Assessing the utility of pre-operative first pass radionuclide angiography to predict right ventricular failure post left ventricular assist device implantation.

INTRODUCTION: Right ventricular failure (RVF) after left ventricular assist device (LVAD) placement is associated with worse outcomes. We hypothesized that decreased right ventricular (RV) ejection fraction (EF) as well as qualitative assessments of RV function and dilation, as assessed by first pass radionuclide angiography (FPRNA), are associated with an increased risk of RVF following LVAD implantation. METHODS: We retrospectively identified 46 patients from 1/2008 to 11/2017 that underwent FPRNA and LVAD implantation. RVF was defined as requiring inotropes for greater than 14 days after LVAD implantation or requiring a right ventricular assist device. FPRNA-derived variables of RV performance and structure were compared between those that did and did not have RVF post implant. Statistical analyses were performed with Mann-Whitney U tests for ordinal and continuous variables. Fisher's exact tests and Pearson's χ2 tests were used for categorical variables. RESULTS: Eight patients developed RVF after device implantation. The average RV EF on FPRNA was 41.45% in those that did not develop RVF and 40.13% in those that did (P = 0.787). RV dilation (P = 0.896) and global RV function (P = 0.827) by FPRNA were not statistically different between the two groups. CONCLUSION: In patients that required FPRNA for further assessment of RV function prior to LVAD implantation, decreased RV EF, RV dilation and global RV function on FPRNA were not associated with an increased risk of RVF.

Evolution and duration of nodules in severe nodular acne on the back: results from a four-week non-interventional, prospective study.

BACKGROUND: Severe nodular acne is characterized by inflammatory nodules and scarring. Their natural evolution and duration are insufficiently investigated. AIM: To investigate the evolution and duration of untreated acne nodules. METHODOLOGY: Four-week, single-centre, non-interventional, prospective study in subjects with severe nodular acne on the back. Nodule evolution and duration was assessed using standardized photographs taken twice weekly. RESULTS: Data from 23 subjects were evaluable. Mean age was 25.1 ± 4.9 years, 87% were males, and mean acne duration was 9.7 ± 6.7 years. At baseline, the overall total nodule count was 132 (mean number: 5.7 ± 3.0 nodules/subject). Among others, the following two main pathways were observed: nodules evolving directly into atrophic scars (31.8%) and nodules evolving towards papules into atrophic scars (37.9%). After 4 weeks, 77.3% of baseline nodules had evolved into atrophic scars. After baseline visit, a total of 247 new nodules (3.1 ± 2.2 nodules/week/subject) with a mean duration of 4.9 ± 2.6 days were observed. The mean duration of new nodules was significantly longer in subjects (n = 16) with ≥6 new nodules compared to subjects (n = 7) with <6 new nodules (5.2 ± 1.4 vs. 3.6 ± 0.8 days; P = 0.008)). There was no correlation between the number of new nodules and acne duration or with the number of baseline nodules. CONCLUSION: This study documents the natural nodule evolution and duration over 4 weeks and showed in 23 patients the scarring potential of untreated severe nodular acne of the back.

Efficacy of a global supportive skin care programme with hydrotherapy after non-metastatic breast cancer treatment: A randomised, controlled study.

This study investigated the efficacy of post-treatment hydrotherapy as supportive care for management of persistent/long-lasting dermatologic adverse events (dAEs) induced in breast cancer survivors by adjuvant therapy, and its impact on quality of life (QoL). Patients in complete remission after standardised (neo)adjuvant chemotherapy, surgery and radiotherapy combination treatment for infiltrating HR+/HER2-breast carcinoma were enrolled in this randomised, multicentre controlled study 1-5 weeks after completing radiotherapy. The control group (CG, n = 33) received best supportive care and the treatment group (HG, n = 35) received 3-weeks of specific hydrotherapy. The primary criterion was change in QoL (QLQ-BR23) after hydrotherapy. Clinical grading of dAEs, cancer-related QoL (QLQ-C30), dermatologic QoL (DLQI) and general psychological well-being (PGWBI) were assessed. Significant dAEs were found at inclusion in both groups (n = 261). Most items showed significantly greater improvement in the HG versus CG group: QLQ-BR23 (breast [p = .0001] and arm symptoms [p = .0015], systemic therapy side effects [p = .0044], body image [p = .0139]), some dAE grading, DLQI (p = .0002) and PGWBI (p = .0028). Xerosis (88% of patients at inclusion) completely healed in all HG patients. Specific hydrotherapy is an effective supportive care for highly prevalent and long-lasting dAEs occurring after early breast cancer treatment, including chemotherapy, and leads to improved QoL and dermatologic toxicities.

