Deposition of PFAS 'forever chemicals' on Mt. Everest.

Mt. Everest, one of the most coveted climbing mountains on earth, also contains the highest altitude chemical contamination on land. For the first time, meltwater and snow samples from Mt. Everest's Khumbu Glacier were analyzed for "forever chemicals" per- and polyfluoroalkyl substances (PFAS). Our research team utilized solid-phase extraction (SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify pollutants sampled from Everest Base Camp, Camp 1, Camp 2, and Everest Balcony. From the 14 PFAS compounds tested for, we found perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexanoic acid (PFHxA) in Mt. Everest snow and meltwater. The highest concentrations found were 26.14 ng/L and 10.34 ng/L PFOS at Base Camp and Camp 2, respectively. However, PFAS species were seen within 1-2 orders of magnitude in all sampling sites with detection, potentially suggesting a widespread presence on the mountain. Our samples are the highest altitude PFAS samples ever retrieved and indicate the need for further sampling both on Mt. Everest and in the below-glacier watershed.

Organic Compounds in a Sub-Antarctic Ice Core: A Potential Suite of Sea Ice Markers.

Investigation of organic compounds in ice cores can potentially unlock a wealth of new information in these climate archives. We present results from the first ever ice core drilled on sub-Antarctic island Bouvet, representing a climatologically important but understudied region. We analyze a suite of novel and more familiar organic compounds in the ice core, alongside commonly measured ions. Methanesulfonic acid shows a significant, positive correlation to winter sea ice concentration, as does a fatty acid compound, oleic acid. Both may be sourced from spring phytoplankton blooms, which are larger following greater sea ice extent in the preceding winter. Oxalate, formate, and acetate are positively correlated to sea ice concentration in summer, but sources of these require further investigation. This study demonstrates the potential application of organic compounds from the marine biosphere in generating multiproxy sea ice records, which is critical in improving our understanding of past sea ice changes.

B-type natriuretic peptide in the evaluation and management of dyspnoea in primary care.

OBJECTIVES: The rapid and accurate diagnosis of heart failure in primary care is a major unmet clinical need. We evaluated the additional use of B-type natriuretic peptide (BNP) levels. DESIGN: A randomized controlled trial. SETTING: Twenty-nine primary care physicians in Switzerland and Germany coordinated by the University Hospital Basel, Switzerland. SUBJECTS: A total of 323 consecutive patients presenting with dyspnoea. INTERVENTIONS: Assignment in a 1 : 1 ratio to a diagnostic strategy including point-of-care measurement of BNP (n = 163) or standard assessment without BNP (n = 160). The total medical cost at 3 months was the primary end-point. Secondary end-points were diagnostic certainty, time to appropriate therapy, functional capacity, hospitalization and mortality. The final diagnosis was adjudicated by a physician blinded to the BNP levels. RESULTS: Heart failure was the final diagnosis in 34% of patients. The number of hospitalizations, functional status and total medical cost at 3 months [median $1655, interquartile range (IQR), 850-3331 vs. $1541, IQR 859-2827; P = 0.68] were similar in both groups. BNP increased diagnostic certainty as defined by the need for further diagnostic work-up (33% vs. 45%; P = 0.02) and accelerated the initiation of the appropriate treatment (13 days vs. 25 days; P = 0.01). The area under the receiver-operating characteristics curve for BNP to identify heart failure was 0.87 (95% confidence interval, 0.81-0.93). CONCLUSIONS: The use of BNP levels in primary care did not reduce total medical cost, but improved some of the secondary end-points including diagnostic certainty and time to initiation of appropriate treatment.

Sensitive cardiac troponin in the diagnosis and risk stratification of acute heart failure.

BACKGROUND: The aim of our study was to investigate the diagnostic and prognostic value of a sensitive cardiac troponin I (s-cTnI) assay in patients with acute heart failure (AHF). METHODS: Sensitive cardiac troponin I was measured in 667 consecutive patients at presentation to the emergency department with acute dyspnoea. Three s-cTnI strata were predefined: below the limit of detection (<0.01 µg L(-1) , undetectable), detectable but still within the normal range (0.01-0.027 µg L(-1) ) and increased (≥0.028 µg L(-1) , ≥99th percentile). The final diagnosis was adjudicated by two independent cardiologists blinded to the s-cTnI levels. Median follow-up in patients with AHF was 371 days. RESULTS: Levels of s-cTnI were higher in patients with AHF (n = 377, 57%) compared to patients with noncardiac causes of acute dyspnoea (median 0.02 vs. <0.01 µg L(-1) , P < 0.001). In patients with AHF, in-hospital mortality increased with increasing s-cTnI in the three strata (2%, 5% and 14%, P < 0.001). One-year mortality also increased with increasing s-cTnI (21%, 33% and 47%, P < 0.001). s-cTnI remained an independent predictor of 1-year mortality [adjusted odds ratio 1.03 for each increase of 0.1 µg L(-1) , 95% confidence interval (CI) 1.02-1.05, P < 0.001] after adjustment for other risk factors including B-type natriuretic peptide. The net reclassification improvement was 68% (P < 0.001), and absolute integrated discrimination improvement was 0.18 (P < 0.001). The diagnostic accuracy of s-cTnI for the diagnosis of AHF as quantified by the area under the receiver operating characteristic curve was 0.78 (95% CI, 0.75-0.82). CONCLUSIONS: Sensitive cardiac troponin I is a strong predictor of short- and long-term prognosis in AHF that helps to reclassify patients in terms of mortality risk. Detectable levels of s-cTnI, even within the normal range, are independently associated with mortality.

