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BACKGROUND: Heart failure (HF) is a serious cardiovascular syndrome that affects nearly 5 million people in the United States. A review of clinical data demonstrates that sudden cardiac death (SCD) accounts for approximately one-third of all HF deaths. This fatal outcome typically involves an unexpected electrical event leading to sustained cardiac arrhythmias resulting in cardiovascular collapse. METHODS AND RESULTS: A systematic review of the literature was performed to serve as the basis for this review. Factors contributing directly to incidence of SCD in the HF population may include significant remodeling of the left ventricle (hypertrophy, dilation, and fibrosis) in addition to increased sympathetic activation. Using specific therapies to limit these mechanisms are beneficial in the HF patient by preventing SCD. Beta-blockers play a key role in the prevention of SCD for patients with HF by limiting the effects of circulating norepinephrine and by reducing left ventricular remodeling. CONCLUSIONS: This review outlines the potential mechanisms and contributing factors of SCD in patients with HF and the impact of beta-blocker usage in the prevention of this fatal outcome for this growing patient population. [ABSTRACT FROM AUTHOR]

This study investigated the effects of carvedilol on right ventricular (RV) volume and systolic function in chronic heart failure patients. Carvedilol treatment resulted in a significant improvement of RV ejection fraction and systolic performance, which paralleled the improvement of systolic function demonstrated in the left ventricle. [ABSTRACT FROM AUTHOR]

Background: Our current understanding of right heart failure (RHF) post-left ventricular assist device (LVAD) is lacking. Recently, a new Interagency Registry for Mechanically Assisted Circulatory Support definition of RHF was introduced. Based on this definition, we investigated natural history, risk factors, and outcomes of post-LVAD RHF., Methods: Patients implanted with continuous flow LVAD between June 2, 2014, and June 30, 2016 and registered in the Interagency Registry for Mechanically Assisted Circulatory Support/Society of Thoracic Surgeons Database were included. RHF incidence and predictors, and survival after RHF were assessed. The manifestations of RHF which were separately analyzed were elevated central venous pressure, peripheral edema, ascites, and use of inotropes., Results: Among 5537 LVAD recipients (mean 57±13 years, 49% destination therapy, support 18.9 months) prevalence of 1-month RHF was 24%. Of these, RHF persisted at 12 months in 5.3%. In contrast, de novo RHF, first identified at 3 months, occurred in 5.1% and persisted at 12 months in 17% of these, and at 6 months occurred in 4.8% and persisted at 12 months in 25%. Higher preimplant blood urea nitrogen (ORs,1.03-1.09 per 5 mg/dL increase; P <0.0001), previous tricuspid valve repair/replacement (ORs, 2.01-10.09; P <0.001), severely depressed right ventricular systolic function (ORs,1.17-2.20; P =0.004); and centrifugal versus axial LVAD (ORs,1.15-1.78; P =0.001) represented risk factors for RHC incidence at 3 months. Patients with persistent RHF at 3 months had the lowest 2-year survival (57%) while patients with de novo RHF or RHF which resolved by 3 months had more favorable survival outcomes (75% and 78% at 2 years, respectively; P <0.001)., Conclusions: RHF at 1 or 3 months post-LVAD was a common and frequently transient condition, which, if resolved, was associated with relatively favorable prognosis. Conversely, de novo, late RHF post-LVAD (>6 months) was more frequently a persistent disorder and associated with increased mortality. The 1-, 3-, and 6-month time points may be used for RHF assessment and risk stratification in LVAD recipients.

Background: Antimicrobial stewardship intervention (ASI) appears to be necessary to realize the full benefits of rapid diagnostic technologies in clinical practice. This study aimed to compare clinical outcomes between early ASI paired with matrix-associated laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) compared with MALDI-TOF with standard of care (SOC) reporting in patients with positive blood cultures., Methods: Adult patients with positive blood cultures and organism speciation via MALDI-TOF admitted between February 2015 and September 2015 were randomized to ASI or SOC in a 1:1 fashion. Patients admitted for at least 48 h following positive culture were included in analyses. ASI was defined as a clinical assessment by a stewardship team member with non-binding treatment recommendations offered to the primary team. The primary outcome was time to definitive therapy. Secondary outcomes included post-culture length of stay (LOS), time to first change in antibiotics, and in-hospital mortality., Results: In total, 149 patients were included in the analyses (76 in the ASI group and 73 in the SOC group). ASI and SOC arms did not differ according to age, sex, comorbidities or severity of illness. Gram-positive organisms were common in both SOC and ASI arms (74.0 vs. 61.8%, P=0.11). Time to definitive therapy was reduced, on average, by 30.3 h in the ASI group (71.6 vs. 41.3 h, P=0.01). Hospital LOS following the first positive blood culture was significantly shorter in the ASI group (8.7 vs. 11.2 days, P=0.049)., Conclusions: ASI combined with MALDI-TOF reduced the time to definitive therapy and time to first change in antibiotics, and was associated with a shorter post-culture LOS., Competing Interests: Declaration of Competing Interest VOB is a current employee of Inflammatix; her work on this project was completed prior to that employment. EMG is a current employee of Janssen Scientific Affairs; her work on this project was completed prior to that employment All other authors report no conflicts of interest., (Copyright © 2021 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Importance: Heart failure with recovered ejection fraction (HFrecEF) is a recently recognized phenotype of patients with a history of reduced left ventricular ejection fraction (LVEF) that has subsequently normalized. It is unknown whether such LVEF improvement is associated with improvements in health status., Objective: To examine changes in health-related quality of life in patients with heart failure with reduced ejection fraction (HFrEF) whose LVEF normalized, compared with those whose LVEF remains reduced and those with HF with preserved EF (HFpEF)., Design, Setting, and Participants: This prospective cohort study was conducted at a tertiary care hospital from November 2016 to December 2018. Consecutive patients seen in a heart failure clinic who completed patient-reported outcome assessments were included. Clinical data were abstracted from the electronic health record. Data analysis was completed from February to December 2020., Main Outcomes and Measures: Changes in Kansas City Cardiomyopathy Questionnaire overall summary score, Visual Analog Scale score, and Patient-Reported Outcomes Measurement Information System domain scores on physical function, fatigue, depression, and satisfaction with social roles over 1-year follow-up., Results: The study group included 319 patients (mean [SD] age, 60.4 [15.5] years; 120 women [37.6%]). At baseline, 212 patients (66.5%) had HFrEF and 107 (33.5%) had HFpEF. At a median follow-up of 366 (interquartile range, 310-421) days, LVEF had increased to 50% or more in 35 patients with HFrEF (16.5%). Recovery of systolic function was associated with heart failure-associated quality-of-life improvement, such that for each 10% increase in LVEF, the Kansas City Cardiomyopathy Questionnaire score improved by an mean (SD) of 4.8 (1.6) points (P = .003). Recovery of LVEF was also associated with improvement of physical function, satisfaction with social roles, and a reduction in fatigue., Conclusions and Relevance: Among patients with HFrEF in this study, normalization of left ventricular systolic function was associated with a significant improvement in health-related quality of life.