Current Perspectives on Systemic Hypertension in Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a prevalent but incompletely understood syndrome. Traditional models of HFpEF pathophysiology revolve around systemic HTN and other causes of increased left ventricular afterload leading to left ventricular hypertrophy (LVH) and diastolic dysfunction. However, emerging models attribute the development of HFpEF to systemic proinflammatory changes secondary to common comorbidities which include HTN. Alterations in passive ventricular stiffness, ventricular-arterial coupling, peripheral microvascular function, systolic reserve, and chronotropic response occur. As a result, HFpEF is heterogeneous in nature, making it difficult to prescribe uniform therapies to all patients. Nonetheless, treating systemic HTN remains a cornerstone of HFpEF management. Antihypertensive therapies have been linked to LVH regression and improvement in diastolic dysfunction. However, to date, no therapies have definitive mortality benefit in HFpEF. Non-pharmacologic management for HTN, including dietary modification, exercise, and treating sleep disordered breathing, may provide some morbidity benefit in the HFpEF population. Future research is need to identify effective treatments, perhaps in more specific subgroups, and focus may need to shift from reducing mortality to improving exercise capacity and symptoms. Tailoring antihypertensive therapies to specific phenotypes of HFpEF may be an important component of this strategy.

The value of a poison control center in preventing unnecessary ED visits and hospital charges: A multi-year analysis.

OBJECTIVE: The purpose of this study is to determine the economic value of the Utah Poison Control Center (UPCC) by examining its contribution to the reduction of unnecessary emergency department (ED) visits and associated charges across multiple years. METHODS: A multi-year (2009-2014) analysis of cross-sectional data was performed. Callers were asked what they would do for a poison emergency if the UPCC was not available. Healthcare charges for ED visits averted were calculated according to insurance status using charges obtained from a statewide database. RESULTS: Of the 10,656 survey attempts, 5018 were completed. Over 30,000 cases were managed on-site each year. Using the proportion of callers who noted they would call 911, visit an ED, or call a physician's office, between 20.0 and 24.2 thousand ED visits were potentially prevented each year of the survey. Between $16.6 and $24.4 million dollars in unnecessary healthcare charges were potentially averted annually. CONCLUSIONS: Compared to the cost of operation, the service UPCC provides demonstrates economic value by reducing ED visits and associated charges. As the majority of patients have private insurance, the largest benefit falls to private payers.

Occult peripheral artery disease is common and limits the benefit achieved in cardiac rehabilitation.

Cardiac rehabilitation (CR) has proven morbidity and mortality benefits in cardiovascular disease, which directly correlates with exercise performance achieved. Many patients in CR exercise at sub-optimal levels, without obvious limitations. Occult lower-extremity peripheral artery disease (PAD) may be a determinant of diminished exercise capacity and reduced benefit obtained from traditional CR. In this prospective study of 150 consecutive patients enrolled in Phase II CR, we describe the prevalence of PAD, the utility of externally validated screening questionnaires, and the observed impact on CR outcomes. Abnormal ankle-brachial indices (ABI) (< 0.9 and >1.4) were observed in 19% of those studied. The Edinburgh Claudication Questionnaire was insensitive for detecting PAD by low ABI in this population, and the Walking Impairment Questionnaire and a modified Gardner protocol demonstrated a lack of typical symptoms with low levels of activity. Importantly, at completion of traditional CR, exercise improvement measured in metabolic equivalents (METs) was worse in those with a low ABI compared to those with a normal ABI (+1.39 vs +2.41 METs, p = 0.002). In conclusion, PAD is common in patients in Phase II CR and often clinically occult. Screening based on standard questionnaires appears insensitive in this population, suggesting a need for a broad-based screening strategy with ABI measurements. In this study, undiagnosed PAD significantly attenuated improvements in exercise performance, which potentially has bearings on future clinical events.

