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  • 2018

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Article

Percutaneous, Thermal, and Pulsed Radiofrequency for Nonmalignant Hip Pain

by Anna Woodbury; G Kao; J Kalangara

2018

  • View Abstract

Abstract:Close

Background: Although radiofrequency (RF) has been used to treat several types of chronic osteoarthritic pain, the role of percutaneous thermal RF ablation and pulsed RF in treating nonmalignant hip pain has not been well established. Objective: To estimate the effectiveness of thermal and pulsed RF therapy in treating nonmalignant hip pain and encourage further research. Study Design: A systematic review of English and non-English articles was performed on 1/20/2017 using the following databases: PubMed (1960-2017), Cochrane Controlled Trials Register (1960-2017), and EMBASE (1966-2017). Studies for which complete articles were not accessible were excluded if primary authors could not be successfully contacted after attempts via at least 2 different mediums. Search terms included RF, hip, and human (“radiofrequency”[All Fields] AND (“hip”[MeSH Terms] AND “humans”[MeSH Terms]). Results: Two clinical trials for hip RF (n  =  32) and a collection of 7 case series or studies (n = 25) met our inclusion criteria. Both trials used percutaneous RF of the periarticular sensory branches of the obturator and femoral nerves near the hip joint. Ten studies were found to be eligible after screening title, abstract, and full text for inclusion and exclusion criteria. Both clinical trials saw improved post procedure pain scores when compared with standard conservative treatment for inoperable chronic hip pain. The overall complication rate of pooled cohort of all cases reviewed was 9.5% (6/57), but did not result in any self-reported injury. Conclusions: There is low quality evidence to suggest that thermal or pulsed RF therapy is a suitable option for chronic inoperable hip pain. Higher quality trials are needed for stronger recommendations.

Article

Bacterial vaginosis modifies the association between hormonal contraception and HIV acquisition

by Lisa Haddad; Kristin Wall; William Kilembe; Bellington Vwalika; Naw H. Khu; Ilene Brill; Elwyn Chomba; Amanda Tichacek; Susan A Allen

2018

Subjects
  • Health Sciences, Medicine and Surgery
  • Health Sciences, Public Health
  • Health Sciences, Epidemiology
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Objective: To examine bacterial vaginosis as an effect modifier for the association between hormonal contraception and incident HIV infection. Design: Serodiscordant couples enrolled in an open longitudinal cohort in Lusaka, Zambia from 1994 to 2012. This analysis was restricted to couples with an HIV-positive man enrolled between1994 and 2002 when a quarterly genital tract examination and HIV testing was performed. Methods: Multivariate Cox models evaluated the association between contraceptive method and HIV-acquisition, stratified by time-varying bacterial vaginosis status. Results: Among 564 couples contributing 1137.2 couple-years of observation, bacterial vaginosis was detected at 15.5% of study visits. Twenty-two of 106 seroconversions occurred during intervals after bacterial vaginosis was detected [12 on no method/nonhormonal method (nonhormonal contraception), two on injectables, eight on oral contraceptive pills (OCPs)]. Unadjusted seroincidence rates per 100 couple-years for nonhormonal contraception, injectable, and OCP users, respectively, during intervals with bacterial vaginosis were 8.3, 20.8, and 31.0 and during intervals without bacterial vaginosis were 8.2, 9.7, and 12.3. In the bacterial vaginosis-positive model, there was a significant increase in incident HIV among those using injectables (adjusted hazard ratio, aHR 6.55, 95% CI 1.14-37.77) and OCPs (aHR 5.20, 95% CI 1.68-16.06) compared with nonhormonal contraception. Hormonal contraception did not increase the hazard of HIV acquisition in bacterial vaginosis-negativ e models. These findings persisted in sensitivity analyses whenever all covariates from the nonstratified model previously published were included, whenever other genital tract findings were excluded from the model and with the addition of condom-less sex and sperm on wet-prep. Conclusion: Future research should consider a potential interaction with bacterial vaginosis whenever evaluating the impact of hormonal contraception on HIV acquisition.