Using serial analysis of myocardial gene expression employing endomyocardial biopsy starting material in a dilated cardiomyopathy cohort, we show that mRNA expression of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) cardiac myocyte receptor ACE2 is up-regulated with remodeling and with reverse remodeling down-regulates into the normal range. The proteases responsible for virus-cell membrane fusion were expressed but not regulated with remodeling. In addition, a new candidate for SARS-CoV-2 cell binding and entry was identified, the integrin encoded by ITGA5 . Up-regulation in ACE2 in remodeled left ventricles may explain worse outcomes in patients with coronavirus disease 2019 who have underlying myocardial disorders, and counteracting ACE2 up-regulation is a possible therapeutic approach to minimizing cardiac damage., (© 2020 The Authors.)

Background: Many patients with a self-reported penicillin allergy go on to tolerate beta-lactam antibiotics. Allergy specialists may be consulted to determine the nature and extent of the allergy. However, electronic allergy records must be appropriately updated such that recommendations are carried forward., Objective: To determine the percentage of patients who have their electronic allergy record updated after an allergy service consult (ASC)., Methods: This was a retrospective study of patients with at least 1 documented beta-lactam allergy and had an ASC during (inpatient) or prior to (outpatient) hospital admission at Northwestern Memorial Hospital and Prentice Women's Hospital in Chicago, Illinois., Results: Within the study period, a total of 26 526 patients were identified as having a documented antibiotic allergy, with 21 657 patients (81.6% of patients with allergies) having a listed beta-lactam allergy. Of these patients, 1689 (7.8%) patients were identified as having an ASC during or prior to admission, with 598 patients meeting inclusion criteria. Changes in the allergy record were recommended by the ASC for 62% (n = 371) of patients; however, the allergy record was updated after the ASC in 74.9% (n = 278) of patients., Conclusion: ASC recommendations to delabel a patient as beta-lactam allergic must result in updating the allergy record in order to optimize future treatment. Given the low proportion of allergy-labeled patients tested, programs outside formal ASCs should be considered.

Objectives: The aim of this study was to evaluate the impact of a shared-care model on outcomes in patients with left ventricular assist devices (LVADs) living in remote locations., Background: Health care delivery through shared-care models has been shown to improve outcomes in patients with chronic diseases. However, the impact of shared-care models on outcomes in patients with LVAD is unknown., Methods: LVAD recipients in the authors' program (2007 to 2018) were classified based on the levels of care provided and training and resources used: level 1, was defined as outpatient primary care without LVAD-specific care; level 2 was level 1 services and outpatient LVAD-specific care; level 3 was level 2 services and inpatient LVAD-specific care and implantation center (IC). The Kaplan-Meier method was used to compare rates of survival, bleeding, pump thrombosis, infection, neurologic events, and readmissions among levels of care., Results: A total of 336 patients were included, with 255 patients (75.9%) cared for in shared-care facilities. Median follow-up was 810 (interquartile range: 321 to 1,096) days. In comparison to patients cared for by IC, patients at levels 2 and 3 shared-care centers had similar rates of death, bleeding, neurologic events, pump thromboses, and infections. However, the rates of death, pump thromboses, and infections were higher for level 1 patients than in IC patients., Conclusions: Shared health care is an effective strategy to deliver care to patients with LVAD living in remote locations. However, patients in shared-care facilities unable to provide LVAD-specific care are at higher risk of unfavorable outcomes. Availability of LVAD-specific care should be strongly considered during patient selection and every effort made to ensure LVAD-specific training and resources are available at shared-care facilities., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate the biologic relevance of cross-platform concordant changes in gene expression in intact human failing/hypertrophied ventricular myocardium undergoing reverse remodeling., Background: Information is lacking on genes and networks involved in remodeled human LVs, and in the associated investigative best practices., Methods: We measured mRNA expression in ventricular septal endomyocardial biopsies from 47 idiopathic dilated cardiomyopathy patients, at baseline and after 3-12 months of β-blocker treatment to effect left ventricular (LV) reverse remodeling as measured by ejection fraction (LVEF). Cross-platform gene expression change concordance was investigated in reverse remodeling Responders (R) and Nonresponders (NR) using 3 platforms (RT-qPCR, microarray, and RNA-Seq) and two cohorts (All 47 subjects (A-S) and a 12 patient "Super-Responder" (S-R) subset of A-S)., Results: For 50 prespecified candidate genes, in A-S mRNA expression 2 platform concordance (CcpT), but not single platform change, was directly related to reverse remodeling, indicating CcpT has biologic significance. Candidate genes yielded a CcpT (PCR/microarray) of 62% for Responder vs. Nonresponder (R/NR) change from baseline analysis in A-S, and ranged from 38% to 100% in S-R for PCR/microarray/RNA-Seq 2 platform comparisons. Global gene CcpT measured by microarray/RNA-Seq was less than for candidate genes, in S-R R/NR 17.5% vs. 38% (P = 0.036). For S-R global gene expression changes, both cross-cohort concordance (CccT) and CcpT yielded markedly greater values for an R/NR vs. an R-only analysis (by 22 fold for CccT and 7 fold for CcpT). Pathway analysis of concordant global changes for R/NR in S-R revealed signals for downregulation of multiple phosphoinositide canonical pathways, plus expected evidence of a β1-adrenergic receptor gene network including enhanced Ca2+ signaling., Conclusions: Two-platform concordant change in candidate gene expression is associated with LV biologic effects, and global expression concordant changes are best identified in an R/NR design that can yield novel information., Competing Interests: This work was funded in part by industry sponsored research awards from GlaxoSmithKline, AstraZeneca and ARCA biopharma (awarded to MRB). The industry funding was unrestricted and without any stipulations, other than receipt of reports of the findings in the form of scientific presentations or manuscripts. MRB was but is no longer a consultant for GlaxoSmithKline, and MRB and IAC are fractional employees of ARCA biopharma. MRB is a founder, officer and director of ARCA biopharma, and none of the information in this manuscript is related to any intellectual property licensed to or being developed by ARCA as the study was conceived, executed and analyzed within MRB’s academic functions and responsibilities. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: The new heart allocation system in the United States prioritizes patients supported by temporary mechanical circulatory support (TMCS) devices over those with uncomplicated durable continuous-flow left ventricular assist devices (CF-LVADs), which may increase the number of patients bridged to transplant with TMCS. Limited data are available in guiding post-transplant outcomes with various TMCS devices. We sought to describe post-transplant outcome and identify clinical variables associated with post-transplant outcome in patients bridged to transplant with TMCS., Methods: Using data from the International Society for Heart and Lung Transplantation Thoracic Transplant Registry, we included subjects who underwent transplantation between 2005 and 2016 with known use of mechanical circulatory support. Pre-transplant recipient, donor, and transplant-specific variables were abstracted. The primary outcome was patient survival at 1-year post-transplant. Outcomes of patients bridged to transplant with TMCS were compared with those of patients bridged with CF-LVADs. Cox regression analyses were performed to identify clinical variables associated with the outcomes., Results: There were 6,528 patients bridged to transplant with the following types of mechanical circulatory support: durable CF-LVADs (n = 6,206), extracorporeal membrane oxygenation (ECMO, n = 134), percutaneous temporary CF-LVADs (n = 75), surgically implanted temporary CF-LVADs (n = 38) or surgically implanted temporary BiVAD (n = 75). Bridging with ECMO (hazard ratio 3.79, 95% confidence interval [CI] 2.69-5.34, p < 0.001) or percutaneous temporary CF-LVADs (hazard ratio 1.83, 95% CI 1.09-3.08, p = 0.02) was independently associated with higher risk of mortality. Additional risk factors included older donor age, female/male donor-recipient match, older recipient age, higher recipient body mass index, higher recipient creatinine, and prolonged ischemic time., Conclusions: This analysis of a large international cohort of patients bridged to transplant with mechanical circulatory support identified ECMO and percutaneous temporary CF-LVADs as predictors of mortality after transplant, along with additional donor and recipient clinical characteristics. These findings may provide guidance to clinicians in decisions on mechanical circulatory support device selection, transplant eligibility, and timing of transplant., (Copyright © 2019 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Gastrointestinal bleeding (GIB) is a leading cause of morbidity during continuous-flow left ventricular assist device (CF-LVAD) support. GIB risk assessment could have important implications for candidate selection, informed consent, and postimplant therapeutic strategies. The aim of the study is to derive and validate a predictive model of GIB in CF-LVAD patients., Methods and Results: CF-LVAD recipients at the Utah Transplantation Affiliated Hospitals program between 2004 and 2017 were included. GIB associated with a decrease in hemoglobin ≥2 g/dL was the primary end point. A weighted score comprising preimplant variables independently associated with GIB was derived and internally validated. A total of 351 patients (median age, 59 years; 82% male) were included. After a median of 196 days, GIB occurred in 120 (34%) patients. Independent predictors of GIB included age >54 years, history of previous bleeding, coronary artery disease, chronic kidney disease, severe right ventricular dysfunction, mean pulmonary artery pressure <18 mm Hg, and fasting glucose >107 mg/dL. A weighted score termed Utah bleeding risk score, effectively stratified patients based on their probability of GIB: low (0-1 points) 4.8%, intermediate (2-4) 39.8%, and high risk (5-9) 83.8%. Discrimination was good in the development sample (c-index: 0.83) and after internal bootstrap validation (c-index: 0.74)., Conclusions: The novel Utah bleeding risk score is a simple tool that can provide personalized GIB risk estimates in CF-LVAD patients. This scoring system may assist clinicians and investigators in designing tailored risk-based strategies aimed at reducing the burden posed by GIB in the individual CF-LVAD patient and healthcare systems.

