Antibiotic Delays and Feasibility of a 1-Hour-From-Triage Antibiotic Requirement: Analysis of an Emergency Department Sepsis Quality Improvement Database.

STUDY OBJECTIVE: We identify factors associated with delayed emergency department (ED) antibiotics and determine feasibility of a 1-hour-from-triage antibiotic requirement in sepsis. METHODS: We studied all ED adult septic patients in accordance with Centers for Medicare & Medicaid Services Severe Sepsis and Septic Shock National Quality Measures in 2 consecutive 12-month intervals. During the second interval, a quality improvement intervention was conducted: a sepsis screening protocol plus case-specific feedback to clinicians. Data were abstracted retrospectively through electronic query and chart review. Primary outcomes were antibiotic delay greater than 3 hours from documented onset of hypoperfusion (per Centers for Medicare & Medicaid Services Severe Sepsis and Septic Shock National Quality Measures) and antibiotic delay greater than 1 hour from triage (per 2018 Surviving Sepsis Campaign recommendations). RESULTS: We identified 297 and 357 septic patients before and during the quality improvement intervention, respectively. Before and during quality improvement intervention, antibiotic delay in accordance with Centers for Medicare & Medicaid Services measures occurred in 30% and 21% of cases (-9% [95% confidence interval -16% to -2%]); and in accordance with 2018 Surviving Sepsis Campaign recommendations, 85% and 71% (-14% [95% confidence interval -20% to -8%]). Four factors were independently associated with both definitions of antibiotic delay: vague (ie, nonexplicitly infectious) presenting symptoms, triage location to nonacute areas, care before the quality improvement intervention, and lower Sequential [Sepsis-related] Organ Failure Assessment scores. Most patients did not receive antibiotics within 1 hour of triage, with the exception of a small subset post-quality improvement intervention who presented with explicit infectious symptoms and triage hypotension. CONCLUSION: The quality improvement intervention significantly reduced antibiotic delays, yet most septic patients did not receive antibiotics within 1 hour of triage. Compliance with the 2018 Surviving Sepsis Campaign would require a wholesale alteration in the management of ED patients with either vague symptoms or absence of triage hypotension.

Below the disappearing marshes of an urban estuary: historic nitrogen trends and soil structure.

Marshes in the urban Jamaica Bay Estuary, New York, USA are disappearing at an average rate of 13 ha/yr, and multiple stressors (e.g., wastewater inputs, dredging activities, groundwater removal, and global warming) may be contributing to marsh losses. Among these stressors, wastewater nutrients are suspected to be an important contributing cause of marsh deterioration. We used census data, radiometric dating, stable nitrogen isotopes, and soil surveys to examine the temporal relationships between human population growth and soil nitrogen; and we evaluated soil structure with computer-aided tomography, surface elevation and sediment accretion trends, carbon dioxide emissions, and soil shear strength to examine differences among disappearing (Black Bank and Big Egg) and stable marshes (JoCo). Radiometric dating and nitrogen isotope analyses suggested a rapid increase in human wastewater nutrients beginning in the late 1840s, and a tapering off beginning in the 1930s when wastewater treatment plants (WWTPs) were first installed. Current WWTPs nutrient loads to Jamaica Bay are approximately 13 995 kg N/d and 2767 kg P/d. At Black Bank, the biomass and abundance of roots and rhizomes and percentage of organic matter on soil were significantly lower, rhizomes larger in diameter, carbon dioxide emission rates and peat particle density significantly greater, and soil strength significantly lower compared to the stable JoCo Marsh, suggesting Black Bank has elevated decomposition rates, more decomposed peat, and highly waterlogged peat. Despite these differences, the rates of accretion and surface elevation change were similar for both marshes, and the rates of elevation change approximated the long-term relative rate of sea level rise estimated from tide gauge data at nearby Sandy Hook, New Jersey. We hypothesize that Black Bank marsh kept pace with sea level rise by the accretion of material on the marsh surface, and the maintenance of soil volume through production of larger diameter rhizomes and swelling (dilation) of waterlogged peat. JoCo Marsh kept pace with sea-level rise through surface accretion and soil organic matter accumulation. Understanding the effects of multiple stressors, including nutrient enrichment, on soil structure, organic matter accumulation, and elevation change will better inform management decisions aimed at maintaining and restoring coastal marshes.