Article

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

by Keith Delman; Dong Shin; Taofeek Owonikoko; Erwin Van Meir; Suresh Ramalingam; Jeffrey Olson; Daniel Brat; Amy Chen; Shishir Maithel; J Liu; T Lichtenberg; KA Hoadley; LM Poisson; AJ Lazar; AD Cherniack; AJ Kovatich; CC Benz; DA Levine; AV Lee; L Omberg; DM Wolf; CD Shriver; V Thorsson

2018

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For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types.

Article

Chronic kidney disease attenuates the plasma metabolome response to insulin.

by Baback Roshanravan; Leila R. Zelnick; Daniel Djucovic; Haiwei Gu; Jessica A. Alvarez; Thomas R Ziegler; Jorge L. Gamboa; Kristina Utzschneider; Bryan Kestenbaum; Jonathan Himmelfarb; Steven E. Kahn; Daniel Raftery; Ian H. de Boer

2018

Subjects
  • Health Sciences, Nutrition
  • Health Sciences, Pharmacology
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Chronic kidney disease (CKD) leads to decreased sensitivity to the metabolic effects of insulin, contributing to protein energy wasting and muscle atrophy. Targeted metabolomics profiling during hyperinsulinemic-euglycemic insulin clamp testing may help identify aberrant metabolic pathways contributing to insulin resistance in CKD. Using targeted metabolomics profiling, we examined the plasma metabolome in 95 adults without diabetes in the fasted state (58 with CKD, 37 with normal glomerular filtration rate [GFR]) who underwent hyperinsulinemic-euglycemic clamp. We assessed heterogeneity in fasting metabolites and the response to insulin to identify potential metabolic pathways linking CKD with insulin resistance. Baseline differences and effect modification by CKD status on changes with insulin clamp testing were adjusted for confounders. Mean GFR among participants with CKD was 37.3 compared with 89.3 ml/min per 1.73 m2 among controls. Fasted-state differences between CKD and controls included abnormalities in tryptophan metabolism, ubiquinone biosynthesis, and the TCA cycle. Insulin infusion markedly decreased metabolite levels, predominantly amino acids and their metabolites. CKD was associated with attenuated insulin-induced changes in nicotinamide, arachidonic acid, and glutamine/glutamate metabolic pathways. Metabolomics profiling suggests disruption in amino acid metabolism and mitochondrial function as putative manifestations or mechanisms of the impaired anabolic effects of insulin in CKD.

Article

A DNA methylation biomarker of alcohol consumption

by C Liu; RE Marioni; AK Hedman; L Pfeiffer; P-C Tsai; LM Reynolds; AC Just; Q Duan; CG Boer; T Tanaka; CE Elks; S Aslibekyan; JA Brody; B Kuehnel; C Herder; Lynn Almli; D Zhi; Y Wang; T Huan; C Yao; MM Mendelson; R Joehanes; L Liang; S-A Love; W Guan; S Shah; AF Mcrae; A Kretschmer; H Prokisch; K Strauch; A Peters; PM Visscher; NR Wray; X Guo; KL Wiggins; Alicia K Smith; EB Binder; Kerry Ressler; MR Irvin; DM Absher; D Hernandez; L Ferrucci; S Bandinelli; K Lohman; J Ding; L Trevisi; S Gustafsson; JH Sandling; L Stolk; AG Uitterlinden; I Yet; JE Castillo-Fernandez; TD Spector; JD Schwartz; P Vokonas; L Lind; Y Li; M Fornage; DK Arnett; NJ Wareham; N Sotoodehnia; KK Ong; JBJ van Meurs; Karen N Conneely; AA Baccarelli; IJ Deary; JT Bell; KE North; Y Liu; M Waldenberger; SJ London; E Ingelsson; D Levy

2018

Subjects
  • Health Sciences, Epidemiology
  • Health Sciences, Public Health
  • Biology, Genetics
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The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (n total = 13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n = 6926) and identified 144 CpGs that provided substantial discrimination (area under the curve = 0.90-0.99) for current heavy alcohol intake (≥42 g per day in men and ≥28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted P < 1×10 -7 . Analysis of the monocyte-derived DNA (n = 1251) identified 62 alcohol-related CpGs at P < 1×10 -7 . In whole-blood samples of people of European ancestry, we detected differential methylation in two neurotransmitter receptor genes, the γ-Aminobutyric acid-A receptor delta and γ-aminobutyric acid B receptor subunit 1; their differential methylation was associated with expression levels of a number of genes involved in immune function. In conclusion, we have identified a robust alcohol-related DNA methylation signature and shown the potential utility of DNA methylation as a clinically useful diagnostic test to detect current heavy alcohol consumption.

