The effect of obligatory Padua prediction scoring in hospitalized medically ill patients: A retrospective cohort study.

BACKGROUND: Venous thromboembolism (VTE) is considered a preventable cause of mortality. The evidence for the benefit of VTE prophylaxis in acute medical patients is non-conclusive. Meta-analysis of RCTs failed to demonstrate reduction of all-cause mortality, while showing higher risk of bleeding. The Israeli Ministry of Health has instructed to assess all acute medical patients for the risk for VTE using the Padua Prediction Score, without mandating prophylaxis. AIM: To evaluate the effect of filling the Padua score on clinical outcomes and VTE prophylaxis rates. METHODS: Retrospective Study was performed in Israel during the years 2014-2017. The participants were divided to Padua compliance vs non-compliance group. Primary outcome: 30-day mortality. Secondary outcomes: 90-day incidence of VTE and suspected major bleeding. A propensity-weighted logistic multiple regression was performed. RESULTS: 18,890 patients were included in the study. The fulfillment of the Padua score was associated with an increased use of VTE prophylaxis, OR 1.66 (95% CI 1.49-1.84). However, there was no reduction of mortality or VTE events, OR 1.13 (95% CI 0.97-1.31) and OR 1.22 (95% CI 0.79-1.8) respectively. Hospitalizations related to hemoglobin decrease were not statistically different between the two groups. CONCLUSIONS: Padua score for the assessment of VTE risk in medical wards was associated with higher administration of pharmacological prophylaxis without reduction in VTE or mortality rate. Its usage should be reassessed as a performance measure.

Self-Reported Mental and Physical Measures in Adult Fontan Patients.

Introduction: The Fontan procedure is a palliative operation for patients with single functional ventricles, arising from a heterogeneous group of heart defects. There is a considerable gap in evidence regarding the self-reported physical and mental health of these patients surviving to adulthood. Methods and Results: We administered the PROMIS® Global Short Form (v 1.2) to Fontan patients during their scheduled clinic visits during 2017−2018. The raw PROMIS scores were subsequently converted to standardized T-scores, where the mean performance was 50 for the general population. We used Cronbach's alpha to assess reliability, with >0.8 considered good. A total of 42 patients were included. The median age was 30 (IQR: 24−34) years and 59% (95% CI: 43−74%) were female. The median time from birth to operation was 4.5 (IQR: 3−8) years, with 55% having an extracardiac Fontan. The questionnaire had good internal reliability with an alpha of 0.87. Seventy-one percent of respondents rated their overall health as "excellent" or "good". The mean T-score for physical health was 46.6, lower than the age-group mean (51.6, p < 0.001). The mean T-score for mental health was 53.3, higher than the age-group mean (48.5, p < 0.001). T-scores showed strong correlation with each other (r = 0.7) and weak correlation with age and time from procedure. There was no association of T-score with diagnosis or operation type. Conclusions: Adult Fontan patients report better mental health despite worse reporting physical health compared with the age group means. Patient-reported measures can provide clinically meaningful insights about the care of patients with complex congenital heart disease.

Large-scale WGS of carbapenem-resistant Acinetobacter baumannii isolates reveals patterns of dissemination of ST clades associated with antibiotic resistance.

OBJECTIVES: To describe the population genetics and antibiotic resistance gene distribution of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates causing infections in three Mediterranean countries. METHODS: Isolates were collected during the 2013-17 AIDA clinical trial in six hospitals in Israel, Greece and Italy. WGS, bioinformatic characterization and antibiotic resistance profiling were performed. RESULTS: In the 247 CRAB isolates characterized in this study, ST distribution varied by country: 29/31 (93.5%) Greek isolates, 34/41 (82.9%) Italian isolates and 70/175 (40.0%) Israeli isolates belonged to ST2. The identified ST2 isolates included eight distinct clades: 2C, 2D and 2H were significantly more common in Italy, while 2F was unique to Greece. The uncommon ST3 was not present among Greek isolates and constituted only 5/41 (12%) Italian isolates. On the other hand, it was much more common among Israeli isolates: 78/175 (44.6%) belonged to ST3. The vast majority of isolates, 240/247 (97.2%), were found to harbour acquired carbapenemases, primarily blaOXA-23. The chromosomal oxaAb (blaOXA-51-like) and ampC genes characteristic of this organism were also ubiquitous. Most (96.4%) ST3 isolates carried a broad-host-range plasmid IncP1α. CONCLUSIONS: The geographical differences in CRAB populations support the theory that clonal spread of CRAB leads to endemicity in hospitals and regions. The close association between antibiotic resistance genes and clades, and between plasmids and STs, suggest that de novo creation of MDR A. baumannii is rare. The clustering of antibiotic resistance genes and plasmids that is unique to each clade/ST, and nearly uniform within clades/STs, suggests that horizontal transmission is rare but crucial to the clade's/ST's success.