Advanced stage anaplastic large cell lymphoma in children and adolescents: results of ANHL0131, a randomized phase III trial of APO versus a modified regimen with vinblastine: a report from the children's oncology group.

BACKGROUND: Optimal therapy for children and adolescents with advanced stage anaplastic large cell lymphoma (ALCL) is unknown. ANHL0131 examined whether a maintenance regimen including vinblastine compared to the standard APO (doxorubicin, prednisone, vincristine, methotrexate, 6-mercaptopurine) regimen would result in superior event-free survival. PROCEDURE: One hundred and twenty five eligible patients were enrolled. Induction was identical for both arms. Post induction patients were randomized to receive APO with vincristine every 3 weeks or a regimen that substituted vincristine with weekly vinblastine (APV). RESULTS: There was no difference between the patients randomized to the APO versus APV arms in either event free survival (EFS) or overall survival (OS) (three year EFS 74% vs. 79%, P = 0.68 and three years OS of 84% vs. 86%, P = 0.87, respectively). Patients in the APV arm required dose reduction secondary to myelosuppression and had a higher incidence of neutropenia as well as infection with neutropenia compared to those in the APO arm (P < 0.001, P = 0.019, respectively). CONCLUSIONS: Treatment with weekly vinblastine instead of every three week vincristine as part of multi-agent maintenance therapy did not result in improvement in EFS or OS. Weekly vinblastine was associated with increased toxicity. (ClinicalTrials.gov Identifier NCT00059839).

Diagnostic suspicion bias and machine learning: Breaking the awareness deadlock for sepsis detection.

Many early warning algorithms are downstream of clinical evaluation and diagnostic testing, which means that they may not be useful when clinicians fail to suspect illness and fail to order appropriate tests. Depending on how such algorithms handle missing data, they could even indicate "low risk" simply because the testing data were never ordered. We considered predictive methodologies to identify sepsis at triage, before diagnostic tests are ordered, in a busy Emergency Department (ED). One algorithm used "bland clinical data" (data available at triage for nearly every patient). The second algorithm added three yes/no questions to be answered after the triage interview. Retrospectively, we studied adult patients from a single ED between 2014-16, separated into training (70%) and testing (30%) cohorts, and a final validation cohort of patients from four EDs between 2016-2018. Sepsis was defined per the Rhee criteria. Investigational predictors were demographics and triage vital signs (downloaded from the hospital EMR); past medical history; and the auxiliary queries (answered by chart reviewers who were blinded to all data except the triage note and initial HPI). We developed L2-regularized logistic regression models using a greedy forward feature selection. There were 1164, 499, and 784 patients in the training, testing, and validation cohorts, respectively. The bland clinical data model yielded ROC AUC's 0.78 (0.76-0.81) and 0.77 (0.73-0.81), for training and testing, respectively, and ranged from 0.74-0.79 in four hospital validation. The second model which included auxiliary queries yielded 0.84 (0.82-0.87) and 0.83 (0.79-0.86), and ranged from 0.78-0.83 in four hospital validation. The first algorithm did not require clinician input but yielded middling performance. The second showed a trend towards superior performance, though required additional user effort. These methods are alternatives to predictive algorithms downstream of clinical evaluation and diagnostic testing. For hospital early warning algorithms, consideration should be given to bias and usability of various methods.

The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma.

We used gene expression profiling to establish a molecular diagnosis of mantle cell lymphoma (MCL), to elucidate its pathogenesis, and to predict the length of survival of these patients. An MCL gene expression signature defined a large subset of MCLs that expressed cyclin D1 and a novel subset that lacked cyclin D1 expression. A precise measurement of tumor cell proliferation, provided by the expression of proliferation signature genes, identified patient subsets that differed by more than 5 years in median survival. Differences in cyclin D1 mRNA abundance synergized with INK4a/ARF locus deletions to dictate tumor proliferation rate and survival. We propose a quantitative model of the aberrant cell cycle regulation in MCL that provides a rationale for the design of cell cycle inhibitor therapy in this malignancy.

Modeling of Usual Care: Vasopressor Initiation for Sepsis With Hypotension.