Conference

Association between one-carbon metabolism indices and DNA methylation status in maternal and cord blood

by Alicia Smith; Anna Knight; H Park; DB Hausman; JM Fleming; VL Bland; G Rosa; EM Kennedy; MA Caudill; O Malysheva; GPA Kauwell; A Sokolow; S Fisher; LB Bailey

2018-11-15

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© 2018, The Author(s). One-carbon metabolism is essential for multiple cellular processes and can be assessed by the concentration of folate metabolites in the blood. One-carbon metabolites serve as methyl donors that are required for epigenetic regulation. Deficiencies in these metabolites are associated with a variety of poor health outcomes, including adverse pregnancy complications. DNA methylation is known to vary with one-carbon metabolite concentration, and therefore may modulate the risk of adverse pregnancy outcomes. This study addresses changes in one-carbon indices over pregnancy and the relationship between maternal and child DNA methylation and metabolite concentrations by leveraging data from 24 mother-infant dyads. Five of the 13 metabolites measured from maternal blood and methylation levels of 993 CpG sites changed over the course of pregnancy. In dyads, maternal and fetal one-carbon concentrations were highly correlated, both early in pregnancy and at delivery. The 993 CpG sites whose methylation levels changed over pregnancy in maternal blood were also investigated for associations with metabolite concentrations in infant blood at delivery, where five CpG sites were associated with the concentration of at least one metabolite. Identification of CpG sites that change over pregnancy may result in better characterization of genes and pathways involved in maintaining a healthy, term pregnancy.

Article

Recent advances in the genomics and therapy of BCR/ABL1-positive and -negative chronic myeloproliferative neoplasms

by Tariq I. Mughal; Jason Gotlib; Ruben Mesa; Steffen Koschmieder; Hanna Khoury; Jorge E Cortes; Tiziano Barbui; Rüdiger Hehlmann; Michael Mauro; Susanne Saussele; Jerald P. Radich; Richard A. Van Etten; Giuseppe Saglio; Srdnan Verstovek; Robert Peter Gale; Omar Abdel-Wahab

2018

Subjects
  • Health Sciences, Oncology
  • Health Sciences, Medicine and Surgery
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This review is based on the presentations and deliberations at the 7th John Goldman Chronic Myeloid Leukemia (CML) and Myeloproliferative Neoplasms (MPN) Colloquium which took place in Estoril, Portugal on the 15th October 2017, and the 11th post-ASH International Workshop on CML and MPN which took place on the 6th-7th December 2016, immediately after the 58th American Society of Hematology Annual Meeting. Rather than present a resume of the proceedings, we have elected to address some of the topical translational research and clinically relevant topics in greater detail. We address recent updates in the genetics and epigenetics of MPN, the mechanisms of transformation by mutant calreticulin, advances in the biology and therapy of systemic mastocytosis, clinical updates on JAK2 inhibitors and other therapeutic approaches for patients with MPNs, cardiovascular toxicity related to tyrosine kinase inhibitors and the concept of treatment-free remission for patients with CML.

