How do different marine engine fuels and wet scrubbing affect gaseous air pollutants and ozone formation potential from ship emissions?

Sulphur Emission Control Areas (SECAs), mandated by the International Maritime Organization (IMO), regulate fuel sulphur content (FSC) to mitigate the environmental and health impact of shipping emissions in coastal areas. Currently, FSC is limited to 0.1% (w/w) within and 0.5% (w/w) outside SECAs, with exceptions for ships employing wet sulphur scrubbers. These scrubbers enable vessels using non-compliant fuels such as high-sulphur heavy fuel oils (HFOs) to enter SECAs. However, while sulphur reduction via scrubbers is effective, their efficiency in capturing other potentially harmful gases remains uncertain. Moreover, emerging compliant fuels like highly aromatic fuels or low-sulphur blends lack characterisation and may pose risks. Over three years, we assessed emissions from an experimental marine engine at 25% and 75% load, representative of manoeuvring and cruising, respectively. First, characterizing emissions from five different compliant and non-compliant fuels (marine gas oil MGO, hydro-treated vegetable oil HVO, high-, low- and ultra-low sulphur HFOs), we calculated emission factors (EF). Then, the wet scrubber gas-phase capture efficiency was measured using compliant and non-compliant HFOs. NOx EF varied among fuels (5200-19700 mg/kWh), with limited scrubber reduction. CO (EF 750-13700 mg/kWh) and hydrocarbons (HC; EF 122-1851 mg/kWh) showed also insufficient abatement. Carcinogenic benzene was notably higher at 25% load and about an order of magnitude higher with HFOs compared to MGO and HVO, with no observed scrubber reduction. In contrast, carbonyls such as carcinogenic formaldehyde and acetaldehyde, acting as ozone precursors, were effectively scrubbed due to their polarity and water solubility. The ozone formation potential (OFP) of all fuels was examined. Significant EF differences between fuels and engine loads were observed, with the wet scrubber providing limited or no reduction of gaseous emissions. We suggest enhanced regulations and emission abatements in the marine sector to mitigate gaseous pollutants harmful to human health and the environment.

Biological impact of sequential exposures to allergens and ultrafine particle-rich combustion aerosol on human bronchial epithelial BEAS-2B cells at the air liquid interface.

The prevalence of allergic diseases is constantly increasing since few decades. Anthropogenic ultrafine particles (UFPs) and allergenic aerosols is highly involved in this increase; however, the underlying cellular mechanisms are not yet understood. Studies observing these effects focused mainly on singular in vivo or in vitro exposures of single particle sources, while there is only limited evidence on their subsequent or combined effects. Our study aimed at evaluating the effect of subsequent exposures to allergy-related anthropogenic and biogenic aerosols on cellular mechanism exposed at air-liquid interface (ALI) conditions. Bronchial epithelial BEAS-2B cells were exposed to UFP-rich combustion aerosols for 2 h with or without allergen pre-exposure to birch pollen extract (BPE) or house dust mite extract (HDME). The physicochemical properties of the generated particles were characterized by state-of-the-art analytical instrumentation. We evaluated the cellular response in terms of cytotoxicity, oxidative stress, genotoxicity, and in-depth gene expression profiling. We observed that single exposures with UFP, BPE, and HDME cause genotoxicity. Exposure to UFP induced pro-inflammatory canonical pathways, shifting to a more xenobiotic-related response with longer preincubation time. With additional allergen exposure, the modulation of pro-inflammatory and xenobiotic signaling was more pronounced and appeared faster. Moreover, aryl hydrocarbon receptor (AhR) signaling activation showed to be an important feature of UFP toxicity, which was especially pronounced upon pre-exposure. In summary, we were able to demonstrate the importance of subsequent exposure studies to understand realistic exposure situations and to identify possible adjuvant allergic effects and the underlying molecular mechanisms.

Conal Septal Hypoplasia in Tetralogy of Fallot-Impact on Clinical Course, Treatment Strategies, and Outcomes After Surgical Intervention.