Usual care regarding vasopressor initiation is ill-defined. We aimed to develop a quantitative "dynamic practice" model for usual care in the emergency department (ED) regarding the timing of vasopressor initiation in sepsis. In a retrospective study of 589 septic patients with hypotension in an urban tertiary care center ED, we developed a multi-variable model that distinguishes between patients who did and did not subsequently receive sustained (>24 h) vasopressor therapy. Candidate predictors were vital signs, intravenous fluid (IVF) volumes, laboratory measurements, and elapsed time from triage computed at timepoints leading up to the final decision timepoint of either vasopressor initiation or ED hypotension resolution without vasopressors. A model with six independently significant covariates (respiratory rate, Glasgow Coma Scale score, SBP, SpO2, administered IVF, and elapsed time) achieved a C-statistic of 0.78 in a held-out test set at the final decision timepoint, demonstrating the ability to reliably model usual care for vasopressor initiation for hypotensive septic patients. The included variables measured depth of hypotension, extent of disease severity and organ dysfunction. At an operating point of 90% specificity, the model identified a minority of patients (39%) more than an hour before actual vasopressor initiation, during which time a median of 2,250 (IQR 1,200-3,300) mL of IVF was administered. This single-center analysis shows the feasibility of a quantitative, objective tool for describing usual care. Dynamic practice models may help assess when management was atypical; such tools may also be useful for designing and interpreting clinical trials.

Constraints on the adjustment of tidal marshes to accelerating sea level rise.

Much uncertainty exists about the vulnerability of valuable tidal marsh ecosystems to relative sea level rise. Previous assessments of resilience to sea level rise, to which marshes can adjust by sediment accretion and elevation gain, revealed contrasting results, depending on contemporary or Holocene geological data. By analyzing globally distributed contemporary data, we found that marsh sediment accretion increases in parity with sea level rise, seemingly confirming previously claimed marsh resilience. However, subsidence of the substrate shows a nonlinear increase with accretion. As a result, marsh elevation gain is constrained in relation to sea level rise, and deficits emerge that are consistent with Holocene observations of tidal marsh vulnerability.

Hedgehog pathway activity in pediatric embryonal rhabdomyosarcoma and undifferentiated sarcoma: a report from the Children's Oncology Group.

BACKGROUND: Aberrant activation of the hedgehog (Hh) signaling pathway is implicated widely in both pediatric and adult malignancies. Inactivation of the Hh regulator PTCH is responsible for the Gorlin cancer predisposition syndrome. The spectrum of tumors found in Gorlin Syndrome includes basal cell carcinoma, medulloblastoma, and rarely, rhabdomyosarcoma (RMS). A previous report utilizing in situ hybridization has provided initial evidence for the expression of Hh targets GLI1 and PTCH in RMS tumors. PROCEDURE: To investigate the role of Hh pathway signaling in pediatric RMS and undifferentiated sarcoma (US) tumors, the expression of Hh pathway targets GLI1 and PTCH was measured. RNA was extracted from archival human tumor specimens collected from pediatric patients enrolled on Intergroup Rhabdomyosarcoma Study III and IV, and subjected to quantitative reverse transcriptase-polymerase chain reaction. RESULTS: Expression of GLI1 with or without PTCH was detected in substantial subsets of embryonal RMS (ERMS) and US tumors but only rarely in alveolar RMS tumors. Neither PTCH mutations nor activating SMO mutations were detected in ERMS tumors with high GLI1 expression. Microarray analysis demonstrated relative overexpression of downstream Hh targets in ERMS tumors with high or intermediate GLI1 expression. Unlike a recent report, Hh pathway activity in ERMS tumors did not correlate with a unique clinical phenotype. CONCLUSIONS: Our findings support a role for Hh pathway activation in the genesis of a subset of ERMS and US tumors. Hh signaling may represent a novel therapeutic target in affected tumors.

Distortion of the Intracranial Pressure Waveform by Extraventricular Drainage System.