Excluded versus included patients in a randomized controlled trial of infections caused by carbapenem-resistant Gram-negative bacteria: relevance to external validity.

BACKGROUND: Population external validity is the extent to which an experimental study results can be generalized from a specific sample to a defined population. In order to apply the results of a study, we should be able to assess its population external validity. We performed an investigator-initiated randomized controlled trial (RCT) (AIDA study), which compared colistin-meropenem combination therapy to colistin monotherapy in the treatment of patients infected with carbapenem-resistant Gram-negative bacteria. In order to examine the study's population external validity and to substantiate the use of AIDA study results in clinical practice, we performed a concomitant observational trial. METHODS: The study was conducted between October 1st, 2013 and January 31st, 2017 (during the RCTs recruitment period) in Greece, Israel and Italy. Patients included in the observational arm of the study have fulfilled clinical and microbiological inclusion criteria but were excluded from the RCT due to receipt of colistin for > 96 h, refusal to participate, or prior inclusion in the RCT. Non-randomized cases were compared to randomized patients. The primary outcome was clinical failure at 14 days of infection onset. RESULTS: Analysis included 701 patients. Patients were infected mainly with Acinetobacter baumannii [78.2% (548/701)]. The most common reason for exclusion was refusal to participate [62% (183/295)]. Non-randomized and randomized patients were similar in most of the demographic and background parameters, though randomized patients showed minor differences towards a more severe infection. Combination therapy was less common in non-randomized patients [31.9% (53/166) vs. 51.2% (208/406), p = 0.000]. Randomized patients received longer treatment of colistin [13 days (IQR 10-16) vs. 8.5 days (IQR 0-15), p = 0.000]. Univariate analysis showed that non-randomized patients were more inclined to clinical failure on day 14 from infection onset [82% (242/295) vs. 75.5% (307/406), p = 0.042]. After adjusting for other variables, non-inclusion was not an independent risk factor for clinical failure at day 14. CONCLUSION: The similarity between the observational arm and RCT patients has strengthened our confidence in the population external validity of the AIDA trial. Adding an observational arm to intervention studies can help increase the population external validity and improve implementation of study results in clinical practice. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov, number NCT01732250 on November 22, 2012.

Outcome of patients with prior coronary bypass surgery admitted with an acute coronary syndrome.

BACKGROUND: Patients with prior coronary artery bypass graft surgery (CABG) are at increased risk for recurrent cardiovascular ischaemic events. Advances in management have improved prognosis of patients with acute coronary syndrome (ACS), yet it is not known whether similar trends exist in patients with prior CABG. AIM: Examine temporal trends in the prevalence, treatment and clinical outcomes of patients with prior CABG admitted with ACS. METHODS: Time-dependent analysis of patients with or without prior CABG admitted with an ACS who enrolled in the ACS Israeli Surveys between 2000 and 2016. Surveys were divided into early (2000-2008) and late (2010-2016) time periods. Outcomes included 30 days major adverse cardiac events (30d MACE) (death, myocardial infarction, stroke, unstable angina, stent thrombosis, urgent revascularisation) and 1-year mortality. RESULTS: Among 15 152 patients with ACS, 1506 (9.9%) had a prior CABG. Patients with prior CABG were older (69 vs 63 years), had more comorbidities and presented more with non-ST elevation-ACS (82% vs 51%). Between time periods, utilisation of antiplatelets, statins and percutaneous interventions significantly increased in both groups (p<0.001 for each). The rate of 30d MACE decreased in patients with (19.1%-12.4%, p=0.001) and without (17.4%-9.5%, p<0.001) prior CABG. However, 1-year mortality decreased only in patients without prior CABG (10.5% vs 7.4%, p<0.001) and remained unchanged in patients with prior CABG. Results were consistent after propensity matching. CONCLUSIONS: Despite an improvement in the management and prognosis of patients with ACS in the last decade, the rate of 1-year mortality of patients with prior CABG admitted with an ACS remained unchanged.