Background: Cardiac allograft vasculopathy (CAV) remains an important source of mortality after heart transplant. The aim of our study was to identify structural and microvasculature changes in severe CAV., Methods and Results: The study group included heart transplant recipients with severe CAV who underwent retransplantation (severe CAV, n=20). Control groups included time from transplant matched cardiac transplant recipients without CAV (transplant control, n=20), severe ischemic cardiomyopathy patients requiring left ventricular assist device implantation (ischemic control, n=18), and normal hearts donated for research (donor control, n=10). We collected baseline demographic information, echocardiography data, and performed histopathologic examination of myocardial microvasculature. Echocardiographic features of severe CAV included lack of eccentric remodeling and presence of significant diastolic dysfunction. In contrast, diastolic function was preserved in transplant control subjects. Histopathologic examination showed increased interstitial fibrosis among severe CAV, transplant controls, and ischemic control patients. Compared with transplant controls, severe CAV subjects had reduced capillary density and increased capillary wall thickness ( P<0.05)., Conclusions: Our results suggest that the marked diastolic dysfunction and resultant symptoms in patients with severe CAV may be secondary to the loss of microvasculature and remodeling of remaining microvessels rather than a consequence of interstitial fibrosis. The clinical significance and potential therapeutic implications of these unique microvasculature characteristics warrant further investigation.

Background: The purpose of this single-center, ecologic study is to characterize the relationship between facility-wide (FacWide) antibiotic consumption and incident health care facility-onset Clostridium difficile infection (HO-CDI)., Methods: FacWide antibiotic consumption and incident HO-CDI were tallied on a monthly basis and standardized, from January 2013 through April 2015. Spearman rank-order correlation coefficients were calculated using matched-months analysis and a 1-month delay. Regression analyses were performed, with P < .05 considered statistically significant., Results: FacWide analysis identified a matched-months correlation between ceftriaxone and HO-CDI (ρ = 0.44, P = .018). A unit of stem cell transplant recipients did not have significant correlation between carbapenems and HO-CDI in matched months (ρ = 0.37, P = .098), but a significant correlation was observed when a 1-month lag was applied (ρ = 0.54, P = .014)., Discussion: Three statistically significant lag associations were observed between FacWide/unit-level antibiotic consumption and HO-CDI, and 1 statistically significant nonlagged association was observed FacWide. Antibiotic consumption may convey extended ward-level risk for incident CDI., Conclusions: Consumption of antibiotic agents may have immediate and prolonged influence on incident CDI. Additional studies are needed to investigate the immediate and delayed associations between antibiotic consumption and C difficile colonization, infection, and transmission at the hospital level., (Published by Elsevier Inc.)