Interleukin family member ST2 and mortality in acute dyspnoea.

OBJECTIVES: The study objective was to investigate the prognostic utility and patient-specific characteristics of ST2 (suppression of tumorigenicity 2), assessed with a novel sensitive assay. BACKGROUND: Suppression of tumorigenicity 2 signalling has been shown to be associated with death in cardiac and pulmonary diseases. DESIGN/SUBJECTS: In an international multicentre cohort design, we prospectively enrolled 1091 patients presenting with acute dyspnoea to the emergency department (ED). ST2 was measured in a blinded fashion using a novel assay and compared to B-type natriuretic peptide (BNP) and NT-proBNP. The primary end-point was mortality within 30 days and 1 year. The prognostic value of ST2 was evaluated in comparison and in addition to BNP and NT-proBNP. RESULTS: Suppression of tumorigenicity 2 concentrations was higher amongst decedents than among survivors (median 85 vs. 43 U mL⁻¹, P < 0.001) and also higher in patients with impaired left ventricular ejection fraction (LVEF) when compared with preserved LVEF (P < 0.001). In receiver operator characteristics analysis, the area under the curve (AUC) for ST2, BNP and NT-proBNP to predict 30-day and 1-year mortality were 0.76, 0.63 and 0.71, and 0.72, 0.71 and 0.73, respectively. The combinations of ST2 with BNP or NT-proBNP improved prediction of mortality provided by BNP or NT-proBNP alone. After multivariable adjustment, ST2 values above the median (50 U mL⁻¹) significantly predicted 1-year mortality (HR 2.3, P < 0.001). CONCLUSION: In patients presenting to the ED with acute dyspnoea, ST2 is a strong and independent predictor of 30-day and 1-year mortality and might improve risk stratification already provided by BNP or NT-proBNP.

Comparison of midregional pro-atrial natriuretic peptide with N-terminal pro-B-type natriuretic peptide in the diagnosis of heart failure.

OBJECTIVES: The concentration of atrial natriuretic peptide (ANP) in the circulation is approximately 10- to 50- fold higher than B-type natriuretic peptide (BNP). We sought to compare the accuracy of midregional pro-atrial natriuretic peptide (MRproANP) measured with a novel sandwich immunoassay with N-terminal pro-B-type natriuretic peptide (NTproBNP) in the diagnosis of heart failure. DESIGN: The diagnosis of heart failure was adjudicated by two independent cardiologists using all available clinical data (including BNP levels) in 287 consecutive patients presenting with dyspnoea to the emergency department (ED). MRproANP and NTproBNP levels were determined at presentation in a blinded fashion. RESULTS: Heart failure was the adjudicated final diagnosis in 154 patients (54%). Median MRproANP was significantly higher in patients with heart failure as compared to patients with other causes of dyspnoea (400 vs. 92 pmol L(-1), P < 0.001). The diagnostic accuracy of MRproANP was very high with an area under the receiver operating characteristic curve of 0.92 and was comparable with that of NTproBNP (0.92, P = 0.791). Moreover, MRproANP provided incremental diagnostic information to BNP and NTproBNP in patients presenting with BNP levels in the grey zone between 100 and 500 pg mL(-1). CONCLUSION: Midregional pro-atrial natriuretic peptide is as accurate in the diagnosis of heart failure as NTproBNP. MRproANP seems to provide incremental information on top of BNP or NT-proBNP in some subgroups and should be further investigated in other studies.

Impact of a high-dose nitrate strategy on cardiac stress in acute heart failure: a pilot study.

BACKGROUND: Intravenous nitrate therapy has been shown to improve short-term outcome of acute heart failure patients treated in the intensive care unit. The potential of a noninvasive high-dose nitrate strategy in the Emergency Department and the general ward remains unknown. METHODS: A total of 128 consecutive acute heart failure patients were either treated with standard therapy or high-dose sublingual and transdermal nitrates on top of standard of care treatment. Cardiac recovery, quantified by B-type natriuretic peptide (BNP) levels during the first 48 h, was the primary endpoint. Secondary endpoints ascertained the safety of the nitrate therapy. RESULTS: The high nitrate group received higher doses of nitrates during the first 48 h compared to the standard therapy group [82.4 mg (46.2-120.6) vs. 20 mg (10-30) respectively, P < 0.001]. The amount of diuretics given in both groups was similar. BNP levels decreased in all patients (P < 0.0001). However, the BNP decrease was larger in the high-dose nitrate group (P < 0.0001). The larger decrease in BNP in the high-dose nitrate group was already apparent 12 h after the initiation of treatment. After 48 h BNP values decreased by an average of 29 +/- 4.9% in the high-dose nitrate strategy group compared to 15 +/- 5.4% during standard therapy. There was a strong trend towards fewer ICU admissions in the high-dose nitrate group [high-dose nitrates: 2 cases (4%) vs. standard therapy: 9 cases (13%); P = 0.06]. During the study period, no intergroup changes were observed in blood pressure, RIFLE classes of acute kidney injury or troponin T. In-hospital and 90-day outcome was similar amongst the two groups. CONCLUSIONS: A noninvasive high-dose nitrate strategy on top of standard therapy is safe and notably accelerates cardiac recovery in patients observed on the general ward.