We sought to characterize the clinical course and outcomes of intervention for Tetralogy of Fallot (TOF) with associated conal septal hypoplasia (CSH) compared to those with identifiable conal septum on initial newborn echocardiogram. We performed a retrospective, 1:2 case-control study of children with TOF anatomy, 33 with CSH and 66 with typical TOF, who underwent surgical repair from 1991-2019 at Children's Wisconsin. Data on echocardiographic anatomic features, systemic oxygen saturations, medical therapies, admissions, palliative interventions, operative strategies, and long-term follow-up were compared. The CSH group had fewer hypercyanotic spells (6% vs 42%, p < 0.001), beta-blockers prescribed (12% vs 41%, p = 0.005), and hospital admissions for cyanosis (12% vs 44%; p = 0.001) prior to any intervention. Of 14 who required palliative intervention, 8 had balloon pulmonary valvuloplasty (BPV) (7 from the CSH group and 1 from the control group), and 6 had systemic-to-pulmonary artery shunts (all from the control group). Definitive repair was performed at a significantly older age in the CSH group (10.2 ± 10 vs 5.6 ± 5.9 months, p = 0.011), with less subpulmonary muscle resection (57.6% in vs 92.4%, p < 0.001) and higher use of a transannular patch (84.8% vs 65.2%, p = 0.040). The average time to surgical reintervention was similar in both groups (9.7 ± 5.9 vs 8.6 ± 6.4 years in controls). We conclude that infants with TOF and CSH have a milder preoperative clinical course with fewer hypercyanotic spells or need for medical therapy. They also respond well to palliative BPV and can safely undergo later definitive repair compared to typical TOF with a well-developed conal septum.

Prognostic utility of echocardiographically derived left ventricular strain in assessing neonatal enteroviral myocarditis outcome.

BACKGROUND: Neonatal enteroviral myocarditis is a rare but potentially fatal illness. We sought to identify echocardiographic markers at diagnosis that could help risk-stratify infants for poor outcome and to characterise late sequelae. METHODS: We reviewed data for infants <30 days of age diagnosed with enteroviral myocarditis between 1999 and 2019 at Children's Wisconsin. Echo measures were collected retrospectively from the initial neonatal study including left ventricular ejection fraction, shortening fraction, diastolic and systolic dimensions, and peak global circumferential and longitudinal strain. RESULTS: Fourteen neonates were diagnosed at an average age of 11 days. All had abnormal left ventricular ejection fraction (mean 38%; range 22-53%) at diagnosis. Three infants died, and one required transplantation during initial hospital. The 10 transplant-free survivors had significantly better global circumferential strain and global longitudinal strain at the initial echo compared to the 4 who died or needed transplant (global circumferential strain -13.2% versus -6.8%, p = 0.005; global longitudinal strain -8.8% versus -4.7%, p = 0.016). All other measures of left ventricular systolic function/dimensions were similar between the two groups. Follow-up data were available for 8/10 survivors; 5/8 had a persistently abnormal echo at an average interval of 8.3 years. 4/8 developed a left ventricular aneurysm that was consistently localised to the posterior basal wall. CONCLUSIONS: Neonatal enteroviral myocarditis carries a high risk of early mortality and late morbidity. Echo-derived left ventricular strain measures have utility in risk stratifying infants with enteroviral myocarditis. Most survivors continue to have late dysfunction necessitating cardiology surveillance and medical therapy.

An alternative in vitro model considering cell-cell interactions in fiber-induced pulmonary fibrosis.

