Risk factors for heart failure in patients with type 2 diabetes mellitus and stage 4 chronic kidney disease treated with bardoxolone methyl

Background: A phase 3 randomized clinical trial was designed to test whether bardoxolone methyl, a nuclear factor erythroid-2–related factor 2 (Nrf2) activator, slows progression to end-stage renal disease in patients with stage 4 chronic kidney disease and type 2 diabetes mellitus. The trial was terminated because of an increase in heart failure in the bardoxolone methyl group; many of the events were clinically associated with fluid retention.<p></p> Methods and Results: We randomized 2,185 patients with type 2 diabetes mellitus (T2DM) and stage 4 chronic kidney disease (CKD) (estimated glomerular filtration rate 15 to <30 mL min−1 1.73 m−2) to once-daily bardoxolone methyl (20 mg) or placebo. We used classification and regression tree analysis to identify baseline factors predictive of heart failure or fluid overload events. Elevated baseline B-type natriuretic peptide and previous hospitalization for heart failure were identified as predictors of heart failure events; bardoxolone methyl increased the risk of heart failure by 60% in patients with these risk factors. For patients without these baseline characteristics, the risk for heart failure events among bardoxolone methyl– and placebo-treated patients was similar (2%). The same risk factors were also identified as predictors of fluid overload and appeared to be related to other serious adverse events.<p></p> Conclusions: Bardoxolone methyl contributed to events related to heart failure and/or fluid overload in a subpopulation of susceptible patients with an increased risk for heart failure at baseline. Careful selection of participants and vigilant monitoring of the study drug will be required in any future trials of bardoxolone methyl to mitigate the risk of heart failure and other serious adverse events.<p></p&gt

Testing the Accuracy and Precision of Wetness Sensors in a Tomato Field and on Turfgrass

Measurements of dew-period duration by painted, flat-plate, electronic wetness sensors at the top of the plant canopy in a tomato field and on adjacent turfgrass were compared with visual observations. The response range of sensors during the onset of dew sometimes exceeded 5 hr. but was less than 1 hr. on other nights. Sensors in the tomato field indicated dew formation occurred as much as 2 hr. earlier or later than dew became visible on adjacent tomato leaflets at the top of the crop canopy. A calibration threshold for sensors derived from a drying curve resulted in the underestimation of dew-period duration by up to 3.8 hr. and was less accurate than an empirically chosen threshold. Dew duration measured by sensors at the top of the tomato canopy and on adjacent turfgrass deviated from visual observation of dew duration at the top of the tomato canopy by about the same amount of time (0.8-hr. difference). These findings emphasize the need to use properly calibrated sensors for dew-period measurements and to calibrate dew-period measurements in a crop canopy

ALMA follows streaming of dense gas down to 40 pc from the supermassive black hole in NGC1097

We present a kinematic analysis of the dense molecular gas in the central 200 parsecs of the nearby galaxy NGC1097, based on Cycle 0 observations with the Atacama Large Millimeter/sub-millimeter Array (ALMA). We use the HCN(4-3) line to trace the densest interstellar molecular gas, and quantify its kinematics, and estimate an inflow rate for the molecular gas. We find a striking similarity between the ALMA kinematic data and the analytic spiral inflow model that we have previously constructed based on ionized gas velocity fields on larger scales. We are able to follow dense gas streaming down to 40 pc distance from the supermassive black hole in this Seyfert 1 galaxy. In order to fulfill marginal stability, we deduce that the dense gas is confined to a very thin disc, and we derive a dense gas inflow rate of 0.09 Msun/yr at 40 pc radius. Combined with previous values from the Ha and CO gas, we calculate a combined molecular and ionized gas inflow rate of 0.2 Msun/yr at 40 pc distance from the central supermassive black hole of NGC1097.Comment: Accepted for Publication in the ApJ Letter

Timing of Decremental Response During Repetitive Nerve Stimulation in Myasthenia Gravis

Background: A decrement >10% detected during repetitive nerve stimulation (RNS) is supportive of considering a diagnosis of myasthenia gravis (MG). Several studies have found that most of this decrement is seen between 4 to 6 min post-exercise. However, there are not available studies analyzing if shorter timing would be sufficient.   Objective: The objective of this study was to evaluate if RNS up to 2 min post-exercise is sufficient to detect a decrement response >10%. Methods: We performed a retrospective chart review study of patients referred to our neuromuscular clinic at The University of Kansas Medical Center with symptoms suggestive of MG from 2013 to 2017. Results: A total of 76 patients with MG and 100 controls were identified.  A significant decrement was detected in 95% of MG patients with abnormal RNS within 2 minutes post-exercise. Conclusion: RNS up to 2 min post-exercise might be sufficient to detect a significant decrement in MG patients.&nbsp

Carbon isotope discrimination in leaves of the common paperbark tree, Melaleuca quinquenervia, as a tool for quantifying past tropical and subtropical rainfall

Quantitative reconstructions of terrestrial climate are highly sought after but rare, particularly in Australia. Carbon isotope discrimination in plant leaves (Δleaf) is an established indicator of past hydroclimate because the fractionation of carbon isotopes during photosynthesis is strongly influenced by water stress. Leaves of the evergreen tree Melaleuca quinquenervia have been recovered from the sediments of some perched lakes on North Stradbroke and Fraser Islands, south-east Queensland, eastern Australia. Here, we examine the potential for using M. quinquenervia ∆leaf as a tracer of past rainfall by analysing carbon isotope ratios (δ13C) of modern leaves. We firstly assess Δleaf variation at the leaf and stand scale and find no systematic pattern within leaves or between leaves due to their position on the tree. We then examine the relationships between climate and Δleaf for an 11 year timeseries of leaves collected in a litter tray. M. quinquenervia retains its leaves for 1-4 years; thus cumulative average climate data are used. There is a significant relationship between annual mean ∆leaf and mean annual rainfall of the hydrological year for 1-4 years (i.e. 365-1460 days) prior to leaf fall (r2=0.64, p=0.003, n=11). This relationship is marginally improved by accounting for the effect of pCO2 on discrimination (r2=0.67, p=0.002, n=11). The correlation between rainfall and Δleaf, and the natural distribution of Melaleuca quinquenervia around wetlands of eastern Australia, Papua New Guinea and New Caledonia offers significant potential to infer past rainfall on a wide range of spatial and temporal scales