OBJECTIVE: To investigate whether intracranial pressure (ICP) waveform measurements obtained from extraventricular drainage (EVD) systems are suitable for the calculation of intracranial elastance (ICE) or cerebrovascular pressure autoregulation (PAR) indices. METHODS: The transfer characteristic of an EVD system is investigated by its step and frequency responses with focus on the low frequency (LF) range from 0.02 to 0.065 Hz (important in PAR) and the location of the system's first resonance frequency (important for ICE). The effects of opening the distal end of the EVD for drainage of cerebrospinal fluid and the presence of trapped air bubbles are also investigated. RESULTS: The EVD system exhibits a first resonant frequency below 4 Hz, resulting in significant distortion of the measured ICP waveform. The frequency response in the LF range only remains flat when the EVD is closed. Opening the drain results in drops in magnitude and phase along the entire frequency range above DC. Air bubbles close to the EVD catheter tip affect the LF range while an air bubble close to the pressure transducer further decreases the first resonant frequency. Tests with actual ICP waveforms confirmed EVD-induced waveform distortions that can lead to erroneous ICE estimation. CONCLUSION: EVD-based ICP measurements distort the waveform morphology. PAR indices based on LF information are only valid if the EVD is closed. EVD-based ICE estimation is to be avoided. SIGNIFICANCE: ICP waveform analyses to derive information about ICE and PAR should be critically questioned if only EVD derived ICP signals are at hand.

Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma.

Using current diagnostic criteria, primary mediastinal B cell lymphoma (PMBL) cannot be distinguished from other types of diffuse large B cell lymphoma (DLBCL) reliably. We used gene expression profiling to develop a more precise molecular diagnosis of PMBL. PMBL patients were considerably younger than other DLBCL patients, and their lymphomas frequently involved other thoracic structures but not extrathoracic sites typical of other DLBCLs. PMBL patients had a relatively favorable clinical outcome, with a 5-yr survival rate of 64% compared with 46% for other DLBCL patients. Gene expression profiling strongly supported a relationship between PMBL and Hodgkin lymphoma: over one third of the genes that were more highly expressed in PMBL than in other DLBCLs were also characteristically expressed in Hodgkin lymphoma cells. PDL2, which encodes a regulator of T cell activation, was the gene that best discriminated PMBL from other DLBCLs and was also highly expressed in Hodgkin lymphoma cells. The genomic loci for PDL2 and several neighboring genes were amplified in over half of the PMBLs and in Hodgkin lymphoma cell lines. The molecular diagnosis of PMBL should significantly aid in the development of therapies tailored to this clinically and pathogenetically distinctive subgroup of DLBCL.

Molecular classification of rhabdomyosarcoma--genotypic and phenotypic determinants of diagnosis: a report from the Children's Oncology Group.

Rhabdomyosarcoma (RMS) in children occurs as two major histological subtypes, embryonal (ERMS) and alveolar (ARMS). ERMS is associated with an 11p15.5 loss of heterozygosity (LOH) and may be confused with nonmyogenic, non-RMS soft tissue sarcomas. ARMS expresses the product of a genomic translocation that fuses FOXO1 (FKHR) with either PAX3 or PAX7 (P-F); however, at least 25% of cases lack these translocations. Here, we describe a genomic-based classification scheme that is derived from the combined gene expression profiling and LOH analysis of 160 cases of RMS and non-RMS soft tissue sarcomas that is at variance with conventional histopathological schemes. We found that gene expression profiles and patterns of LOH of ARMS cases lacking P-F translocations are indistinguishable from conventional ERMS cases. A subset of tumors that has been histologically classified as RMS lack myogenic gene expression. However, classification based on gene expression is possible using as few as five genes with an estimated error rate of less than 5%. Using immunohistochemistry, we characterized two markers, HMGA2 and TFAP2ss, which facilitate the differential diagnoses of ERMS and P-F RMS, respectively, using clinical material. These objectively derived molecular classes are based solely on genomic analysis at the time of diagnosis and are highly reproducible. Adoption of these molecular criteria may offer a more clinically relevant diagnostic scheme, thus potentially improving patient management and therapeutic RMS outcomes.

Validation of a 'Usual Care' Model for Vasopressor Initiation in a Cohort of Emergency Department Patients with Sepsis.

