Lane Medical Library

Redox response of actinide materials to highly ionizing radiation.

Nat Commun. 2015;6:6133

Authors: Tracy CL, Lang M, Pray JM, Zhang F, Popov D, Park C, Trautmann C, Bender M, Severin D, Skuratov VA, Ewing RC

Abstract
Energetic radiation can cause dramatic changes in the physical and chemical properties of actinide materials, degrading their performance in fission-based energy systems. As advanced nuclear fuels and wasteforms are developed, fundamental understanding of the processes controlling radiation damage accumulation is necessary. Here we report oxidation state reduction of actinide and analogue elements caused by high-energy, heavy ion irradiation and demonstrate coupling of this redox behaviour with structural modifications. ThO2, in which thorium is stable only in a tetravalent state, exhibits damage accumulation processes distinct from those of multivalent cation compounds CeO2 (Ce(3+) and Ce(4+)) and UO3 (U(4+), U(5+) and U(6+)). The radiation tolerance of these materials depends on the efficiency of this redox reaction, such that damage can be inhibited by altering grain size and cation valence variability. Thus, the redox behaviour of actinide materials is important for the design of nuclear fuels and the prediction of their performance.

PMID: 25626111 [PubMed - as supplied by publisher]

Ethical Testing of Experimental Ebola Treatments.

JAMA. 2015 Jan 27;313(4):421-422

Authors: Kanters S, Thorlund K, Mills EJ

PMID: 25626046 [PubMed - as supplied by publisher]

Heterogeneity in Meta-analysis of FDG-PET Studies to Diagnose Lung Cancer.

JAMA. 2015 Jan 27;313(4):419

Authors: Mills EJ, Jansen JP, Kanters S

PMID: 25626041 [PubMed - as supplied by publisher]

Markov State Models Provide Insights into Dynamic Modulation of Protein Function.

Acc Chem Res. 2015 Jan 3;

Authors: Shukla D, Hernández CX, Weber JK, Pande VS

Abstract
Conspectus Protein function is inextricably linked to protein dynamics. As we move from a static structural picture to a dynamic ensemble view of protein structure and function, novel computational paradigms are required for observing and understanding conformational dynamics of proteins and its functional implications. In principle, molecular dynamics simulations can provide the time evolution of atomistic models of proteins, but the long time scales associated with functional dynamics make it difficult to observe rare dynamical transitions. The issue of extracting essential functional components of protein dynamics from noisy simulation data presents another set of challenges in obtaining an unbiased understanding of protein motions. Therefore, a methodology that provides a statistical framework for efficient sampling and a human-readable view of the key aspects of functional dynamics from data analysis is required. The Markov state model (MSM), which has recently become popular worldwide for studying protein dynamics, is an example of such a framework. In this Account, we review the use of Markov state models for efficient sampling of the hierarchy of time scales associated with protein dynamics, automatic identification of key conformational states, and the degrees of freedom associated with slow dynamical processes. Applications of MSMs for studying long time scale phenomena such as activation mechanisms of cellular signaling proteins has yielded novel insights into protein function. In particular, from MSMs built using large-scale simulations of GPCRs and kinases, we have shown that complex conformational changes in proteins can be described in terms of structural changes in key structural motifs or "molecular switches" within the protein, the transitions between functionally active and inactive states of proteins proceed via multiple pathways, and ligand or substrate binding modulates the flux through these pathways. Finally, MSMs also provide a theoretical toolbox for studying the effect of nonequilibrium perturbations on conformational dynamics. Considering that protein dynamics in vivo occur under nonequilibrium conditions, MSMs coupled with nonequilibrium statistical mechanics provide a way to connect cellular components to their functional environments. Nonequilibrium perturbations of protein folding MSMs reveal the presence of dynamically frozen glass-like states in their conformational landscape. These frozen states are also observed to be rich in β-sheets, which indicates their possible role in the nucleation of β-sheet rich aggregates such as those observed in amyloid-fibril formation. Finally, we describe how MSMs have been used to understand the dynamical behavior of intrinsically disordered proteins such as amyloid-β, human islet amyloid polypeptide, and p53. While certainly not a panacea for studying functional dynamics, MSMs provide a rigorous theoretical foundation for understanding complex entropically dominated processes and a convenient lens for viewing protein motions.

