Citations

Abstract Background: The gut metabolome may be associated with the incidence and progression of numerous diseases. The composition of the gut metabolome can be captured by measuring metabolite levels in the feces. However, there are little data describing the effect of fecal sample collection methods on metabolomic measures. Methods: We collected fecal samples from 18 volunteers using four methods: no solution, 95% ethanol, fecal occult blood test (FOBT) cards, and fecal immunochemical test (FIT). One set of samples was frozen after collection (day 0), and for 95% ethanol, FOBT, and FIT, a second set was frozen after 96 hours at room temperature. We evaluated (i) technical reproducibility within sample replicates, (ii) stability after 96 hours at room temperature for 95% ethanol, FOBT, and FIT, and (iii) concordance of metabolite measures with the putative “gold standard,” day 0 samples without solution. Results: Intraclass correlation coefficients (ICC) estimating technical reproducibility were high for replicate samples for each collection method. ICCs estimating stability at room temperature were high for 95% ethanol and FOBT (median ICC > 0.87) but not FIT (median ICC = 0.52). Similarly, Spearman correlation coefficients (rs) estimating metabolite concordance with the “gold standard” were higher for 95% ethanol (median rs = 0.82) and FOBT (median rs = 0.70) than for FIT (median rs = 0.40). Conclusions: Metabolomic measurements appear reproducible and stable in fecal samples collected with 95% ethanol or FOBT. Concordance with the “gold standard” is highest with 95% ethanol and acceptable with FOBT. Impact: Future epidemiologic studies should collect feces using 95% ethanol or FOBT if interested in studying fecal metabolomics. Cancer Epidemiol Biomarkers Prev; 25(11); 1483–90. ©2016 AACR.

Abstract BACKGROUND Current recommendations for screening for monoclonal gammopathies include serum protein electrophoresis (PEL), imunofixation electrophoresis (IFE), and free light chain (FLC) ratios to identify or rule out an M-protein. The aim of this study was to examine the feasibility of an assay based on immunoenrichment and MALDI-TOF-MS (MASS-SCREEN) to qualitatively screen for M-proteins. METHODS Serum from 556 patients previously screened for M-proteins by PEL and IFE were immunopurified using a κ/λ-specific nanobody bead mixture. Following purification, light chains (LC) were released from their heavy chains by reduction. MALDI-TOF analysis was performed and the mass-to-charge LC distributions were visually examined for the presence of an M-protein by both unblinded and blinded analysts. RESULTS In unblinded analysis, MASS-SCREEN detected 100% of the PEL-positive samples with an analytical sensitivity and specificity of 96% and 81% using IFE positivity as the standard. In a blinded analysis using 6 different laboratory personnel, consensus was reached in 92% of the samples. Overall analytical sensitivity and specificity were reduced to 92% and 80%, respectively. FLC ratios were found to be abnormal in 28% of MASS-SCREEN–negative samples, suggesting FLC measurements need to be considered in screening. CONCLUSIONS MASS-SCREEN could replace PEL in a panel that would include FLC measurements. Further studies and method development should be performed to validate the clinical sensitivity and specificity and to determine if this panel will suffice as a general screen for monoclonal proteins.

ABSTRACT Cellular senescence is a fundamental mechanism by which cells remain metabolically active yet cease dividing and undergo distinct phenotypic alterations, including upregulation of p16Ink4a, profound secretome changes, telomere shortening, and decondensation of pericentromeric satellite DNA. Because senescent cells accumulate in multiple tissues with aging, these cells and the dysfunctional factors they secrete, termed the senescence-associated secretory phenotype (SASP), are increasingly recognized as promising therapeutic targets to prevent age-related degenerative pathologies, including osteoporosis. However, the cell type(s) within the bone microenvironment that undergoes senescence with aging in vivo has remained poorly understood, largely because previous studies have focused on senescence in cultured cells. Thus in young (age 6 months) and old (age 24 months) mice, we measured senescence and SASP markers in vivo in highly enriched cell populations, all rapidly isolated from bone/marrow without in vitro culture. In both females and males, p16Ink4a expression by real-time quantitative polymerase chain reaction (rt-qPCR) was significantly higher with aging in B cells, T cells, myeloid cells, osteoblast progenitors, osteoblasts, and osteocytes. Further, in vivo quantification of senescence-associated distension of satellites (SADS), ie, large-scale unraveling of pericentromeric satellite DNA, revealed significantly more senescent osteocytes in old compared with young bone cortices (11% versus 2%, p < 0.001). In addition, primary osteocytes from old mice had sixfold more (p < 0.001) telomere dysfunction-induced foci (TIFs) than osteocytes from young mice. Corresponding with the age-associated accumulation of senescent osteocytes was significantly higher expression of multiple SASP markers in osteocytes from old versus young mice, several of which also showed dramatic age-associated upregulation in myeloid cells. These data show that with aging, a subset of cells of various lineages within the bone microenvironment become senescent, although senescent myeloid cells and senescent osteocytes predominantly develop the SASP. Given the critical roles of osteocytes in orchestrating bone remodeling, our findings suggest that senescent osteocytes and their SASP may contribute to age-related bone loss. © 2016 American Society for Bone and Mineral Research

