance of these hyperactivations and how they are linked to more direct measures of neuronal function remain largely unknown. Here, we investigated how working memory load (WML)-dependent BOLD activation was related to an electrophysiological measure of interhemispheric transfer time (IHTT) in a sample of 18 msTBI patients and 26 demographically matched controls from the UCLA RAPBI (Recovery after Pediatric Brain Injury) study. In the context of highly similar fMRI task performance, a subgroup of TBI patients with slow IHTT had greater BOLD activation with higher WML than both healthy control children and a subgroup of msTBI patients with normal IHTT. Slower IHTT treated as a continuous variable was also associated with BOLD hyperactivation in the full TBI sample and in controls. Higher WML-dependent BOLD activation was related to better performance on a clinical cognitive performance index, an association that was more pronounced within the patient group with slow IHTT. Our previous work has shown that a subgroup of children with slow IHTT after pediatric msTBI has increased risk for poor white matter organization, long-term neurodegeneration, and poor cognitive outcome. BOLD hyperactivations after msTBI may reflect neuronal compensatory processes supporting higher-order capacity demanding cognitive functions in the context of inefficient neuronal transfer of information. The link between BOLD hyperactivations and slow IHTT adds to the multi-modal validation of this electrophysiological measure as a promising biomarker. This Open Access article is distributed under the terms of the Creative Commons License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

Traumatic brain injury can cause extensive damage to the white matter (WM) of the brain. These disruptions can be especially damaging in children, whose brains are still maturing. Diffusion magnetic resonance imaging (dMRI) is the most commonly used method to assess WM organization, but it has limited resolution to differentiate causes of WM disruption. Magnetic resonance spectroscopy (MRS) yields spectra showing the levels of neurometabolites that can indicate neuronal/axonal health, inflammation, membrane proliferation/turnover, and other cellular processes that are on-going post-injury. Previous analyses on this dataset revealed a significant division within the msTBI patient group, based on interhemispheric transfer time (IHTT); one subgroup of patients (TBI-normal) showed evidence of recovery over time, while the other showed continuing degeneration (TBI-slow). We combined dMRI with MRS to better understand WM disruptions in children with moderate-severe traumatic brain injury (msTBI). Tracts with poorer WM organization, as shown by lower FA and higher MD and RD, also showed lower N-acetylaspartate (NAA), a marker of neuronal and axonal health and myelination. We did not find lower NAA in tracts with normal WM organization. Choline, a marker of inflammation, membrane turnover, or gliosis, did not show such associations. We further show that multi-modal imaging can improve outcome prediction over a single modality, as well as over earlier cognitive function measures. Our results suggest that demyelination plays an important role in WM disruption post-injury in a subgroup of msTBI children and indicate the utility of multi-modal imaging.

Objective:To examine longitudinal trajectories of white matter organization in pediatric moderate/severe traumatic brain injury (msTBI) over a 12-month period.Methods:We studied 21 children (16 M/5 F) with msTBI, assessed 2–5 months postinjury and again 13–19 months postinjury, as well as 20 well-matched healthy control children. We assessed corpus callosum function through interhemispheric transfer time (IHTT), measured using event-related potentials, and related this to diffusion-weighted MRI measures of white matter (WM) microstructure. At the first time point, half of the patients with TBI had significantly slower IHTT (TBI-slow-IHTT, n = 11) and half were in the normal range (TBI-normal-IHTT, n = 10).Results:The TBI-normal-IHTT group did not differ significantly from healthy controls, either in WM organization in the chronic phase or in the longitudinal trajectory of WM organization between the 2 evaluations. In contrast, the WM organization of the TBI-slow-IHTT group was significantly lower than in healthy controls across a large portion of the WM. Longitudinal analyses showed that the TBI-slow-IHTT group experienced a progressive decline between the 2 evaluations in WM organization throughout the brain.Conclusions:We present preliminary evidence suggesting a potential biomarker that identifies a subset of patients with impaired callosal organization in the first months postinjury who subsequently experience widespread continuing and progressive degeneration in the first year postinjury.

BACKGROUND A 2015 American Association for the Surgery of Trauma trial reported a 32% mortality for pelvic fracture patients in shock. Angioembolization (AE) is the most common intervention; the Maryland group revealed time to AE averaged 5 hours. The goal of this study was to evaluate the time to intervention and outcomes of an alternative approach for pelvic hemorrhage. We hypothesized that preperitoneal pelvic packing (PPP) results in a shorter time to intervention and lower mortality. METHODS In 2004, we initiated a PPP protocol for pelvic fracture hemorrhage. RESULTS During the 11-year study, 2,293 patients were admitted with pelvic fractures; 128 (6%) patients underwent PPP (mean age, 44 ± 2 years; Injury Severity Score (ISS), 48 ± 1.2). The lowest emergency department systolic blood pressure was 74 mm Hg and highest heart rate was 120. Median time to operation was 44 minutes and 3 additional operations were performed in 109 (85%) patients. Median RBC transfusions before SICU admission compared with the 24 postoperative hours were 8 versus 3 units (p < 0.05). After PPP, 16 (13%) patients underwent AE with a documented arterial blush.Mortality in this high-risk group was 21%. Death was due to brain injury (9), multiple organ failure (4), pulmonary or cardiac failure (6), withdrawal of support (4), adverse physiology (3), and Mucor infection (1). Of those patients with physiologic exhaustion, 2 died in the operating room at 89 and 100 minutes after arrival, whereas 1 died 9 hours after arrival. CONCLUSIONS PPP results in a shorter time to intervention and lower mortality compared with modern series using AE. Examining mortality, only 3 (2%) deaths were attributed to the immediate sequelae of bleeding with physiologic failure. With time to death under 100 minutes in 2 patients, AE is unlikely to have been feasible. PPP should be used for pelvic fracture-related bleeding in the patient who remains unstable despite initial transfusion. LEVEL OF EVIDENCE Therapeutic study, level IV.