PMID: 25625937 [PubMed - as supplied by publisher]

Optimization of an Injectable Tendon Hydrogel: The Effects of Platelet-Rich Plasma and Adipose-Derived Stem Cells on Tendon Healing In Vivo.

Tissue Eng Part A. 2015 Jan 27;

Authors: Chiou GJ, Crowe C, McGoldrick R, Hui K, Pham H, Chang J

Abstract
Introduction: Acute and chronic tendon injuries would benefit from stronger and more expeditious healing. We hypothesize that supplementation of a biocompatible tendon hydrogel with platelet-rich plasma (PRP) and adipose-derived stem cells (ASCs) would augment the tendon healing process. Methods: Using 55 Wistar rats, a full-thickness defect was created within the mid-substance of each Achilles tendon by adding one of five experimental conditions: 1) saline control (50-μL), 2) hydrogel (50-μL), 3) hydrogel (45-μL) + PRP (5-μL), 4) hydrogel (45-μL) + 2x106-ASCs/mL in PBS (5-μL) and 5) hydrogel (45-μL) + 2x106-ASCs/mL in PRP (5-μL). Hydrogel was developed from decellularized, human cadaveric tendons. Fresh rat PRP was obtained per Amable et al.'s technique (25), and green fluorescent protein/luciferase-positive rat ASCs were utilized. Rats were sacrificed at weeks 1, 2, 4, and 8 after injury. Real-time, in vivo bioluminescence imaging of groups with ASCs was performed. Upon sacrifice, Achilles tendons underwent biomechanical and histological evaluation. Comparisons across groups were analyzed using the 2-sample Z-test for proportions and the Student's t-test for independent samples. Significance was set at p<0.05. Results: 1) Bioluminescence imaging demonstrated that total photon flux was significantly increased for hydrogel + PRP + ASCs, versus hydrogel + ASCs for each post-operative day imaged (p<0.03). 2) Mean ultimate failure load (UFL) was increased for hydrogel augmented with PRP and/or ASCs versus hydrogel alone at week 2 (p<0.03). By week 4, hydrogel alone reached a similar mean UFL to hydrogel augmented with PRP and/or ASCs (p>0.3). However, at week 8, hydrogel with PRP and ASCs demonstrated increased strength over other groups (p<0.05) except for hydrogel with PRP (p=0.25). 3) Upon histologic analysis, hematoxylin and eosin staining showed increased extracellular matrix formation in groups containing PRP and increased cellularity in groups containing ASCs. Groups containing both PRP and ASCs demonstrated both of these characteristics. Conclusion: PRP and ASCs are easily accessible, bioactive products that have potentiating effects on tendon hydrogel. Augmentation with these two factors encourages earlier mechanical strength and functional restoration. Thus, biochemically tendon hydrogel augmented with PRP and/or ASCs serves as a promising therapeutic modality for augmenting the tendon healing process after injury.

PMID: 25625433 [PubMed - as supplied by publisher]

Theory in population biology, or biologically inspired mathematics?

Theor Popul Biol. 2015 Jan 24;

Authors: Rosenberg NA

PMID: 25625316 [PubMed - as supplied by publisher]

Cataract surgery in the glaucoma patient.

