A novel host-protein assay outperforms routine parameters for distinguishing between bacterial and viral lower respiratory tract infections

Bacterial and viral lower respiratory tract infections (LRTIs) are often clinically indistinguishable, leading to antibiotic overuse. We compared the diagnostic accuracy of a new assay that combines 3 host-biomarkers (TRAIL, IP-10, CRP) with parameters in routine use to distinguish bacterial from viral LRTIs. Study cohort included 184 potentially eligible pediatric and adult patients. Reference standard diagnosis was based on adjudication by an expert panel following comprehensive clinical and laboratory investigation (including respiratory PCRs). Experts were blinded to assay results and assay performers were blinded to reference standard outcomes. Evaluated cohort included 88 bacterial and 36 viral patients (23 did not fulfill inclusion criteria; 37 had indeterminate reference standard outcome). Assay distinguished bacterial from viral LRTI patients with sensitivity of 0.93 ± 0.06 and specificity of 0.91 ± 0.09, outperforming routine parameters, including WBC, CRP and chest x-ray signs. These findings support the assay's potential to help clinicians avoid missing bacterial LRTIs or overusing antibiotics.     

TIP60-miR-22 axis as a prognostic marker of breast cancer progression

MicroRNAs (miRNAs) are 22- to 24-nucleotide, small, non-coding RNAs that bind to the 3′UTR of target genes to control gene expression. Consequently, their dysregulation contributes to many diseases, including diabetes and cancer. miR-22 is up-regulated in numerous metastatic cancers and recent studies have suggested a role for miR-22 in promoting stemness and metastasis. TIP60 is a lysine acetyl-transferase reported to be down-regulated in cancer but the molecular mechanism of this reduction is still unclear. In this study, we identify TIP60 as a target of miR-22. We show a negative correlation in the expression of TIP60 and miR-22 in breast cancer patients, and show that low levels of TIP60 and high levels of miR-22 are associated with poor overall survival. Furthermore, pathway analysis using high miR-22/low TIP60 and low miR-22/high TIP60 breast cancer patient datasets suggests association of TIP60/miR-22 with epithelial-mesenchymal transition (EMT), a key alteration in progression of cancer cells. We show that blocking endogenous miR-22 can restore TIP60 levels, which in turn decreases the migration and invasion capacity of metastatic breast cancer cell line. These results provide mechanistic insight into TIP60 regulation and evidence for the utility of the combination of TIP60 and miR-22 as prognostic indicator of breast cancer progression.     

Contrast‐Enhanced Echocardiographic Evaluation of a Giant Saphenous Vein Graft Aneurysm

A 61‐year‐old man presented with unstable angina 16 years after undergoing coronary artery bypass grafting with a left internal mammary artery graft to the left anterior descending coronary artery and a sequential saphenous vein graft (SVG) to the right coronary artery and an obtuse marginal branch. Transthoracic echocardiography (TTE) with a Philips iE33 machine and an S5 transducer revealed a 5.3 cm × 4.6 cm mass with a central echolucent area, surrounded by a peripheral zone of increased echodensity adjacent to, and partially compressing, the right atrium. Contrast echocardiography following an intravenous bolus injection of Definity revealed late appearance of contrast within the mass consistent with a giant SVG aneurysm. Coronary artery bypass graft angiography revealed a giant aneurysm in the SVG proximal to the RCA anastomosis; the distal limb of the graft to the obtuse marginal branch was occluded. Under intravascular ultrasound guidance, a 7‐mm spider filter was placed in the distal graft; then, a 6 mm × 10 cm Viabahn self‐expanding nitinol polyethylene terephthalate‐covered stent was deployed in the SVG with good seal zones proximally and distally. A follow‐up contrast‐enhanced transthoracic echocardiogram 1 day postprocedure revealed partial thrombosis of the aneurysm cavity. Ultrasound contrast did not appear in the aneurysm following intravenous injection, consistent with complete exclusion from the systemic circulation. This is the first report demonstrating feasibility of contrast‐enhanced transthoracic echocardiography for the diagnosis of SVG aneurysm and confirming procedural success by documenting exclusion from the systemic circulation following intervention.     

Rising Proportion of Young Individuals With Rectal and Colon Cancer

Background

Recent trends have identified increasing number of young individuals with rectal and colon cancers. These individuals, who are younger than 50 years old, in most instances would not meet screening guidelines. We aimed to report the characteristics and trend of the rising proportion of young individuals being diagnosed with rectal and colon cancers at our institutions.

A Flexible Urban Health Index for Small Area Disparities

Available urban health metrics focus primarily on large area rankings. Less has been done to develop an index that provides information about level of health and health disparities for small geographic areas. Adopting a method used by the Human Development Index, we standardized indicators for small area units on a (0, 1) interval and combined them using their geometric mean to form an Urban Health Index (UHI). Disparities were assessed using the ratio of the highest to lowest decile and measurement of the slope of the eight middle deciles (middle; 80 %) of the data. We examined the sensitivity of the measure to weighting, to changes in the method, to correlation among indicators, and to substitution of indicators. Using seven health determinants and applying these methods to the 128 census tracts in the city of Atlanta, USA, we found a disparity ratio of 5.92 and a disparity slope of 0.54, suggesting substantial inequality and heterogeneity of risk. The component indicators were highly correlated; their systematic removal had a small effect on the results. Except in extreme cases, weighting had a little effect on the rankings. A map of Atlanta census tracts exposed a swath of high disparity. UHI rankings, ratio, and slope were resistant to alteration in composition and to non-extreme weighting schemes. This empirical evaluation was limited to a single realization, but suggests that a flexible tool, whose method rather than content is standardized, may be of use for local evaluation, for decision making, and for area comparison.