Traumatic brain injury (TBI) is a significant public health concern, and can be especially disruptive in children, derailing on-going neuronal maturation in periods critical for cognitive development. There is considerable heterogeneity in post-injury outcomes, only partially explained by injury severity. Understanding the time course of recovery, and what factors may delay or promote recovery, will aid clinicians in decision-making and provide avenues for future mechanism-based therapeutics. We examined regional changes in brain volume in a pediatric/adolescent moderate-severe TBI (msTBI) cohort, assessed at two time points. Children were first assessed 2–5 months post-injury, and again 12 months later. We used tensor-based morphometry (TBM) to localize longitudinal volume expansion and reduction. We studied 21 msTBI patients (5 F, 8–18 years old) and 26 well-matched healthy control children, also assessed twice over the same interval. In a prior paper, we identified a subgroup of msTBI patients, based on interhemispheric transfer time (IHTT), with significant structural disruption of the white matter (WM) at 2–5 months post injury. We investigated how this subgroup (TBI-slow, N = 11) differed in longitudinal regional volume changes from msTBI patients (TBI-normal, N = 10) with normal WM structure and function. The TBI-slow group had longitudinal decreases in brain volume in several WM clusters, including the corpus callosum and hypothalamus, while the TBI-normal group showed increased volume in WM areas. Our results show prolonged atrophy of the WM over the first 18 months post-injury in the TBI-slow group. The TBI-normal group shows a different pattern that could indicate a return to a healthy trajectory., Highlights • Studied differences in regional volume change longitudinally between TBI and control. • Found decreases in TBI group in white matter, gray matter and subcortical regions • Changes in regional volume were associated with changes in cognitive performance. • Compared subgroups within TBI group based on interhemispheric transfer time (IHTT) • TBI-slow group seems to drive TBI vs. control results, show prolonged degeneration.

Background We implemented expanded screening criteria for blunt cerebrovascular injuries (BCVIs) in an attempt to capture the remaining 20% of patients not historically identified with earlier protocols. We hypothesized that these expanded criteria would capture the additional 20% of BCVI patients not previously identified. Methods Screening criteria for BCVI were expanded in 2011 after identifying new injury patterns. The study population included 4 years prior (2007 to 2010; classic) and following (2011 to 2014; expanded) implementation of expanded criteria. Results BCVIs were identified in 386 patients: 150 during the classic period (2.36% incidence) and 236 in the expanded period (2.99% incidence). In the expanded period, 155 patients were imaged based on classic screening criteria, 62 on expanded criteria (21 complex skull fractures, 20 upper rib fractures, 6 mandible fractures, 2 scalp degloving, 1 great vessel injury, and 12 combination), and 19 for other injuries and symptoms. Conclusions There was a significant increase in the identification of BCVI following the adoption of expanded screening criteria, resulting in a substantial reduction of missed injuries. Expanded criteria should be adopted when screening for BCVI.

Limited access to healthy foods in low-income areas is well documented as part of “the new hunger” in the United States. Characterized by easy access to nutrient-poor processed food and blocked access to foods that secure dietary health and sustain well-being, “the new hunger” has been linked in public health and social science literature to obesogenic environments, defined as both food and built environments that promote obesity. The paper examines how non-governmental organizations work within distinct policy ecologies to improve food access and food security and promote community health, focusing on one high-impact Mobile Farmers’ Market Program that was successful in building community infrastructure to promote dietary health and improve food security at the community level through improved food access. We offer this case study of a NGO–community collaboration to better understand the role of formal and informal social networks between NGO actors and different community stakeholders, including market customers, in communicating and realizing city policy goals and positive program interventions in support of community health.

Objectives:Following pediatric moderate-to-severe traumatic brain injury (msTBI), few predictors have been identified that can reliably identify which individuals are at risk for long-term cognitive difficulties. This study sought to determine the relative contribution of detailed descriptors of injury severity as well as demographic and psychosocial factors to long-term cognitive outcomes after pediatric msTBI.Methods:Participants included 8- to 19-year-olds, 46 with msTBI and 53 uninjured healthy controls (HC). Assessments were conducted in the post-acute and chronic stages of recovery. Medical record review provided details regarding acute injury severity. Parents also completed a measure of premorbid functioning and behavioral problems. The outcome of interest was four neurocognitive measures sensitive to msTBI combined to create an index of cognitive performance.Results:Results indicated that none of the detailed descriptors of acute injury severity predicted cognitive performance. Only the occurrence of injury, parental education, and premorbid academic competence predicted post-acute cognitive functioning. Long-term cognitive outcomes were best predicted by post-acute cognitive functioning.Discussion:The findings suggest that premorbid factors influence cognitive outcomes nearly as much as the occurrence of a msTBI. Furthermore, of youth with msTBI who initially recover to a level of moderate disability or better, a brief cognitive battery administered within several months after injury can best predict which individuals will experience poor long-term cognitive outcomes and require additional services. (JINS, 2016,22, 1–8)

Traumatic brain injury (TBI) can cause widespread and prolonged brain degeneration. TBI can affect cognitive function and brain integrity for many years after injury, often with lasting effects in children, whose brains are still immature. Although TBI varies in how it affects different individuals, image analysis methods such as tensor-based morphometry (TBM) can reveal common areas of brain atrophy on magnetic resonance imaging (MRI), secondary effects of the initial injury, which will differ between subjects. Here we studied 36 pediatric moderate to severe TBI (msTBI) participants in the post-acute phase (1–6 months post-injury) and 18 msTBI participants who returned for their chronic assessment, along with well-matched controls at both time-points. Participants completed a battery of cognitive tests that we used to create a global cognitive performance score. Using TBM, we created three-dimensional (3D) maps of individual and group differences in regional brain volumes. At both the post-acute and chronic time-points, the greatest group differences were expansion of the lateral ventricles and reduction of the lingual gyrus in the TBI group. We found a number of smaller clusters of volume reduction in the cingulate gyrus, thalamus, and fusiform gyrus, and throughout the frontal, temporal, and parietal cortices. Additionally, we found extensive associations between our cognitive performance measure and regional brain volume. Our results indicate a pattern of atrophy still detectable 1-year post-injury, which may partially underlie the cognitive deficits frequently found in TBI.

We present the case of a 16-year-old boy who presented with fatigue, polyuria, and polydipsia while on chemotherapy for his relapsed acute lymphoblastic leukemia (ALL). Blood gas examination confirmed the diagnosis of hyperosmolar hyperglycemic state. The etiology for his hyperglycemia was most likely a result of oral glucocorticoid therapy combined with asparaginase therapy-both are a cornerstone of induction chemotherapy for ALL. The patient was aggressively rehydrated with saline, and medications were administered to correct his hyperkalemia. He was then slowly brought to euglycemia with a continuous infusion of insulin. Although hyperosmolar hyperglycemic state is rare during the treatment of ALL, frontline providers should be aware of this diagnosis because of the significant risk of hypovolemic shock and death if correction of hyperglycemia occurs prior to complete fluid resuscitation.

