Stress testing and non-invasive coronary angiography in patients with suspected coronary artery disease: time for a new paradigm

Diagnosis and management of coronary artery disease represents major challenges to our health care system, affecting millions of patients each year. Until recently, the diagnosis of coronary artery disease was possible only through cardiac catheterization and invasive coronary angiography. To avoid the risks of an invasive procedure, stress testing is often employed for an initial assessment of patients with suspected coronary artery disease, serving as a gatekeeper for cardiac catheterization. With the emergence of non-invasive coronary angiography, the question arises if such a strategy is still sensible, particularly, in view of only a modest agreement between stress testing results and the presence of coronary artery disease established by cardiac catheterization. Much data in support of the diagnostic accuracy and prognostic value of non-invasive coronary angiography by computed tomography have emerged within the last few years. These data challenge the role of stress testing as the initial imaging modality in patients with suspected coronary artery disease. This article reviews the clinical utility, limitations, as well as the hazards of stress testing compared with non-invasive coronary artery imaging by computed tomography. Finally, the implications of this review are discussed in relation to clinical practice

Secular Trends in Breast Cancer Risk Among Women With HIV Initiating ART in North America

Background: Studies suggest lower risk of breast cancer in women with HIV versus without HIV. These estimates may be biased by lower life expectancy and younger age distribution of women with HIV. Our analysis evaluated this bias and characterized secular trends in breast cancer among women with HIV initiating antiretroviral therapy. We hypothesized breast cancer risk would increase over time as mortality decreased. Setting: Women with HIV prescribed antiretroviral therapy in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) from 1997 through 2016. Methods: We estimated breast cancer hazard (cause-specific hazard ratios) and cumulative incidence accounting for competing risks (subdistribution hazard ratios) to assess changes in breast cancer risk over time. This was assessed overall (1997-2016) and within/across calendar periods. Analyses were adjusted for race/ethnicity and inverse probability weighted for cohort. Cumulative incidence was graphically assessed by calendar period and race/ethnicity. Results: We observed 11,587 women during 1997-2016, contributing 63 incident breast cancer diagnoses and 1,353 deaths [73,445 person-years (median followup = 4.5 years)]. Breast cancer cumulative incidence was 3.2% for 1997-2016. We observed no secular trends in breast cancer hazard or cumulative incidence. There were annual declines in the hazard and cumulative incidence of death (cause-specific hazard ratios and subdistribution hazard ratios: 0.89, 95% confidence interval: 0.87 to 0.91) which remained within and across calendar periods. Conclusions: These findings contradict the hypothesis of increasing breast cancer risk with declining mortality over time among women with HIV, suggesting limited impact of changing mortality on breast cancer risk. Additional inquiry is merited as survival improves among women with HIV

Current and Past Immunodeficiency Are Associated with Higher Hospitalization Rates among Persons on Virologically Suppressive Antiretroviral Therapy for up to 11 Years

Background: Persons with human immunodeficiency virus (PWH) with persistently low CD4 counts despite efficacious antiretroviral therapy could have higher hospitalization risk. Methods: In 6 US and Canadian clinical cohorts, PWH with virologic suppression for ≥1 year in 2005-2015 were followed until virologic failure, loss to follow-up, death, or study end. Stratified by early (years 2-5) and long-term (years 6-11) suppression and lowest presuppression CD4 count 500 cells/μL had aIRRs of 1.44 during early suppression (95% confidence interval [CI], 1.01-2.06), and 1.67 (95% CI, 1.03-2.72) during long-term suppression. Among patients with lowest presuppression CD4 count ≥200 (56%), patients with current CD4 351-500 vs >500 cells/μL had an aIRR of 1.22 (95% CI,. 93-1.60) during early suppression and 2.09 (95% CI, 1.18-3.70) during long-term suppression. Conclusions: Virologically suppressed patients with lower CD4 counts experienced higher hospitalization rates and could potentially benefit from targeted clinical management strategies

Projected WIMP sensitivity of the LUX-ZEPLIN dark matter experiment

LUX-ZEPLIN (LZ) is a next-generation dark matter direct detection experiment that will operate 4850 feet underground at the Sanford Underground Research Facility (SURF) in Lead, South Dakota, USA. Using a two-phase xenon detector with an active mass of 7 tonnes, LZ will search primarily for low-energy interactions with weakly interacting massive particles (WIMPs), which are hypothesized to make up the dark matter in our galactic halo. In this paper, the projected WIMP sensitivity of LZ is presented based on the latest background estimates and simulations of the detector. For a 1000 live day run using a 5.6-tonne fiducial mass, LZ is projected to exclude at 90% confidence level spin-independent WIMP-nucleon cross sections above 1.4 × 10-48cm2 for a 40 GeV/c2 mass WIMP. Additionally, a 5σ discovery potential is projected, reaching cross sections below the exclusion limits of recent experiments. For spin-dependent WIMP-neutron(-proton) scattering, a sensitivity of 2.3 × 10−43 cm2 (7.1 × 10−42 cm2) for a 40 GeV/c2 mass WIMP is expected. With underground installation well underway, LZ is on track for commissioning at SURF in 2020

