Malnutrition is common in patients with chronic heart failure (CHF) and is associated with adverse outcomes, but it is uncertain how malnutrition should best be evaluated.
This prospective cohort ...study aims to compare the short-term prognostic value of 9 commonly used malnutrition tools in patients with CHF.
We assessed, simultaneously, 3 simple tools Controlling Nutritional Status (CONUT) score, Geriatric Nutritional Risk Index, and Prognostic Nutritional Index, 3 multidimensional tools Malnutrition Universal Screening Tool, Mini Nutritional Assessment–Short Form (MNA-SF), Subjective Global Assessment, and 3 laboratory tests (serum cholesterol, albumin, and total lymphocyte count) in consecutive patients with CHF attending a routine follow-up. The primary end point was all-cause mortality; the secondary end point was the combination of all-cause hospitalization and all-cause mortality.
In total, 467 patients 67% male, median age 76 y (range: 21–98 y), median N-terminal pro-B-type natriuretic peptide (NT-proBNP) 1156 ng/L were enrolled. During a median follow-up of 554 d, 82 (18%) patients died and 201 (43%) patients either had a nonelective hospitalization or died. In models corrected for age, hemoglobin (Hb), renal function, New York Heart Association (NYHA) class, NTproBNP, BMI, and comorbidities, all malnutrition tools, except total lymphocyte count and serum cholesterol, were independently associated with worse morbidity and mortality. A base model for predicting mortality, including age, NYHA class, log NT-proBNP, Hb, renal function, and comorbidities, had a C-statistic of 0.757. CONUT (C-statistic = 0.777), among simple tools; MNA-SF (C-statistic = 0.776), among multidimensional tools; and albumin (C-statistic = 0.773), among biochemical tests, increased model performance most compared with the base model. Patients with serum albumin <30 g/L had a 6-fold increase in mortality compared with patients with albumin ≥35 g/L.
Malnutrition is strongly associated with adverse outcomes in patients with CHF. Measuring serum albumin provides comparable prognostic information to simple or multidimensional malnutrition tools.
This study sought to report the prevalence of frailty, classification performance, and agreement among 3 frailty assessment tools and 3 screening tools in chronic heart failure (CHF) patients.
...Frailty is common in patients with CHF. There are many available frailty tools, but no standard method for evaluating frailty.
We used the following frailty screening tools: the clinical frailty scale (CFS); the Derby frailty index; and the acute frailty network frailty criteria. We used the following frailty assessment tools: the Fried criteria; the Edmonton frailty score; and the Deficit Index.
A total of 467 consecutive ambulatory CHF patients (67% male; median age: 76 years; interquartile range IQR: 69 to 82 years; median N-terminal pro–B-type natriuretic peptide: 1,156 ng/l IQR: 469 to 2,463 ng/l) and 87 control patients (79% male; median age: 73 years; IQR: 69 to 77 years) were studied. The prevalence of frailty using the different tools was higher in CHF patients than in control patients (30% to 52% vs. 2% to 15%, respectively). Frail patients tended to be older, have worse symptoms, higher N-terminal pro–B-type natriuretic peptide levels, and more comorbidities. Of the screening tools, CFS had the strongest correlation and agreement with the assessment tools (correlation coefficient: 0.86 to 0.89, kappa coefficient: 0.65 to 0.72, depending on the frailty assessment tools, all p < 0.001). CFS had the highest sensitivity (87%) and specificity (89%) among screening tools and the lowest misclassification rate (12%) among all 6 frailty tools in identifying frailty according to the standard combined frailty index.
Frailty is common in CHF patients and is associated with increasing age, comorbidities, and severity of heart failure. CFS is a simple screening tool that identifies a similar group using more lengthy assessment tools.
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The recent clinical availability of the PARP inhibitor olaparib (Lynparza) opens the door for potential therapeutic repurposing for non‐oncological indications. Considering (a) the preclinical ...efficacy data with PARP inhibitors in non‐oncological diseases and (b) the risk–benefit ratio of treating patients with a compound that inhibits an enzyme that has physiological roles in the regulation of DNA repair, we have selected indications, where (a) the severity of the disease is high, (b) the available therapeutic options are limited, and (c) the duration of PARP inhibitor administration could be short, to provide first‐line options for therapeutic repurposing. These indications are as follows: acute ischaemic stroke; traumatic brain injury; septic shock; acute pancreatitis; and severe asthma and severe acute lung injury. In addition, chronic, devastating diseases, where alternative therapeutic options cannot halt disease development (e.g. Parkinson's disease, progressive multiple sclerosis or severe fibrotic diseases), should also be considered. We present a preclinical and clinical action plan for the repurposing of PARP inhibitors.