Diagnosis, prognosis, treatment, and development of new therapies for diseases or syndromes depend on a reliable means of identifying phenotypes associated with distinct predictive probabilities for these various objectives. Left ventricular ejection fraction (LVEF) provides the current basis for combined functional and structural phenotyping in heart failure by classifying patients as those with heart failure with reduced ejection fraction (HFrEF) and those with heart failure with preserved ejection fraction (HFpEF). Recently the utility of LVEF as the major phenotypic determinant of heart failure has been challenged based on its load dependency and measurement variability. We review the history of the development and adoption of LVEF as a critical measurement of LV function and structure and demonstrate that, in chronic heart failure, load dependency is not an important practical issue, and we provide hemodynamic and molecular biomarker evidence that LVEF is superior or equal to more unwieldy methods of identifying phenotypes of ventricular remodeling. We conclude that, because it reliably measures both left ventricular function and structure, LVEF remains the best current method of assessing pathologic remodeling in heart failure in both individual clinical and multicenter group settings. Because of the present and future importance of left ventricular phenotyping in heart failure, LVEF should be measured by using the most accurate technology and methodologic refinements available, and improved characterization methods should continue to be sought., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: This study was designed to evaluate the safety, tolerability and haemodynamic effects of BMS-986231, a novel second-generation nitroxyl donor with potential inotropic, lusitropic and vasodilatory effects in patients hospitalized with decompensated heart failure and reduced ejection fraction (HFrEF)., Methods and Results: Forty-six patients hospitalized with decompensated HFrEF were enrolled into four sequential dose-escalation cohorts in this double-blind, randomized, placebo-controlled Phase 2a study. Patients with baseline pulmonary capillary wedge pressure (PCWP) of ≥20 mmHg and a cardiac index of ≤2.5 L/min/m 2 received one 6-h i.v. infusion of BMS-986231 (at 3, 5, 7 or 12 µg/kg/min) or placebo. BMS-986231 produced rapid and sustained reductions in PCWP, as well as consistent reductions in time-averaged pulmonary arterial systolic pressure, pulmonary arterial diastolic pressure and right atrial pressure. BMS-986231 increased non-invasively measured time-averaged stroke volume index, cardiac index and cardiac power index values, and decreased total peripheral vascular resistance. There was no evidence of increased heart rate, drug-related arrhythmia or symptomatic hypotension with BMS-986231. Analyses of adverse events throughout the 30-day follow-up did not identify any toxicities specific to BMS-986231, with the potential exception of infrequent mild-to-moderate headaches during infusion. There were no treatment-related serious adverse events., Conclusions: BMS-986231 demonstrated a favourable safety and haemodynamic profile in patients hospitalized with advanced heart failure. Based on preclinical data and these study's findings, it is possible that the haemodynamic benefits may be mediated by inotropic and/or lusitropic as well as vasodilatory effects. The therapeutic potential of BMS-986231 should be further assessed in patients with heart failure., (© 2017 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: The relationship between antibiotic consumption and resistance is relatively well defined at the population/ecologic level. Increases in antimicrobial consumption correlate with increased antibiotic resistance for clinical and surveillance isolates. However, the impact of antimicrobial consumption on nosocomial transmission of resistant bacteria is less well defined. This study explores the association between antimicrobial consumption, hand hygiene, and horizontal resistant organism transmission., Methods: A retrospective cohort pilot study was conducted. Vancomycin-resistant Enterococcus spp. (VRE) horizontal transmission events during a 2-year period were identified. VRE transmission events were defined as isolation of genetically similar VRE strain-types (determined using pulsed field gel electrophoresis) from patients who were temporally and geographically co-localized within our hospital. The Centers for Disease Control and Prevention Antimicrobial Use and Resistance Module was utilized to collect antibacterial consumption data of commonly utilized agents. Hand hygiene was quantified using floor-by-floor peer audit data. Regression techniques were employed to assess population-level relationships between study variables and transmission events., Results: One hundred nineteen transmission events were identified. Hand hygiene estimates were homogeneous and did not correlate with VRE transmission rates. Stepwise-multivariate linear regression revealed that aztreonam consumption was associated with a lower rate of transmissions in the medical intensive care unit (P=0.031), and carbapenem consumption was associated with a higher rate of VRE transmission events on one of two oncology floors (P=0.033)., Discussion/conclusion: Consumption of aztreonam and carbapenems was associated with VRE horizontal transmission rates. Further studies are necessary to identify other associations and elucidate the full clinical significance of this finding., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Implementation of partial nitritation anammox (PNA) in the mainstream (municipal wastewater treatment) is still under investigation. Microbial community structure and reactor type can influence the performance of PNA reactor; yet, little is known about the role of the community composition of the inoculum and the reactor configuration under mainstream conditions. Therefore, this study investigated the community structure of inocula of different origin and their consecutive community dynamics in four different lab-scale PNA reactors with 16S rRNA gene amplicon sequencing. These reactors were operated for almost 1 year and subjected to realistic seasonal temperature fluctuations as in moderate climate regions, that is, from 20°C in summer to 10°C in winter. The sequencing analysis revealed that the bacterial community in the reactors comprised: (1) a nitrifying community (consisting of anaerobic ammonium-oxidizing bacteria (AnAOB), ammonia-oxidizing bacteria (AOB), and nitrite-oxidizing bacteria (NOB)); (2) different heterotrophic denitrifying bacteria and other putative heterotrophic bacteria (HB). The nitrifying community was the same in all four reactors at the genus level, although the biomasses were of different origin. Community dynamics revealed a stable community in the moving bed biofilm reactors (MBBR) in contrast to the sequencing batch reactors (SBR) at the genus level. Moreover, the reactor design seemed to influence the community dynamics, and reactor operation significantly influenced the overall community composition. The MBBR seems to be the reactor type of choice for mainstream wastewater treatment., (© 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.)

Heart failure (HF) in the United States represents a significant burden for patients and a tremendous strain on the healthcare system. Patients receiving a diagnosis of HF can be placed into 1 of 4 New York Heart Association (NYHA) functional classifications; the greatest proportion of patients are in the NYHA class II category, which is defined as patients having a slight limitation of physical activity but who are comfortable at rest, and for whom ordinary physical activity results in symptoms of HF. Because the severity of NYHA class II HF may be perceived as mild or unalarming by this definition, the urgency to treat this type of HF may be overlooked. However, these patients are optimal candidates for active intervention because their HF is at a critical point on the disease progression continuum when untoward changes can be halted or reversed. This review discusses the physiological consequences of NYHA class II HF with reduced ejection fraction and describes recent clinical trials that have demonstrated a therapeutic benefit for patients in this population. In doing so, we hope to establish that patients with NYHA class II disease merit careful attention and to provide reassurance to the treating community that options are available for these patients.

Background: An on call infectious diseases (ID) pharmacist may be used as a resource for physicians, pharmacists, and other health care providers to help answer questions regarding anti-infective agents. Objective: To assess type, requestor, resources dedicated, and temporal trends of questions received through an ID pharmacist on call pager program. A secondary objective was to gather insight as to how this information was utilized to inform educational initiatives. Methods: This was a retrospective study of questions received by the ID pharmacist on call via pager at a large academic medical center. Question data were documented in a central database and analyzed to assess temporal trends and question type, and qualitatively analyzed to determine areas for targeted educational efforts. Results: The ID pharmacist on call recorded 545 questions during the 1-year study period; questions were composed of various antimicrobial agent-related queries, including antibiotic spectrum and selection (n = 251, 46.1%), dosing of antimicrobials (n = 195, 35.8%), and drug monitoring (n = 26, 4.8%). Targeted educational initiatives secondary to questions received included pharmacist education regarding the use of polymyxin antibiotics and antibiotic dosing protocol updates. Conclusions: An ID pharmacist on call pager program was utilized to inquire about antibiotic spectrum and selection for the majority of questions. Records of questions received may be utilized to direct educational efforts and create or revise targeted resources for pharmacists and other clinicians., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2017.)