Response of canopy nitrogen uptake to a rapid decrease in bulk nitrate deposition in two eastern Canadian boreal forests.

A few studies have reported a recent and rapid decline in NO3(-) deposition in eastern North America. Whether this trend can be observed at remote boreal sites with low rates of N deposition and how it could impact canopy uptake (CU) of N remain unknown. Here we report trends between 1997/1999 and 2012 for precipitation, throughfall N deposition as well as inorganic N CU for two boreal forest sites of Quebec, Canada, with contrasted N deposition rates and tree species composition. NO3(-) bulk deposition declined by approximately 50% at both sites over the studied period while no change was observed for NH4(+). As a result, the contribution of NH4(+) to inorganic N deposition changed from ~33% to more than 50% during the study period. On average, 52-59% of N deposition was intercepted by the canopy, the retention being higher for NH4(+) (60-67%) than for NO3(-) (45-54%). The decrease in NO3(-) bulk deposition and the increase in the NH4(+):NO3(-) ratio had important impacts on N-canopy interactions. The contribution of NH4(+) CU to that of total inorganic N CU increased at both sites but the trend was significant only at Tirasse (lowest N deposition). At this site, absolute NO3(-) CU significantly decreased (as did total N CU) during the study period, a consequence of the strong relationship (r(2) = 0.88) between NO3(-) bulk deposition and NO3(-) CU. Our data suggest that N interactions with forest canopies may change rapidly with changes in N deposition as well as with tree species composition.

Tree species partition N uptake by soil depth in boreal forests.

It is recognized that the coexistence of herbaceous species in N-depleted habitats can be facilitated by N partitioning; however, the existence of such a phenomenon for trees has not yet been demonstrated. Here, we show from both foliage and soil 15N natural abundance values and from a 12-year in situ 15N addition experiment, that black spruce (Picea mariana) and jack pine (Pinus banksiana), two widespread species of the Canadian boreal forest, take up N at different depths. While black spruce takes up N from the organic soil, jack pine acquires it deeper within the highly N-depleted mineral soil. Systematic difference in foliar 15N natural abundance between the two species across seven sites distributed throughout the eastern Canadian boreal forest shows that N spatial partitioning is a widespread phenomenon. Distinct relationships between delta15N and N concentration in leaves of both species further emphasize their difference in N acquisition strategies. This result suggests that such complementary mechanisms of N acquisition could facilitate tree species coexistence in such N-depleted habitats and could contribute to the positive biodiversity-productivity relationship recently revealed for the eastern Canadian boreal forest, where jack pine is present. It also has implications for forest management and provides new insights to interpret boreal forest regeneration following natural or anthropogenic perturbations.

Transcatheter Aortic Valve Replacement for Left Ventricular Assist Device-Related Aortic Regurgitation: The Michigan Medicine Experience.

Background: Aortic regurgitation (AR) is common and detrimental in patients with left ventricular assist devices (LVADs). Off-label use of transcatheter aortic valve replacement (TAVR) has emerged as a potential treatment option. Further data are required regarding the feasibility and outcomes of TAVR to treat AR in LVAD recipients. Methods: A retrospective review of all patients with LVADs who underwent TAVR for the treatment of AR at a single center was performed. All echocardiograms were independently reviewed to ensure accuracy. Results: Eleven patients with continuous-flow LVADs underwent TAVR for AR. All patients had moderate or severe AR with New York Heart Association (NYHA) class III and IV symptoms. Implantation of more than 1 valve was required in 4 (36.3%) patients; 1 patient died during the procedure because of valve migration into the left ventricle and 1 patient died in-hospital after TAVR. Of 9 (81.8%) patients discharged alive, 8 (72.7%) were alive at 12 months and all survivors had improvement in AR severity, natriuretic peptide levels, left ventricle end-diastolic diameter, and NYHA class. Five (62.5%) survivors had a large improvement (>20 points) in the Kansas City Cardiomyopathy Questionnaire score at 1 year. One survivor experienced heart failure, requiring hospitalization, within 1 year. Conclusions: In this single-center series, TAVR for the treatment of AR in patients with LVADs is technically challenging but feasible in select patients and may produce durable improvements in AR severity, functional status, and quality of life.