Search for annual and diurnal rate modulations in the LUX experiment

Various dark matter models predict annual and diurnal modulations of dark matter interaction rates in Earth-based experiments as a result of the Earth’s motion in the halo. Observation of such features can provide generic evidence for detection of dark matter interactions. This paper reports a search for both annual and diurnal rate modulations in the LUX dark matter experiment using over 20 calendar months of data acquired between 2013 and 2016. This search focuses on electron recoil events at low energies, where leptophilic dark matter interactions are expected to occur and where the DAMA experiment has observed a strong rate modulation for over two decades. By using the innermost volume of the LUX detector and developing robust cuts and corrections, we obtained a stable event rate of 2.3±0.2  cpd/keVee/tonne, which is among the lowest in all dark matter experiments. No statistically significant annual modulation was observed in energy windows up to 26  keVee. Between 2 and 6  keVee, this analysis demonstrates the most sensitive annual modulation search up to date, with 9.2σ tension with the DAMA/LIBRA result. We also report no observation of diurnal modulations above 0.2  cpd/keVee/tonne amplitude between 2 and 6  keVee.Various dark matter models predict annual and diurnal modulations of dark matter interaction rates in Earth-based experiments as a result of the Earth's motion in the halo. Observation of such features can provide generic evidence for detection of dark matter interactions. This paper reports a search for both annual and diurnal rate modulations in the LUX dark matter experiment using over 20 calendar months of data acquired between 2013 and 2016. This search focuses on electron recoil events at low energies, where leptophilic dark matter interactions are expected to occur and where the DAMA experiment has observed a strong rate modulation for over two decades. By using the innermost volume of the LUX detector and developing robust cuts and corrections, we obtained a stable event rate of 2.3$\pm$0.2~cpd/keV$_{\text{ee}}$/tonne, which is among the lowest in all dark matter experiments. No statistically significant annual modulation was observed in energy windows up to 26~keV$_{\text{ee}}$. Between 2 and 6~keV$_{\text{ee}}$, this analysis demonstrates the most sensitive annual modulation search up to date, with 9.2$\sigma$ tension with the DAMA/LIBRA result. We also report no observation of diurnal modulations above 0.2~cpd/keV$_{\text{ee}}$/tonne amplitude between 2 and 6~keV$_{\text{ee}}$

Long-term survival comparison between primary transplant and upfront curative treatment with salvage transplant for early stage hepatocellular carcinoma

Summary: Background: Whether primary liver transplantation (PLT) or upfront curative treatment with salvage liver transplantation (SLT) is a better treatment option for early hepatocellular carcinoma (HCC) is controversial. This study aims to compare the long-term survival starting from the time of primary treatment between the two approaches for early HCC using propensity score matching (PSM) analysis. Methods: From 1995 to 2014, 175 patients with early HCC undergoing either PLT (n = 149) or SLT (n = 26) were retrospectively reviewed in a prospectively collected database. Patients' demographic data, tumor characteristics, short-term and long-term outcome were compared between two groups after PSM. Results: After matching, the baseline characteristics were comparable between mPLT group (n = 45) and mSLT group (n = 25). The tumor recurrence rate after transplant was significantly higher in mSLT group than mPLT group (28% vs. 15.6%). Calculating from the time of primary treatment, the 1, 3, and 5-year overall survival rates were comparable between mPLT group (97.8%, 91.1% and 86.3%) and mSLT group (100%, 95% and 85%). However, the 1, 3, and 5-year recurrence-free survival rates were significantly better in mPLT group than mSLT group (95.6% vs. 90%, 86.6% vs. 80% and 84.3% vs. 70%). SLT approach and high pre-treatment serum alpha-fetoprotein level (>200 ηg/mL) were poor prognostic factors for recurrence-free survival after transplant. Conclusions: PLT may be a better treatment option for early HCC, whereas SLT approach for HCC should be cautiously considered under the circumstance of organ shortage. Keywords: Primary transplantation, Salvage transplantation, Hepatocellular carcinoma, Propensity score matchin