Potential Utility of Cardiorenal Biomarkers for Prediction and Prognostication of Worsening Renal Function in Acute Heart Failure

Background: Multiple different pathophysiologic processes can contribute to worsening renal function (WRF) in acute heart failure. Methods and Results: We retrospectively analyzed 787 patients with acute heart failure for the relationship between changes in serum creatinine and biomarkers including brain natriuretic peptide, high sensitivity cardiac troponin I, galectin 3, serum neutrophil gelatinase-associated lipocalin, and urine neutrophil gelatinase-associated lipocalin. WRF was defined as an increase of greater than or equal to 0.3 mg/dL or 50% in creatinine within first 5 days of hospitalization. WRF was observed in 25% of patients. Changes in biomarkers and creatinine were poorly correlated (r < 0.21) and no biomarker predicted WRF better than creatinine. In the multivariable Cox analysis, brain natriuretic peptide and high sensitivity cardiac troponin I, but not WRF, were significantly associated with the 1-year composite of death or heart failure hospitali-zation. WRF with an increasing urine neutrophil gelatinase-associated lipocalin predicted an increased risk of heart failure hospitalization. Conclusions: Biomarkers were not able to predict WRF better than creatinine. The 1-year outcomes were associated with biomarkers of cardiac stress and injury but not with WRF, whereas a kidney injury bio-marker may prognosticate WRF for heart failure hospitalization

Short-term prognostic implications of serum and urine neutrophil gelatinase-associated lipocalin in acute heart failure:findings from the AKINESIS study

AIMS: Kidney impairment has been associated with worse outcomes in acute heart failure (AHF), although recent studies challenge this association. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel biomarker of kidney tubular injury. Its prognostic role in AHF has not been evaluated in large cohorts. The present study aimed to determine if serum NGAL (sNGAL) or urine NGAL (uNGAL) is superior to creatinine for predicting short-term outcomes in AHF. METHODS AND RESULTS: The study was conducted in an international, multicentre, prospective cohort consisting of 927 patients with AHF. Admission and peak values of sNGAL, uNGAL and uNGAL/urine creatinine (uCr) ratio were compared to admission and peak serum creatinine (sCr). The composite endpoints were death, initiation of renal replacement therapy, heart failure (HF) readmission and any emergent HF-related outpatient visit within 30 and 60 days, respectively. The mean age of the cohort was 69 years and 62% were male. The median length of stay was 6 days. The composite endpoint occurred in 106 patients and 154 patients within 30 and 60 days, respectively. Serum NGAL was more predictive than uNGAL and the uNGAL/uCr ratio but was not superior to sCr (area under the curve [AUC]; admission sNGAL 0.61 [95% confidence interval (CI) 0.55-0.67] and 0.59 [95% CI 0.54-0.65], peak sNGAL 0.60 [95% CI 0.54-0.66] and 0.57 [95% CI 0.52-0.63], admission sCr 0.60 [95% CI 0.54-0.64] and 0.59 [95% CI 0.53-0.64] [area under the curve: admission sNGAL 0.61, 95% confidence interval (CI) 0.55-0.67, and 0.59, 95% CI 0.54-0.65; peak sNGAL: 0.60, 95% CI 0.54-0.66, and 0.57, 95% CI 0.52-0.63; admission sCr: 0.60, 95% CI 0.54-0.64, and 0.59, 95% CI 0.53-0.64, at 30 and 60 days, respectively], peak sCr 0.61 [95% CI 0.55-0.67] and 0.59 [95% CI 0.54-0.64] at 30 and 60 days, respectively). NGAL was not predictive of the composite endpoint in multivariate analysis. CONCLUSIONS: Serum NGAL outperformed uNGAL but neither was superior to admission or peak sCr for predicting adverse events