Linked Articles
This article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc
In patients with chronic heart failure (CHF), malnutrition might be related to right heart dysfunction and venous congestion, which predispose to bowel oedema and malabsorption, thereby leading to ...malnutrition. We explored the relation between congestion, malnutrition and mortality in a large cohort of ambulatory patients with CHF.
We assessed malnutrition using the Geriatric Nutritional Risk Index (GNRI). Congestion was defined by echocardiography (raised right atrial pressure (RAP)=dilated inferior vena cava≥21 mm/raised pulmonary artery systolic pressure (PAsP)=transtricuspid gradient of ≥36 mm Hg/right ventricular systolic dysfunction (RVSD)=tricuspid annular plane systolic excursion <17 mm).
Of the 1058 patients enrolled, CHF was confirmed in 952 (69% males, median age 75 (IQR: 67-81) years, median N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) 1141 (IQR: 465-2562) ng/L). 39% had HF with -reduced ejection fraction (left ventricular ejection fraction, LVEF <40%) and 61% had HF with normal (HeFNEF, LVEF ≥40% and NT-pro-BNP >125 ng/L) ejection fraction. Overall, 14% of patients were malnourished (GNRI ≤98). 35% had raised RAP, 23% had raised PAsP and 38% had RVSD. Congestion was associated with malnutrition. During a median follow-up of 1683 days (IQR: 1096-2230 days), 461 (44%) patients died. Malnutrition was an independent predictor of mortality. Patients who were malnourished with both RVSD and increased RAP had much worse outcome compared with non-malnourished patients without RVSD who had normal RAP.
Malnutrition and congestion are modestly correlated and each is independently associated with increased mortality in patients with CHF. Patients with HF with both malnutrition and congestion as evidenced by right heart dysfunction should be managed with additional vigilance.
Abstract
Aims
Plasma concentrations of high-sensitivity C-reactive protein (hsCRP) are often raised in chronic heart failure (CHF) and might indicate inflammatory processes that could be a ...therapeutic target. We aimed to study the associations between hsCRP, mode and cause of death in patients with CHF.
Methods and results
We enrolled 4423 patients referred to a heart failure clinic serving a local population. CHF was defined as relevant symptoms or signs with either a reduced left ventricular ejection fraction <40% or raised plasma concentrations of amino-terminal pro-B type natriuretic peptide (NT-proBNP >125 pg/mL). The median interquartile range (IQR) plasma hsCRP for patients diagnosed with CHF (n = 3756) was 3.9 (1.6–8.5) mg/L and 2.7 (1.3–5.1) mg/L for those who were not (n = 667; P < 0.001). Patients with hsCRP ≥10 mg/L (N = 809; 22%) were older and more congested than those with hsCRP <2 mg/L (N = 1117, 30%). During a median follow-up of 53 (IQR 28–93) months, 1784 (48%) patients with CHF died. Higher plasma hsCRP was associated with greater mortality, independent of age, symptom severity, creatinine, and NT-proBNP. Comparing a hsCRP ≥10 mg/L to <2 mg/L, the hazard ratio for all-cause mortality was 2.49 (95% confidence interval 2.19–2.84; P < 0.001), for cardiovascular (CV) mortality was 2.26 (1.91–2.68; P < 0.001), and for non-CV mortality was 2.96 (2.40–3.65; P < 0.001).
Conclusion
In patients with CHF, a raised plasma hsCRP is associated with more congestion and a worse prognosis. The proportion of deaths that are non-CV also increases with higher hsCRP.
Summary
Phosphorus cycling exerts significant influence upon soil fertility and productivity – processes largely controlled by microbial activity. We adopted phenotypic and metagenomic approaches to ...investigate phosphatase genes within soils. Microbial communities in bare fallowed soil showed a marked capacity to utilise phytate for growth compared with arable or grassland soil communities. Bare fallowed soil contained lowest concentrations of orthophosphate. Analysis of metagenomes indicated phoA, phoD and phoX, and histidine acid and cysteine phytase genes were most abundant in grassland soil which contained the greatest amount of NaOH‐EDTA extractable orthophosphate. Beta‐propeller phytase genes were most abundant in bare fallowed soil. Phylogenetic analysis of metagenome sequences indicated the phenotypic shift observed in the capacity to mineralise phytate in bare fallow soil was accompanied by an increase in phoD, phoX and beta‐propeller phytase genes coding for exoenzymes. However, there was a remarkable degree of genetic similarity across the soils despite the differences in land‐use. Predicted extracellular ecotypes were distributed across a greater range of soil structure than predicted intracellular ecotypes, suggesting that microbial communities subject to the dual stresses of low nutrient availability and reduced access to organic material in bare fallowed soils rely upon the action of exoenzymes.