Usual care regarding vasopressor (VP) initiation is ill-defined. We aimed to further validate a quantitative model for usual care in the Emergency Department (ED) regarding the timing of VP initiation in sepsis. We retrospectively studied a cohort of adult critically-ill ED patients who also received antibiotics in the ED. We applied a multivariable model previously developed from another patient cohort which distinguishes between time points at which patients were or were not subsequently started on a continuous VP infusion. The model has six independently significant predictors (respiratory rate, Glasgow Coma Scale score, systolic blood pressure, SpO2, administered intravenous fluids, and elapsed time). The outcome was initiation of VP infusion, either within the ED or within 6 hours after leaving the ED. We applied the model to all time points, beginning when all model input parameters were first available for a given patient, and ending when either VP were first started, or the patient left the ED. Out of 55,963 adult ED patients during the two-year study interval, we identified 1,629 who met our inclusion criteria. The area under the receiver operating characteristic curve was 0.81 for all patients, and 0.72 for the subset with at least one hypotensive blood pressure measurement. At a model threshold with sensitivity and specificity 0.74 and 0.74, respectively, the median advance detection time was 170.5 minutes (IQR 53 - 363).

Behavioral therapy intervention trial to improve sleep quality and cancer-related fatigue.

BACKGROUND: To determine whether sleep quality and fatigue associated with breast cancer adjuvant chemotherapy treatments can be improved with behavioral therapy (BT) [Individualized Sleep Promotion Plan (ISPP)] including modified stimulus control, modified sleep restriction, relaxation therapy, and sleep hygiene. METHODS: Randomized-controlled trial based on Piper Integrated Fatigue Model, 219 stages I-IIIA breast cancer patients. Prior to the initial chemotherapy treatment, BT participants developed an ISPP plan that was regularly reinforced and revised. Controls received healthy eating information and attention. Pittsburgh Sleep Quality Index (PSQI), daily diary, actigraph, and Piper Fatigue Scale (PFS) data were collected 2 days prior, during the 7 days after each treatment, and 30 days after the last treatment. Repeated measures analysis of variance was used. RESULTS: Prior to chemotherapy, participants reported mild fatigue and fairly poor sleep quality. All variables changed over time. A group by time interaction was found for sleep quality (PSQI) improving in the BT group. Diary revealed group differences on number of awakenings, minutes awake after sleep onset, and sleep efficiency. Fatigue (PFS) was similar between groups. CONCLUSIONS: The BT group showed improved sleep quality over time and better sleep (diary). Perceptions of improved sleep quality over time are not consistently associated with diary or actigraph, or result in lower fatigue.

Clustering Blood Pressure Trajectories in Septic Shock in the Emergency Department.

Hemodynamic management of sepsis in the emergency department relies on fluid resuscitation and vasoactive therapy to maintain adequate blood pressure and end-organ perfusion. While typical practice targets certain thresholds of blood pressure (such as 65 mmHg mean arterial or 90 mmHg systolic blood pressure [SBP]), little consideration is given to temporal dynamics of blood pressure. In this work, we use unsupervised learning methods to reveal characteristic SBP trajectories in the two hours either surrounding the start of hypotensive episodes (SBP <; 90 mmHg) or immediately preceding the initiation of vasopressor therapy. Our results show that hypotensive episodes tended to either resolve very quickly (within 40 minutes) or extend for prolonged periods (at least 1 hour). Those with prolonged hypotension constituted 74% of all patients with at least one measurement of SBP <; 90 mmHg. Of them, patients who entered hypotension by a large, acute drop from a normal SBP over the preceding hour had a greater incidence of subsequent vasopressor administration than those with a more gradual decline into hypotension. Overall, our results suggest that a significant subset of patients, especially those with stable but low SBP, should have received vasopressors when they did not, or should have received them sooner. Dynamic trajectories appear to be important factors in clinical practice of hemodynamic management of sepsis.

Long-term outcomes of autologous stem cell transplantation for follicular non-Hodgkin lymphoma: effect of histological grade and Follicular International Prognostic Index.