Cognitive Aging in Zebrafish

BACKGROUND: Age-related impairments in cognitive functions represent a growing clinical and social issue. Genetic and behavioral characterization of animal models can provide critical information on the intrinsic and environmental factors that determine the deterioration or preservation of cognitive abilities throughout life. METHODOLOGY/PRINCIPAL FINDINGS: Behavior of wild-type, mutant and gamma-irradiated zebrafish (Danio rerio) was documented using image-analysis technique. Conditioned responses to spatial, visual and temporal cues were investigated in young, middle-aged and old animals. The results demonstrate that zebrafish aging is associated with changes in cognitive responses to emotionally positive and negative experiences, reduced generalization of adaptive associations, increased stereotypic and reduced exploratory behavior and altered temporal entrainment. Genetic upregulation of cholinergic transmission attenuates cognitive decline in middle-aged achesb55/+ mutants, compared to wild-type siblings. In contrast, the genotoxic stress of gamma-irradiation accelerates the onset of cognitive impairment in young zebrafish. CONCLUSIONS/SIGNIFICANCE: These findings would allow the use of powerful molecular biological resources accumulated in the zebrafish field to address the mechanisms of cognitive senescence, and promote the search for therapeutic strategies which may attenuate age-related cognitive decline

Relation of Decongestion and Time to Diuretics to Biomarker Changes and Outcomes in Acute Heart Failure

Prompt treatment may mitigate the adverse effects of congestion in the early phase of heart failure (HF) hospitalization, which may lead to improved outcomes. We analyzed 814 acute HF patients for the relationships between time to first intravenous loop diuretics, changes in biomarkers of congestion and multiorgan dysfunction, and 1-year composite end point of death or HF hospitalization. B-type natriuretic peptide (BNP), high sensitivity cardiac troponin I (hscTnI), urine and serum neutrophil gelatinase-associated lipocalin, and galectin 3 were measured at hospital admission, hospital day 1, 2, 3 and discharge. Time to diuretics was not correlated with the timing of decongestion defined as BNP decrease >= 30% compared with admission. Earlier BNP decreases but not time to diuretics were associated with earlier and greater decreases in hscTnI and urine neutrophil gelatinase-associated lipocalin, and lower incidence of the composite end point. After adjustment for confounders, only no BNP decrease at discharge was significantly associated with mortality but not the composite end point (p = 0.006 and p = 0.062, respectively). In conclusion, earlier time to decongestion but not the time to diuretics was associated with better biomarker trajectories. Residual congestion at discharge rather than the timing of decongestion predicted a worse prognosis. (C) 2021 The Authors. Published by Elsevier Inc

Decongestion, kidney injury and prognosis in patients with acute heart failure

Background: In patients with acute heart failure (AHF), the development of worsening renal function with appropriate decongestion is thought to be a benign functional change and not associated with poor prognosis. We investigated whether the benefit of decongestion outweighs the risk of concurrent kidney tubular damage and leads to better outcomes.& nbsp;Methods: We retrospectively analyzed data from the AKINESIS study, which enrolled AHF patients requiring intravenous diuretic therapy. Urine neutrophil gelatinase-associated lipocalin (uNGAL) and B-type natriuretic peptide (BNP) were serially measured during the hospitalization. Decongestion was defined as >= 30% BNP decrease at discharge compared to admission. Univariable and multivariable Cox models were assessed for oneyear mortality.& nbsp;Results: Among 736 patients, 53% had >= 30% BNP decrease at discharge. Levels of uNGAL and BNP at each collection time point had positive but weak correlations (r = 30% BNP decrease was a significant predictor after multivariable adjustment.& nbsp;Conclusions: Among AHF patients treated with diuretic therapy, decongestion was generally not associated with kidney tubular damage assessed by uNGAL. Kidney tubular damage with adequate decongestion does not impact outcomes; however, kidney injury without adequate decongestion is associated with a worse prognosis

Precise measurements of the properties of the B-1(5721)(0,+) and B-2*(5747)(0,+) states and observation of B-+,B-0 pi(-,+) mass structures

Invariant mass distributions of B+π− and B0π+ combinations are investigated in order to study excited B mesons. The analysis is based on a data sample corresponding to 3.0 fb−1 of pp collision data, recorded by the LHCb detector at centre-of-mass energies of 7 and 8 TeV. Precise measurements of the masses and widths of the B1(5721)0,+ and B2(5747)0,+ states are reported. Clear enhancements, particularly prominent at high pion transverse momentum, are seen over background in the mass range 5850-6000 MeV in both B+π− and B0π+ combinations. The structures are consistent with the presence of four excited B mesons, labelled BJ (5840)0,+ and BJ (5960)0,+, whose masses and widths are obtained under different hypotheses for their quantum numbers