The concept of optimizing health care by understanding and generating knowledge from previous evidence, ie, the Learning Health-care System (LHS), has gained momentum and now has national prominence. Meanwhile, the rapid adoption of electronic health records (EHRs) enables the data collection required to form the basis for facilitating LHS. A prerequisite for using EHR data within the LHS is an infrastructure that enables access to EHR data longitudinally for health-care analytics and real time for knowledge delivery. Additionally, significant clinical information is embedded in the free text, making natural language processing (NLP) an essential component in implementing an LHS. Herein, we share our institutional implementation of a big data-empowered clinical NLP infrastructure, which not only enables health-care analytics but also has real-time NLP processing capability. The infrastructure has been utilized for multiple institutional projects including the MayoExpertAdvisor, an individualized care recommendation solution for clinical care. We compared the advantages of big data over two other environments. Big data infrastructure significantly outperformed other infrastructure in terms of computing speed, demonstrating its value in making the LHS a possibility in the near future.

Venous thromboembolism (VTE), encompassing pulmonary embolism (PE) and deep venous thrombosis (DVT), is a major cause of morbidity and mortality of particular relevance for intensivists and hospitalists. Acute VTE is usually managed with parenteral unfractionated heparin or low-molecular-weight heparin, followed by an oral vitamin K antagonist. Data are lacking for optimal treatment of less common occurrences, such as upper extremity DVT, and for approaches such as thrombolysis for PE associated with early signs of hemodynamic compromise or inferior vena cava filters when anticoagulation is contraindicated. Direct oral anticoagulants (DOACs) including apixaban, dabigatran, edoxaban, and rivaroxaban are now added to the armamentarium of agents available for acute management of VTE and/or reducing the risk of recurrence. This review outlines an algorithmic approach to acute VTE treatment: from aggressive therapies when anticoagulation may be inadequate, to alternative choices when anticoagulation is contraindicated, to anticoagulant options in the majority of patients in whom anticoagulation is appropriate. Evidence-based guidelines and the most recent DOAC clinical trial data are discussed in the context of the standard of care. Situations and treatment approaches for which data are unavailable or insufficient are identified. VTE therapy in care transitions is discussed, as are choices for secondary prevention.

Objectives/HypothesisTo present an overview of the barriers to the implementation of clinical practice guidelines (CPGs) in thyroid cancer management and to introduce a computer‐based clinical support system.Data SourcesPubMed.Review Methods: A review of studies on adherence to CPGs was conducted.ResultsAwareness and adoption of CPGs is low in thyroid cancer management. Barriers to implementation include unfamiliarity with the CPGs and financial concerns. Effective interventions to improve adherence are possible, especially when they are readily accessible at the point of care delivery. Computerized clinical support systems show particular promise. The authors introduce the clinical decision making modules (CDMMs) of the Thyroid Cancer Care Collaborative, a thyroid cancer‐specific electronic health record. These computer‐based modules can assist clinicians with implementation of these recommendations in clinical practice.ConclusionComputer‐based support systems can help clinicians understand and adopt the thyroid cancer CPGs. By integrating patient characteristics and guidelines at the point of care delivery, the CDMMs can improve adherence to the guidelines and help clinicians provide high‐quality, evidence‐based, and individualized patient care in the management of differentiated thyroid cancer. Laryngoscope, 126:2640–2645, 2016

This study was undertaken to determine the impact of shared decision-making when selecting a sedation option, from no sedation (local anesthetic), minimal sedation (anxiolysis with a benzodiazepine) or moderate sedation (benzodiazepine and opiate), for venous access device placement (port-a-cath and tunneled catheters) on patient choice, satisfaction and recovery time. This is an IRB-approved, HIPPA-compliant, retrospective study of 198 patients (18–85 years old, 60% female) presenting to an ambulatory vascular interventional radiology department for venous access device placement between 22 October 2014 and 7 October 2015. Patients were educated about sedation options and given the choice of undergoing the procedure with no sedation (local anesthetic only), or minimal or moderate sedation. Satisfaction was assessed through three survey questions. No sedation was selected by 53/198 (27%), minimal sedation by 71/198 (36%) and moderate sedation by 74/198 (37%). All subjects would recommend the option to another patient and valued the opportunity to select a sedation option. Post-procedure recovery time differences were statistically significant ( p<0.0001) with median recovery times of 0 minutes for no sedation, 38 minutes for minimal sedation and 64 minutes for moderate sedation. In conclusion, patient sedation preference for venous access device placement is variable, signifying there is a role for shared decision-making as it empowers the patient to select the option most aligned with his or her goals. The procedure is well-tolerated, associated with high satisfaction, and the impact on departmental flow is notable because patients choosing no or minimal sedation results in a decreased post-procedure recovery time burden.