Particularly since the wide-ranging health effects of asbestos exposure became known, great emphasis has been placed on detailed toxicity testing of known but also newly developed fiber materials. Exposure to respirable pollutants like fibers can lead to tissue injury causing lung diseases such as pulmonary fibrosis or cancer. In order to detect the toxic potential of such aerosols at an early stage, the development of suitable test systems is essential. In this study, we illustrate the development of an advanced in vitro cell model closely resembling the physiological structure of the alveoli, and we highlight its advantages over simpler models to predict pro-fibrotic changes. For this reason, we analyzed the cytotoxic effects of fiber-like multi-walled carbon nanotubes after 24 and 48 h exposure, and we investigated inflammatory, genotoxic and pro-fibrotic changes occurring in the developed triple culture consisting of lung epithelial cells, macrophages and fibroblasts compared to a co-culture of epithelial cells and fibroblasts or a mono culture of epithelial cells. In summary, the triple culture system is more precisely able to detect a pro-fibrotic phenotype including epithelial-mesenchymal transition as well as secondary genotoxicity, even if exhibiting lower cytotoxicity in contrast to the less advanced systems. These effects might be traced back to the complex interplay between the different cell types, all of which play an important role in the inflammatory response, which precedes wound healing, or even fibrosis or cancer development.

Contact force ablation of accessory pathways in pediatric patients.

INTRODUCTION: Contact force (CF) catheters provide feedback confirming adequate tissue contact for optimal lesion size and minimal complications. CF ablation catheters have resulted in decreased procedure times and improved outcomes for ablation of atrial fibrillation in adults. There is limited data evaluating CF use for accessory pathway (AP) ablation or in pediatric patients. The aim of our study was to compare a cohort who underwent AP ablation with a CF catheter to historical controls, evaluating for differences in procedure times, number of lesions, and outcomes. METHODS: A retrospective chart review of CF ablation cases at Children's Wisconsin performed between June 2015 to April 2018 was compared to a historical control cohort of traditional radiofrequency (RF) ablations between June 2012 and June 2015. 43 patients with APs underwent 49 CF ablation procedures (18 males, 13.6 ± 3 years old) and a control cohort consisted of 77 procedures in 69 patients (38 males, 12.4 ± 4 years). RESULTS: The groups did not differ significantly on procedure time (CF 2.01 ± 0.48 h, control 1.53 ± 0.48 h, p = .37), or total lesions administered (CF and control 7 ± 6 lesions, p = .89). CF cases showed a trend toward improvement in acute success (98% CF, 90% controls, p = .15) though with increased recurrence compared to controls (13% CF, 4.3% controls, p = .16), neither being statistically significant. CONCLUSION: Our study suggests that ablation outcomes using CF are comparable to traditional RF ablation in pediatric patients with APs.

Role of echocardiographic scoring systems in predicting successful biventricular versus univentricular palliation in neonates with critical aortic stenosis.

BACKGROUND: There are several published echo-derived scores to help predict successful biventricular versus univentricular palliation in neonates with critical aortic stenosis. This study aims to determine whether any published scoring system accurately predicted outcomes in these neonates. METHODS: Single centre, retrospective cohort study including neonates who underwent aortic valve intervention (surgical valvotomy or balloon valvuloplasty) with the intention of biventricular circulation. Primary outcome was survival with biventricular circulation at hospital discharge. Data from their initial neonatal echocardiogram were used to compute the following scores - Rhodes, CHSS 1, Discriminant, CHSS 2, and 2 V. RESULTS: Between 01/1999 and 12/2017, 68 neonates underwent aortic valve intervention at a median age of 4 days (range 1-29 days); 35 surgical valvotomy and 33 balloon valvuloplasty. Survival with biventricular circulation was maintained in 60/68 patients at hospital discharge. Of the remaining eight patients, three were converted to univentricular palliation, four died, and one underwent heart transplant prior to discharge. None of the binary score predictions of biventricular versus univentricular (using that score's proposed cut-offs) were significantly associated with the observed outcome in this cohort. A high percentage of those predicted to need univentricular palliation had successful biventricular repair: 89.4% by Rhodes, 79.3% by CHSS 1, 85.2% by Discriminant, and 66.7% by CHSS 2 score. The 2 V best predicted outcome and agreed with the local approach in most cases. CONCLUSION: This study highlights the limitations of and need for alternative scoring systems/cut-offs for consistently accurate echocardiographic prediction of early outcome in neonates with critical aortic stenosis.

Detection of monohydroxylated polycyclic aromatic hydrocarbons in urine and particulate matter using LC separations coupled with integrated SPE and fluorescence detection or coupled with high-resolution time-of-flight mass spectrometry.

