BACKGROUND: Autologous stem cell transplantation (autoSCT) can extend remission of mantle cell lymphoma (MCL), but the management of subsequent relapse is challenging. METHODS: We examined consecutive patients with MCL who underwent autoSCT at Veterans Affairs Puget Sound Health Care System between 2009 and 2017 (N=37). RESULTS: Ten patients experienced disease progression after autoSCT and were included in this analysis. Median progression free survival after autoSCT was 1.8 years (range, 0.3–7.1) and median overall survival after progression was only 0.7 years (range, 0.1 to not reached). The 3 patients who survived more than 1 year after progression were treated with ibrutinib. CONCLUSION Our findings suggest that ibrutinib can achieve relatively prolonged control of MCL progressing after autoSCT.

A systematic phylogenetic footprinting approach was performed to identify conserved transcription factor binding sites (TFBSs) in mammalian promoter regions using human, mouse and rat sequence alignments. We found that the score distributions of most binding site models did not follow the Gaussian distribution required by many statistical methods. Therefore, we performed an empirical test to establish the optimal threshold for each model. We gauged our computational predictions by comparing with previously known TFBSs in the PCK1 gene promoter of the cytosolic isoform of phosphoenolpyruvate carboxykinase, and achieved a sensitivity of 75% and a specificity of approximately 32%. Almost all known sites overlapped with predicted sites, and several new putative TFBSs were also identified. We validated a predicted SP1 binding site in the control of PCK1 transcription using gel shift and reporter assays. Finally, we applied our computational approach to the prediction of putative TFBSs within the promoter regions of all available RefSeq genes. Our full set of TFBS predictions is freely available at http://bfgl.anri.barc.usda.gov/tfbsConsSites.

BACKGROUND: Our goal was to determine whether postoperative delirium is associated with inpatient complication rates after primary elective total hip arthroplasty (THA). METHODS: Using the National Inpatient Sample, we analyzed records of patients who underwent primary elective THA from 2000 through 2009 to identify patients with delirium (n = 13,551) and without delirium (n = 1,992,971) and to assess major perioperative complications (acute renal failure, death, myocardial infarction, pneumonia, pulmonary embolism, and stroke) and minor perioperative complications (deep vein thrombosis, dislocation, general procedural complication, hematoma, seroma, and wound infection). Patient age, sex, length of hospital stay, and number of comorbidities were assessed. We used multivariate logistic regression to determine the association of delirium with complication rates (significance, p < 0.01). RESULTS: Patients with delirium were older (mean, 75 ± 0.2 vs. 65 ± 0.1 years), were more likely to be male (56% vs. 52%), had longer hospital stays (mean, 5.7 ± 0.07 vs. 3.8 ± 0.02 days), and had more comorbidities (mean, 2.8 ± 0.03 vs. 1.4 ± 0.01) (all p < 0.001) versus patients without delirium. Patients with delirium were more likely to have major (11% vs. 3%) and minor (17% vs. 7%) perioperative complications versus patients without delirium (both p < 0.001). When controlling for age, sex, and number of comorbidities, delirium was independently associated with major and minor complications (odds ratio, 2.0; 95% confidence interval, 1.7 to 2.3). CONCLUSIONS: Delirium is an independent risk factor for major and minor perioperative complications after primary elective THA.
Arthroplasty, Replacement, Hip* ; Comorbidity ; Delirium* ; Dislocations ; Hematoma ; Humans ; Inpatients ; Length of Stay ; Logistic Models ; Male ; Myocardial Infarction ; Pneumonia ; Postoperative Complications ; Pulmonary Embolism ; Renal Insufficiency ; Risk Factors ; Seroma ; Thrombosis ; Veins ; Wounds and Injuries