Anthracycline cardiotoxicity in the elderly cancer patient: a SIOG expert position paper.

BACKGROUND: Comorbidities and risk factors likely to complicate treatment are common in elderly cancer patients. Anthracyclines remain the cornerstone of first-line therapy for non-Hodgkin's lymphoma (NHL) and metastatic and early breast cancer but can cause congestive heart failure. Elderly patients are at increased risk of this event and measures to reduce it should be considered. METHODS: A committee of experts in breast cancer and NHL met under the auspices of the International Society for Geriatric Oncology to review the literature and make recommendations, based on level of evidence, for the assessment, treatment and monitoring of elderly patients requiring anthracyclines. RESULTS AND RECOMMENDATIONS: Use of anthracycline-based chemotherapy illustrates many of the dilemmas facing elderly cancer patients. Age in itself should not prevent access to potentially curative treatment or treatment that prolongs life or improves its quality. The risk of cardiotoxicity with conventional anthracyclines is increased by the following factors: an existing or history of heart failure or cardiac dysfunction; hypertension, diabetes and coronary artery disease; older age (independent of comorbidities and performance status); prior treatment with anthracyclines; higher cumulative dose of anthracyclines and short infusion duration. The fact that cumulative and irreversible cardiotoxicity is likely to be greater in this population than among younger patients calls for effective pretreatment screening for risk factors, rigorous monitoring of cardiac function and early intervention. Use of liposomal anthracycline formulations, prolonging the infusion time for conventional anthracyclines and cardioprotective measures should be considered. However, when treatment is being given with curative intent, care should be taken to ensure reduced cardiotoxicity is not achieved at the expense of efficacy.

Strontium ranelate decreases the incidence of new caudal vertebral fractures in a growing mouse model with spontaneous fractures by improving bone microarchitecture.

UNLABELLED: Young mice over-expressing Runx2 fail to gain bone relative to wild type mice with growth and present spontaneous fractures. It allows, for the first time in rodents, direct assessment of anti-fracture efficacy of strontium ranelate which was able to decrease caudal vertebrae fracture incidence through an improvement of trabecular and cortical architecture. INTRODUCTION: The aim was to investigate whether strontium ranelate was able to decrease fracture incidence in mice over-expressing Runx2, model of severe developmental osteopenia associated with spontaneous vertebral fractures. METHODS: Transgenic mice and their wild type littermates were treated by oral route with strontium ranelate or vehicle for 9 weeks. Caudal fracture incidence was assessed by repeated X-rays, resistance to compressive loading by biochemical tests, and bone microarchitecture by histomorphometry. RESULTS: Transgenic mice receiving strontium ranelate had significantly fewer new fractures occurring during the 9 weeks of the study (-60%, p < 0.05). In lumbar vertebrae, strontium ranelate improves resistance to compressive loading (higher ultimate force to failure, +120%, p < 0.05) and trabecular microarchitecture (higher bone volume and trabecular number, lower trabecular separation, +60%, +50%, -39%, p < 0.05) as well as cortical thickness (+17%, p < 0.05). In tibiae, marrow cavity cross-section area and equivalent diameter were lower (-39%, -21%, p < 0.05). The strontium level in plasma and bone was in the same range as the values measured in treated postmenopausal women. CONCLUSIONS: This model allows, for the first time, direct assessment of anti-fracture efficacy of strontium ranelate treatment in rodents. In these transgenic mice, strontium ranelate was able to decrease caudal vertebral fracture incidence through an improvement of trabecular and cortical architecture.

Burnout and Well-Being Among Cardiology Fellowship Program Directors.

