Efficacy of needle-placement technique in radiofrequency ablation for treatment of lumbar facet arthropathy.

BACKGROUND:Many studies have assessed the efficacy of radiofrequency ablation to denervate the facet joint as an interventional means of treating axial low-back pain. In these studies, varying procedural techniques were utilized to ablate the nerves that innervate the facet joints. To date, no comparison studies have been performed to suggest superiority of one technique or even compare the prevalence of side effects and complications. MATERIALS AND METHODS:A retrospective chart review was performed on patients who underwent a lumbar facet denervation procedure. Each patient's chart was analyzed for treatment technique (early versus advanced Australian), preprocedural visual numeric scale (VNS) score, postprocedural VNS score, duration of pain relief, and complications. RESULTS:Pre- and postprocedural VNS scores and change in VNS score between the two groups showed no significant differences. Patient-reported benefit and duration of relief was greater in the advanced Australian technique group (P=0.012 and 0.022, respectively). The advanced Australian technique group demonstrated a significantly greater median duration of relief (4 months versus 1.5 months, P=0.022). Male sex and no pain-medication use at baseline were associated with decreased postablation VNS scores, while increasing age and higher preablation VNS scores were associated with increased postablation VNS scores. Despite increasing age being associated with increased postablation VNS scores, age and the advanced Australian technique were found to confer greater patient self-reported treatment benefit. CONCLUSION:The advanced Australian technique provides a significant benefit over the early Australian technique for the treatment of lumbar facet pain, both in magnitude and duration of pain relief

An online database for brain disease research

BACKGROUND: The Stanley Medical Research Institute online genomics database (SMRIDB) is a comprehensive web-based system for understanding the genetic effects of human brain disease (i.e. bipolar, schizophrenia, and depression). This database contains fully annotated clinical metadata and gene expression patterns generated within 12 controlled studies across 6 different microarray platforms. DESCRIPTION: A thorough collection of gene expression summaries are provided, inclusive of patient demographics, disease subclasses, regulated biological pathways, and functional classifications. CONCLUSION: The combination of database content, structure, and query speed offers researchers an efficient tool for data mining of brain disease complete with information such as: cross-platform comparisons, biomarkers elucidation for target discovery, and lifestyle/demographic associations to brain diseases

Association of serum markers with improvement in clinical response measures after treatment with golimumab in patients with active rheumatoid arthritis despite receiving methotrexate: results from the GO-FORWARD study

Abstract Introduction The goal of this study was to identify serum markers that are modulated by treatment with golimumab with or without methotrexate (MTX) and are associated with clinical response. Methods Sera were collected at weeks 0 and 4 from a total of 336 patients (training dataset, n = 100; test dataset, n = 236) from the GO-FORWARD study of patients with active rheumatoid arthritis despite MTX. Patients were randomly assigned to receive placebo plus MTX; golimumab, 100 mg plus placebo; golimumab, 50 mg plus MTX; or golimumab, 100 mg plus MTX. Subcutaneous injections were administered every 4 weeks. Samples were tested for select inflammatory, bone, and cartilage markers and for protein profiling using multianalyte profiles. Results Treatment with golimumab with or without MTX resulted in significant decreases in a variety of serum proteins at week 4 as compared with placebo plus MTX. The American College of Rheumatology (ACR) 20, ACR 50, and Disease Activity Score (DAS) 28 responders showed a distinct biomarker profile compared with nonresponding patients. Conclusions ACR 20 and ACR 50 responders among the golimumab/golimumab + MTX-treated patients had a distinct change from baseline to week 4 in serum protein profile as compared with nonresponders. Some of these changed markers were also associated with multiple clinical response measures and improvement in outcome measures in golimumab/golimumab + MTX-treated patients. Although the positive and negative predictive values of the panel of markers were modest, they were stronger than C-reactive protein alone in predicting clinical response to golimumab. Trial registration http://ClinicalTrials.gov identification number: NCT00264550

Serum markers associated with clinical improvement in patients with ankylosing spondylitis treated with golimumab

Pathophysiology and treatment of rheumatic disease

Nocturia as an Unrecognized Symptom of Uncontrolled Hypertension in Black Men Aged 35 to 49 Years.

Background Hypertension is assumed to be asymptomatic. Yet, clinically significant nocturia (≥2 nightly voids) constitutes a putative symptom of uncontrolled hypertension. Black men with hypertension may be prone to nocturia because of blunted nocturnal blood pressure ( BP ) dipping, diuretic drug use for hypertension, and comorbidity that predisposes to nocturia. Here, we test the hypothesis that nocturia is a common and potentially reversible symptom of uncontrolled hypertension in black men. Methods and Results We determined the strength of association between nocturia (≥2 nightly voids) and high BP (≥135/85 mm Hg) by conducting in-person health interviews and measuring BP with an automated monitor in a large community-based sample of black men in their barbershops. Because nocturia is prevalent and steeply age-dependent after age 50 years, we studied men aged 35 to 49 years. Among 1673 black men (mean age, 43±4 years [ SD ]), those with hypertension were 56% more likely than men with normotension to have nocturia after adjustment for diabetes mellitus and sleep apnea (adjusted odds ratio, 1.56; 95% CI , 1.25-1.94 [ P<0.0001]). Nocturia prevalence varied by hypertension status, ranging from 24% in men with normotension to 49% in men whose hypertension was medically treated but uncontrolled. Men with untreated hypertension were 39% more likely than men with normotension to report nocturia ( P=0.02), whereas men whose hypertension was treated and controlled were no more likely than men with normotension to report nocturia ( P=0.69). Conclusions Uncontrolled hypertension was an independent determinant of clinically important nocturia in a large cross-sectional community-based study of non-Hispanic black men aged 35 to 49 years. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unqiue identifier: NCT 02321618