A high-performance liquid chromatographic (HPLC) method with integrated solid-phase extraction for the determination of 1-hydroxypyrene and 1-, 2-, 3-, 4- and 9-hydroxyphenanthrene in urine was developed and validated. After enzymatic treatment and centrifugation of 500 µL urine, 100 µL of the sample was directly injected into the HPLC system. Integrated solid-phase extraction was performed on a selective, copper phthalocyanine modified packing material. Subsequent chromatographic separation was achieved on a pentafluorophenyl core-shell column using a methanol gradient. For quantification, time-programmed fluorescence detection was used. Matrix-dependent recoveries were between 94.8 and 102.4%, repeatability and reproducibility ranged from 2.2 to 17.9% and detection limits lay between 2.6 and 13.6 ng/L urine. A set of 16 samples from normally exposed adults was analyzed using this HPLC-fluorescence detection method. Results were comparable with those reported in other studies. The chromatographic separation of the method was transferred to an ultra-high-performance liquid chromatography pentafluorophenyl core-shell column and coupled to a high-resolution time-of-flight mass spectrometer (HR-TOF-MS). The resulting method was used to demonstrate the applicability of LC-HR-TOF-MS for simultaneous target and suspect screening of monohydroxylated polycyclic aromatic hydrocarbons in extracts of urine and particulate matter.

Determination of air pollution-related biomarkers of exposure in urine of travellers between Germany and China using liquid chromatographic and liquid chromatographic-mass spectrometric methods: a pilot study.

OBJECTIVE: The influence of different exposures to PM2.5 (particulate matter with an aerodynamic diameter below 2.5 µm) on the concentrations of biomarkers of exposure and oxidative stress should be investigated. For this purpose, urine samples from individuals travelling from Germany to China were collected and analysed. MATERIALS: Robust LC and LC-MS/MS methods were established for the determination of biomarkers including 8-hydroxy-2'-deoxyguanosine, malondialdehyde, F2α-isoprostanes and hydroxylated polycyclic aromatic hydrocarbons. As a pilot study, nine volunteers travelled from Germany (mean daily concentration of PM2.5: 21 µg/m3) to China (mean daily concentration of PM2.5: 108 µg/m3). Urine samples were collected before and after the trip. RESULTS: In samples collected after return to Germany, the median concentrations of oxidative stress biomarkers were observed to be higher than in samples collected before leaving Germany. Decreasing trends were observed in the sequences of samples collected after return in the following weeks. Correlations were found between exposure and oxidative stress biomarkers. CONCLUSION: Travellers are ideal models for PM pollution-induced acute health effects study. Exposure to PM pollution can cause oxidative stress and damage.

The Association of Central-Line-Associated Bloodstream Infections With Central-Line Utilization Rate and Maintenance Bundle Compliance Among Types of PICUs.

OBJECTIVE: Central-line-associated bloodstream infections comprise 25% of device-associated infections. Compared with other units, PICUs demonstrate a higher central-line-associated bloodstream infections prevalence. Prior studies have not investigated the association of central-line-associated bloodstream infections prevalence, central-line utilization, or maintenance bundle compliance between specific types of PICUs. DESIGN: This study analyzed monthly aggregate data regarding central-line-associated bloodstream infections prevalence, central-line utilization, and maintenance bundle compliance between three types of PICUs: 1) PICUs that do not care for cardiac patients (PICU); 2) PICUs that provide care for cardiac and noncardiac patients (C/PICU); or 3) designated cardiac ICUs (CICU). SETTING: The included units submitted data as part of The Children's Hospital Association PICU central-line-associated bloodstream infections collaborative from January 1, 2011, to December 31, 2013. PATIENTS: Patients admitted to PICUs in collaborative institutions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The overall central-line-associated bloodstream infections prevalence was low (1.37 central-line-associated bloodstream infections events/1,000 central-line days) and decreased over the time of the study. Central-line-associated bloodstream infections prevalence was not related to the type of PICU although C/PICU tended to have a higher central-line-associated bloodstream infections prevalence (p = 0.055). CICU demonstrated a significantly higher central-line utilization ratio (p < 0.001). However, when examined on a unit level, central-line utilization was not related to the central-line-associated bloodstream infections prevalence. The central-line maintenance bundle compliance rate was not associated with central line-associated bloodstream infections prevalence in this unit-level investigation. Neither utilization rate nor compliance rate changed significantly over time in any of the types of units. CONCLUSIONS: Although this unit-level analysis did not demonstrate an association between central-line-associated bloodstream infections prevalence and central-line utilization and maintenance bundle compliance, optimization of both should continue, further decreasing central-line-associated bloodstream infections prevalence. In addition, investigation of patient-specific factors may aid in further central-line-associated bloodstream infections eradication.