BACKGROUND: The number of patients with systemic lupus erythematosus (herein, lupus) undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA) is increasing. There is disagreement about the effect of lupus on perioperative complication rates. We hypothesized that lupus would be associated with higher complication rates in patients who undergo elective primary THA or TKA. METHODS: Records of more than 6.2 million patients from the National Inpatient Sample who underwent elective primary THA or TKA from 2000 to 2009 were reviewed. Patients with lupus (n = 38,644) were compared with those without lupus (n = 6,173,826). Major complications were death, pulmonary embolism, myocardial infarction, stroke, pneumonia, and acute renal failure. Minor complications were wound infection, seroma, deep vein thrombosis, hip dislocation, wound dehiscence, and hematoma. Patient age, sex, duration of hospital stay, and number of Elixhauser comorbidities were assessed for both groups. Multivariate logistic regression models using comorbidities, age, and sex as covariates were used to assess the association of lupus with major and minor perioperative complications. The alpha level was set to 0.001. RESULTS: Among patients who underwent THA, those with lupus were younger (mean age, 56 vs. 65 years), were more likely to be women (87% vs. 56%), had longer hospital stays (mean, 4.0 vs. 3.8 days), and had more comorbidities (mean, 2.5 vs. 1.4) than those without lupus (all p < 0.001). In patients with THA, lupus was independently associated with major complications (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1 to 1.7) and minor complications (OR, 1.2; 95% CI, 1.0 to 1.5). Similarly, among patients who underwent TKA, those with lupus were younger (mean, 62 vs. 67 years), were more likely to be women (93% vs. 64%), had longer hospital stays (mean, 3.8 vs. 3.7 days), and had more comorbidities (mean, 2.8 vs. 1.7) than those without lupus (all p < 0.001). However, in TKA patients, lupus was not associated with greater odds of major complications (OR, 1.2; 95% CI, 0.9 to 1.4) or minor complications (OR, 1.1; 95% CI, 0.9 to 1.3). CONCLUSIONS Lupus is an independent risk factor for major and minor perioperative complications in elective primary THA but not TKA.

A systematic phylogenetic footprinting approach was performed to identify conserved transcription factor binding sites (TFBSs) in mammalian promoter regions using human, mouse and rat sequence alignments. We found that the score distributions of most binding site models did not follow the Gaussian distribution required by many statistical methods. Therefore, we performed an empirical test to establish the optimal threshold for each model. We gauged our computational predictions by comparing with previously known TFBSs in the PCK1 gene promoter of the cytosolic isoform of phosphoenolpyruvate carboxykinase, and achieved a sensitivity of 75% and a specificity of approximately 32%. Almost all known sites overlapped with predicted sites, and several new putative TFBSs were also identified. We validated a predicted SP1 binding site in the control of PCK1 transcription using gel shift and reporter assays. Finally, we applied our computational approach to the prediction of putative TFBSs within the promoter regions of all available RefSeq genes. Our full set of TFBS predictions is freely available at http://bfgl.anri.barc.usda.gov/tfbsConsSites.
Algorithms ; Amino Acid Sequence ; Animals ; Base Sequence ; Binding Sites ; genetics ; Cell Line, Tumor ; Computational Biology ; methods ; Conserved Sequence ; Electrophoretic Mobility Shift Assay ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Luciferases ; genetics ; metabolism ; Mice ; Normal Distribution ; Oligonucleotides ; genetics ; metabolism ; Phosphoenolpyruvate Carboxykinase (GTP) ; genetics ; Promoter Regions, Genetic ; genetics ; Protein Binding ; Rats ; Recombinant Fusion Proteins ; genetics ; metabolism ; Regulatory Sequences, Nucleic Acid ; genetics ; Reproducibility of Results ; Sp1 Transcription Factor ; genetics ; metabolism ; Transcription Factors ; metabolism ; Transfection

