Invasive Pulmonary Aspergillosis in Critically Ill Patients with Hantavirus Infection, Austria.

We investigated a cohort of 370 patients in Austria with hantavirus infections (7.8% ICU admission rate) and detected 2 cases (cumulative incidence 7%) of invasive pulmonary aspergillosis; 1 patient died. Hantavirus-associated pulmonary aspergillosis may complicate the course of critically ill patients who have hemorrhagic fever with renal syndrome.

Soluble urokinase plasminogen activator receptor (suPAR) in bronchoalveolar fluid and blood in critically ill patients-a prospective cohort study.

INTRODUCTION: Soluble urokinase plasminogen activator receptor (suPAR) is a biologically active protein and increased levels are associated with worse outcomes in critically ill patients. suPAR in bronchoalveolar fluid (BALF) may be helpful to differentiate between types of acute respiratory distress syndrome (ARDS) and may have potential for early detection of fungal infection. METHODS: We prospectively investigated levels of suPAR in BALF and serum in critically ill patients who underwent bronchoscopy for any reason at the ICU of the Department of Internal Medicine, Medical University of Graz, Graz, Austria. RESULTS: Seventy-five patients were available for analyses. Median age was 60 [25th-75th percentile: 50-69] years, 27% were female, and median SOFA score was 12 [11-14] points. Serum suPAR levels were significantly associated with ICU mortality in univariable logistic regression analysis. There was no correlation between BALF and serum suPAR. Serum suPAR was higher in ARDS patients at 11.2 [8.0-17.2] ng/mL compared to those without ARDS at 7.1 [3.7-10.1] (p < 0.001). BALF-suPAR was significantly higher in patients with evidence of fungal lung infection compared to patients without fungal infection both in the general cohort (7.6 [3.2-9.4] vs 2.5 [1.1-5.3], p = 0.013) and in the subgroup of ARDS (7.2 [3.1-39.2] vs 2.5 [1.0-5.2], p = 0.022). All patients were classified as putative/probable invasive aspergillosis. CONCLUSION: We found significant higher levels of serum suPAR in ARDS patients compared to those not fulfilling ARDS criteria. Serum and BALF-suPAR were significantly higher in those patients with evidence for invasive pulmonary aspergillosis. These findings may suggest testing this biomarker for early diagnosis of fungal infection in a greater cohort.

Intraspecific variation in crayfish behavioral traits affects leaf litter breakdown in streams.

Although intraspecific trait variation is increasingly recognized as affecting ecosystem processes, few studies have examined the ecological significance of among-population variation in behavioral traits in natural ecosystems. In freshwater habitats, crayfish are consumers that can influence ecosystem structure (e.g., macroinvertebrate communities) and function (e.g., leaf litter breakdown). To test whether crayfish behavioral traits (activity, boldness, and foraging voracity) are major contributors of leaf litter breakdown rates in the field, we collected rusty crayfish (Faxonius rusticus) from eight streams across the midwestern USA and measured behaviors using laboratory assays. At the same streams, we measured breakdown rates of leaf packs that were accessible or inaccessible to crayfish. Our results provide evidence that among-population variation in crayfish boldness and foraging voracity was a strong predictor of leaf litter breakdown rates, even after accounting for commonly appreciated environmental drivers (water temperature and human land use). Our results suggest that less bold rusty populations (i.e., emerged from shelter more slowly) had greater direct impacts on leaf litter breakdown than bold populations (P = 0.001, r2 = 0.85), potentially because leaf packs can be both a shelter and food resource to crayfish. Additionally, we found that foraging voracity was negatively related to breakdown rates in leaf packs that were inaccessible to crayfish (P = 0.025, r2 = 0.60), potentially due to a trophic cascade from crayfish preying on other invertebrates that consume leaf litter. Overall, our results add to the growing evidence that trait variation in animals may be important for understanding freshwater ecosystem functioning.

COVID-19 associated Pulmonary Aspergillosis in Patients Admitted to the Intensive Care Unit: Impact of Antifungal Prophylaxis.