Venous Thromboembolism Prophylaxis in Acute Medically Ill Patients: A Retrospective Cohort Study.

OBJECTIVE: Current guidelines recommend pharmacologic prophylaxis for medical patients at high risk for venous thromboembolism. We aimed to assess the benefit and safety of venous thromboembolism prophylaxis in acutely ill medical patients hospitalized. METHODS: We prepared a retrospective cohort study in a tertiary hospital in Israel with patients hospitalized in medical departments with an admission lasting more than 48 hours during 2014-2017. PRIMARY OUTCOME: 30-day mortality. SECONDARY OUTCOMES: 90-day incidence of pulmonary embolism, symptomatic deep vein thrombosis, and major bleeding. Propensity-weighted logistic multivariate analysis was performed. RESULTS: A total of 18,890 patient-unique episodes were included in the analysis. Of them, 3206 (17.0%) received prophylaxis. A total of 1309 (6.9%) died, 540/3206 (16.8%) of those who received venous thromboembolism prophylaxis and 769/15,864 (4.9%) of those who did not. Prophylaxis was not associated with a reduction in mortality, multivariable-adjusted odds ratio propensity-weighted (OR) 0.99 (95% confidence interval [CI], 0.84-1.14). One hundred forty-two patients (0.7%) developed venous thromboembolism, 44/3206 (1.4%) of those who received prophylaxis and 98/15,864 (0.6%) of those who did not. Prophylaxis was not associated with reduction in venous thromboembolism in the whole cohort, multivariable-adjusted propensity-weighted OR 1.09 (95% CI, 0.52-2.29). Prophylaxis was associated with an increase in major bleeding (multivariable-adjusted propensity-weighted OR 1.24; 95% CI, 1.04-1.48). CONCLUSION: The current practice of routinely administering venous thromboembolism prophylaxis to medically ill patients considered at high risk for thrombosis resulted in a high risk for bleeding without a clear clinical benefit, and should be reassessed.

A risk score based on simple angiographic characteristics to aid in choosing the optimal revascularization strategy for patients with multivessel disease presenting with ST-elevation myocardial infarction.

BACKGROUND: The optimal revascularization strategy is not clearly defined for patients with ST-elevation myocardial infarction with multivessel disease (MV-STEMI). We aimed to develop a simple angiographic risk score for identifying patients with MV-STEMI that might benefit from a multivessel percutaneous coronary intervention (MV-PCI), compared to a PCI for only the infarct-related artery (IRA-PCI). METHODS AND RESULTS: This retrospective study acquired data from a single-center STEMI registry on 841 consecutive patients with MV-STEMI (645 IRA-PCI and 196 MV-PCI). Patients were stratified according to high- and low-risk scores. We devised a score based on three characteristics of non-culprit lesions previously reported to predict overall mortality (proximal left anterior descending artery involvement, maximal % stenosis, and number of involved vessels). The primary endpoint was major adverse cardiac events (MACEs: a composite of death/MI/urgent repeat revascularization). After a median follow-up of 1909 days, MACE occurred in 205/841 (24.4%) patients. MACE risk was higher in the high-risk than in the low-risk group (HR 1.43, P < 0.001). In comparing the IRA-PCI and MV-PCI approaches within each risk group, we found that these revascularization strategies had differential effects on outcome. Compared to the MV-PCI, IRA-PCI was associated with less MACE in the low-risk group (HR 0.597, P = 0.033), and more MACE in the high-risk group (HR 3.14, P < 0.001). CONCLUSION: For patients with MV-STEMI that undergo primary PCI, a simple risk score based on three angiographic characteristics could identify patients at high risk of future adverse events. This score might facilitate choosing the optimal revascularization strategy.