Background: Organism detection by 16S ribosomal RNA (rRNA) PCR followed by amplicon sequencing identification may help guide antimicrobial treatment in culture-negative patients. The objectives of this study were to assess the effect of a positive versus negative 16S rRNA PCR on antibiotic length of therapy (LOT) and rate of antibiotic discontinuation., Methods: Patients with a sterile site, direct-specimen 16S rRNA PCR negative, and suspected active infection were matched 1:1 with 16S rRNA PCR positive patients based on specimen site and retrospectively evaluated., Results: Ninety patients were included (n=45 positive and negative). 16S rRNA PCR negative patients had shorter median LOT (33days [IQR 8-46] versus 43days [IQR 29-51], P=0.02). Antibiotics were discontinued more frequently in 16S rRNA PCR negative patients (38% versus 4%, P<0.01)., Conclusions: For culture-negative patients with suspected sterile site infection, a negative, direct-specimen 16S rRNA PCR may help discontinue antibiotics and decrease LOT., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Methicillin-susceptible Staphylococcus aureus (MSSA) infections have been successfully treated both with cefazolin and antistaphylococcal penicillins; cefazolin appears effective in MSSA bloodstream infections (BSIs). Thus, our antimicrobial stewardship programme (ASP) implemented a clinical pathway supporting cefazolin use in MSSA-BSIs and restricting oxacillin use to infectious diseases (ID) consultation due to cefazolin's lower cost and more convenient dosing. This before and after quasi-experimental study was conducted to describe the impact on outcomes and process of care measures associated with implementing this pathway among patients with MSSA-BSI. Definitive treatment with cefazolin increased over the study period from 17.3% to 69.8% post-implementation. Clinical failure (5.8% vs. 2.3%; P = 0.62) and in-hospital mortality (3.8% vs. 0%; P = 0.50) were rare pre- and post-implementation. Median hospital length of stay among survivors was similar between pre- and post-implementation periods (P = 0.31). Duration of bacteraemia [median (IQR) 3 (2-4) days vs. 2 (2-3) days; P = 0.002] and rates of re-infection after culture clearance (9.6% vs. 0%; P = 0.06) were reduced post-implementation. Frequency of source control (P = 0.71) and time to source control (P = 0.52) were similar between study periods. Significant increases in ID consultations (33.3% [3/9] vs. 73.3% [22/30]; P = 0.047) and median (IQR) 24-h daily doses [2 (1-3) g vs. 6 (3-6) g; P < 0.01] were seen for patients treated with cefazolin post-implementation. ASPs may find implementation of a similar pathway to be an effective means of improving the care of patients infected with MSSA., (Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Background: In dilated cardiomyopathies (DCMs) changes in expression of protein-coding genes are associated with reverse remodeling, and these changes can be regulated by microRNAs (miRs). We tested the general hypothesis that dynamic changes in myocardial miR expression are predictive of β-blocker-associated reverse remodeling., Methods: Forty-three idiopathic DCM patients (mean left ventricular ejection fraction 0.24 ± 0.09) were treated with β-blockers. Serial ventriculography and endomyocardial biopsies were performed at baseline, and after 3 and 12 months of treatment. Changes in RT-PCR (candidate miRs) or array-measured miRs were compared based on the presence (R) or absence (NR) of a reverse-remodeling response, and a miR-mRNA-function pathway analysis (PA) was performed., Results: At 3 months, 2 candidate miRs were selectively changed in Rs, decreases in miR-208a-3p and miR-591. PA revealed changes in miR-mRNA interactions predictive of decreased apoptosis and myocardial cell death. At 12 months, 5 miRs exhibited selective changes in Rs (decreases in miR-208a-3p, -208b-3p, 21-5p, and 199a-5p; increase in miR-1-3p). PA predicted decreases in apoptosis, cardiac myocyte cell death, hypertrophy, and heart failure, with increases in contractile and overall cardiac functions., Conclusions: In DCMs, myocardial miRs predict the time-dependent reverse-remodeling response to β-blocker treatment, and likely regulate the expression of remodeling-associated miRs., Trial Registration: ClinicalTrials.gov NCT01798992., Funding: NIH 2R01 HL48013, 1R01 HL71118 (Bristow, PI); sponsored research agreements from Glaxo-SmithKline and AstraZeneca (Bristow, PI); NIH P20 HL101435 (Lowes, Port multi-PD/PI); sponsored research agreement from Miragen Therapeutics (Port, PI)., Competing Interests: C.C. Sucharov, J.D. Port, and M.R. Bristow have stock (each less than 0.1% of total outstanding shares) in Miragen Therapeutics, and M.R. Bristow is member of the Miragen Scientific Advisory Board.

We present the case of two patients with idiopathic dilated cardiomyopathy and moderate aortic valve regurgitation that were treated with a bioprosthetic valve at the time of the left ventricular assist device (LVAD) implantation. A few months later, patients revealed partial recovery in the left ventricle systolic function. Both patients, during the LVAD turndown protocol, reported the onset of chest pain. The transthoracic echocardiography revealed the presence of a new transaortic pressure gradient. We confirmed the presence of a fused bioprosthetic valve by further performing a transesophageal echocardiogram and a left and right heart catheterization. Replacement of aortic valve at the time of an LVAD implantation constitutes a challenging case. Although a mechanical valve is contraindicated due to the increased thromboembolic risk, selecting a bioprosthetic valve increases the risk of valve leaflets fusion. The consequences of this phenomenon should be acknowledged in LVAD patients undergoing aortic valve replacement with a bioprosthetic, especially under the view of LVAD explantation for those revealing myocardial recovery under mechanical unloading.

Benchmarks for antimicrobial consumption measured in antimicrobial days are beginning to emerge. The relationship between the traditional measure of days of therapy and antimicrobial days is unclear. We observed a high intermethod correlation (R2=0.99): antimicrobial days were 1.9-fold lower than days of therapy across agents. Individual institutions should correlate these measures. Infect Control Hosp Epidemiol 2016;37:971-973.

Background: Immune allosensitization can be triggered by continuous-flow left ventricular assist devices (CF LVAD). However, the effect of this type of allosensitization on post-transplant outcomes remains controversial. This study examined the post-transplant course in a contemporary cohort of patients undergoing transplantation with and without LVAD bridging., Methods: We included consecutive patients who were considered for cardiac transplant from 2006 to 2015. Serum alloantibodies were detected with single-antigen beads on the Luminex platform (One Lambda Inc., Canoga Park, CA). Allosensitization was defined as calculated panel reactive antibody (cPRA) > 10%. cPRA was determined at multiple times. LVAD-associated allosensitization was defined as development of cPRA > 10% in patients with cPRA ≤ 10% before LVAD implantation. Post-transplant outcomes of interest were acute cellular rejection (ACR), antibody-mediated rejection (AMR), and survival., Results: Allosensitization status was evaluated in 268 patients (20% female). Mean age was 52 ± 12 years, and 132 (49.3%) received CF LVADs. After LVAD implant, 30 patients (23%) became newly sensitized, and the level of sensitization appeared to diminish in many of these patients while awaiting transplant. During the study period, 225 of 268 patients underwent transplant, and 43 did not. A CF LVAD was used to bridge 50% of the transplant recipients. Compared with patients without new sensitization or those already sensitized at baseline, the patients with LVAD-associated sensitization had a higher risk of ACR (p = 0.049) and higher risk of AMR (p = 0.018) but a similar intermediate-term post-transplant survival. The patients who did not receive a transplant had higher level of allosensitization, with a baseline cPRA of 20% vs 6% in those who received an allograft and a high risk (40%) of death during follow-up., Conclusions: New allosensitization takes place in > 20% of patents supported with CF LVADs. Among patients who undergo transplant, this results in a higher risk of ACR and AMR, but survival remains favorable, likely due to the efficacy of current management after transplant. However, mortality in sensitized patients who do not reach transplant remains high, and new approaches are necessary to meet the needs of this group of patients., (Published by Elsevier Inc.)