Middle East Afr J Ophthalmol. 2015 Jan-Mar;22(1):10-7

Authors: Kung JS, Choi DY, Cheema AS, Singh K

Abstract
To summarize the role of cataract surgery in the glaucoma patient, in terms of the effect on intraocular pressure (IOP) as well as diagnostic and therapeutic considerations for those with both conditions. Recent evidence suggests that cataract extraction may produce a significant and sustained IOP reduction in individuals with open-angle glaucoma, ocular hypertension, and angle-closure glaucoma. Cataract removal may improve the practitioner's ability to interpret perimetric testing, and re-establishing perimetric and optic nerve imaging baselines is recommended after cataract surgery. The sequence of cataract surgery relative to glaucoma surgery impacts the likelihood of complications and surgical success. There are multiple benefits to perform cataract surgery prior to glaucoma surgery while cataract surgery after trabeculectomy increases the risk of subsequent filtration failure. As "minimally invasive glaucoma surgeries" continue to improve in terms of efficacy, there is an evolving role for combined cataract and glaucoma surgery in patients with early to moderate stages of glaucoma.

PMID: 25624668 [PubMed - in process]

Ocean fronts drive marine fishery production and biogeochemical cycling.

Proc Natl Acad Sci U S A. 2015 Jan 26;

Authors: Woodson CB, Litvin SY

Abstract
Long-term changes in nutrient supply and primary production reportedly foreshadow substantial declines in global marine fishery production. These declines combined with current overfishing, habitat degradation, and pollution paint a grim picture for the future of marine fisheries and ecosystems. However, current models forecasting such declines do not account for the effects of ocean fronts as biogeochemical hotspots. Here we apply a fundamental technique from fluid dynamics to an ecosystem model to show how fronts increase total ecosystem biomass, explain fishery production, cause regime shifts, and contribute significantly to global biogeochemical budgets by channeling nutrients through alternate trophic pathways. We then illustrate how ocean fronts affect fishery abundance and yield, using long-term records of anchovy-sardine regimes and salmon abundances in the California Current. These results elucidate the fundamental importance of biophysical coupling as a driver of bottom-up vs. top-down regulation and high productivity in marine ecosystems.

PMID: 25624488 [PubMed - as supplied by publisher]

How Do Integrated Health Care Systems Address Racial and Ethnic Disparities in Colon Cancer?

J Clin Oncol. 2015 Jan 26;

Authors: Rhoads KF, Patel MI, Ma Y, Schmidt LA

Abstract
PURPOSE: Colorectal cancer (CRC) disparities have persisted over the last two decades. CRC is a complex disease requiring multidisciplinary care from specialists who may be geographically separated. Few studies have assessed the association between integrated health care system (IHS) CRC care quality, survival, and disparities. The purpose of this study was to determine if exposure to an IHS positively affects quality of care, risk of mortality, and disparities.
PATIENTS AND METHODS: This retrospective secondary-data analysis study, using the California Cancer Registry linked to state discharge abstracts of patients treated for colon cancer (2001 to 2006), compared the rates of National Comprehensive Cancer Network (NCCN) guideline-based care, the hazard of mortality, and racial/ethnic disparities in an IHS versus other settings.
RESULTS: More than 30,000 patient records were evaluated. The IHS had overall higher rates of adherence to NCCN guidelines. Propensity score-matched Cox models showed an independent and protective association between care in the IHS and survival (hazard ratio [HR], 0.87; 95% CI, 0.85 to 0.90). This advantage persisted across stage groups. Black race was associated with increased hazard of mortality in all other settings (HR, 1.15; 95% CI, 1.04 to 1.27); however, there was no disparity within the IHS for any minority group (P > .11 for all groups) when compared with white race.
CONCLUSION: The IHS delivered higher rates of evidence-based care and was associated with lower 5-year mortality. Racial/ethnic disparities in survival were absent in the IHS. Integrated systems may serve as the cornerstone for developing accountable care organizations poised to improve cancer outcomes and eliminate disparities under health care reform.

PMID: 25624437 [PubMed - as supplied by publisher]

Predicting Cancer Drug Response: Advancing the DREAM.

Cancer Discov. 2015 Jan 26;

Authors: Altman RB

Abstract
SUMMARY: The DREAM challenge is a community effort to assess current capabilities in systems biology. Two recent challenges focus on cancer cell drug sensitivity and drug synergism, and highlight strengths and weaknesses of current approaches. Cancer Discov; 5(3); 1-3. ©2015 AACR.