Pediatric Specialty Transport Teams Are Not Associated With Decreased 48-Hour Pediatric Intensive Care Unit Mortality: A Propensity Analysis of the VPS, LLC Database.

OBJECTIVE: The purpose of this study was to determine if pediatric specialty pediatric team (SPT) interfacility-transported children from community emergency departments to a pediatric intensive care unit (PICU) have improved 48-hour mortality. METHODS: This is a multicenter, historic cohort analysis of the VPS, LLC PICU clinical database (VPS, LLC, Los Angeles, CA) for all PICU directly admitted pediatric patients ≤ 18 years of age from January 1, 2007, to March 31, 2009. Categoric variables were analyzed by the chi-square and Mann-Whitney tests for non-normally distributed continuous variables. The propensity score was determined by multiple logistic regression analysis. Nearest neighbor matching developed emergency medical services SPT pairs by similar propensity score. Multiple regression analyses of the matched pairs determined the association of SPT with 48-hour PICU mortality. P values < .05 were considered significant. RESULTS: This study included 3,795 PICU discharges from 12 hospitals. SPT-transported children were more severely ill, younger in age, and more likely to have a respiratory diagnosis (P < .0001). Unadjusted 48-hour PICU mortality was statistically significantly higher for SPT transports (2.04% vs. 0.070%, P = .0028). Multiple regressions adjusted for propensity score, illness severity, and PICU site showed no significant difference in 48-hour PICU mortality. CONCLUSION: No significant difference in adjusted 48-hour PICU mortality for children transported by transport team type was discovered.

Acute Pancreatitis in the Pediatric Intensive Care Unit.

AIM: The aim of this study is to describe the demographics and outcomes of children with a discharge diagnosis of acute pancreatitis (AP) from the pediatric intensive care unit (PICU). METHODS: Data for this retrospective cohort study were obtained from a multisite, clinical PICU database. PICU discharges with a primary or secondary diagnosis of AP (SAP) between 2009 and 2013 from 113 centers were reviewed. We also obtained the Pediatric Index of Mortality 2 Risk of Mortality (PIM2ROM), an indicator of the severity of illness. RESULTS: Of 360,162 PICU discharges, 2026 with a diagnosis of AP were analyzed further (0.56%)-331 had a primary diagnosis of AP, whereas 1695 had a SAP. Among children with primary AP, median PIM2ROM was 1.0% (interquartile range [IQR] 0.8%-1.4%). Fifty-five children with primary AP (16.6%) required mechanical ventilation (MV) for a median of 3.8 days (IQR 1.0-9.3). The length of stay (LOS) in PICU was a median of 2.95 days (IQR 1.53-5.90). Only 1 patient died (mortality 0.3%). Among children with secondary AP, median PIM2ROM was 1.1% (IQR 0.8%-4.0%). A total of 711 children (42.0%) with secondary AP required MV for a median of 5.8 days (IQR 1.8-14.0). PICU LOS was a median of 4.43 days (IQR 1.84-11.22). There were 115 deaths in this group (mortality 6.8%). Median PIM2ROM, PICU LOS, mortality (all P < 0.001), and length of MV (P = 0.035) were significantly greater in children with secondary AP than with primary AP. CONCLUSIONS: Unlike in adult series, children with AP rarely die. Patients with secondary AP experience more morbidity and mortality than patients with primary AP.