Colistin plus meropenem for carbapenem-resistant Gram-negative infections: in vitro synergism is not associated with better clinical outcomes.

OBJECTIVES: In vitro models showing synergism between polymyxins and carbapenems support combination treatment for carbapenem-resistant Gram-negative (CRGN) infections. We tested the association between the presence of in vitro synergism and clinical outcomes in patients treated with colistin plus meropenem. METHODS: This was a secondary analysis of AIDA, a randomized controlled trial comparing colistin with colistin-meropenem for severe CRGN infections. We tested in vitro synergism using a checkerboard assay. Based on the fractional inhibitory concentration (ΣFIC) index for each colistin-meropenem combination, we categorized results as synergistic, antagonistic or additive/indifferent. The primary outcome was clinical failure at 14 days. Secondary outcomes were 14- and 28-day mortality and microbiological failure. RESULTS: The sample included 171 patients with infections caused by carbapenem-resistant Acinetobacter baumannii (n = 131), Enterobacteriaceae (n = 37) and Pseudomonas aeuruginosa (n = 3). In vitro testing showed synergism for 73 isolates, antagonism for 20 and additivism/indifference for 78. In patients who received any colistin plus meropenem, clinical failure at 14 days was 59/78 (75.6%) in the additivism/indifference group (reference category), 54/73 (74.0%) in the synergism group (adjusted odds ratio (aOR) 0.76, 95% CI 0.31-1.83), and 11/20 (55%) in the antagonism group (aOR 0.77, 95% CI 0.22-2.73). There was no significant difference between groups for any secondary outcome. Comparing the synergism group to patients treated with colistin monotherapy, synergism was not protective against 14-day clinical failure (aOR 0.52, 95% CI 0.26-1.04) or 14-day mortality (aOR1.09, 95% CI 0.60-1.96). DISCUSSION: In vitro synergism between colistin and meropenem via checkerboard method did not translate into clinical benefit.

Predicting the risk of late futile outcome after transcatheter aortic valve implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) for aortic stenosis (AS) risk assessment is still developing and mostly concerned with mortality in the periprocedural period. We therefore sought to develop and then validate a score to predict 1-year adverse outcome. METHODS: Patients that underwent TAVI for severe AS in the Israeli registry. Patients with unsuccessful/suboptimal implantation were excluded. The cohort was split to derivation/validation cohorts by a ratio of 70:30. The outcome was defined as 1-year composite of mortality, stroke, and no improvement in NYHA class (vs. baseline). Logistic regression was used to fit the prediction model. RESULTS: Out of 2,440 patients meeting inclusion criteria, 276 were excluded, leaving 2,160 patients for both cohorts. At 1 year, 299 (14%) patients experienced the adverse ("futile") outcome. The derived prediction model included mean aortic valve (AV) gradient, previous pacemaker, previous oncological disease, need for diuretics, baseline NYHA class, hemoglobin and creatinine levels, and nonfemoral access site. The model's area under the curve (AUC) was 0.69 in the derivation and 0.70 in the validation cohort. Performance of other scores in the validation cohort were lower (0.60 for STS, 0.55 for Euroscore2, 0.56 for TVT score, and 0.53 for TAVI2-score, p = .03). Based on three risk tiers, patients had a low risk (20/306, 7% futility), a medium risk (50/304, 17%), and high risk (18/37, 49%) for futility. CONCLUSIONS: The TAVI futility risk model can be used to provide further insight regarding prediction measures and/or patients' outcomes outside of the periprocedural period (NCT02023060).

Validation of the DAPT score in real-world patients undergoing coronary stent implantation.