PMID: 25623160 [PubMed - as supplied by publisher]

Completeness of main outcomes across randomized trials in entire discipline: survey of chronic lung disease outcomes in preterm infants.

BMJ. 2015;350:h72

Authors: Ioannidis JP, Horbar JD, Ovelman CM, Brosseau Y, Thorlund K, Buus-Frank ME, Mills EJ, Soll RF

Abstract
OBJECTIVE: To map the availability of information on a major clinical outcome-chronic lung disease-across the randomized controlled trials in systematic reviews of an entire specialty, specifically interventions in preterm infants.
DESIGN: Survey of systematic reviews.
DATA SOURCES: Cochrane Database of Systematic Reviews.
STUDY SELECTION AND METHODS: All Cochrane systematic reviews (as of November 2013) that had evaluated interventions in preterm infants. We identified how many of those systematic reviews had looked for information on chronic lung disease, how many reported on chronic lung disease, and how many of the randomized controlled trials included in the systematic reviews reported on chronic lung disease. We also randomly selected 10 systematic reviews that did not report on chronic lung disease and 10 that reported on any such outcomes and identified whether any information on chronic lung disease appeared in the primary reports of the randomized controlled trials but not in the systematic reviews.
MAIN OUTCOME MEASURES: Whether availability of chronic lung disease outcomes differed by type of population and intervention and whether additional non-extracted data might have been available in trial reports.
RESULTS: 174 systematic reviews with 1041 trials exclusively concerned preterm infants. Of those, 105 reviews looked for chronic lung disease outcomes, and 79 reported on these outcomes. Of the 1041 included trials, 202 reported on chronic lung disease at 28 days and 200 at 36 weeks postmenstrual; 320 reported on chronic lung disease with any definition. The proportion of systematic reviews that looked for or reported on chronic lung disease and the proportion of trials that reported on chronic lung disease was larger in preterm infants with respiratory distress or support than others (P<0.001) and differed across interventions (P<0.001). Even for trials on children with ventilation interventions, only 56% (48/86) reported on chronic lung disease. In the random sample, 45 of 84 trials (54%) had no outcomes on chronic lung disease in the systematic reviews, and only 9/45 (20%) had such information in the primary trial reports.
CONCLUSIONS: Most trials included in systematic reviews of interventions on preterm infants are missing information on one of the most common serious outcomes in this population. Use of standardized clinical outcomes that would have to be collected and reported by default in all trials in a given specialty should be considered.

PMID: 25623087 [PubMed - in process]

Imagine a journey through time and space.

Nat Neurosci. 2015 Jan 27;18(2):163-4

Authors: Giocomo LM

PMID: 25622569 [PubMed - in process]

A DNA-based molecular probe for optically reporting cellular traction forces.

Nat Methods. 2014 Dec;11(12):1229-32

Authors: Blakely BL, Dumelin CE, Trappmann B, McGregor LM, Choi CK, Anthony PC, Duesterberg VK, Baker BM, Block SM, Liu DR, Chen CS

Abstract
We developed molecular tension probes (TPs) that report traction forces of adherent cells with high spatial resolution, can in principle be linked to virtually any surface, and obviate monitoring deformations of elastic substrates. TPs consist of DNA hairpins conjugated to fluorophore-quencher pairs that unfold and fluoresce when subjected to specific forces. We applied TPs to reveal that cellular traction forces are heterogeneous within focal adhesions and localized at their distal edges.

PMID: 25306545 [PubMed - indexed for MEDLINE]

Cumulative alkylating agent exposure and semen parameters in adult survivors of childhood cancer: a report from the St Jude Lifetime Cohort Study.