Diffuse axonal injury contributes to the long-term functional morbidity observed after pediatric moderate/severe traumatic brain injury (msTBI). Whole-brain proton magnetic resonance echo-planar spectroscopic imaging was used to measure the neurometabolite levels in the brain to delineate the course of disruption/repair during the first year post-msTBI. The association between metabolite biomarkers and functional measures (cognitive functioning and corpus callosum [CC] function assessed by interhemispheric transfer time [IHTT] using an event related potential paradigm) was also explored. Pediatric patients with msTBI underwent assessments at two times (post-acutely at a mean of three months post-injury, n = 31, and chronically at a mean of 16 months post-injury, n = 24). Healthy controls also underwent two evaluations, approximately 12 months apart. Post-acutely, in patients with msTBI, there were elevations in choline (Cho; marker for inflammation and/or altered membrane metabolism) in all four brain lobes and the CC and decreases in N-acetylaspartate (NAA; marker for neuronal and axonal integrity) in the CC compared with controls, all of which normalized by the chronic time point. Subgroups of TBI showed variable patterns chronically. Patients with slow IHTT had lower lobar Cho chronically than those with normal IHTT; they also did not show normalization in CC NAA whereas those with normal IHTT showed significantly higher levels of CC NAA relative to controls. In the normal IHTT group only, chronic CC Cho and NAA together explained 70% of the variance in long-term cognitive functioning. MR based whole brain metabolic evaluations show different patterns of neurochemistry after msTBI in two subgroups with different outcomes. There is a dynamic relationship between prolonged inflammatory responses to brain damage, reparative processes/remyelination, and subsequent neurobehavioral outcomes. Multimodal studies allow us to test hypotheses about degenerative and reparative processes in patient groups that have divergent functional outcome, with the ultimate goal of developing targeted therapeutic agents.

Annually, more than 2 million patients are admitted with emergency general surgery (EGS) conditions. Emergency general surgery cases comprise 11% of all general surgery operations, yet account for 47% of mortalities and 28% of complications. Using the statewide general surgery Michigan Surgical Quality Collaborative (MSQC) data, we previously confirmed that wide variations in EGS outcomes were unrelated to case volume/complexity. We assessed whether patient care model (PCM) affected EGS outcomes.There were 34 hospitals that provided data for PCM, resources, surgeon practice patterns, and comprehensive MSQC patient data from January 1, 2008 to December 31, 2016 (general surgery cases = 126,494; EGS cases = 39,023). Risk and reliability adjusted outcomes were determined using hierarchical multivariable logistic regression analysis with multiple clinical covariates and PCM.The general surgery service (GSS) model was more common (73%) than acute care surgery (ACS, 27%). Emergency general surgery 30-day mortality was 4.1% (intestinal resections 11.6%). The ACS model was associated with a reduction of 31% in mortality (odds ratio [OR] 0.69; 95% CI 0.52-0.92] for EGS cases, related to decreased mortality in the intestinal resection cohort (8.5% ACS vs 12% GSS, p0.0001). Morbidity in EGS was 17.4% (9.7% elective); highest (40%) in intestinal resection, and PCM did not affect morbidity. We identified specific variables for an optimal EGS risk adjustment model.This is the first multi-institutional study to identify that an ACS model is associated with a significant 31% mortality reduction in EGS using prospectively collected, clinically obtained, research-quality collaborative data. We identified that new risk adjustment models are necessary for EGS outcomes evaluations.

Objective: To describe how the County of San Diego linked information from a communicable disease registry and syndromic surveillance system to further describe cases associated with a large hepatitis A outbreak. Specifically, to detail the linkage process which resulted in a longitudinal understanding of individuals’ hospital visits before, during, and after the reported hepatitis A incident. Introduction: With increasing availability of syndromic meaningful use data, new approaches to disease surveillance utilizing linkages to other data systems are possible. Expanded communicable disease information may be valuable during outbreaks or other public health emergencies. San Diego County is experiencing a significant and protracted hepatitis A outbreak. The disease has been transmitted person-to-person through close contact or through a fecally-contaminated environment, and has been primarily affecting homeless people and injection and non-injection illicit drug users. As of August 31, 2017, there were nearly 400 cases with 15 deaths. Approximately, 70% of the cases were hospitalized. This is one of the nation’s largest hepatitis A outbreaks since the introduction of the hepatitis A vaccine in 1995. Additional cases are expected over the next twelve months. The population affected by this outbreak presents some challenges for outbreak response. It is often a difficult population to reach. In addition, many have multiple comorbidities and often have health care seeking behaviors that differ from the general population. Using the medical record number (MRN) to link hepatitis A disease cases from the communicable disease registry to syndromic HL7 messages for emergency department visits and hospitalizations enabled the identification of additional hospital encounters the cases may have had before, during, or following their hepatitis A disease incident. This allowed an exploration of the ways in which this unique population interacted with the health care system in the context of a communicable disease outbreak. This presentation will highlight the steps to link information across surveillance systems, the results, the challenges, and the benefits of linked information to public health departments. Methods: Electronic information from a communicable disease registry system and syndromic surveillance HL7 data from participating hospitals were utilized. The patient’s MRN, available in both systems, was used to link the records. The syndromic data for this project included syndromic messages from 90 days prior to the first outbreak-related hepatitis A case in November 2016 through August 31, 2017. Records with no MRN present, were unmatchable, or records with an encrypted MRN were excluded. The communicable disease registry data included outbreak-related hepatitis A cases from November 2016 through August 2017. Records were excluded if the disease incident was associated with a hospital not currently providing syndromic surveillance information. The linked dataset will continue to be updated as the outbreak progresses. Using the linked data, relevant dates and date ranges were determined for each case, including onset of hepatitis A-associated illness, hepatitis A exposure windows, infectious periods, and a 90 day post-illness period allowing for identification of possible relapsing illness patterns. Based on these dates, hepatitis A case-patients who had HL7 messages for emergency department or hospitalization visits prior to, during, and following their hepatitis A episode were identified. Interactions with the health care system were summarized and case studies were developed. Results: During the study time period, 396 outbreak-related hepatitis A case reports were received and documented in the communicable disease registry and nearly 18 million syndromic HL7 messages were received. After the exclusions, the MRN from 130 hepatitis A cases were linked to one or more syndromic HL7 messages associated with visits to an emergency department or inpatient hospital admissions. A total of 616 hospital encounters were documented among the 130 linked cases which reflects an overall average of 4.7 visits per case. Many of these case-patients had numerous health care visits before, during, and after their hepatitis A episode. Among the 130 linked cases, 56% (n=73) of the cases linked to one or more hospital visits other than the visit in which they were diagnosed with hepatitis A. Many of these visits were made during their infectious period prior to being treated for hepatitis A. In addition, with the available data to date, 25% (n=33) of the linked cases had additional hospital visits following their hepatitis A diagnosis. These and other findings were used to provide additional outbreak response recommendations and shape additional surveillance and case monitoring approaches. Conclusions: The use of MRN to link records from a communicable disease registry to syndromic HL7 data is a viable tool for public health departments looking to obtain additional information about communicable disease cases and enhance surveillance and disease control activities. In this study, the linkage yielded a more complete profile of patient outcomes and health care-seeking behaviors of individuals diagnosed with hepatitis A. The County of San Diego gained a broader understanding of a unique population’s interactions with the health care system, including the identification of missed opportunities for vaccination and earlier diagnosis. The information was then leveraged to improve vaccination and other outreach and prevention efforts.