OBJECTIVES: To assess the external validity of the Dual Antiplatelet Therapy (DAPT) score decision tool in real world patients. METHODS AND RESULTS: Retrospective study using an all comers PCI registry. We compared the rates of myocardial infarction (MI) and actionable bleeding between 12 vs. 12+ months DAPT stratified by DAPT score category. Of 12,162 patients, 4471 (36.8%) completed a year of DAPT without events. The high DAPT score stratum patients were older and had a higher comorbidity burden. Overall, 12+ months DAPT duration was associated with reduced rates of MI (2.8% vs. 4.0%, p = 0.025) and similar rates of bleeding (2.6% vs. 1.9%, p = 0.281) compared to 12 months DAPT, but when stratified by DAPT score stratum, there was no difference in any of the outcomes in both high score group, (3.7% vs. 5.3%, p = 0.111 and 2.0% vs. 1.8%, p = 0.800, for MI and bleeding, respectively) and low score patients (2.7% vs. 3.1%, p = 0.656 and 2.8% vs. 2.0%, p = 0.308, for MI and bleeding, respectively). Overall clinical events (MI + bleeding) was again similar between patients treated with 12+ vs. 12 months DAPT (5.5% vs. 6.2%, p = 0.535 and 5.1% vs. 4.4%, p = 0.503 for high and low DAPT score, respectively). CONCLUSIONS: for real world patients completing 1 year of DAPT post PCI, rates of MI, actionable bleeding, and their combination did not differ between those treated with 12+ vs. 12 months DAPT stratified by DAPT score stratum. Clinicians should be aware of the DAPT score's limitations. Further studies examining the validity of the DAPT score in larger cohorts are required.

Meta-analysis of studies examining the external validity of the dual antiplatelet therapy score.

AIMS: The dual antiplatelet therapy (DAPT) score is meant to aid clinicians choose the DAPT duration but attempts to examine the external validity of the DAPT score and its decision tool have reported mostly disappointing results. Our aim was to perform a meta-analysis of all available data on the external validity of the DAPT score. METHODS AND RESULTS: We conducted a meta-analysis of studies that examined the external validity of the DAPT score/its decision tool. Seven studies (77 274 patients) were included. Follow-up ranged from 6 to 24 (median 18) months. Overall, high (≥2) DAPT score was associated with increased risk for myocardial infarction (MI)/stent thrombosis (ST) [odds ratio (OR) 1.54, 95% confidence interval (CI) 1.41-1.69; P < 0.01], and lower risk for bleeding (OR 0.84, 95% CI 0.73-0.97; P = 0.01). In the high DAPT score stratum, extended (12-24 months), as compared to standard (6-12 months) DAPT duration was associated with a reduction in the risk for MI/ST (OR 0.67, 95% CI 0.48-0.94; P = 0.02), and no difference in the risk for bleeding (OR 1.04, 95% CI 0.65-1.66; P = 0.88), while in the low DAPT score stratum, extended DAPT duration was associated with no difference in the risk for MI/ST (OR 1.04, 95% CI 0.76-1.43; P = 0.80), and an increased risk for bleeding (OR 1.58, 95% CI 1.15-2.15; P < 0.01). CONCLUSIONS: This first meta-analysis of studies examining the external validation of the DAPT score and its decision tool, our results suggest that the DAPT score is useful both for stratifying post-percutaneous coronary intervention patients into risk strata for future ischaemic and bleeding events as well aiding in choosing the optimal DAPT duration for the individual patient.

Temporal Trends in the Characteristics, Management and Outcomes of Patients With Acute Coronary Syndrome According to Their Killip Class.