BACKGROUND: We aimed to compare the diagnostic accuracy of the Alere Triage Cardio3 Tropinin I (TnI) assay (Alere, Inc., USA) and the PathFast cTnI-II (Mitsubishi Chemical Medience Corporation, Japan) against the central laboratory assay Singulex Erenna TnI assay (Singulex, USA). METHODS: Using the Markers in the Diagnosis of Acute Coronary Syndromes (MIDAS) study population, we evaluated the ability of three different assays to identify patients with acute myocardial infarction (AMI). The MIDAS dataset, described elsewhere, is a prospective multicenter dataset of emergency department (ED) patients with suspected acute coronary syndrome (ACS) and a planned objective myocardial perfusion evaluation. Myocardial infarction (MI) was diagnosed by central adjudication. RESULTS: The C-statistic with 95% confidence intervals (CI) for diagnosing MI by using a common population (n=241) was 0.95 (0.91-0.99), 0.95 (0.91-0.99), and 0.93 (0.89-0.97) for the Triage, Singulex, and PathFast assays, respectively. Of samples with detectable troponin, the absolute values had high Pearson (R(P)) and Spearman (R(S)) correlations and were R(P)=0.94 and R(S)=0.94 for Triage vs Singulex, R(P)=0.93 and R(S)=0.85 for Triage vs PathFast, and R(P)=0.89 and R(S)=0.73 for PathFast vs Singulex. CONCLUSIONS: In a single comparative population of ED patients with suspected ACS, the Triage Cardio3 TnI, PathFast, and Singulex TnI assays provided similar diagnostic performance for MI.
Acute Coronary Syndrome/*diagnosis ; Biomarkers/analysis ; Emergency Service, Hospital ; Humans ; Laboratories/standards ; Myocardial Infarction/diagnosis ; *Point-of-Care Systems ; Prospective Studies ; Reagent Kits, Diagnostic ; Sensitivity and Specificity ; Troponin I/*analysis

Objective: To determine the utility of a highly sensitive troponin assay when utilized in the emergency department. Methods The FAST-TRAC study prospectively enrolled >1,500 emergency department patients with suspected acute coronary syndrome within 6 hours of symptom onset and 2 hours of emergency department presentation. It has several unique features that are not found in the majority of studies evaluating troponin. These include a very early presenting population in whom prospective data collection of risk score parameters and the physician’s clinical impression of the probability of acute coronary syndrome before any troponin data were available. Furthermore, two gold standard diagnostic definitions were determined by a pair of cardiologists reviewing two separate data sets; one that included all local troponin testing results and a second that excluded troponin testing so that diagnosis was based solely on clinical grounds. By this method, a statistically valid head-to-head comparison of contemporary and high sensitivity troponin testing is obtainable. Finally, because of a significant delay in sample processing, a unique ability to define the molecular stability of various troponin assays is possible.Trial registration ClinicalTrials.gov Identifier NCT00880802

The Division of Cancer Prevention of the National Cancer Institute (NCI) and the Office of Disease Prevention of the National Institutes of Health co-sponsored the Translational Advances in Cancer Prevention Agent Development Meeting on August 27 to 28, 2020. The goals of this meeting were to foster the exchange of ideas and stimulate new collaborative interactions among leading cancer prevention researchers from basic and clinical research; highlight new and emerging trends in immunoprevention and chemoprevention as well as new information from clinical trials; and provide information to the extramural research community on the significant resources available from the NCI to promote prevention agent development and rapid translation to clinical trials. The meeting included two plenary talks and five sessions covering the range from pre-clinical studies with chemo/immunopreventive agents to ongoing cancer prevention clinical trials. In addition, two NCI informational sessions describing contract resources for the preclinical agent development and cooperative grants for the Cancer Prevention Clinical Trials Network were also presented.

The Division of Cancer Prevention of the National Cancer Institute (NCI) and the Office of Disease Prevention of the National Institutes of Health co-sponsored the Translational Advances in Cancer Prevention Agent Development Meeting on August 27 to 28, 2020. The goals of this meeting were to foster the exchange of ideas and stimulate new collaborative interactions among leading cancer prevention researchers from basic and clinical research; highlight new and emerging trends in immunoprevention and chemoprevention as well as new information from clinical trials; and provide information to the extramural research community on the significant resources available from the NCI to promote prevention agent development and rapid translation to clinical trials. The meeting included two plenary talks and five sessions covering the range from pre-clinical studies with chemo/immunopreventive agents to ongoing cancer prevention clinical trials. In addition, two NCI informational sessions describing contract resources for the preclinical agent development and cooperative grants for the Cancer Prevention Clinical Trials Network were also presented.