Background This phase II CALGB trial evaluated the activity and safety of an extended induction schedule of galiximab (G) plus rituximab (R) in untreated follicular lymphoma (FL). Patients and methods Patients with previously untreated FL (grades 1, 2, 3a) received 4 weekly infusions of G + R, followed by an additional dose every 2 months four times. International Workshop Response Criteria were used to evaluate response. Results Sixty-one patients were treated and antibody infusions were well tolerated. The overall response rate (ORR) is 72.1% (95% confidence interval 59.2% to 82.9%): 47.6% complete response (CR)/unconfirmed complete response (CRu) and 24.6% partial response. At a median follow-up time of 4.3 years (range, 0.3–5.3 years) median progression-free survival (PFS) is 2.9 years. Notably, Follicular Lymphoma International Prognostic Index (FLIPI) correlated with ORR, CR rate, and PFS, and the low-risk FLIPI group (n = 12) achieved a 92% ORR, 75% CR/CRu rate, and 75% 3-year PFS. Conclusions An extended induction schedule of G + R in previously untreated FL is well tolerated and appears particularly efficacious in those patients with low-risk FLIPI scores. In addition, this trial served as the initial platform for additional CALGB ‘doublet’ combination regimes of rituximab plus other novel targeted agents.

Purpose Lenalidomide and rituximab (LR) are active agents in follicular lymphoma (FL). Combination regimens have not been previously assessed in randomized studies. Patients and Methods The Cancer and Leukemia Group B (Alliance) 50401 trial is a randomized phase II trial studying rituximab (375 mg/m2 weekly for 4 weeks), lenalidomide (15 mg per day on days 1 to 21, followed by 7 days of rest, in cycle 1 and then 20 mg per day on days 1 to 21, followed by 7 days of rest, in cycles 2 to 12), or LR. The rituximab-alone arm was discontinued as a result of poor accrual. Eligibility included recurrent FL and prior rituximab with time to progression of ≥ 6 months from last dose. Aspirin or heparin was recommended for patients at high thrombosis risk. Results Ninety-one patients (lenalidomide, n = 45; LR, n = 46) received treatment; median age was 63 years (range, 34 to 89 years), and 58% were intermediate or high risk according to the Follicular Lymphoma International Prognostic Index. In the lenalidomide and LR arms, grade 3 to 4 adverse events occurred in 58% and 53% of patients, with 9% and 11% of patients experiencing grade 4 toxicity, respectively; grade 3 to 4 adverse events included neutropenia (16% v 20%, respectively), fatigue (9% v 13%, respectively), and thrombosis (16% [n = 7] v 4% [n = 2], respectively; P = .157). Thirty-six percent of lenalidomide patients and 63% of LR patients completed 12 cycles. Lenalidomide alone was associated with more treatment failures, with 22% of patients discontinuing treatment as a result of adverse events. Dose-intensity exceeded 80% in both arms. Overall response rate was 53% (20% complete response) and 76% (39% complete response) for lenalidomide alone and LR, respectively (P = .029). At the median follow-up of 2.5 years, median time to progression was 1.1 year for lenalidomide alone and 2 years for LR (P = .0023). Conclusion LR is more active than lenalidomide alone in recurrent FL with similar toxicity, warranting further study in B-cell non-Hodgkin lymphoma as a platform for addition of novel agents.

Author(s): Pieracci, Fredric M; Johnson, Jeffrey L; Stovall, Robert T; Jurkovich, Gregory J

Refinement of criteria for both screening and initiation of empiric therapy in ventilator-associated pneumonia (VAP) will minimize antibiotic overuse. We hypothesized that variables within the commonly used Clinical Pulmonary Infection Score (CPIS) have unfavorable test performance characteristics.Consecutive bronchoalveolar lavage (BAL) cultures obtained from surgical intensive care unit patients were abstracted (2009-2012). Ventilator-associated pneumonia was defined as ≥10(5) cfu/mL. The CPIS both without (CPISclinical) and with (CPISclinical+GS) the result of gram stain (GS) was calculated. Test performance characteristics for the sample, as well as several subgroups, were compared.One thousand thirteen lower respiratory tract cultures from 492 patients were analyzed; 438 (43.2%) of cultures were classified as VAP, and 310 of 492 patients (62.4%) had ≥1 episode of VAP. Both CPISclinical and CPISclinical+GS had poor discrimination for VAP (Receiver-operating characteristic area under the curve=0.55 and 0.66, respectively). Sensitivity of CPISclinical using a threshold of6 was 21%; the lowest threshold for CPISclinical for which the sensitivity was at least 85% was 3. The highest sensitivity among the individual CPIS components was new CXR infiltrate (91.1%). Among the subset of cultures sent during the early VAP window (days intubated 2-5), organisms on GS had a sensitivity of 93.3%. The CPISclinical, CPISclinical+GS, organisms, and neutrophils on GS parameters all became less accurate in both the late VAP window and when screening for recurrent VAP. Every case of VAP had at least one of the following: 1) fever; 2) new CXR infiltrate, or 3) organisms on GS.In this series of BALs, traditional screening tools for VAP missed the majority of microbiological confirmed cases. Screening based on either new CXR infiltrate or fever yielded an acceptably high sensitivity. The only scenario identified in which empiric antibiotics could be withheld safely was the absence of organisms on GS in the early VAP window.

Outcome after a traumatic brain injury (TBI) is quite variable, and this variability is not solely accounted for by severity or demographics. Identifying sub-groups of patients who recover faster or more fully will help researchers and clinicians understand sources of this variability, and hopefully lead to new therapies for patients with a more prolonged recovery profile. We have previously identified two subgroups within the pediatric TBI patient population with different recovery profiles based on an ERP-derived (event-related potential) measure of interhemispheric transfer time (IHTT). Here we examine structural network topology across both patient groups and healthy controls, focusing on the ‘rich-club’ - the core of the network, marked by high degree nodes. These analyses were done at two points post-injury - 2-5 months (post-acute), and 13-19 months (chronic). In the post-acute time-point, we found that the TBI-slow group, those showing longitudinal degeneration, showed hyperconnectivity within the rich-club nodes relative to the healthy controls, at the expense of local connectivity. There were minimal differences between the healthy controls and the TBI-normal group (those patients who show signs of recovery). At the chronic phase, these disruptions were no longer significant, but closer analysis showed that this was likely due to the loss of power from a smaller sample size at the chronic time-point, rather than a sign of recovery. We have previously shown disruptions to white matter (WM) integrity that persist and progress over time in the TBI-slow group, and here we again find differences in the TBI-slow group that fail to resolve over the first year post-injury.