Based on the historical Killip Classification, higher Killip class is associated with increased mortality in patients with acute coronary syndrome (ACS), yet data on current prognosis are lacking. We sought to examine temporal trends in the management and outcomes of patients admitted with an ACS by Killip class and to assess its contemporary prognostic value. Time-dependent analysis (early-period 2000 to 2008 vs late-period 2010 to 2016) in patients with lower (=1) and higher (≥2) Killip classes in a national ACS survey. Clinical outcomes included 30d MACE (death, myocardial infarction, stroke, unstable angina, stent thrombosis, urgent revascularization) and 1-year mortality. Included were 9,736 and 5,288 patients in the early and late time-periods of which 18.5% and 11.5% were categorized as higher Killip class, respectively (p <0.001). Baseline co-morbidities (diabetes, hypertension, dyslipidemia) were more prevalent in the late versus early time periods in both study groups (p <0.001). Rates of 30d MACE decreased in both Killip classes (p <0.001), yet 1-year mortality decreased only in patients with lower Killip class (p = 0.02), and remained extremely high (30%) in patients with higher Killip class (p = 0.75). Killip class was a significant independent predictor for 1-year mortality, both in the early (adjusted hazard ratio 3.23, confidence interval 2.8, 3.7) and late (adjusted hazard ratio 4.13, confidence interval 3.21, 5.32) time periods. In conclusion, even in the current era, patients presenting with ACS and higher Killip class have poor 1-year survival. Efforts should focus on improving the adherence to guideline-recommended therapies. The Killip classification system is still a reliable prognostic tool.

Effect of Intramural Course of Coronary Arteries Assessed by Computed Tomography Angiography in Patients With Hypertrophic Cardiomyopathy.

This study evaluated the prevalence, anatomical pattern, and prognostic implications of an intramural course of the coronary arteries in patients with hypertrophic cardiomyopathy (HC). The study population consisted of 92 patients with HC and 100 patients without HC. The presence of an intramural course of the coronary arteries was evaluated by coronary computed tomography angiography (CTA), and its length and depth were measured. During follow-up, the occurrence of unstable angina requiring hospitalization, myocardial infarction, and all-cause mortality was evaluated. An intramural course of the coronary arteries was more common in patients with HC than patients without HC (62% vs 25%, p <0.001). In the patients with an intramural coronary artery course, those with HC had a longer course (29.1 ± 15.3 mm vs 23.0 ± 13.0 mm; p = 0.037) with deeper penetration into the left ventricular myocardium (2.8 ± 1.2 mm vs 2.1 ± 0.8 mm; p = 0.007) and more involvement of multiple coronary arteries (38% vs 4%; p <0.001). During follow-up (mean 5.5 ± 3.5 years), cardiac events occurred in 17 of 57 patients (29.8%) with an intramural course and 11 of 35 (31.4%) without an intramural course (p = 0.87). On Kaplan-Meier survival analysis, there was no difference in cumulative event rate between HC patients with or without an intramural course (p = 0.89, log rank test). In conclusion, patients with HC have a high rate of an intramural course of the coronary arteries on CTA. The number of involved arteries and the length and depth of the intramural course differ between patients with and without HC, but apparently have no association with worse clinical outcomes.

Meta-analysis of Polymyxin Use in Patients.

In this chapter, we systematically reviewed studies that assessed polymyxin's effectiveness and summarized results through meta-analysis. The outcomes addressed were all-cause mortality, assuming that for patients with severe multidrug-resistant infections survival is the most important outcome, and resistance development, important for future patients. Most clinical data on polymyxins in the literature are from retrospective, observational studies at high risk of bias. The majority of clinical studies were unpowered to examine mortality controlling for other risk factors. The studies had no control of dosage regimens and treatment modifications. We identified several areas of missing data, in particular randomized controlled trials (RCTs) examining treatment options for carbapenem-resistant Gram-negative bacteria, different dosage regimens, polymyxins versus alternative antibiotics (e.g. aminoglycosides, tigecycline), and monotherapy versus specific combination therapies. Ideally, mortality and development of resistance should be examined in RCTs, with further longitudinal studies required for the latter.

Immunosuppression reduction in liver and kidney transplant recipients with suspected bacterial infection: A multinational survey.