A Review of Pharmacologic Treatment for Compulsive Buying Disorder

At present, no treatment recommendations can be made for compulsive buying disorder. Recent studies have found evidence for the efficacy of psychotherapeutic options, but less is known regarding the best pharmacologic treatment. The purpose of this review is to present and analyze the available published evidence on the pharmacological treatment of compulsive buying disorder. To achieve this, we conducted a review of studies focusing on the pharmacological treatment of compulsive buying by searching the PubMed/MEDLINE database. Selection criteria were applied, and 21 studies were identified. Pharmacological classes reported included antidepressants, mood stabilizers, opioid antagonists, second-generation antipsychotics, and N-methyl-D-aspartate receptor antagonists. We found only placebo-controlled trials for fluvoxamine; none showed effectiveness against placebo. Three open-label trials reported clinical improvement with citalopram; one was followed by a double-blind discontinuation. Escitalopram was effective in an open-label trial but did not show efficacy in the double-blind phase. Memantine was identified as effective in a pilot open-label study. Fluoxetine, bupropion, nortriptyline, clomipramine, topiramate and naltrexone were only reported to be effective in clinical cases. According to the available literature, there is no evidence to propose a specific pharmacologic agent for compulsive buying disorder. Future research is required for a better understanding of both pathogenesis and treatment of this disorder.info:eu-repo/semantics/publishedVersio

Extraintestinal Manifestations of Pediatric Inflammatory Bowel Disease: Prevalence, Presentation, and Anti-TNF Treatment.

There is a paucity of data on extraintestinal manifestations (EIM) and their treatment in pediatric patients with inflammatory bowel disease (IBD). Since 2008, the Pediatric Swiss IBD Cohort Study has collected data on the pediatric IBD population in Switzerland. Data on 329 patients were analyzed retrospectively. A total of 55 patients (16.7%) experienced 1-4 EIM (39 Crohn disease, 12 ulcerative colitis, and 4 IBD-unclassified patients). At IBD onset, presence of EIM was more frequent than in the adult population (8.5% vs 5.0%, P = 0.014). EIM were more frequent in Crohn disease when compared to ulcerative colitis/IBD-unclassified (22.5% vs 10.3%, P = 0.003). The most prevalent EIM were peripheral arthritis (26/329, 7.9%) and aphthous stomatitis (24/329, 7.3%). Approximately 27.6% of all EIM appeared before IBD diagnosis. Median time between IBD diagnosis and occurrence of first EIM was 1 month (-37.5-149.0). Thirty-one of the 55 patients (56.4%) were treated with 1 or more anti-tumor necrosis factor (TNF) agents. IBD patients with EIM were more likely to be treated with anti-TNF compared to those without (56.4% vs 35.0%, P = 0.003). Response rates to anti-TNF depended on underlying EIM and were best for peripheral arthritis (61.5%) and uveitis (66.7%). In a cohort of pediatric patients with IBD, EIM were frequently encountered. In up to 30%, EIM appeared before IBD diagnosis. Knowledge of these findings may translate into an increased awareness of underlying IBD, thereby decreasing diagnostic delay. Anti-TNF for the treatment of certain EIM is effective, although a substantial proportion of new EIM may present despite ongoing anti-TNF therapy

Uncovering the genomic basis of an extraordinary plant invasion

Invasive species are a key driver of the global biodiversity crisis, but the drivers of invasiveness, including the role of pathogens, remain debated. We investigated the genomic basis of invasiveness in Ambrosia artemisiifolia (common ragweed), introduced to Europe in the late 19th century, by resequencing 655 ragweed genomes, including 308 herbarium specimens collected up to 190 years ago. In invasive European populations, we found selection signatures in defense genes and lower prevalence of disease-inducing plant pathogens. Together with temporal changes in population structure associated with introgression from closely related Ambrosia species, escape from specific microbial enemies likely favored the plant's remarkable success as an invasive species.Peer reviewe