Traumatic brain injury (TBI) is the leading cause of death and disability in children, and can lead to long lasting functional impairment. Many factors influence outcome, but imaging studies examining effects of individual variables are limited by sample size. Roughly 20-40% of hospitalized TBI patients experience seizures, but not all of these patients go on to develop a recurrent seizure disorder. Here we examined differences in structural network connectivity in pediatric patients who had sustained a moderate-severe TBI (msTBI). We compared those who experienced early post-traumatic seizures to those who did not; we found network differences months after seizure activity stopped. We also examined correlations between network measures and a common measure of injury severity, the Glasgow Coma Scale (GCS). The global GCS score did not have a detectable relationship to brain integrity, but sub-scores of the GCS (eyes, motor, verbal) were more closely related to imaging measures.

Traumatic brain injury (TBI) causes extensive damage to the white matter (WM) of the brain, which can be evaluated with diffusion-weighted magnetic resonance imaging (dMRI). Diffusion MRI can be used to map the WM tracts and their integrity, but offers limited understanding of the biochemical basis of any differences. Magnetic resonance spectroscopy (MRS) measures neural metabolites that reflect neuronal health, inflammation, demyelination, and other consequences of TBI. We combined whole-brain MRS with dMRI to investigate WM dysfunction following pediatric TBI, using “tract-based spectroscopy”. Deficits in N-acetylaspartate (NAA) correspond to regions of deficits in WM integrity, but choline showed minimal overlap with WM deficits. NAA is a marker of neuronal health, while choline is an inflammatory marker. A partial F-test showed that MRS measures improved our ability to predict long-term cognitive function. This is the first paper to combine MRS with dMRI-derived tracts on a whole-brain scale, offering insights into the biochemical correlates of WM tract dysfunction, following injury and potentially in other WM disorders.

Outcomes after traumatic brain injury (TBI) are variable and only partially predicted by acute injury factors. With rich datasets, we can examine how numerous factors – cognitive scores, acute injury variables, demographic variables, and brain imaging variables – are interrelated and aid in outcome prediction. To help study this rich data, we applied CorEx, a novel method for unsupervised machine learning. CorEx decodes the hierarchical structure, identifying latent causes of dependence in the data. It groups predictor variables based on their joint information and inter-dependence. We examined 21 TBI patients 2-5 months post-injury along with healthy controls; both groups were assessed again 12 months later. Although we were limited in the number of participants, this tool for exploratory analysis found potential relationships between change in cognitive scores over the 12-month period and baseline brain volumes. Certain regional brain volumes measured post-injury could serve as predictors of patient recovery. As future planned analyses will examine greater sample sizes, we hope to perform follow-up statistical analysis of variables identified by CorEx in independent data.

BACKGROUND: Older patients with traumatic brain injury (TBI) may be at high risk of death after hospitalization. The purpose of this study was to characterize long-term mortality of older TBI patients who survived to discharge. We hypothesized that predictors of postdischarge mortality differed from those of inpatient mortality. METHODS: A retrospective cohort study was performed on TBI patients older than 55 years admitted to our Level I trauma center between July 1, 2006, and December 31, 2011. Postdischarge deaths were identified by matching patient data with local vital records up to December 31, 2011, when data collection was terminated (censoring). Patients were categorized by age, comorbidities, history of preinjury anticoagulant/prescription antiplatelet agent therapy, injury severity indices, initial TBI type, prehospital living status, discharge location, and discharge condition. The effect of risk factors on postdischarge mortality was evaluated by Cox proportional hazards modeling. RESULTS: Of 353 patients, 322 (91.2%) survived to discharge. Postdischarge mortality was 19.8% (n = 63) for the study period. Of the postdischarge deaths, 54.0% died within 6 months of discharge, and 68.3% died within 1 year. Median days to death after discharge or censoring were 149 and 410, respectively. Factors associated with death after discharge included age, preinjury anticoagulant use, higher number of Charlson comorbidities, discharge to a long-term care facility, and severe disability. Factors related to injury severity (i.e., Injury Severity Score [ISS], initial Glasgow Coma Scale [GCS] score) and preinjury prescription antiplatelet agent use, previously found to predict inpatient death, did not predict postdischarge mortality. CONCLUSION: Older TBI patients who survive to discharge have a significant risk of death within 1 year. Predictors of postdischarge mortality and inpatient death differ. Death after discharge is largely a function of overall health status. Monitoring health status and continued aggressive management of comorbidities after discharge may be essential in determining long-term outcomes. LEVEL OF EVIDENCE: Epidemiologic/retrospective cohort analysis, level III. Language: en

Her blood pressure is 92/48 mm Hg, and her electrocardiogram shows abnormalities. What is going on?

BACKGROUND: The diagnosis of blunt abdominal trauma can be challenging and resource intensive. Observation with serial clinical assessments plays a major role in the evaluation of these patients, but the time required for intra-abdominal injury to become clinically apparent is unknown. The purpose of this study was to determine the amount of time required for an intra-abdominal injury to become clinically apparent after blunt abdominal trauma via physical examination or commonly followed clinical values. METHODS: A retrospective review of patients who sustained blunt trauma resulting in intra-abdominal injury between June 2010 and June 2012 at a Level 1 academic trauma center was performed. Patient demographics, injuries, and the amount of time from emergency department admission to sign or symptom development and subsequent diagnosis were recorded. All diagnoses were made by computed tomography or at the time of surgery. Patient transfers from other hospitals were excluded. RESULTS: Of 3,574 blunt trauma patients admitted to the hospital, 285 (8%) experienced intra-abdominal injuries. The mean (SD) age was 36 (17) years, the majority were male (194 patients, 68%) and the mean (SD) Injury Severity Score (ISS) was 21 (14). The mean (SD) time from admission to diagnosis via computed tomography or surgery was 74 (55) minutes. Eighty patients (28%) required either surgery (78 patients, 17%) or radiographic embolization (2 patients, 0.7%) for their injury. All patients who required intervention demonstrated a sign or symptom of their intra-abdominal injury within 60 minutes of arrival, although two patients were intervened upon in a delayed fashion. All patients with a blunt intra-abdominal injury manifested a clinical sign or symptom of their intra-abdominal injury, resulting in their diagnosis within 8 hours 25 minutes of arrival to the hospital. CONCLUSION: All diagnosed intra-abdominal injuries from blunt trauma manifested clinical signs or symptoms that could prompt imaging or intervention, leading to their diagnosis within 8 hours 25 minutes of arrival to the hospital. All patients who required an intervention for their injury manifested a sign or symptom of their injury within 60 minutes of arrival. (J Trauma Acute Care Surg. 2014;76:1020Y1023. Copyright * 2014 by Lippincott Williams & Wilkins) LEVEL OF EVIDENCE: Therapeutic study, level IV. Epidemiologic study, level III.