B-type natriuretic peptide and C-terminal-pro-endothelin-1 for the prediction of severely impaired peak oxygen consumption.

OBJECTIVE: To assess the utility of B-type natriuretic peptide (BNP) and C-terminal-pro-endothelin-1 (CT-proET-1) to predict a severely impaired peak oxygen consumption (peak VO(2), < 14 mL kg(-1) min(-1)) in patients referred for cardiopulmonary exercise testing. DESIGN: Cross-sectional study. SETTING: Tertiary care center. METHODS: Peak VO(2), BNP and CT-proET-1 were assessed in 141 consecutive patients referred for cardiopulmonary exercise testing. RESULTS: B-type natriuretic peptide [median (interquartile range) 48 (38-319) vs. 33 (15-86) pg mL(-1); P = 0.002] and CT-proET-1 [87 (76-95) vs. 60 (52-74) pmol L(-1); P < 0.001] were higher in patients with a peak VO(2) < 14 mL kg(-1) min(-1) (n = 30) than in those with a peak VO(2) > or = 14 mL kg(-1) min(-1) (n = 111). CT-pro-ET-1 had a higher area under the receiver-operator-characteristics curve (AUC) to predict a peak VO(2) < 14 mL kg(-1) min(-1) than BNP (0.79 vs. 0.68; P = 0.04). The optimal BNP cut-off of 37.2 pg mL(-1) had a sensitivity of 80% and a specificity of 56%. The optimal CT-proET-1 cut-off of 74.4 pmol L(-1) had a sensitivity of 80% and specificity of 76%. A five-item score composed of body mass index, diabetes, forced expiratory volume within the first second, alveolo-arterial oxygen pressure difference, and BNP had an AUC of 0.88 to predict a peak VO(2) < 14 mL kg(-1) min(-1). Adding CT-proET-1 to the score resulted in an AUC of 0.92. CONCLUSIONS: C-terminal-pro-endothelin-1 is superior to BNP for the prediction of a peak VO(2) < 14 mL kg(-1) min(-1) in patients referred for CPET. A score incorporating body mass index, diabetes status, spirometry, blood gases, BNP and CT-proET-1 improves the prediction of a peak VO(2) < 14 mL kg(-1) min(-1) based on single biomarkers.

Prospective survey of antibiotic utilization in pediatric hospitalized patients to identify targets for improvement of prescription.

BACKGROUND: The rise in the use of antibiotics has resulted in increasing health care costs and the emergence of resistant bacteria. Little is known about the general misuse of antibiotics in hospitalized children. We evaluated the utilization of antibiotics in a pediatric teaching hospital aiming to identify targets for improvement of prescription. PATIENTS AND METHODS: Clinical, radiological, laboratory and treatment data of patients hospitalized in a pediatric medical and a pediatric surgery ward were prospectively collected during a 6-week period. A subsequent review of the collected data by a pediatric infectious diseases specialist, taking into consideration existing in-house treatment guidelines, was carried out. RESULTS: A total of 125 (36%) of 349 patients was prescribed 246 antibiotics. The median length of hospital stay for children prescribed antibiotics was 5 days (range, 2-30 days) and for those not prescribed 3 days (1-32 days; p < 0.001). Of 154 patients in the medical ward, 64 (42%) received antibiotics, compared to 61 (31%) of 195 patients in the surgical ward (p < 0.05). Empirical prescriptions were more frequent than prophylactic ones, which were more frequent than therapeutic prescriptions (136 [55%] vs 94 [38%] vs 16 [7%]; p < 0.001). Overall, 85% of the prescriptions were considered justified. The rates of inappropriate prescriptions were similar in the medical and surgical ward, and higher for therapeutic (19%) or prophylactic treatment (18%) than for empirical treatment (12%). Higher inappropriate prescription rates were noted for macrolides than for co-trimoxazole and beta-lactams (50% vs 18% and 15%, respectively; p < 0.05). CONCLUSION: Efforts need to be undertaken towards continuous education of medical staff on judicious antibiotic use, as well as ensuring compliance with existing guidelines. Improvement in the availability of rapid diagnostic methods to discern viral from bacterial infections may help reduce the numbers of empiric therapies in favor of pathogen-targeted therapeutic treatments.