BACKGROUND: There is no consensus on the optimal management of immunosuppression during bacterial infections among solid organ transplant recipients. METHODS: A multicenter, cross-sectional survey, of high-volume kidney and liver transplant centers across US and Europe. Structured questionnaires including six multiple-choice questions concerning the management of immunosuppression during infection were distributed among 381 centers. RESULTS: A total of 124 (33%) centers fully completed the questionnaire: 67 liver, 57 kidney centers. Participating centers reported heterogenous approaches to immunosuppression management for all types of immunosuppressive drugs. Notably, kidney centers reported similar frequencies of either discontinuation (19%), continuation (19%), or dose reduction (17.5%) of antimetabolites; discontinuation only for life-threatening infection (17.5%) or case by case decisions (27%). Calcineurin inhibitors (CNI) management was heterogenous mostly among liver centers, with 8% discontinuing the CNI, 18% continuing, and 22% reducing dose. Heterogenous approaches to management of steroids and inhibitors of the mammalian target of rapamycin were also demonstrated. CONCLUSIONS: Immunosuppression management during bacterial infection is heterogenous in US and European centers. Immunosupression reduction (ISR) during infection is a common practice, though supported by limited evidence. Demonstrating high heterogeneity in the approach to ISR, together with the equivocal results of clinical studies, support consideration of an interventional clinical trial.

Management of Iron Deficiency in Heart Failure.

Anemia is a common finding in patients with heart failure (HF). The cause for anemia is multifactorial, with iron deficiency being the most common cause. Anemia with HF is an established predictor of morbidity and mortality. Iron deficiency in systolic HF, even without anemia, has been associated with increased mortality, increased hospitalizations, and decreased functional capacity and quality of life measures. Data from several randomized controlled trials and meta-analyses of iron deficiency and systolic HF show a beneficial effect for intravenous (IV) iron in terms of quality of life and functional capacity (improvements in 6-min walk test, and improvements in New York Heart Association functional class), as well as decreased hospitalizations for HF and reduction in cardiovascular mortality rates. Limited evidence exists for a beneficial effect of IV iron in diastolic dysfunction. Patients with symptomatic systolic HF should undergo an anemia diagnostic work-up. When iron deficiency (defined as ferritin <100 ng/mL or serum ferritin 100-299 ng/mL and transferrin saturation <20%) is present, current evidence supports treating HF patients with iron deficiency with IV iron.

International comparison of acute myocardial infarction care and outcomes using quality indicators.

OBJECTIVE: To compare temporal changes in European Society of Cardiology (ESC) acute myocardial infarction (AMI) quality indicator (QI) attainment in the UK and Israel. METHODS: Data cross-walking using information from the Myocardial Ischaemia National Audit Project and the Acute Coronary Syndrome in Israel Survey for matching 2-month periods in 2006, 2010 and 2013 was used to compare country-specific attainment of 14 ESC AMI QIs. RESULTS: Patients in the UK (n=17 068) compared with Israel (n=5647) were older, more likely to be women, and had less diabetes, dyslipidaemia and heart failure. Baseline ischaemic risk was lower in Israel than the UK (Global Registry of Acute Coronary Events (GRACE) risk, 110.5 vs 121.0). Overall, rates of coronary angiography (87.6% vs 64.8%) and percutaneous coronary intervention (70.3% vs 41.0%) were higher in Israel compared with the UK. Composite QI performance increased more in the UK (1.0%-86.0%) than Israel (70.2%-78.0%). Mortality rates at 30 days declined in each country, with lower rates in Israel in 2013 (4.2% vs 7.6%). Composite QI adherence adjusted for GRACE risk score was inversely associated with 30-day mortality (OR 0.95; CI 0.95 to 0.97, p<0.001). CONCLUSIONS: International comparisons of guideline recommended AMI care and outcomes can be quantified using the ESC AMI QIs. International implementation of the ESC AMI QIs may reveal country-specific opportunities for improved healthcare delivery.

Early Administration of Protein in Critically Ill Patients: A Retrospective Cohort Study.