While the incidence of postinjury multiple-organ failure (MOF) has declined during the past decade, temporal trends of its morbidity, mortality, presentation patterns, and health care resources use have been inconsistent. The purpose of this study was to describe the evolving epidemiology of postinjury MOF from 2003 to 2010 in multiple trauma centers sharing standard treatment protocols."Inflammation and Host Response to Injury Collaborative Program" institutions that enrolled more than 20 eligible patients per biennial during the 2003 to 2010 study period were included. The patients were aged 16 years to 90 years, sustained blunt torso trauma with hemorrhagic shock (systolic blood pressure90 mm Hg, base deficit ≥ 6 mEq/L, blood transfusion within the first 12 hours), but without severe head injury (motor Glasgow Coma Scale [GCS] score4). MOF temporal trends (Denver MOF score3) were adjusted for admission risk factors (age, sex, body max index, Injury Severity Score [ISS], systolic blood pressure, and base deficit) using survival analysis.A total of 1,643 patients from four institutions were evaluated. MOF incidence decreased over time (from 17% in 2003-2004 to 9.8% in 2009-2010). MOF-related death rate (33% in 2003-2004 to 36% in 2009-2010), intensive care unit stay, and mechanical ventilation duration did not change over the study period. Adjustment for admission risk factors confirmed the crude trends. MOF patients required much longer ventilation and intensive care unit stay, compared with non-MOF patients. Most of the MOF-related deaths occurred within 2 days of the MOF diagnosis. Lung and cardiac dysfunctions became less frequent (57.6% to 50.8%, 20.9% to 12.5%, respectively), but kidney and liver failure rates did not change (10.1% to 12.5%, 15.2% to 14.1%).Postinjury MOF remains a resource-intensive, morbid, and lethal condition. Lung injury is an enduring challenge and should be a research priority. The lack of outcome improvements suggests that reversing MOF is difficult and prevention is still the best strategy.Epidemiologic study, level III.

To improve long-term outcomes for Burkitt leukaemia/lymphoma (BL) or aggressive lymphomas in adults, we assessed the benefit of adding rituximab and filgrastim support to a dose-dense modified chemotherapy regimen from the Cancer and Leukemia Group B (CALGB) 9251 trial. One hundred and five patients (aged 19-79 years) were enrolled; 27% were >60 years old; 47% had high or high-intermediate risk by International Prognostic Index (IPI) criteria. Common severe toxicities included stomatitis/upper gastrointestinal toxicity (69%), renal insufficiency (10%), neurological events (25%) and pulmonary events (18%). Seven died from treatment-related causes (one central nervous system bleed, four infections, two respiratory failure); five were >60 years old. Results in this adult population are encouraging as complete response (CR) was observed in 83% and 4-year event-free (EFS) and overall survivals (OS) were 74% and 78%, respectively. Results compare favourably to our prior chemotherapy alone study (CALGB 9251) but despite this, high-risk patients still had worse outcomes. In conclusion, short duration, intensive chemo-immunotherapy is feasible and should be considered in adults with BL as it results in high remission rates and durable remissions.

IntroductionRib fractures in elderly patients are associated with increased morbidity and mortality. Predicting which patients are at risk for complications is an area of debate. Current models use anatomic, physiologic or laboratory parameters in isolation to answer this question. The ‘RibScore’ is an anatomic model that assesses fracture severity. Given that frailty is a major driver of adverse outcomes in the elderly, we hypothesize that the combined analysis of fracture severity, physiologic reserve and current pulmonary function are better predictors of respiratory compromise in this population.MethodsThis is a retrospective chart review of 263 trauma patients age ≥55 from January 2014 to June 2017. Criteria included blunt mechanism and ≥ 1 rib fracture identified by CT. Variables indicating adverse pulmonary outcomes were defined by: pneumonia, respiratory failure and tracheostomy. Three models were assessed: (1) RibScore, (2) Modified Frailty Index (mFI) and (3) initial partial pressure of carbondioxide (PaCO2).ResultsA total of 263 patients met inclusion criteria. 13% developed pulmonary complications. Increased RibScore, mFI and PaCO2 were each statistically associated with risk of complications. Receiver operating characteristics area under the curve analysis of individual models predicted complications with the following concordance statistic (CS): anatomic (RibScore) yielded a CS of 0.79 (95% CI 0.69 to 0.89); physiologic (mFI) yielded a CS of 0.83 (95% CI 0.75 to 0.91) and laboratory (PaCO2) yielded a CS of 0.88 (95% CI 0.80 to 0.95). The PaCO2 had the highest discriminative ability of the three individual models. Combining all three models yielded the best performance with a CS of 0.90 (95% CI 0.81 to 0.97).DiscussionThe RibScore maintains discriminative ability in the elderly. However, models based on mFI and PaCO2 individually outperform the RibScore. A combination of all three models yields the highest discriminative ability. This combined approach is best for assessing the severity of rib fractures and prediction of complications in the elderly.Level of evidencePrognostic Study, Level III.

1. B. Jason Brotherton, MD* 2. Irving Steinberg, PharmD* 3. Jeffrey L. Johnson, MD* 1. *LAC + USC Medical Center, Los Angeles, CA. A 4-year-old girl presents with 1 week of fever, vomiting, and increased sleepiness. Her medical history includes cerebral palsy, intellectual disability, and epilepsy treated with carbamazepine (CBZ) for the past 2 years. The last change in CBZ dosing was 2 months ago after a seizure. The girl’s mother reports that she repeated several doses of CBZ after emesis for the past 2 days. Of note, the family travelled to Mexico 3 weeks ago. On physical examination, the girl’s temperature is 102°F (38.8°C); other vital signs are normal for age. She appears fatigued but is easily aroused. When not stimulated during the physical examination, she quickly goes back to sleep. Results of her neurologic evaluation are unchanged from her baseline hypertonia and hyperreflexia. She has scleral icterus. Her abdomen is soft and nontender, with a palpable liver edge 3 cm below the right costal margin. Initial laboratory findings document thrombocytopenia (77×103/μL [77×109/L]), aspartate aminotransferase (AST) 4231 U/L (70.66 μkat/L), alanine aminotransferase (ALT) 2660 U/L (44.42 μkat/L), alkaline phosphatase 375 U/L (6.26 μkat/L), total bilirubin 7.3 mg/dL (124.86 μmol/L), conjugated bilirubin 5.8 mg/dL (99.2 μmol/L), prothrombin time (PT) 23.7 seconds, and international normalized ratio 2.09. Serum CBZ concentration is 25.5 mg/L (therapeutic range, 4–12 mg/L). White blood cell count is 6900/μL (6.9×109/L), with 57% neutrophils, 34.8% lymphocytes, 7.7% monocytes, 0.3% eosinophils, and 0.2% basophils. …