Evidence-Based Pediatric Outcome Predictors to Guide the Allocation of Critical Care Resources in a Mass Casualty Event.

OBJECTIVE: ICU resources may be overwhelmed by a mass casualty event, triggering a conversion to Crisis Standards of Care in which critical care support is diverted away from patients least likely to benefit, with the goal of improving population survival. We aimed to devise a Crisis Standards of Care triage allocation scheme specifically for children. DESIGN: A triage scheme is proposed in which patients would be divided into those requiring mechanical ventilation at PICU presentation and those not, and then each group would be evaluated for probability of death and for predicted duration of resource consumption, specifically, duration of PICU length of stay and mechanical ventilation. Children will be excluded from PICU admission if their mortality or resource utilization is predicted to exceed predetermined levels ("high risk"), or if they have a low likelihood of requiring ICU support ("low risk"). Children entered into the Virtual PICU Performance Systems database were employed to develop prediction equations to assign children to the exclusion categories using logistic and linear regression. Machine Learning provided an alternative strategy to develop a triage scheme independent from this process. SETTING: One hundred ten American PICUs SUBJECTS: : One hundred fifty thousand records from the Virtual PICU database. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The prediction equations for probability of death had an area under the receiver operating characteristic curve more than 0.87. The prediction equation for belonging to the low-risk category had lower discrimination. R for the prediction equations for PICU length of stay and days of mechanical ventilation ranged from 0.10 to 0.18. Machine learning recommended initially dividing children into those mechanically ventilated versus those not and had strong predictive power for mortality, thus independently verifying the triage sequence and broadly verifying the algorithm. CONCLUSION: An evidence-based predictive tool for children is presented to guide resource allocation during Crisis Standards of Care, potentially improving population outcomes by selecting patients likely to benefit from short-duration ICU interventions.

The Supported vs Unsupported Ross in Pediatric Patients: Neoaortic Root and Ventricular Function.

BACKGROUND: The supported Ross is used to mitigate the neoaortic root dilation that has been described with the unsupported Ross. There is limited literature assessing the efficacy of the supported Ross in young patients. In this study, the fate of the neoaortic root was compared in the supported and unsupported Ross procedure in adolescent patients. METHODS: A retrospective review was performed of patients who underwent the Ross procedure between 1996 and 2019. An analysis was conducted of patients aged 10 to 18 years who underwent the supported and unsupported Ross operation, without a Konno enlargement, to assess for longitudinal echocardiographic changes. Given differences in follow-up time, both regression analysis and Mann-Whitney nonparametric tests were used to correct for time from discharge to most recent follow-up. RESULTS: The median follow-up time for supported and unsupported Ross patients without a Konno enlargement was 2.90 years (0.21-13.03 years) and 12.13 years (2.63-19.47 years), respectively. Unsupported Ross patients experienced a higher rate of change per year in the aortic annulus (P = .003 and P = .014) and aortic sinus (P = .002 and P = .002) diameters, respectively. There was no significant difference in the rate of change of end-diastolic left ventricular internal diameter (P = .703 and P = .92) and aortic insufficiency (P = .687 and P = .215) between the supported and unsupported Ross patients. CONCLUSIONS: Progressive dilation of the neoaortic root in unsupported Ross patients is significantly mitigated with the supported Ross with excellent stability. The supported Ross is safe and effective and may play an increasing role in the management of children with aortic disease.

Incidence and risk factors for venous thromboembolism in critically ill children with cardiac disease.

