Publications

BACKGROUND AND STUDY AIMS

 Many studies have reported on laterally spreading tumors (LSTs), but systematic reviews of the data to determine their risk of containing submucosal invasion (SMI) are lacking. We systematically screened and analyzed the available literature to provide a more solid basis for evidence-based treatment.

METHODS

 We conducted a systematic search in PubMed, Embase, the Cochrane Library, and Scopus for published articles until July 2017. We estimated pooled prevalence or odds ratios (ORs) with 95 % confidence intervals (CIs), using random-effects models. We classified endoscopic subtypes into granular LST, which comprises the homogeneous and nodular mixed subtypes, and non-granular LST, which comprises the flat elevated and pseudodepressed subtypes.

RESULTS

 We identified 2949 studies, of which 48 were included. Overall, 8.5 % (95 %CI 6.5 % - 10.5 %) of LSTs contained SMI. The risk of SMI differed among the LST subtypes: 31.6 % in non-granular pseudodepressed LSTs (95 %CI 19.8 % - 43.4 %), 10.5 % in granular nodular mixed LSTs (95 %CI 5.9 % - 15.1 %), 4.9 % in non-granular flat elevated LSTs (95 %CI 2.1 % - 7.8 %), and 0.5 % in granular homogenous LSTs (95 %CI 0.1 % - 1.0 %). SMI was more common in distally rather than in proximally located LSTs (OR 2.50, 95 %CI 1.24 - 5.02). The proportion of SMI increased with lesion size (10 - 19 mm, 4.6 %; 20 - 29 mm, 9.2 %; ≥ 30 mm, 16.5 %). The pooled prevalence of patients with one or more LSTs in the general colonoscopy population was 0.8 % (95 %CI 0.6 % - 1.1 %).

CONCLUSION

 The majority of LSTs are non-invasive at the time of colonoscopic detection and can be treated with (piecemeal) endoscopic mucosal resection. Pretreatment diagnosis of endoscopic subtype, specifying areas of concern (nodule or depression), determines those LSTs at highest risk of containing SMI, where en bloc resection is the preferred therapy.

OBJECTIVE

We undertook this study of echocardiographic classification of diastolic function by three different algorithms to determine: (1) how frequently each algorithm classified patients and (2) how well the results agreed with one another.

BACKGROUND

Several algorithms exist to grade diastolic function (DF), the Mayo Clinic scheme of Redfield et al (Mayo 2003) and the 2 ASE guideline documents of 2009 and 2016 (ASE 2009 and ASE 2016).

METHODS

A total of 200 consecutive echocardiograms were retrospectively analyzed; mean age of patients 60.3 ± 3.5 years, 45% male. Echocardiograms were performed using Intersocietal Accreditation Commission guidelines. Diastolic function was assessed by Mayo 2003 and ASE 2009 and 2016. Coexisting conditions affecting DF analysis, such as mitral annular calcification (MAC), were tabulated. Data were compared using a paired t-test. Concordance between algorithms was assessed using the Kappa statistic.

RESULTS

A total of 117 of 200 studies (58.5%) were excluded for the presence of coexisting conditions (51.5%), poor image quality (2.5%), or incomplete data (4.5%). Thirty-three of the remaining 83 studies (40%) received the same grade of DF based on assessments made using the Mayo 2003 and ASE 2016 algorithms; the Kappa statistic was 0.20. 36 of the 83 studies (43%) received the same grade of DF based on assessments made using the ASE 2009 and ASE 2016 algorithms; the Kappa statistic was 0.25.

CONCLUSION

Assessment of diastolic function via echocardiography cannot be reliably accomplished in approximately 50% of patients using current guidelines. Further, when studies are suitable for assessment, widely used guidelines yield discordant results.

Research on disease causation often attempts to isolate the effects of individual factors, including individual genes or environmental factors. This reductionist approach has generated many discoveries, but misses important interactive and cumulative effects that may help explain the broad range of variability in disease occurrence observed across studies and individuals. A disease rarely results from a single factor, and instead results from a broader combination of factors, characterized here as intrinsic (I) and extrinsic (E) factors. Intrinsic vulnerability or resilience emanates from a variety of both fixed and shifting biological factors including genetic traits, while extrinsic factors comprise all biologically-relevant external stressors encountered across the lifespan. The I×E concept incorporates the multi-factorial and dynamic nature of health and disease and provides a unified, conceptual basis for integrating results from multiple areas of research, including genomics, G×E, developmental origins of health and disease, and the exposome. We describe the utility of the I×E concept to better understand and characterize the cumulative impact of multiple extrinsic and intrinsic factors on individual and population health. New research methods increasingly facilitate the measurement of multifactorial and interactive effects in epidemiological and toxicological studies. Tiered or indicator-based approaches can guide the selection of potentially relevant I and E factors for study and quantification, and exposomics methods may eventually produce results that can be used to generate a response function over the life course. Quantitative data on I×E interactive effects should generate a better understanding of the variability in human response to environmental factors. The proposed I×E concept highlights the role for broader study design in order to identify extrinsic and intrinsic factors amenable to interventions at the individual and population levels in order to enhance resilience, reduce vulnerability and improve health.

A diagnosis of brucellosis can be difficult because routine culture and serological methods exhibit variable sensitivity and specificity. We present the use of a metagenomic next- generation sequencing assay to diagnose a case of neurobrucellosis from cerebrospinal fluid, resulting in the institution of appropriate antibiotic treatment and a favorable clinical outcome.

BACKGROUND

Inflammation is associated with the downregulation of drug metabolizing enzymes and transporters. Thus, we investigated the chronic inflammatory state associated with HIV-infection as a source of pharmacokinetic variability of atazanavir. We also explored the association of total bilirubin concentrations with markers of inflammation and endothelial activation.

METHODS

Apparent oral clearance (CL/F) of atazanavir was estimated from plasma samples collected from participants in AIDS Clinical Trials Group Study A5202. Several inflammatory and endothelial activation biomarkers were measured at baseline and weeks 24 and 96 as part of metabolic sub-study A5224s: high-sensitivity C-reactive protein (hsCRP), interleukin-6, tumor necrosis factor alpha and its soluble receptors, soluble vascular cellular and intracellular adhesion molecules, and total bilirubin. Statistical analysis was performed by a matrix of correlation coefficients between atazanavir CL/F and biomarker concentrations measured at week 24. The correlation between atazanavir clearance and percentage change in bilirubin from baseline to weeks 24 and 96, and between biomarkers and bilirubin concentrations at each week were also evaluated.

RESULTS

Among 107 participants, there were no significant correlations observed between atazanavir CL/F and inflammatory and endothelial activation biomarkers measured at week 24 (P ≥ 0.24). As expected, bilirubin increased with increasing exposure to atazanavir (rho = - 0.25, P = 0.01). Bilirubin concentrations were inversely correlated (P < 0.01) with each of the biomarkers except hsCRP.

CONCLUSIONS

Atazanavir CL/F did not correlate with the inflammatory biomarkers changes. Inflammatory-mediated inhibition of cytochrome P450 3A may have been attenuated due to atazanavir-associated increases of bilirubin, which has known anti-inflammatory properties.