Purpose: A methodology for predicting how long the on-hand inventory of a given medication will last during a supply shortage is described; a practical example of application of the methodology is provided., Methods: Single-site data on consumption of i.v. tobramycin over an eight-month evaluation period were collected using commercial software that tabulates barcode-assisted medication administration (BCMA) events; administered doses were standardized as 1200-mg "vial-equivalents" and summed over the review period. The total number of vial-equivalents consumed was divided by the number of "non-zero weeks of consumption" (i.e., weeks during which any tobramycin use occurred) to obtain a mean ± S.D. weekly consumption rate; this rate was multiplied by the total i.v. tobramycin on-hand supply (in vial-equivalents) to determine the mean number of potentially sustainable weeks of therapy in the event a shortage were to restrict the future supply of the drug., Results: Overall, 99.6 vial-equivalents of i.v. tobramycin were used during the evaluation period. The mean ± S.D. number of vial-equivalents used per non-zero week of consumption was 3.11 ± 1.26. A manual count of pharmacy inventory revealed that 102.9 vial-equivalents were available at the time of analysis. The mean predicted duration of supply was 33 weeks (95% confidence interval, -126 to 192 weeks)., Conclusion: Available BCMA data on tobramycin consumption over eight months were used to calculate the mean number of weeks the on-hand supply of the drug could be expected to last during a persistent drug shortage., (Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

Purpose: The integration of specialty pharmacy services and existing outpatient clinical pharmacy services within an infectious diseases (ID) clinic to optimize the care of patients with human immunodeficiency virus (HIV) infection is described., Summary: The management of HIV-infected patients is a highly specialized area of practice, often requiring use of complex medication regimens for reduction of HIV-associated morbidity and mortality prophylaxis and treatment of opportunistic infections, and prevention of HIV transmission. To maximize the effectiveness and safety of treatment with antiretroviral agents and associated pharmacotherapies, an interdisciplinary team is often involved in patient care. At Chicago-based Northwestern Medicine (NM), the outpatient ID clinic has long worked with an interdisciplinary care team including physicians, clinical pharmacists, nurses, and social workers to care for patients with HIV infection. In April 2014, specialty pharmacy services for patients with HIV infection were added to the NM ID clinic's care model to help maintain continuity of care and enhance patient follow-up. The care model includes well-defined roles for clinical pharmacists, pharmacy residents and students on rotation, and licensed pharmacy technicians. Specialty pharmacy services, including medication education, prescription fulfillment, assistance with medication access (e.g., navigation of financial assistance programs, completion of prior-authorization requests), and treatment monitoring, allow for closed-loop medication management of the HIV-infected patient population., Conclusion: Integration of specialty pharmacy services with the interdisciplinary care provided in the outpatient NM ID clinic has enhanced continuity of care for patients with HIV infection in terms of prescription filling, medication counseling, and adherence monitoring., (Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

Benchmarks for judicious use of antimicrobials are needed. Metrics such as defined daily doses (DDDs) and days of therapy (DOTs) quantify antimicrobial consumption. However, benchmarking with these metrics is complicated by interhospital variability. Thus, it is important for each hospital to monitor its own temporal consumption trends. Time series analyses allow trends to be detected; however, many of these methods are complex. We present simple regressive methods and caveats in using them to define potential antibiotic over- and underutilizations., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Background: Little is known about mixed cellular and antibody-mediated rejection (MR) in heart transplantation. It remains unclear whether cardiac MR has distinctive pathologic and clinical features beyond those of simultaneous cellular rejection (CR) and antibody-mediated rejection (AMR). In this study we systematically explore the pathologic and clinical characteristics of MR in heart transplantation., Methods: The UTAH Cardiac Transplant Program database was queried for transplant recipients who survived long enough to have at least one endomyocardial biopsy (EMB) between 1985 and 2014. Only EMBs with both CR and AMR scores documented were included. In addition to detailed pathologic analyses, we also examined the incidence and prevalence of MR, the likelihood to transition from and to MR, and mortality associated with MR., Results: Patients (n = 1,207) with a total of 28,484 EMBs met the study inclusion criteria. The overall prevalence of MR was 7.8% and it was nearly twice as frequent within the first year post-transplant. Mild MR was by far the most common occurrence and was typically preceded by an immune active state. When CR increased in severity, AMR tended to follow, but the reverse was not true. On pathology, individual features of CR and AMR were more easily separated in cases of mild MR, whereas they substantially overlapped in more severe cases. MR was associated with a significant cardiovascular death risk that was incremental with severity., Conclusions: MR is not common, usually occurs early after transplant, and is associated with worse outcomes. MR reflects a complex interplay between cellular and humoral processes, which varies with rejection severity., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: With increasing age, human ventricular myocardium exhibits selective downregulation of β1-adrenergic receptors (β1-ARs). We tested the hypothesis that sex differences exist in age-related changes in β1-ARs., Methods: Left (LV) and right (RV) ventricular tissue was obtained from 61 unplaceable potential organ donor hearts ages 1 to 71 years with no known cardiac history and from LVs removed from 56 transplant recipients with idiopathic dilated cardiomyopathy. β1-AR and β2-AR densities, the frequency of β1-AR389 gene variants, and β-AR function were determined., Results: Sex had a marked effect on the age-related decrease in β1-ARs. Female LVs had more pronounced downregulation (by 42% [p < 0.001] vs 22% [p = 0.21] in 31 male LVs) comparing the youngest (average age, 15.3 ± 5.5 years) to the oldest (average age, 50.8 ± 9.1 years) sub-groups. On regression analyses, female LVs exhibited a closer relationship between β1-AR density and age (r = -0.78, p <0.001 vs r = -0.46, p = 0.009 in males), with a second-degree polynomial yielding the best fit. There was no statistically significant relationship of β1-ARs to age in female or male idiopathic dilated cardiomyopathy LVs., Conclusions: Sex affects age-related β-AR downregulation in normal human ventricles, with females exhibiting more profound decreases with increasing age. The curvilinear relationship between age and receptor density that plateaus around age 40 in women suggests an effect of sex hormones on β1-AR expression in the human heart., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Partial Nitritation/Anammox (PN/A) is a well-established technology for side-stream nitrogen removal from highly concentrated, warm wastewaters. The focus has now shifted to weakly concentrated municipal wastewaters with much lower concentrations and temperatures. The major challenge is the temperature, which ranges from moderate 20 °C in summer to cold 10 °C in winter. For this study, the most frequently used configurations for side-stream applications were exposed to a slow temperature reduction from 20 °C to 10 °C to simulate a realistic temperature gradient. To evaluate the behavior of the different biomasses based on their properties, four lab reactors were operated in two different configurations. Synthetic wastewater was used to avoid side effects of heterotrophic growth. Differences in the response of the different reactor systems to this temperature gradient clearly indicated, that the geometry of the biomass has a major impact on the overall PN/A performance at low temperatures: While anammox activity in suspended biomass suffered already at 15 °C, it persevered in granular biomass as well as in biofilms on carriers for temperatures down to <13 °C. Further, anammox activity in thicker biofilms was less affected than in thinner biofilms and even adaption to low temperatures was observed., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: The elevated baseline heart rate (HR) of a heart transplant recipient has previously been considered inconsequential. However, we hypothesized that a resting HR above 100 beats per minute (bpm) may be associated with morbidity and mortality., Methods: The U.T.A.H. Cardiac Transplant Program studied patients who received a heart transplant between 2000 and 2011. Outpatient HR values for each patient were averaged during the first year post-transplant. The study cohort was divided into two groups: the tachycardic (TC) (HR > 100 bpm) and the non-TC group (HR ≤ 100 bpm) in which mortality, incidence of rejection, and cardiac allograft vasculopathy were compared., Results: Three hundred and ten patients were included as follows: 73 in the TC and 237 in the non-TC group. The TC group had a higher risk of a 10-yr all-cause mortality (p = 0.004) and cardiovascular mortality (p = 0.044). After adjustment for donor and recipient characteristics in multivariable logistic regression analysis, the hazard ratio was 3.9, (p = 0.03, CI: 1.2-13.2) and 2.6 (p = 0.02, CI: 1.2-5.5) for cardiovascular mortality and all-cause mortality, respectively., Conclusion: Heart transplant recipients with elevated resting HR appear to have higher mortality than those with lower resting HR. Whether pharmacologically lowering the HR would result in better outcomes warrants further investigation., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