Although results of autologous stem cell transplantation (SCT) for recurrent follicular non-Hodgkin lymphoma (NHL) have been previously reported, the long-term results and evaluation of prognostic factors in a large patient population receiving this therapy are difficult to find in the literature. To address these issues, we evaluated 248 patients with recurrent follicular NHL treated with high-dose chemotherapy and autologous SCT between 7/87 and 6/03. According to the World Health Organization (WHO) classification system, 64 patients (26%) had follicular NHL grade 1 (FL 1), 98 (40%) had FL 2, and 86 (35%) had FL 3. At the time of transplantation, 88 of the patients (35%) had a Follicular Lymphoma International Prognostic Index (FLIPI) score of low risk, 87 (35%) had an intermediate-risk FLIPI score, 37 (15%) had a high-risk FLIPI score, and 36 (15%) had at least 1 missing value, preventing calculation of the FLIPI score. The 5-year overall survival (OS) for all patients was 63%, and the 5-year progression-free survival (PFS) was 44%. In a multivariate analysis, a histological grade of FL 3, a high-risk FLIPI score at the time of transplantation, and having received 3 or more previous chemotherapy regimens were significant factors for predicting a worse OS. In addition, the use of a transplantation regimen including a monoclonal antibody decreased the relative risk of progressive lymphoma. These data suggest that transplantation earlier in the course of the disease for patients with follicular lymphoma with use of a monoclonal antibody-based regimen may lead to improved outcomes.

ATM, CTLA4, MNDA, and HEM1 in high versus low CD38 expressing B-cell chronic lymphocytic leukemia.

PURPOSE: In B-cell chronic lymphocytic leukemia (CLL), high CD38 expression has been associated with unfavorable clinical course, advanced disease, resistance to therapy, shorter time to first treatment, and shorter survival. However, the genes associated with CLL patient subgroups with high and low CD38 expression and their potential role in disease progression is not known. EXPERIMENTAL DESIGN: To identify the genes associated with the clinical disparity in CLL patients with high versus low CD38 expression, transcriptional profiles were obtained from CLL cells from 39 different patients using oligonucleotide microarray. Gene expression was also compared between CLL cells and B cells from healthy individuals. RESULTS: Gene expression analysis identified 76 differentially expressed genes in CD38 high versus low groups. Out of these genes, HEM1, CTLA4, and MNDA were selected for further studies and their differential expression was confirmed by real-time PCR. HEM1 overexpression was associated with poor outcome, whereas the overexpression of CTLA4 and MNDA was associated with good outcome. Down-regulation of HEM1 expression in patient CLL cells resulted in a significant increase in their susceptibility to fludarabine-mediated killing. In addition, when gene expression patterns in CD38 high and low CLL cells were compared with normal B-cell profiles, ATM expression was found to be significantly lower in CD38 high compared with CD38 low CLL as confirmed by real-time reverse transcription-PCR. CONCLUSIONS: These results identify the possible genes that may be involved in cell proliferation and survival and, thus, determining the clinical behavior of CLL patients expressing high or low CD38.

Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells.

BACKGROUND: Patients with follicular lymphoma may survive for periods of less than 1 year to more than 20 years after diagnosis. We used gene-expression profiles of tumor-biopsy specimens obtained at diagnosis to develop a molecular predictor of the length of survival. METHODS: Gene-expression profiling was performed on 191 biopsy specimens obtained from patients with untreated follicular lymphoma. Supervised methods were used to discover expression patterns associated with the length of survival in a training set of 95 specimens. A molecular predictor of survival was constructed from these genes and validated in an independent test set of 96 specimens. RESULTS: Individual genes that predicted the length of survival were grouped into gene-expression signatures on the basis of their expression in the training set, and two such signatures were used to construct a survival predictor. The two signatures allowed patients with specimens in the test set to be divided into four quartiles with widely disparate median lengths of survival (13.6, 11.1, 10.8, and 3.9 years), independently of clinical prognostic variables. Flow cytometry showed that these signatures reflected gene expression by nonmalignant tumor-infiltrating immune cells. CONCLUSIONS: The length of survival among patients with follicular lymphoma correlates with the molecular features of nonmalignant immune cells present in the tumor at diagnosis.

The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma.