A whole blood gene expression-based signature for smoking status

BACKGROUND: Smoking is the leading cause of preventable death worldwide and has been shown to increase the risk of multiple diseases including coronary artery disease (CAD). We sought to identify genes whose levels of expression in whole blood correlate with self-reported smoking status. METHODS: Microarrays were used to identify gene expression changes in whole blood which correlated with self-reported smoking status; a set of significant genes from the microarray analysis were validated by qRT-PCR in an independent set of subjects. Stepwise forward logistic regression was performed using the qRT-PCR data to create a predictive model whose performance was validated in an independent set of subjects and compared to cotinine, a nicotine metabolite. RESULTS: Microarray analysis of whole blood RNA from 209 PREDICT subjects (41 current smokers, 4 quit ≤ 2 months, 64 quit > 2 months, 100 never smoked; NCT00500617) identified 4214 genes significantly correlated with self-reported smoking status. qRT-PCR was performed on 1,071 PREDICT subjects across 256 microarray genes significantly correlated with smoking or CAD. A five gene (CLDND1, LRRN3, MUC1, GOPC, LEF1) predictive model, derived from the qRT-PCR data using stepwise forward logistic regression, had a cross-validated mean AUC of 0.93 (sensitivity=0.78; specificity=0.95), and was validated using 180 independent PREDICT subjects (AUC=0.82, CI 0.69-0.94; sensitivity=0.63; specificity=0.94). Plasma from the 180 validation subjects was used to assess levels of cotinine; a model using a threshold of 10 ng/ml cotinine resulted in an AUC of 0.89 (CI 0.81-0.97; sensitivity=0.81; specificity=0.97; kappa with expression model = 0.53). CONCLUSION: We have constructed and validated a whole blood gene expression score for the evaluation of smoking status, demonstrating that clinical and environmental factors contributing to cardiovascular disease risk can be assessed by gene expression

Gene Expression Profiling of Bronchoalveolar Lavage Cells Preceding a Clinical Diagnosis of Chronic Lung Allograft Dysfunction.

BackgroundChronic Lung Allograft Dysfunction (CLAD) is the main limitation to long-term survival after lung transplantation. Although CLAD is usually not responsive to treatment, earlier identification may improve treatment prospects.MethodsIn a nested case control study, 1-year post transplant surveillance bronchoalveolar lavage (BAL) fluid samples were obtained from incipient CLAD (n = 9) and CLAD free (n = 8) lung transplant recipients. Incipient CLAD cases were diagnosed with CLAD within 2 years, while controls were free from CLAD for at least 4 years following bronchoscopy. Transcription profiles in the BAL cell pellets were assayed with the HG-U133 Plus 2.0 microarray (Affymetrix). Differential gene expression analysis, based on an absolute fold change (incipient CLAD vs no CLAD) >2.0 and an unadjusted p-value ≤0.05, generated a candidate list containing 55 differentially expressed probe sets (51 up-regulated, 4 down-regulated).ResultsThe cell pellets in incipient CLAD cases were skewed toward immune response pathways, dominated by genes related to recruitment, retention, activation and proliferation of cytotoxic lymphocytes (CD8+ T-cells and natural killer cells). Both hierarchical clustering and a supervised machine learning tool were able to correctly categorize most samples (82.3% and 94.1% respectively) into incipient CLAD and CLAD-free categories.ConclusionsThese findings suggest that a pathobiology, similar to AR, precedes a clinical diagnosis of CLAD. A larger prospective investigation of the BAL cell pellet transcriptome as a biomarker for CLAD risk stratification is warranted

An Unorthodox Introduction to QCD

These are lecture notes presented at the 2017 CTEQ Summer School at the University of Pittsburgh and the 2018 CTEQ Summer School at the University of Puerto Rico, Mayaguez. The title is a reference to hep-th/0309149 and introduces perturbative QCD and its application to jet substructure from a bottom-up perspective based on the approximation of QCD as a weakly-coupled, conformal field theory. Using this approach, a simple derivation of the Sudakov form factor with soft gluon emission modeled as a Poisson process is presented. Topics of the identification and discrimination of quark- versus gluon-initiated jets and jet grooming are also discussed.Comment: 16 pages, 18 figures. Comments welcome!, v2: updated to include both lectures from the 2018 CTEQ schoo

Smoking Enhances Risk for New External Genital Warts in Men

Repeat episodes of HPV-related external genital warts reflect recurring or new infections. No study before has been sufficiently powered to delineate how tobacco use, prior history of EGWs and HIV infection affect the risk for new EGWs. Behavioral, laboratory and examination data for 2,835 Multicenter AIDS Cohort Study participants examined at 21,519 semi-annual visits were evaluated. Fourteen percent (391/2835) of men reported or were diagnosed with EGWs at 3% (675/21,519) of study visits. Multivariate analyses showed smoking, prior episodes of EGWs, HIV infection and CD4+ T-lymphocyte count among the infected, each differentially influenced the risk for new EGWs