Amyloid Myopathy as an Inclusion Body Myositis Mimic

Introduction: Amyloid myopathy is a rare presentation of systemic amyloidosis. Amyloid myopathy can be initially misdiagnosed as sporadic inclusion body myositis (IBM). Methods: We report 4 cases of amyloid myopathy clinically mimicking inclusion body myositis and initially thought to be phenotypically IBM by neuromuscular experts. Results: Case 1 is an 81-year-old woman who presented with distal arm and proximal leg asymmetric weakness (myopathy pattern 4). Case 2 is a 76-year-old man with primary systemic amyloidosis who presented with myopathy pattern 4 and progressive dysphagia for four years. Case 3 is an 82-year-old man with progressive myopathy pattern 4 weakness and swallowing difficulty. Case 4 is a 62-year-old man with progressive bilateral finger flexor weakness. Muscle biopsies in all 4 cases showed perivascular amyloid deposits Discussion: Amyloid myopathy may be clinically indistinguishable from IBM. Muscle biopsy is of critical importance in the evaluation of patients suspected to have IBM

Factors associated with reporting multiple causes of death

BACKGROUND: There is analytical potential for multiple cause of death data collected from death certificates. This study examines relationships of multiple causes of death as a function of factors available on the death certificate (demographics of decedent, place of death, type of certifier, disposal method, whether an autopsy was performed, and year of death). METHODS: Data from 326,332 Minnesota death certificates from 1990–1998 are examined. Underlying and non-underlying causes of death are examined (based on record axis codes) as well as demographic and death-related covariates. Associations between covariates and prevalence of multiple causes of death and conditional probability of underlying compared to non-underlying causes of death are examined. The occurrence of ischemic heart disease or diabetes as underlying causes are specifically examined. RESULTS: Both the probability of multiple causes of death and the proportion of underlying cause compared to non-underlying cause of death are associated with demographic characteristics of the deceased and other non-medical conditions related to filing death certificate such as place of death. CONCLUSIONS: Multiple cause of death data provide a potentially useful way of looking for inaccuracies in reporting of causes of death. Differences across demographics in the proportion of time a cause is selected as underlying compared to non-underlying exist and can potentially provide useful information about the overall impact of causes of death in different populations

Imaging Biomarkers in Prostate Stereotactic Body Radiotherapy: A Review and Clinical Trial Protocol

Advances in imaging have changed prostate radiotherapy through improved biochemical control from focal boost and improved detection of recurrence. These advances are reviewed in the context of prostate stereotactic body radiation therapy (SBRT) and the ARGOS/CLIMBER trial protocol. ARGOS/CLIMBER will evaluate 1) the safety and feasibility of SBRT with focal boost guided by multiparametric MRI (mpMRI) and 18F-PSMA-1007 PET and 2) imaging and laboratory biomarkers for response to SBRT. To date, response to prostate SBRT is most commonly evaluated using the Phoenix Criteria for biochemical failure. The drawbacks of this approach include lack of lesion identification, a high false-positive rate, and delay in identifying treatment failure. Patients in ARGOS/CLIMBER will receive dynamic 18F-PSMA-1007 PET and mpMRI prior to SBRT for treatment planning and at 6 and 24 months after SBRT to assess response. Imaging findings will be correlated with prostate-specific antigen (PSA) and biopsy results, with the goal of early, non-invasive, and accurate identification of treatment failure

Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes:Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study

Background: Increases in measured inulin clearance, measured creatinine clearance, and estimated glomerular filtration rate (eGFR) have been observed with bardoxolone methyl in 7 studies enrolling approximately 2,600 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The largest of these studies was Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), a multinational, randomized, double-blind, placebo-controlled phase 3 trial which enrolled patients with T2D and CKD stage 4. The BEACON trial was terminated after preliminary analyses showed that patients randomized to bardoxolone methyl experienced significantly higher rates of heart failure events. We performed post-hoc analyses to characterize changes in kidney func-tion induced by bardoxolone methyl. Methods: Patients in -BEACON (n = 2,185) were randomized 1: 1 to receive oncedaily bardoxolone methyl (20 mg) or placebo. We compared the effects of bardoxolone methyl and placebo on a post-hoc composite renal endpoint consisting of = 30% decline from baseline in eGFR, eGFR <15 mL/min/1.73 m2, and end-stage renal disease (ESRD) events (provision of dialysis or kidney transplantation). Results: Consistent with prior studies, patients randomized to bardoxolone methyl experienced mean increases in eGFR that were sustained through study week 48. Moreover, increases in eGFR from baseline were sustained 4 weeks after cessation of treatment. Patients randomized to bardoxolone methyl were significantly less likely to experience the composite renal endpoint (hazards ratio 0.48 [95% CI 0.36-0.64]; p <0.0001). Conclusions: Bardoxolone methyl preserves kidney function and may delay the onset of ESRD in patients with T2D and stage 4 CKD. (C) 2018 The Author(s) Published by S. Karger AG, Base