OBJECTIVES: The third annual Cardiovascular Diseases (CV) Fellowship Program Directors (PDs) Survey sought to understand burnout and well-being among CV fellowship PDs. BACKGROUND: Physician burnout is a common phenomenon. Data on burnout among cardiologists, specifically CV PDs, remain limited. METHODS: The survey contained 8 questions examining satisfaction, stress, and burnout among CV fellowship PDs. Burnout was defined based on the self-reported presence of ≥1 symptom of burnout, constant feelings of burnout, or complete burnout. RESULTS: Survey response rate was 57%. Most respondents were men (78%) and 54% represented university-based programs. Eighty percent reported satisfaction with their current job as PD, and 96% identified interactions with fellows as a driver of their satisfaction. Forty-five percent reported feeling a great deal of stress from their job. Stress was higher among women PDs, early-career PDs, and PDs of larger and university-based programs. Twenty-one percent reported some symptoms of burnout, and only 36% reported enjoyment without stress or burnout. Rates of enjoyment without stress or burnout were higher among men and late-career PDs, PDs of smaller programs, and PDs of community-based programs. Seventeen percent of PDs reported a high likelihood of resigning in the next year, of which the most common reason was the tasks of PDs were becoming overwhelming. CONCLUSIONS: Most CV fellowship PDs are satisfied with their position, but stress and burnout remain common. Women PDs, early-career PDs, and PDs of larger, university-based programs demonstrate more adverse markers of well-being. Opportunities exist to support CV fellowship PDs in their critical role.

Data structures and compression algorithms for genomic sequence data.

MOTIVATION: The continuing exponential accumulation of full genome data, including full diploid human genomes, creates new challenges not only for understanding genomic structure, function and evolution, but also for the storage, navigation and privacy of genomic data. Here, we develop data structures and algorithms for the efficient storage of genomic and other sequence data that may also facilitate querying and protecting the data. RESULTS: The general idea is to encode only the differences between a genome sequence and a reference sequence, using absolute or relative coordinates for the location of the differences. These locations and the corresponding differential variants can be encoded into binary strings using various entropy coding methods, from fixed codes such as Golomb and Elias codes, to variables codes, such as Huffman codes. We demonstrate the approach and various tradeoffs using highly variables human mitochondrial genome sequences as a testbed. With only a partial level of optimization, 3615 genome sequences occupying 56 MB in GenBank are compressed down to only 167 KB, achieving a 345-fold compression rate, using the revised Cambridge Reference Sequence as the reference sequence. Using the consensus sequence as the reference sequence, the data can be stored using only 133 KB, corresponding to a 433-fold level of compression, roughly a 23% improvement. Extensions to nuclear genomes and high-throughput sequencing data are discussed. AVAILABILITY: Data are publicly available from GenBank, the HapMap web site, and the MITOMAP database. Supplementary materials with additional results, statistics, and software implementations are available from http://mammag.web.uci.edu/bin/view/Mitowiki/ProjectDNACompression.

Leaf life span optimizes annual biomass production rather than plant photosynthetic capacity in an evergreen shrub.

SUMMARY: *Owing to nitrogen (N) translocation towards new leaves, the shedding of old leaves can increase the whole-plant carbon gain. It occurs when their photosynthetic nitrogen use efficiency (PNUE) declines below a given threshold. *Here, we investigated variations in net photosynthetic capacity (A(max)), N resorption and PNUE in populations of Rhododendron ferrugineum presenting different mean leaf life spans (LLS). *Both populations had comparable annual leaf surface area production and A(max) across leaf-age cohorts. Branch photosynthetic capacity was up to 95% higher in the population with the longer LLS mainly because of the high contribution of old leaves to the total leaf area. Despite lower N concentrations, old leaves maintained relatively high A(max) and consequently PNUE that were higher than or similar to the values found in current-year leaves. *As the ratio of PNUE in old to PNUE in new leaves was always higher than the fraction of leaf N resorbed during leaf shedding, we concluded that leaf shedding did not improve plant photosynthetic capacity. We suggest that in R. ferrugineum, leaf shedding is mainly controlled by the leaf storage function and, therefore, that models aiming to explain LLS should not only consider the leaf carbon assimilation function, particularly in nutrient-poor habitats.

Program Directors Survey on Diversity in Cardiovascular Training Programs.