For women infected with the human immunodeficiency virus (HIV) who become pregnant, the use of combination antiretroviral therapy (ART) significantly reduces transmission of HIV from mother to child. Selection of an appropriate ART regimen for use among pregnant women requires consideration of numerous factors including maternal and fetal safety, antiretroviral pharmacokinetics, and regimen efficacy. Optimization of antiretroviral pharmacokinetics during pregnancy requires special consideration because pregnancy-associated changes in drug absorption, distribution, metabolism, and excretion are known to occur throughout pregnancy and postpartum. Understanding antiretroviral placental transfer may offer additional insight into each drug's potential role in preventing HIV transmission in utero and may also have implications regarding viral resistance in cases where transmission does occur. In this review, we summarize key published data describing antiretroviral pharmacokinetics in pregnant women, providing suggestions for clinical application of these data where appropriate., (© 2015 Pharmacotherapy Publications, Inc.)

Background: When β-blockers produce reverse-remodeling in idiopathic dilated cardiomyopathy, they partially reverse changes in fetal-adult/contractile protein, natriuretic peptide, SR-Ca(2+)-ATPase gene program constituents. The objective of the current study was to further test the hypothesis that reverse-remodeling is associated with favorable changes in myocardial gene expression by measuring additional contractile, signaling, and metabolic genes that exhibit a fetal/adult expression predominance, are thyroid hormone-responsive, and are regulated by β1-adrenergic receptor signaling. A secondary objective was to identify which of these putative regulatory networks is most closely associated with observed changes., Methods and Results: Forty-seven patients with idiopathic dilated cardiomyopathy (left ventricular ejection fraction, 0.24±0.09) were randomized to the adrenergic-receptor blockers metoprolol (β1-selective), metoprolol+doxazosin (β1/α1), or carvedilol (β1/β2/α1). Serial radionuclide ventriculography and endomyocardial biopsies were performed at baseline, 3, and 12 months. Expression of 50 mRNA gene products was measured by quantitative polymerase chain reaction. Thirty-one patients achieved left ventricular ejection fraction reverse-remodeling response defined as improvement by ≥0.08 at 12 months or by ≥0.05 at 3 months (Δ left ventricular ejection fraction, 0.21±0.10). Changes in gene expression in responders versus nonresponders were decreases in NPPA and NPPB and increases in MYH6, ATP2A2, PLN, RYR2, ADRA1A, ADRB1, MYL3, PDFKM, PDHX, and CPT1B. All except PDHX involved increase in adult or decrease in fetal cardiac genes, but 100% were concordant with changes predicted by inhibition of β1-adrenergic signaling., Conclusions: In addition to known gene expression changes, additional calcium-handling, sarcomeric, adrenergic signaling, and metabolic genes were associated with reverse-remodeling. The pattern suggests a fetal-adult paradigm but may be because of reversal of gene expression controlled by a β1-adrenergic receptor gene network., Clinical Trial Registration: URL: www.clinicaltrials.gov. Unique Identifier: NCT01798992., (© 2015 American Heart Association, Inc.)

This study shows the start-up and operation of a full-scale sequencing batch reactor (SBR) with a volume of 550 m³ for deammonification of reject water from sludge dewatering over the first 650 days of operation. The SBR was operated with discontinuous aeration and achieved an optimum of around 85% of ammonium removal at a load of 0.17 kg m⁻³ d⁻¹. The application of batch tests for the activity measurement of aerobic ammonium and nitrite oxidizing bacteria and anaerobic ammonium oxidizing bacteria were proven to support the identification of setbacks in reactor operation. Furthermore, the calculation of the oxygen uptake rates from online oxygen measurements helped to explain the overall reactor performance. The aeration regime is a key parameter for stable operation of such an SBR for deammonification. At aeration/non-aeration time ranges from 6-9 min, the best results with respect to turnover rates and low nitrate production were achieved. Compared with the nitrification/denitrification SBR operated in parallel with methanol as the carbon source, a significant reduction in costs for energy and chemicals was achieved. The costs for maintenance slightly increased.