Lancet Oncol. 2014 Oct;15(11):1215-23

Authors: Green DM, Liu W, Kutteh WH, Ke RW, Shelton KC, Sklar CA, Chemaitilly W, Pui CH, Klosky JL, Spunt SL, Metzger ML, Srivastava D, Ness KK, Robison LL, Hudson MM

Abstract
BACKGROUND: Few data define the dose-specific relation between alkylating agent exposure and semen variables in adult survivors of childhood cancer. We undertook this study to test the hypothesis that increased exposure to alkylating agents would be associated with decreased sperm concentration in a cohort of adult male survivors of childhood cancer who were not exposed to radiation therapy for their childhood cancer.
METHODS: We did semen analysis on 214 adult male survivors of childhood cancer (median age 7·7 years [range 0·01-20·3] at diagnosis, 29·0 years [18·4-56·1] at assessment, and a median of 21·0 years [10·5-41·6] since diagnosis) who had received alkylating agent chemotherapy but no radiation therapy. Alkylating agent exposure was estimated using the cyclophosphamide equivalent dose (CED). Odds ratios (ORs) and 95% CIs for oligospermia (sperm concentration >0 and <15 million per mL) and azoospermia were calculated with logistic regression modelling.
FINDINGS: Azoospermia was noted in 53 (25%) of 214 participants, oligospermia in 59 (28%), and normospermia (sperm concentration ≥15 million per mL) in 102 (48%) participants. 31 (89%) of 35 participants who received CED less than 4000 mg/m(2) were normospermic. CED was negatively correlated with sperm concentration (correlation coefficient=-0·37, p<0·0001). Mean CED was 10 830 mg/m(2) (SD 7274) in patients with azoospermia, 8480 mg/m(2) (4264) in patients with oligospermia, and 6626 mg/m(2) (3576) in patients with normospermia. In multivariable analysis, CED was significantly associated with an increased risk per 1000 mg/m(2) CED for azoospermia (OR 1·22, 95% CI 1·11-1·34), and for oligospermia (1·14, 1·04-1·25), but age at diagnosis and age at assessment were not.
INTERPRETATION: Impaired spermatogenesis was unlikely when the CED was less than 4000 mg/m(2). Although sperm concentration decreases with increasing CED, there was substantial overlap of CED associated with normospermia, oligospermia, and azoospermia. These data can inform pretreatment patient counselling and use of fertility preservation services.
FUNDING: US National Cancer Institute, American Lebanese Syrian Associated Charities.

PMID: 25239573 [PubMed - indexed for MEDLINE]

Syncope risk stratification tools vs clinical judgment: an individual patient data meta-analysis.

Am J Med. 2014 Nov;127(11):1126.e13-25

Authors: Costantino G, Casazza G, Reed M, Bossi I, Sun B, Del Rosso A, Ungar A, Grossman S, D'Ascenzo F, Quinn J, McDermott D, Sheldon R, Furlan R

Abstract
BACKGROUND: There have been several attempts to derive syncope prediction tools to guide clinician decision-making. However, they have not been largely adopted, possibly because of their lack of sensitivity and specificity. We sought to externally validate the existing tools and to compare them with clinical judgment, using an individual patient data meta-analysis approach.
METHODS: Electronic databases, bibliographies, and experts in the field were screened to find all prospective studies enrolling consecutive subjects presenting with syncope to the emergency department. Prediction tools and clinical judgment were applied to all patients in each dataset. Serious outcomes and death were considered separately during emergency department stay and at 10 and 30 days after presenting syncope. Pooled sensitivities, specificities, likelihood ratios, and diagnostic odds ratios, with 95% confidence intervals, were calculated.
RESULTS: Thirteen potentially relevant papers were retrieved (11 authors). Six authors agreed to share individual patient data. In total, 3681 patients were included. Three prediction tools (Osservatorio Epidemiologico sulla Sincope del Lazio [OESIL], San Francisco Syncope Rule [SFSR], Evaluation of Guidelines in Syncope Study [EGSYS]) could be assessed by the available datasets. None of the evaluated prediction tools performed better than clinical judgment in identifying serious outcomes during emergency department stay, and at 10 and 30 days after syncope.
CONCLUSIONS: Despite the use of an individual patient data approach to reduce heterogeneity among studies, a large variability was still present. Current prediction tools did not show better sensitivity, specificity, or prognostic yield compared with clinical judgment in predicting short-term serious outcome after syncope. Our systematic review strengthens the evidence that current prediction tools should not be strictly used in clinical practice.