Purpose Concerns regarding neurocognitive toxicity of whole-brain radiotherapy (WBRT) have motivated development of alternative, dose-intensive chemotherapeutic strategies as consolidation in primary CNS lymphoma (PCNSL). We performed a multicenter study of high-dose consolidation, without WBRT, in PCNSL. Objectives were to determine: one, rate of complete response (CR) after remission induction therapy with methotrexate, temozolomide, and rituximab (MT-R); two, feasibility of a two-step approach using high-dose consolidation with etoposide plus cytarabine (EA); three, progression-free survival (PFS); and four, correlation between clinical and molecular prognostic factors and outcome. Patients and Methods Forty-four patients with newly diagnosed PCNSL were treated with induction MT-R, and patients who achieved CR received EA consolidation. We performed a prospective analysis of molecular prognostic biomarkers in PCNSL in the setting of a clinical trial. Results The rate of CR to MT-R was 66%. The overall 2-year PFS was 0.57, with median follow-up of 4.9 years. The 2-year time to progression was 0.59, and for patients who completed consolidation, it was 0.77. Patients age > 60 years did as well as younger patients, and the most significant clinical prognostic variable was treatment delay. High BCL6 expression correlated with shorter survival. Conclusion CALGB 50202 demonstrates for the first time to our knowledge that dose-intensive consolidation for PCNSL is feasible in the multicenter setting and yields rates of PFS and OS at least comparable to those of regimens involving WBRT. On the basis of these encouraging results, an intergroup study has been activated comparing EA consolidation with myeloablative chemotherapy in this randomized trial in PCNSL, in which neither arm involves WBRT.

BACKGROUND Rituximab combined with chemotherapy has improved the survival of previously untreated patients with follicular lymphoma (FL). Nevertheless, many patients neither want nor can tolerate chemotherapy, leading to interest in biological approaches. Epratuzumab is a humanized anti-CD22 monoclonal antibody with efficacy in relapsed FL. Because both rituximab and epratuzumab have single-agent activity in FL, the antibody combination was evaluated as initial treatment of patients with FL. METHODS Fifty-nine untreated patients with FL received epratuzumab 360 mg/m2 with rituximab 375 mg/m2 weekly for 4 induction doses. This combination was continued as extended induction in weeks 12, 20, 28, and 36. Response assessed by computed tomography was correlated with clinical risk factors, [18F]fluorodeoxyglucose positron emission tomography findings at week 3, Fcγ polymorphisms, immunohistochemical markers, and statin use. RESULTS Therapy was well-tolerated, with toxicities similar to expected with rituximab monotherapy. Fifty-two (88.2%) evaluable patients responded, including 25 complete responses (42.4%) and 27 partial responses (45.8%). At 3 years follow-up, 60% of patients remain in remission. Follicular Lymphoma International Prognostic Index (FLIPI) risk strongly predicted progression-free survival (P = .022). CONCLUSIONS The high response rate and prolonged time to progression observed with this antibody combination are comparable to those observed after standard chemoimmunotherapies and further support the development of biologic, nonchemotherapeutic approaches for these patients. Cancer 2013;119:3797–3804. © 2013 American Cancer Society.

Background Urinary tract infection (UTI) in trauma patients is associated with increased mortality. Whether the urinalysis (UA) is an adequate test for a urinary source of fever in the ICU trauma patient has not been demonstrated. We hypothesized that the UA is a valuable screen for UTI in the febrile, critically ill trauma patient. Study Design All trauma ICU patients in our surgical ICU who had a fever (temperature >38.0°C), urinary catheter, UA, and a urine culture between January 1, 2011 and December 13, 2011 were reviewed. A positive UA was defined as positive leukocyte esterase, positive nitrite, WBC > 10/high power field, or presence of bacteria. A positive urine culture was defined as growth of ≥10 5 colony forming units (cfu) of an organism irrespective of the UA result or ≥10 3 cfu in the setting of a positive UA. A UTI was defined as positive urine culture without an alternative cause of the fever. Results There were 232 UAs from 112 patients that met criteria. The majority (75%) of patients were men; the mean age was 40 (±16) years. Of the 232 UAs, 90 (38.7%) were positive. There were 14 UTIs. The sensitivity, specificity, positive predictive value, and negative predictive value of the UA for UTI were 100%, 65.1%, 15.5%, and 100%, respectively. Conclusions A negative UA reliably excludes a catheter-associated UTI in the febrile, trauma ICU patient with a 100% negative predictive value, and it can rapidly direct the clinician toward more likely sources of fever and reduce unnecessary urine cultures.

BACKGROUND Rhabdomyolysis following trauma has been associated with renal impairment. Nevertheless, the literature is scant in risk assessment of acute kidney injury (AKI) and survival in children experiencing posttraumatic rhabdomyolysis. METHODS After institutional review board approval was obtained, the registry of an urban trauma center was reviewed for pediatric (age < 18 years) trauma admissions with available creatine kinase (CK) values. Variables extracted included demographics and trauma severity indices along with serum creatine, CK, and Blood Urea Nitrogen (BUN) values. AKI was defined per pediatric RIFLE (Risk, Injury, Failure, Loss, End stage) definition. Regression models were deployed to determine the independent risk factors for AKI and CK levels. RESULTS Overall, 521 patients constituted the study sample. AKI occurred in 70 patients (13.4%), with correlation to CK values in excess of 3,000 IU/L (41.4% vs. 4.9%, adjusted p < 0.001). Independent risk factors for AKI proved to be CK level of 3,000 or greater (adjusted odds ratio [AOR], 11.02; 95% confidence interval [CI], 4.56-26.64; p < 0.001), Injury Severity Score (ISS) of 15 or less (AOR, 0.25; 95% CI, 0.10-0.61), Glasgow Coma Scale (GCS) score of 8 or less (AOR, 15.00; 95% CI, 4.98-44.94), abdominal Abbreviated Injury Scale (AIS) score of 3 or less (AOR, 3.14; 95% CI, 1.04-5.36), imaging studies with contrast of 3 or less (AOR, 3.81; 95% CI, 1.37-10.57), blunt mechanism of injury (AOR, 2.76; 95% CI, 1.17-6.49), administration of nephrotoxic agents (AOR, 4.81; 95% CI, 1.23-18.79), and requirement for fluids administration in the emergency department (AOR, 2.36; 95% CI, 1.04-5.36). Mortality in the study sample with CK values of 3,000 or greater versus less than 3,000 IU/L did not reach statistical significance (25.0% vs. 9.3%, adjusted p = 0.787). CONCLUSION AKI in pediatric posttraumatic rhabdomyolysis occurs in 13% of trauma patients. CK values of 3,000 IU/L or greater pose a significant adjusted risk for AKI. Aggressive monitoring of CK values in pediatric trauma patients is warranted. LEVEL OF EVIDENCE Prognostic study, level III.