It is currently uncertain whether early administration of protein improves patient outcomes. We examined mortality rates of critically ill patients receiving early compared to late protein administration. This was a retrospective cohort study of mixed ICU patients receiving enteral or parenteral nutritional support. Patients receiving >0.7 g/kg/d protein within the first 3 days were considered the early protein group and those receiving less were considered the late protein group. The latter were subdivided into late-low group (LL) who received a low protein intake (<0.7 g/kg/d) throughout their stay and the late-high group (LH) who received higher doses (>0.7 g/kg/d) of protein following their first 3 days of admission. The outcome measure was all-cause mortality 60 days after admission. Of the 2253 patients included in the study, 371 (36%) in the early group, and 517 (43%) in the late-high group had died (p < 0.001 for difference). In multivariable Cox regression analysis, while controlling for confounders, early protein administration was associated with increased survival (HR 0.83, 95% CI 0.71⁻0.97, p = 0.017). Administration of protein early in the course of critical illness appears to be associated with improved survival in a mixed ICU population, even after adjusting for confounding variables.

Transcatheter Aortic Valve Replacement in Oncology Patients With Severe Aortic Stenosis.

OBJECTIVES: The authors sought to collect data on contemporary practice and outcome of transcatheter aortic valve replacement (TAVR) in oncology patients with severe aortic stenosis (AS). BACKGROUND: Oncology patients with severe AS are often denied valve replacement. TAVR may be an emerging treatment option. METHODS: A worldwide registry was designed to collect data on patients who undergo TAVR while having active malignancy. Data from 222 cancer patients from 18 TAVR centers were compared versus 2,522 "no-cancer" patients from 5 participating centers. Propensity-score matching was performed to further adjust for bias. RESULTS: Cancer patients' age was 78.8 ± 7.5 years, STS score 4.9 ± 3.4%, 62% men. Most frequent cancers were gastrointestinal (22%), prostate (16%), breast (15%), hematologic (15%), and lung (11%). At the time of TAVR, 40% had stage 4 cancer. Periprocedural complications were comparable between the groups. Although 30-day mortality was similar, 1-year mortality was higher in cancer patients (15% vs. 9%; p < 0.001); one-half of the deaths were due to neoplasm. Among patients who survived 1 year after the TAVR, one-third were in remission/cured from cancer. Progressive malignancy (stage III to IV) was a strong mortality predictor (hazard ratio: 2.37; 95% confidence interval: 1.74 to 3.23; p < 0.001), whereas stage I to II cancer was not associated with higher mortality compared with no-cancer patients. CONCLUSIONS: TAVR in cancer patients is associated with similar short-term but worse long-term prognosis compared with patients without cancer. Among this cohort, mortality is largely driven by cancer, and progressive malignancy is a strong mortality predictor. Importantly, 85% of the patients were alive at 1 year, one-third were in remission/cured from cancer. (Outcomes of Transcatheter Aortic Valve Implantation in Oncology Patients With Severe Aortic Stenosis [TOP-AS]; NCT03181997).

Predictive equations versus measured energy expenditure by indirect calorimetry: A retrospective validation.

BACKGROUND & AIMS: Measuring resting energy expenditure (REE) via indirect calorimetry (IC) in intensive care unit (ICU) patient is the gold standard recommended by guidelines. However technical difficulties hinder its use and predictive equations are largely used instead. We sought to validate commonly used equations using a large cohort of patients. METHODS: Patients hospitalized from 2003 to 2015 in a 16-bed ICU at a university-affiliated, tertiary care hospital who had IC measurement to assess caloric targets were included. Data was drawn from a computerized system and included REE and other variables required by equations. Measurements were restricted to 5 REE per patient to avoid bias. Equation performance was assessed by comparing means, standard deviations, correlation, concordance and agreement, which was defined as a measurement within 85-115% of measured REE. A total of 8 equations were examined. RESULTS: A total of 3573 REE measurements in 1440 patients were included. Mean patient age was 58 years and 65% were male. A total of 562 (39%) patients had >2 REE measurements. Standard deviation of REE ranged from 430 to 570 kcal. The Faisy equation had the least mean difference (90 Kcal); Harris-Benedict had the highest correlation (52%) and agreement (50%) and Jolliet the highest concordance (62%). Agreement within 10% of caloric needs was met only in a third of patients. CONCLUSIONS: Predictive equations have low performance when compared to REE in ICU patients. We therefore suggest that predictive equations cannot wholly replace indirect calorimetry for the accurate estimation of REE in this population.