Cardiac disease is a risk factor for venous thromboembolism (VTE) in children. In this study, we investigated the incidence and risk factors of VTE in critically ill children with cardiac disease, who were prospectively followed-up for VTE after admission to a tertiary care pediatric intensive care unit (PICU). Risk factors were compared between VTE cases and (1) patients in the cohort who did not develop VTE and (2) the next three cardiac patients sequentially admitted to the PICU (case control). Forty-one cases of VTE were identified from 1070 admissions (3.8%). Thirty-seven percent of VTE cases were central venous catheter (CVC)-associated, and 56% of cases were intracardiac. Sixty-six percent of patients were receiving anticoagulation at the time of VTE diagnosis. Increased VTE incidence was associated with unscheduled PICU admission, age <6 months, extracorporeal membrane oxygenation, increased number of CVCs, increased number of CVC days, higher risk of mortality score, and longer PICU stay. Using logistic regression, VTE was associated with single-ventricle physiology (odds ratio [OR] 11.2, 95% CI 3.0-41.9), widened arterial-to-somatic oxygen saturation gradient (SpO(2)-rSO(2) >30) (OR 4.3, 95% CI 1.1-16), and more CVC days (OR 1.1, 95% CI 1.04-1.13). Risk factors for VTE in critically ill children with cardiac disease include younger age, single-ventricle cardiac lesions, increased illness severity, unscheduled PICU admission, and complicated hospital course.

Extended Infusion ß-Lactams for the Treatment of Gram-Negative Bacteremia in Children.

OBJECTIVE: The pharmacokinetics of ß-lactam antibiotics favor administration via an extended infusion. Although literature to support extended infusion ß-lactams exists for adults, few data are available in pediatrics, especially among patients with bacteremia. The purpose of this study was to compare clinical outcomes between extended and standard infusions in children with Gram-negative bacteremia. METHODS: This retrospective chart analysis included hospitalized patients ages 0 to 18 years who received at least 72 hours of cefepime, meropenem, or piperacillin-tazobactam between January 1, 2013 and July 30, 2021. Clinical outcomes included duration of antibiotic therapy, hospital length of stay, readmission within 30 days, all-cause mortality, time to blood culture clearance, and time to normalization of inflammatory markers. RESULTS: A total of 124 patients (51 extended infusion, 73 standard infusion) met criteria for evaluation. Duration of antibiotic therapy was shorter in the extended infusion group (6.6 days versus 10.2 days; p = 0.01). There were no differences in hospital length of stay, readmission rates, all-cause mortality, time to normalization of inflammatory markers, or time to blood culture clearance. CONCLUSIONS: Use of extended infusion ß-lactam antibiotics in children with Gram-negative bacteremia was associated with shorter durations of therapy and should be the preferred method of administration when feasible.

Construction of an In Vitro Air-Liquid Interface Exposure System to Assess the Toxicological Impact of Gas and Particle Phase of Semi-Volatile Organic Compounds.

Anthropogenic activities and industrialization render continuous human exposure to semi-volatile organic compounds (SVOCs) inevitable. Occupational monitoring and safety implementations consider the inhalation exposure of SVOCs as critically relevant. Due to the inherent properties of SVOCs as gas/particle mixtures, risk assessment strategies should consider particle size-segregated SVOC association and the relevance of released gas phase fractions. We constructed an in vitro air-liquid interface (ALI) exposure system to study the distinct toxic effects of the gas and particle phases of the model SVOC dibutyl phthalate (DBP) in A549 human lung epithelial cells. Cytotoxicity was evaluated and genotoxic effects were measured by the alkaline and enzyme versions of the comet assay. Deposited doses were assessed by model calculations and chemical analysis using liquid chromatography tandem mass spectrometry. The novel ALI exposure system was successfully implemented and revealed the distinct genotoxic effects of the gas and particle phases of DBP. The empirical measurements of cellular deposition and the model calculations of the DBP particle phase were concordant.The model SVOC DBP showed that inferred oxidative DNA damage may be attributed to particle-related effects. While pure gas phase exposure may follow a distinct mechanism of genotoxicity, the contribution of the gas phase to total aerosol was comparably low.

A comparative study of persistent DNA oxidation and chromosomal instability induced in vitro by oxidizers and reference airborne particles.