BACKGROUND: The survival of patients with diffuse large-B-cell lymphoma after chemotherapy is influenced by molecular features of the tumors. We used the gene-expression profiles of these lymphomas to develop a molecular predictor of survival. METHODS: Biopsy samples of diffuse large-B-cell lymphoma from 240 patients were examined for gene expression with the use of DNA microarrays and analyzed for genomic abnormalities. Subgroups with distinctive gene-expression profiles were defined on the basis of hierarchical clustering. A molecular predictor of risk was constructed with the use of genes with expression patterns that were associated with survival in a preliminary group of 160 patients and was then tested in a validation group of 80 patients. The accuracy of this predictor was compared with that of the international prognostic index. RESULTS: Three gene-expression subgroups--germinal-center B-cell-like, activated B-cell-like, and type 3 diffuse large-B-cell lymphoma--were identified. Two common oncogenic events in diffuse large-B-cell lymphoma, bcl-2 translocation and c-rel amplification, were detected only in the germinal-center B-cell-like subgroup. Patients in this subgroup had the highest five-year survival rate. To identify other molecular determinants of outcome, we searched for individual genes with expression patterns that correlated with survival in the preliminary group of patients. Most of these genes fell within four gene-expression signatures characteristic of germinal-center B cells, proliferating cells, reactive stromal and immune cells in the lymph node, or major-histocompatibility-complex class II complex. We used 17 genes to construct a predictor of overall survival after chemotherapy. This gene-based predictor and the international prognostic index were independent prognostic indicators. CONCLUSIONS: DNA microarrays can be used to formulate a molecular predictor of survival after chemotherapy for diffuse large-B-cell lymphoma.

Evaluation of the effectiveness of 3D vascular stereoscopic models in anatomy instruction for first year medical students.

The head and neck region is one of the most complex areas featured in the medical gross anatomy curriculum. The effectiveness of using three-dimensional (3D) models to teach anatomy is a topic of much discussion in medical education research. However, the use of 3D stereoscopic models of the head and neck circulation in anatomy education has not been previously studied in detail. This study investigated whether 3D stereoscopic models created from computed tomographic angiography (CTA) data were efficacious teaching tools for the head and neck vascular anatomy. The test subjects were first year medical students at the University of Mississippi Medical Center. The assessment tools included: anatomy knowledge tests (prelearning session knowledge test and postlearning session knowledge test), mental rotation tests (spatial ability; presession MRT and postsession MRT), and a satisfaction survey. Results were analyzed using a Wilcoxon rank-sum test and linear regression analysis. A total of 39 first year medical students participated in the study. The results indicated that all students who were exposed to the stereoscopic 3D vascular models in 3D learning sessions increased their ability to correctly identify the head and neck vascular anatomy. Most importantly, for students with low-spatial ability, 3D learning sessions improved postsession knowledge scores to a level comparable to that demonstrated by students with high-spatial ability indicating that the use of 3D stereoscopic models may be particularly valuable to these students with low-spatial ability. Anat Sci Educ 10: 34-45. © 2016 American Association of Anatomists.

Classification models to predict vasopressor administration for septic shock in the emergency department.

Optimal management of sepsis and septic shock in the emergency department (ED) involves timely decisions related to intravenous fluid resuscitation and initiation of vasoactive medication support. A decision-support tool trained on electronic health record data, can help improve this complex decision. We retrospectively extracted vital signs, lab measurements, and fluid administration information from 807 patient visits over a two-year period to a major ED. Patients selected for inclusion had a high likelihood of septic shock. We trained binary classifiers to discriminate between patients administered vasopressors in the ED and those not administered vasopressors at any point. Using features extracted from the entire ED visit record yielded a maximum area under the receiver-operating characteristic curve (AUC) of 0.798 (95% CI 0.725-0.849) in a hold-out test set. In a separate task, we used individual vital signs observations with lab results to predict vasopressor administration, yielding a maximum AUC of 0.762 (95% CI 0.748-0.777). Lastly, we trained separate classifiers for different subgroups of vital signs observations. These subgroups were defined by the cumulative number of fluid boluses delivered at the time of the observation. The maximum AUC achieved by any of these classifiers was 0.815 (95% CI 0.784-0.853), occurring for vital signs observations made after 2 bolus administrations. Classifiers in all tasks significantly outperformed existing clinical tools for assessing prognosis in ED sepsis. This work shows how relatively few features can provide instantaneous and accurate prediction of need for an intervention that is typically a complex clinical decision.