Article

Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci

by Taj Azarian; Patrick K. Mitchell; Maria Georgieva; Claudette M. Thompson; Amel Ghouila; Andrew J. Pollard; Anne von Gottberg; Mignon du Plessis; Martin Antonio; Brenda A. Kwambana-Adams; Stuart C. Clarke; Dean Everett; Jennifer Cornick; Ewa Sadowy; Waleria Hryniewicz; Anna Skoczynska; Jennifer C. Moisi; Lesley McGee; Bernard Beail; Benjamin J. Metcalf; Robert Breiman; P.L. Ho; Raymond Reid; Katherine L. O'Brien; Rebecca A. Gladstone; Stephen D. Bentley; William P. Hanage

2018

Subjects
  • Biology, Microbiology
  • Biology, Virology
  • Biology, Parasitology
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Streptococcus pneumoniae serotype 3 remains a significant cause of morbidity and mortality worldwide, despite inclusion in the 13-valent pneumococcal conjugate vaccine (PCV13). Serotype 3 increased in carriage since the implementation of PCV13 in the USA, while invasive disease rates remain unchanged. We investigated the persistence of serotype 3 in carriage and disease, through genomic analyses of a global sample of 301 serotype 3 isolates of the Netherlands 3 –31 (PMEN31) clone CC180, combined with associated patient data and PCV utilization among countries of isolate collection. We assessed phenotypic variation between dominant clades in capsule charge (zeta potential), capsular polysaccharide shedding, and susceptibility to opsonophagocytic killing, which have previously been associated with carriage duration, invasiveness, and vaccine escape. We identified a recent shift in the CC180 population attributed to a lineage termed Clade II, which was estimated by Bayesian coalescent analysis to have first appeared in 1968 [95% HPD: 1939–1989] and increased in prevalence and effective population size thereafter. Clade II isolates are divergent from the pre-PCV13 serotype 3 population in non-capsular antigenic composition, competence, and antibiotic susceptibility, the last of which resulting from the acquisition of a Tn916-like conjugative transposon. Differences in recombination rates among clades correlated with variations in the ATP-binding subunit of Clp protease, as well as amino acid substitutions in the comCDE operon. Opsonophagocytic killing assays elucidated the low observed efficacy of PCV13 against serotype 3. Variation in PCV13 use among sampled countries was not independently correlated with the CC180 population shift; therefore, genotypic and phenotypic differences in protein antigens and, in particular, antibiotic resistance may have contributed to the increase of Clade II. Our analysis emphasizes the need for routine, representative sampling of isolates from disperse geographic regions, including historically under-sampled areas. We also highlight the value of genomics in resolving antigenic and epidemiological variations within a serotype, which may have implications for future vaccine development.

Article

Breech at the Border: An Atypical Case of Invasive Haemophilus influenzae in a Patient on a Novel Immunotherapeutic

by Jessica Howard-Anderson; Sarah Satola; Matthew Collins

2018

Subjects
  • Health Sciences, Immunology
  • Biology, Microbiology
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Haemophilus influenzae rarely causes pyogenic infections in the female genital tract, and even less commonly does this lead to systemic infections. Novel monoclonal antibody therapies targeting interleukin-17 may impair mucosal immunity, but increased risk for H. influenzae infections has not been documented. Here, we describe a case of H. influenzae bacteremia associated with pyosalpinx and hypothesize that immunomodulatory treatment for psoriasis predisposed our patient to this infection.

Article

Meningitis outbreak investigation in Nkoranza South Municipality in Brong Ahafo Region, Ghana, February, 2016

by Ernest Konadu Asiedu; Kofi Mensah Nyarko; Ernest Kenu; Edwin Andrew Afari; Joseph Asamoah Frimpong; Meeyoung Mattie Park; Scott McNabb; Florence Nzilanye Iddrisah

2018

Subjects
  • Health Sciences, Epidemiology
  • Health Sciences, Public Health
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The occurrence of communicable diseases highlights the need to have well-trained field epidemiologists at the forefront in the fight against these diseases, especially during an outbreak. Training for outbreak investigation is most effective when participants can develop their competencies in a practical exercise. This is a simulation of the steps in meningitis outbreak investigation conducted in Ghana in February 2016 by Ghana Field Epidemiology Training Programme (FELTP) residents and the public health technical team of the Nkoranza South Municipality as a field epidemiologist. This case study is suited to reinforce principles and skills already covered in a lecture or in background reading by providing a practical training beyond the scope of theoretical learning. It is primarily intended for training novice public health practitioners who should be able to complete the exercises in 3 hours.
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