PMID: 24862309 [PubMed - indexed for MEDLINE]

Physiological and electrochemical effects of different electron acceptors on bacterial anode respiration in bioelectrochemical systems.

Bioresour Technol. 2014 Jul;164:270-5

Authors: Yang Y, Xiang Y, Xia C, Wu WM, Sun G, Xu M

Abstract
To understand the interactions between bacterial electrode respiration and the other ambient bacterial electron acceptor reductions, alternative electron acceptors (nitrate, Fe2O3, fumarate, azo dye MB17) were added singly or multiply into Shewanella decolorationis microbial fuel cells (MFCs). All the added electron acceptors were reduced simultaneously with current generation. Adding nitrate or MB17 resulted in more rapid cell growth, higher flavin concentration and higher biofilm metabolic viability, but lower columbic efficiency (CE) and normalized energy recovery (NER) while the CE and NER were enhanced by Fe2O3 or fumarate. The added electron acceptors also significantly influenced the cyclic voltammetry profile of anode biofilm probably via altering the cytochrome c expression. The highest power density was observed in MFCs added with MB17 due to the electron shuttle role of the naphthols from MB17 reduction. The results provided important information for MFCs applied in practical environments where contains various electron acceptors.

PMID: 24862003 [PubMed - indexed for MEDLINE]

Arsenic in the multi-aquifer system of the Mekong Delta, Vietnam: analysis of large-scale spatial trends and controlling factors.

Environ Sci Technol. 2014 Jun 3;48(11):6081-8

Authors: Erban LE, Gorelick SM, Fendorf S

Abstract
Groundwater exploitation is rising in the Mekong Delta, Vietnam, potentially exacerbating arsenic contamination from natural sources. We investigate trends and controls on contamination patterns throughout the Delta's multi-aquifer system as observed in a spatially exhaustive data set of arsenic measured in >40,000 wells, 10.5% of which exceed the WHO drinking water standard for arsenic (10 μg/L). We relate strong trends in the distribution of contamination among well samples to explanatory variables derived from 3D ancillary physicochemical data sets using logistic regression models. Parsimonious models describe much of the observed variability in arsenic occurrence, which differs considerably between subsets of wells tapping shallow versus deeper aquifer groups. In the shallowest Holocene-Pleistocene aquifers, arsenic occurrence is best described by distance to the Mekong river channels and delta front, depth, and location within fault-bounded zones of the region. The same model, however, fails to explain observations in the deeper group of Pliocene-Miocene aquifers. Among these deeper units, arsenic occurrence is rare except among older wells in near-river, heavily pumped areas. Our analysis is the first to examine both natural and anthropogenically mediated contributions to the distribution of arsenic throughout the Mekong Delta's multi-aquifer system, with implications for management of similarly affected basins throughout Southeast Asia.

PMID: 24849074 [PubMed - indexed for MEDLINE]

Anaerobic treatment of low-strength wastewater: a comparison between single and staged anaerobic fluidized bed membrane bioreactors.

Bioresour Technol. 2014 Aug;165:75-80

Authors: Bae J, Shin C, Lee E, Kim J, McCarty PL

Abstract
Performance of a single anaerobic fluidized membrane bioreactor (AFMBR) was compared with that of a staged anaerobic fluidized membrane bioreactor system (SAF-MBR) that consisted of an anaerobic fluidized bed bioreactor (AFBR) followed by an AFMBR. Both systems were fed with an equal COD mixture (200mg/L) of acetate and propionate at 25°C. COD removals of 93-96% were obtained by both systems, independent of the hydraulic retention times (HRT) of 2-4h. Over more than 200d of continuous operation, trans-membrane pressure (TMP) in both systems was less than 0.2bar without significant membrane fouling as a result of the scouring of membrane surfaces by the moving granular activated carbon particles. Results of bulk liquid suspended solids, extracellular polymeric substances (EPS), and soluble microbial products (SMP) analyses also revealed no significant differences between the two systems, indicating the single AFMBR is an effective alternative to the SAF-MBR system.