Purpose The purpose of this study was to determine remission induction frequency when bortezomib was combined with daunorubicin and cytarabine in previously untreated older adults with acute myeloid leukemia (AML) and safety of bortezomib in combination with consolidation chemotherapy consisting of intermediate-dose cytarabine (Int-DAC). Patients and Methods Ninety-five adults (age 60 to 75 years; median, 67 years) with previously untreated AML (including therapy-related and previous myelodysplastic syndrome) received bortezomib 1.3 mg/m2 intravenously (IV) on days 1, 4, 8, and 11 with daunorubicin 60 mg/m2 on days 1 through 3 and cytarabine 100 mg/m2 by continuous IV infusion on days 1 through 7. Patients who achieved complete remission (CR) received up to two courses of consolidation chemotherapy with cytarabine 2 gm/m2 on days 1 through 5 with bortezomib. Three cohorts with escalating dose levels of bortezomib were tested (0.7, 1.0, and 1.3 mg/m2). Dose-limiting toxicities were assessed during the first cycle of consolidation. The relationship between cell surface expression of CD74 and clinical outcome was assessed. Results Frequency of CR was 65% (62 of 95), and 4% of patients (four of 95) achieved CR with incomplete platelet recovery (CRp). Eleven patients developed grade 3 sensory neuropathy. Bortezomib plus Int-DAC proved tolerable at the highest dose tested. Lower CD74 expression was associated with CR/CRp (P = .04) but not with disease-free or overall survival. Conclusion The addition of bortezomib to standard 3 + 7 daunorubicin and cytarabine induction chemotherapy for AML resulted in an encouraging remission rate. The maximum tested dose of bortezomib administered in combination with Int-DAC for remission consolidation was 1.3 mg/m2 and proved tolerable. Further testing of this regimen is planned.

A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R 2 between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases.

BACKGROUND: In contrast to the established principles of ‘‘damage-control orthopedics’’ for temporary external fixation of long bone or pelvic fractures, the ‘‘ideal’’ timing and modality of fixation of unstable spine fractures in severely injured patients remains controversial. METHODS: A prospective cohort study was designed to evaluate the safety and efficacy of a standardized ‘‘spine damage-control’’ (SDC) protocol for the acute management of unstable thoracic and lumbar spine fractures in severely injured patients. A total of 112 consecutive patients with unstable thoracic or lumbar spine fractures and Injury Severity Score (ISS) of greater than 15 were prospectively enrolled in this study from October 1, 2008, to December 31, 2011. Acute posterior spinal fixation within 24 hours was performed in 42 patients (SDC group), and 70 patients underwent definitive operative spine fixation in a delayed fashion (‘‘delayed surgery’’[DS] group). Both cohorts were prospectively analyzed for baseline demographics, length of operative time, amount of intraoperative blood loss, total hospital length of stay, number of ventilator-dependent days, and incidence of early postoperative complications. RESULTS: The mean time to initial spine fixation was significantly decreased in the SDC group (8.9 [1.7] hours vs. 98.7 [22.4] hours, p G 0.01). The SDC cohort had a reduced mean length of operative time (2.4 [0.7] hours vs. 3.9 [1.3] hours), length of hospital stay (14.1 [2.9] days vs. 32.6 [7.8] days), and number of ventilator-dependent days (2.2 [1.5] days vs. 9.1 [2.4] days), compared with the DS group (p G 0.05). Furthermore, the complication rate was decreased in the SDC group with regard to wound complications (2.4% vs. 7.1%), urinary tract infections (4.8% vs. 21.4%), pulmonary complications (14.3% vs. 25.7%), and pressure sores (2.4% vs. 8.6%), compared with the DS cohort (p G 0.05). CONCLUSION: A standardized SDC protocol represents a safe and efficient treatment strategy for severely injured patients with associated unstable thoracic or lumbar fractures. (J Trauma Acute Care Surg. 2013;74: 590Y596. Copyright* 2013 by Lippincott Williams & Wilkins) LEVEL OF EVIDENCE: Therapeutic study, level III.

Relapsed Hodgkin lymphoma remains a clinical challenge, with few non-cytotoxic treatment options. CD80 is a surface antigen that normally functions as a co-stimulatory molecule but is aberrantly and uniformly expressed on Reed–Sternberg cells. Galiximab is a primatized monoclonal antibody against CD80, with a favorable toxicity profile demonstrated in other lymphomas. Cancer and Leukemia Group B (CALGB) 50602 (Alliance) tested single-agent galiximab in a highly refractory group of patients with Hodgkin lymphoma (median 3 prior regimens, 83% failing after prior stem cell transplant) to determine the efficacy. The overall response rate was 10.3% and the median progression-free survival was 1.6 months. Galiximab was well-tolerated, with minimal grade 3 or 4 toxicities. Despite this preclinical rationale, single-agent galiximab had limited activity in heavily pretreated Hodgkin lymphoma.

Analogous to organ injury scales developed for trauma, a scoring system is needed for acute care surgery. The purpose of this study was to develop a disease severity score (DSS) for acute appendicitis, the most common surgical emergency.A panel of acute care surgery experts reviewed the literature and developed a DSS for acute appendicitis as follows: grade 1, inflamed; Grade 2, gangrenous; Grade 3, perforated with localized free fluid; Grade 4, perforated with a regional abscess; and Grade 5, perforated with diffuse peritonitis. We applied the DSS to 1,000 consecutive patients undergoing appendectomy from 1999 to 2009 and examined its association with outcomes (mortality, length of hospital stay, incidence of in-hospital, and postdischarge complications). Of the 1,000 patients, 82 were excluded owing to negative or interval appendectomy or advanced end-stage renal disease.Among 918 eligible patients, the DSS distribution was Grade 1 at 62.4%, Grade 2 at 13.0%, Grade 3 at 18.7%, Grade 4 at 4.4%, and Grade 5 at 1.5%. Statistical analyses indicated a stepwise risk increase in adverse outcomes with higher DSS grades (c statistics ≥ 0.75 for all outcomes). Covariates (age, sex, and type of surgical access) did not add to the predictive power of DSS.Based on this single-institution study, the proposed appendicitis DSS seems to be a useful tool. This DSS can inform future, national efforts, which can build on the knowledge provided by the present investigation. This DSS may be useful for comparing therapeutic modalities, planning resource use, improving programs, and adjusting reimbursementEpidemiologic study, level III.