Adverse health effects driven by airborne particulate matter (PM) are mainly associated with reactive oxygen species formation, pro-inflammatory effects, and genome instability. Therefore, a better understanding of the underlying mechanisms is needed to evaluate health risks caused by exposure to PM. The aim of this study was to compare the genotoxic effects of two oxidizing agents (menadione and 3-chloro-1,2-propanediol) with three different reference PM (fine dust ERM-CZ100, urban dust SRM1649, and diesel PM SRM2975) on monocytic THP-1 and alveolar epithelial A549 cells. We assessed DNA oxidation by measuring the oxidized derivative 8-hydroxy-2'-deoxyguanosine (8-OHdG) following short and long exposure times to evaluate the persistency of oxidative DNA damage. Cytokinesis-block micronucleus cytome assay was performed to assess chromosomal instability, cytostasis, and cytotoxicity. Particles were characterized by inductively coupled plasma mass spectrometry in terms of selected elemental content, the release of ions in cell medium and the cellular uptake of metals. PM deposition and cellular dose were investigated by a spectrophotometric method on adherent A549 cells. The level of lipid peroxidation was evaluated via malondialdehyde concentration measurement. Despite differences in the tested concentrations, deposition efficiency, and lipid peroxidation levels, all reference PM samples caused oxidative DNA damage to a similar extent as the two oxidizers in terms of magnitude but with different oxidative DNA damage persistence. Diesel SRM2975 were more effective in inducing chromosomal instability with respect to fine and urban dust highlighting the role of polycyclic aromatic hydrocarbons derivatives on chromosomal instability. The persistence of 8-OHdG lesions strongly correlated with different types of chromosomal damage and revealed distinguishing sensitivity of cell types as well as specific features of particles versus oxidizing agent effects. In conclusion, this study revealed that an interplay between DNA oxidation persistence and chromosomal damage is driving particulate matter-induced genome instability.

Effect of Atmospheric Aging on Soot Particle Toxicity in Lung Cell Models at the Air-Liquid Interface: Differential Toxicological Impacts of Biogenic and Anthropogenic Secondary Organic Aerosols (SOAs).

BACKGROUND: Secondary organic aerosols (SOAs) formed from anthropogenic or biogenic gaseous precursors in the atmosphere substantially contribute to the ambient fine particulate matter [PM ≤2.5µm in aerodynamic diameter (PM2.5)] burden, which has been associated with adverse human health effects. However, there is only limited evidence on their differential toxicological impact. OBJECTIVES: We aimed to discriminate toxicological effects of aerosols generated by atmospheric aging on combustion soot particles (SPs) of gaseous biogenic (ß-pinene) or anthropogenic (naphthalene) precursors in two different lung cell models exposed at the air-liquid interface (ALI). METHODS: Mono- or cocultures of lung epithelial cells (A549) and endothelial cells (EA.hy926) were exposed at the ALI for 4 h to different aerosol concentrations of a photochemically aged mixture of primary combustion SP and ß-pinene (SOAßPIN-SP) or naphthalene (SOANAP-SP). The internally mixed soot/SOA particles were comprehensively characterized in terms of their physical and chemical properties. We conducted toxicity tests to determine cytotoxicity, intracellular oxidative stress, primary and secondary genotoxicity, as well as inflammatory and angiogenic effects. RESULTS: We observed considerable toxicity-related outcomes in cells treated with either SOA type. Greater adverse effects were measured for SOANAP-SP compared with SOAßPIN-SP in both cell models, whereas the nano-sized soot cores alone showed only minor effects. At the functional level, we found that SOANAP-SP augmented the secretion of malondialdehyde and interleukin-8 and may have induced the activation of endothelial cells in the coculture system. This activation was confirmed by comet assay, suggesting secondary genotoxicity and greater angiogenic potential. Chemical characterization of PM revealed distinct qualitative differences in the composition of the two secondary aerosol types. DISCUSSION: In this study using A549 and EA.hy926 cells exposed at ALI, SOA compounds had greater toxicity than primary SPs. Photochemical aging of naphthalene was associated with the formation of more oxidized, more aromatic SOAs with a higher oxidative potential and toxicity compared with ß-pinene. Thus, we conclude that the influence of atmospheric chemistry on the chemical PM composition plays a crucial role for the adverse health outcome of emissions. https://doi.org/10.1289/EHP9413.