BACKGROUND: Women and minorities are under-represented in cardiovascular disease (CVD) specialties. It remains unknown how characteristics of the CVD learning environment affect diversity and how program directors (PDs) approach these critical issues. OBJECTIVES: The second annual Cardiovascular PD Survey aimed to investigate characteristics of the CVD learning environment that may affect diversity and strategies PDs use to approach these issues. METHODS: The survey contained 20 questions examining U.S.-based CVD PD perceptions of diversity in CVD and related characteristics of the CVD fellowship learning environment. RESULTS: In total, 58% of PDs completed the survey. Responding programs demonstrated geographic diversity. The majority were university-based or -affiliated. A total of 86% of PDs felt diversity in CVD as a field needs to increase, and 70% agreed that training programs could play a significant role in this. In total, 89% of PDs have attempted to increase diversity in fellowship recruitment. The specific strategies used were associated with PD sex and the presence of under-represented minority trainees in the program. PDs identified lack of qualified candidates and overall culture of cardiology as the 2 most significant barriers to augmenting diversity. A majority of programs have support systems in place for minority fellows or specific gender groups, including procedures to report issues of harassment or an unsafe learning environment. PDs identified shared best practices for recruitment and implicit bias training, among others, as important resources in their efforts to support diversity in CVD training. CONCLUSIONS: Diversity is important to CVD PDs. They are striving to increase it in their programs through recruitment and strategies directed toward the fellowship learning environment. The CVD community has opportunities to standardize strategies and provide national resources to support PDs in these critical efforts.

Design of the ocular coil, a new device for non-invasive drug delivery.

Eye drops and ointments are the most prescribed methods for ocular drug delivery. However, due to low drug bioavailability, rapid drug elimination, and low patient compliance there is a need for improved ophthalmic drug delivery systems. This study provides insights into the design of a new drug delivery device that consists of an ocular coil filled with ketorolac loaded PMMA microspheres. Nine different ocular coils were created, ranging in wire diameter and coiled outer diameter. Based on its microsphere holding capacity and flexibility, one type of ocular coil was selected and used for further experiments. No escape of microspheres was observed after bending the ocular coil at curvature which reflect the in vivo situation in human upon positioning in the lower conjunctival sac. Shape behavior and tissue contact were investigated by computed tomography imaging after inserting the ocular coil in the lower conjunctival fornix of a human cadaver. Thanks to its high flexibility, the ocular coil bends along the circumference of the eye. Because of its location deep in the fornix, it appears unlikely that in vivo, the ocular coil will interfere with eye movements. In vitro drug release experiments demonstrate the potential of the ocular coil as sustained drug delivery device for the eye. We developed PMMA microspheres with a 26.5 ± 0.3 wt% ketorolac encapsulation efficiency. After 28 days, 69.9% ± 5.6% of the loaded ketorolac was released from the ocular coil when tested in an in vitro lacrimal system. In the first three days high released dose (48.7% ± 5.4%) was observed, followed by a more gradually release of ketorolac. Hence, the ocular coil seems a promising carrier for ophthalmic drugs delivery in the early postoperative time period.

Diagnostic Accuracy of FDG PET/CT in Suspected LVAD Infections: A Case Series, Systematic Review, and Meta-Analysis.

OBJECTIVES: The purpose of this study was to describe our experience with fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography computed tomography (PET/CT) in diagnosing left ventricular assist device (LVAD) infections and perform a meta-analysis of published studies to determine overall diagnostic accuracy. BACKGROUND: Device-related infections are a common complication of LVADs and are linked to worse outcomes. Diagnosis of LVAD infections remains challenging. FDG PET/CT has demonstrated good diagnostic accuracy in several other infectious conditions. METHODS: This was a single-center, retrospective case series of FDG PET/CT scans in suspected LVAD infection between September 2015 and February 2018. A systematic review of PubMed from database inception through March 2018 was also conducted to identify additional studies. RESULTS: Nineteen FDG PET/CT scans were identified for the retrospective case series. The systematic review identified an additional 3 publications, for a total of 4 studies involving 119 scans assessing diagnostic performance. Axial (n = 36) and centrifugal (n = 83) flow LVADs were represented. Pooled sensitivity was 92% (95% confidence interval [CI]: 82% to 97%) and specificity was 83% (95% CI: 24% to 99%) for FDG PET/CT in diagnosing LVAD infections. Summary receiver-operating characteristic curve analysis demonstrated an AUC of 0.94 (95% CI: 0.91 to 0.95). CONCLUSIONS: FDG PET/CT for suspected LVAD infections demonstrates good diagnostic accuracy, with overall high sensitivity but variable specificity.