PMID: 24630367 [PubMed - indexed for MEDLINE]

The frequency and severity of cardiovascular toxicity from targeted therapy in advanced renal cell carcinoma patients.

JACC Heart Fail. 2013 Feb;1(1):72-8

Authors: Hall PS, Harshman LC, Srinivas S, Witteles RM

Abstract
OBJECTIVES: The purpose of this study was to document the incidence and extent of cardiovascular toxicity among advanced renal cell carcinoma patients treated with newer targeted cancer agents.
BACKGROUND: The potential for targeted cancer agents to induce cardiovascular toxicity has been increasingly recognized, but the overall incidence and extent of toxicity have not been well characterized. Early detection of asymptomatic patients could preempt symptomatic toxicity and reduce treatment-related morbidity and mortality.
METHODS: The incidence of hypertension, left ventricular dysfunction, and heart failure was assessed for all advanced renal cell carcinoma patients treated with targeted therapies at our institution between 2004 and 2011. Grading was performed according to the Common Terminology Criteria for Adverse Events version 4.0.
RESULTS: Cardiovascular toxicity developed in 116 of 159 patients (73%), including 52 of 159 patients (33%) when hypertension was excluded. Toxicity varied from occurrences of asymptomatic drops in left ventricular ejection fraction to rises in N-terminal-pro-B-type natriuretic peptide to severe heart failure. The tyrosine kinase inhibitor sunitinib was the agent most frequently used, with 66 of 101 sunitinib-treated patients (65%) developing a form of cardiovascular toxicity, including 32 of 101 patients (32%), excluding hypertension. Other VEGF inhibitors such as bevacizumab, sorafenib, and pazopanib also elicited significant cardiovascular toxicity with incidences ranging from 51% to 68%.
CONCLUSIONS: The frequency and severity of cardiovascular toxicity in advanced renal cell carcinoma patients treated with targeted cancer therapies are high.

PMID: 24621801 [PubMed - indexed for MEDLINE]

Visit-to-visit systolic blood pressure variability and outcomes in hemodialysis.

J Hum Hypertens. 2014 Jan;28(1):18-24

Authors: Chang TI, Flythe JE, Brunelli SM, Muntner P, Greene T, Cheung AK, Chertow GM

Abstract
Visit-to-visit blood pressure variability (VTV-BPV) is an independent risk factor for cardiovascular events and death in the general population. We sought to determine the association of VTV-BPV with outcomes in patients on hemodialysis, using data from a National Institutes of Health-sponsored randomized trial (the HEMO study). We used the coefficient of variation (CV) and the average real variability in systolic blood pressure (SBP) as metrics of VTV-BPV. In all, 1844 out of 1846 randomized subjects had at least three visits with SBP measurements and were included in the analysis. Median follow-up was 2.5 years (interquartile range 1.3-4.3 years), during which time there were 869 deaths from any cause and 408 (adjudicated) cardiovascular deaths. The mean pre-dialysis SBP CV was 9.9 ± 4.6%. In unadjusted models, we found a 31% higher risk of death from any cause per 10% increase in VTV-BPV. This association was attenuated after multivariable adjustment but remained statistically significant. Similarly, we found a 28% higher risk of cardiovascular death per 10% increase in VTV-BPV, which was attenuated and no longer statistically significant in fully adjusted models. The associations among VTV-BPV, death and cardiovascular death were modified by baseline SBP. In a diverse, well-dialyzed cohort of patients on maintenance hemodialysis, VTV-BPV, assessed using metrics of variability in pre-dialysis SBP, was associated with a higher risk of all-cause mortality and a trend toward higher risk of cardiovascular mortality, particularly in patients with a lower baseline SBP.

PMID: 23803593 [PubMed - indexed for MEDLINE]