Partial nitritation-anammox (PN-A) has gained increasing interest for municipal wastewater treatment in recent years due to its high energy-saving potential. Moving the PN-A technology from side- to mainstream exhibited a set of challenges. Conditions are quite different, with much lower ammonium concentrations and temperatures. Biomass retention becomes highly important due to the even lower growth rates. This study compared two laboratory-scale reactors, a sequencing batch reactor (SBR) and a moving bed biofilm reactor (MBBR), employing realistic seasonal temperature variations over a 1-year period. The results revealed that both systems had to face decreasing ammonium conversion rates and nitrite accumulation at temperatures lower than 12°C. The SBR did not recover from the loss in anammox activity even when the temperature increased again. The MBBR only showed a short nitrite peak and recovered its initial ammonium turnover when the temperature rose back to >15°C. The SBR had higher biomass specific rates, indicating that suspended sludge is less diffusion-limited but also more susceptible to biomass wash-out. However, the MBBR showed the more stable performance also at low temperatures and managed to recover. Ex situ batch activity tests supported reactor operation data by providing additional insight with respect to specific biomass activities.

Partial nitritation/anammox (PN/A) has been one of the most innovative developments in biological wastewater treatment in recent years. With its discovery in the 1990s a completely new way of ammonium removal from wastewater became available. Over the past decade many technologies have been developed and studied for their applicability to the PN/A concept and several have made it into full-scale. With the perspective of reaching 100 full-scale installations in operation worldwide by 2014 this work presents a summary of PN/A technologies that have been successfully developed, implemented and optimized for high-strength ammonium wastewaters with low C:N ratios and elevated temperatures. The data revealed that more than 50% of all PN/A installations are sequencing batch reactors, 88% of all plants being operated as single-stage systems, and 75% for sidestream treatment of municipal wastewater. Additionally an in-depth survey of 14 full-scale installations was conducted to evaluate practical experiences and report on operational control and troubleshooting. Incoming solids, aeration control and nitrate built up were revealed as the main operational difficulties. The information provided gives a unique/new perspective throughout all the major technologies and discusses the remaining obstacles., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Municipal wastewater collected in areas with moderate climate is subjected to a gradual temperature decrease from around 20 °C in summer to about 10 °C in winter. A lab-scale moving bed biofilm reactor (MBBR) with carrier material (K3 from AnoxKaldnes) was used to test the tolerance of the overall partial nitritation/anammox process to this temperature gradient. A synthetic influent, containing only ammonium and no organic carbon was used to minimize denitrification effects. After stable reactor operation at 20 °C, the temperature was slowly reduced by 2 °C per month and afterward held constant at 10 °C. Along the temperature decrease, the ammonium conversion dropped from an average of 40 gN m(-3) d(-1) (0.2 gN kgTSS h(-1)) at 20 °C to about 15 gN m(-3) d(-1) (0.07 gN kg TSS h(-1)) at 10 °C, while the effluent concentration was kept <8 mg NH4-N l(-1) during the whole operation. This also resulted in doubling of the hydraulic retention time over the temperature ramp. The MBBR with its biofilm on 10 mm thick carriers proved to sufficiently sustain enough biomass to allow anammox activity even at 10 °C. Even though there was a minor nitrite-build up when the temperature dropped below 12.5 °C, reactor performance recovered as the temperature decrease continued. Microbial community analysis by 16S rRNA amplicon analysis revealed a relatively stable community composition over the entire experimental period.

The exploitation of a lag phase in nitrate production after anoxic periods is a promising approach to suppress nitrite oxidizing bacteria, which is crucial for implementation of the combined partial nitritation-anammox process. An in-depth study of the actual lag phase in nitrate production after short anoxic periods was performed with varied temperatures and air flow rates. In monitored batch experiments, biomass from four different full-scale partial nitritation-anammox plants was subjected to anoxic periods of 5-60 min. Ammonium and the nitrite that was produced were present to reproduce reactor conditions and enable ammonium and nitrite oxidation at the same time. The lag phase observed in nitrite oxidation exceeded the lag phase in ammonium oxidation after anoxic periods of more than 15-20 min. Lower temperatures slowed down the conversion rates but did not affect the lag phases. The operational oxygen concentration in the originating full scale plants strongly affected the length of the lag phase, which could be attributed to different species of Nitrospira spp. detected by DGGE and sequencing analysis.

Single-stage nitritation-anammox combines the growth of aerobic ammonium-oxidizing bacteria (AOB) and anaerobic ammonium oxidizing bacteria (AnAOB) in one reactor. The necessary compromise of their milieu conditions often leads to the growth of nitrite-oxidizing bacteria (NOB). For this study, a sequencing batch reactor (SBR) for nitritation-anammox was operated for 180 days with sewage sludge reject water (removal capacity, 0.4 kg N m(-3) day(-1)). The growth of NOB was favored by enhanced oxygen supply rather than extended aerobic phases. Suspended-type biomass from this SBR was taken regularly and sieved into three size fractions (all of them <1,000 μm). Batch experiments as well as fluorescence in situ hybridization were performed to study the distribution and activity of AnAOB, AOB, and NOB within those size fractions. Both the measured conversion rates and detected abundances decreased with increasing size fraction. The highest anammox conversion rates (15 g NH4 (+)-N per kilogram VSS per hour) and the highest abundances of Brocadia fulgida were found in the medium size fraction (100-315 μm). The batch experiments proved to be accurate tools for the monitoring of multiple processes in the reactor. The results were representative for reactor performance during the 6 months of reactor operation.

Objectives: This study sought to prospectively investigate the longitudinal effects of continuous-flow left ventricular assist device (LVAD) unloading on myocardial structure and systolic and diastolic function., Background: The magnitude, timeline, and sustainability of changes induced by continuous-flow LVAD on the structure and function of the failing human heart are unknown., Methods: Eighty consecutive patients with clinical characteristics consistent with chronic heart failure requiring implantation of a continuous-flow LVAD were prospectively enrolled. Serial echocardiograms (at 1, 2, 3, 4, 6, 9, and 12 months) and right heart catheterizations were performed after LVAD implant. Cardiac recovery was assessed on the basis of improvement in systolic and diastolic function indices on echocardiography that were sustained during LVAD turn-down studies., Results: After 6 months of LVAD unloading, 34% of patients had a relative LV ejection fraction increase above 50% and 19% of patients, both ischemic and nonischemic, achieved an LV ejection fraction ≥ 40%. LV systolic function improved as early as 30 days, the greatest degree of improvement was achieved by 6 months of mechanical unloading and persisted over the 1-year follow up. LV diastolic function parameters also improved as early as 30 days after LVAD unloading, and this improvement persisted over time. LV end-diastolic and end-systolic volumes decreased as early as 30 days after LVAD unloading (113 vs. 77 ml/m(2), p < 0.01, and 92 vs. 60 ml/m(2), p < 0.01, respectively). LV mass decreased as early as 30 days after LVAD unloading (114 vs. 95 g/m(2), p < 0.05) and continued to do so over the 1-year follow-up but did not reach values below the normal reference range, suggesting no atrophic remodeling after prolonged LVAD unloading., Conclusions: Continuous-flow LVAD unloading induced in a subset of patients, both ischemic and nonischemic, early improvement in myocardial structure and systolic and diastolic function that was largely completed within 6 months, with no evidence of subsequent regression., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)