On the basis of the ACCORD trial, FOLFIRINOX is effective in metastatic pancreatic adenocarcinoma (PDAC), making it a rational choice for locally advanced PDAC (LA). Aims of this study are to ...evaluate the accuracy of imaging in determining the resectability of PDAC and to determine the surgical and clinicopathologic outcomes of pancreatic resections after neoadjuvant FOLFIRINOX therapy.
Clinicopathologic data were retrospectively collected for surgical PDAC patients receiving neoadjuvant FOLFIRINOX or no neoadjuvant therapy between April 2011 and February 2014. Americas Hepato-Pancreato-Biliary Association/Society of Surgical Oncology/Society for Surgery of the Alimentary Tract consensus guidelines defined LA and borderline. Imaging was reviewed by a blinded senior pancreatic surgeon.
Of 188 patients undergoing resection for PDAC, 40 LA/borderline received FOLFIRINOX and 87 received no neoadjuvant therapy. FOLFIRINOX resulted in a significant decrease in tumor size, yet 19 patients were still classified as LA and 9 as borderline. Despite post-FOLFIRINOX imaging suggesting continued unresectability, 92% had an R0 resection. When compared with no neoadjuvant therapy, FOLFIRINOX resulted in significantly longer operative times (393 vs 300 minutes) and blood loss (600 vs 400 mL), but significantly lower operative morbidity (36% vs 63%) and no postoperative pancreatic fistulas. Length of stay (6 vs 7 days), readmissions (20% vs 30%), and mortality were equivalent (1% vs 0%). On final pathology, the FOLFIRINOX group had a significant decrease in lymph node positivity (35% vs 79%) and perineural invasion (72% vs 95%). Median follow-up was 11 months with a significant increase in overall survival with FOLFIRINOX.
After neoadjuvant FOLFIRINOX imaging no longer predicts unresectability. Traditional pathologic predictors of survival are improved, and morbidity is decreased in comparison to patients with clearly resectable cancers at the time of presentation.
Guidelines on heart failure (HF) define iron deficiency (ID) as a serum ferritin <100 ng/mL or, when 100-299 ng/mL, a transferrin saturation (TSAT) <20%. Inflammation (common in HF) may hinder ...interpretation of serum ferritin.
This study sought to investigate how different definitions of ID affect its prevalence and relationship to prognosis in ambulatory patients with chronic HF.
Prevalence, relationship with patients' characteristics, and outcomes of various ID definitions were evaluated among patients with HF referred to a regional clinic (Hull LifeLab) from 2001 to 2019.
Of 4,422 patients with HF (median age 75 years range: 68-82 years, 60% men, 32% with reduced left ventricular ejection fraction), 46% had TSAT <20%, 48% had serum iron ≤13 μmol/L, 57% had serum ferritin <100 ng/mL, and 68% fulfilled current guideline criteria for ID, of whom 35% had a TSAT >20%. Irrespective of definition, ID was more common in women and those with more severe symptoms, anemia, or preserved ejection fraction. TSAT <20% and serum iron ≤13 μmol/L, but not guideline criteria, were associated with higher 5-year mortality (HR: 1.27; 95% CI: 1.14-1.43; P < 0.001; and HR: 1.37; 95% CI: 1.22-1.54; P < 0.001, respectively). Serum ferritin <100 ng/mL tended to be associated with lower mortality (HR: 0.91; 95% CI: 0.81-1.01; P = 0.09).
Different definitions of ID provide discordant results for prevalence and prognosis. Definitions lacking specificity may attenuate the benefits of intravenous iron observed in trials while definitions lacking sensitivity may exclude patients who should receive intravenous iron. Prespecified subgroup analyses of ongoing randomized trials should address this issue.
Advances in genome sequencing and assembly technologies are generating many high-quality genome sequences, but assemblies of large, repeat-rich polyploid genomes, such as that of bread wheat, remain ...fragmented and incomplete. We have generated a new wheat whole-genome shotgun sequence assembly using a combination of optimized data types and an assembly algorithm designed to deal with large and complex genomes. The new assembly represents >78% of the genome with a scaffold N50 of 88.8 kb that has a high fidelity to the input data. Our new annotation combines strand-specific Illumina RNA-seq and Pacific Biosciences (PacBio) full-length cDNAs to identify 104,091 high-confidence protein-coding genes and 10,156 noncoding RNA genes. We confirmed three known and identified one novel genome rearrangements. Our approach enables the rapid and scalable assembly of wheat genomes, the identification of structural variants, and the definition of complete gene models, all powerful resources for trait analysis and breeding of this key global crop.
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