Early after the beginning of the coronavirus disease 2019 (COVID-19)-pandemic, it was observed that critically ill patients in the intensive care unit (ICU) were susceptible to developing secondary fungal infections, particularly COVID-19 associated pulmonary aspergillosis (CAPA). Here we report our local experience on the impact of mold active antifungal prophylaxis on CAPA occurrence in critically ill COVID-19 patients. This is a monocentric, prospective cohort study including all consecutive patients with COVID-19 associated acute respiratory failure who were admitted to our local medical ICU. Based on the treating physician's discretion, patients may have received antifungal prophylaxis or not. All patients were retrospectively characterized as having CAPA according to the 2020 ECMM/ISHAM consensus definitions. Seventy-seven patients were admitted to our medical ICU during April 2020 and May 2021 and included in the study. The majority of patients received invasive-mechanical ventilation (61%). Fifty-three patients (68.8%) received posaconazole prophylaxis. Six cases of probable CAPA were diagnosed within clinical routine management. All six cases were diagnosed in the non-prophylaxis group. The incidence of CAPA in the overall study cohort was 0.57 events per 100 ICU days and 2.20 events per 100 ICU days in the non-prophylaxis group. No difference of cumulative 84-days survival could be observed between the two groups (p = 0.115). In this monocentric cohort, application of posaconazole prophylaxis in patients with COVID-19 associated respiratory failure did significantly reduce the rate of CAPA.

Early attainment of isavuconazole target concentration using an increased loading dose in critically ill patients with extracorporeal membrane oxygenation.

BACKGROUND: In critically ill patients with extracorporeal membrane oxygenation (ECMO) attainment of target concentration of isavuconazole is delayed using the routine loading dose. OBJECTIVES: We investigated the influence of increasing the first loading dose of isavuconazole on plasma concentrations in critically ill patients treated with ECMO. METHODS: Fifteen patients were included in this study, and isavuconazole concentrations were measured at several timepoints starting 2 h after the first isavuconazole dose up to 168 h. By interim analysis of isavuconazole concentrations and meticulous screening for adverse events, the first loading dose was stepwise increased from 200 to 300 mg, and finally to 400 mg. RESULTS: Seven of 15 patients (47%) received standard isavuconazole loading dosage with 200 mg as the first dose, 3/15 (20%) received 300 mg, and 5/15 (33%) received 400 mg isavuconazole as the first dose, followed by subsequent standard dosing in all patients. In patients receiving 400 mg as the first dose all isavuconazole concentrations were significantly higher at timepoints up to the first 24 h, resulting in higher proportions of isavuconazole concentrations ≥1 mg/L compared with patients with other loading dosages. In timepoints ≥24 h after isavuconazole initiation all patient groups reached comparable plasma concentrations, regardless of the first loading dose regimen. We did not observe concentrations above ≥5 mg/L or any adverse events related to isavuconazole administration. CONCLUSIONS: In critically ill patients with ECMO the 400 mg loading dose of isavuconazole resulted in immediate median isavuconazole plasma concentrations ≥1 mg/L and remained constant above this threshold after the first loading dose.

Leaching of select per-/poly-fluoroalkyl substances, pharmaceuticals, and hormones through soils amended with composted biosolids.

The use of organic amendments to enhance soil health is increasingly being identified as a strategy to improve residential landscapes while also reducing the need for external inputs (e.g., fertilizers, irrigation). Composted biosolids are a re-purposed waste product that can be used in organic amendments to improve the overall sustainability of a municipality by enhancing residential soil carbon content while simultaneously reducing waste materials. However, the biosolids-based feedstock of these compost products has the potential to be a source of organic contaminants. We conducted a laboratory-based soil column experiment to evaluate the potential for different commercially available compost products to act as a source of emerging organic contaminants in residential landscapes. We compared two biosolids-based compost products, a manure-based compost product, and a control (no compost) treatment by irrigating soil columns for 30 days and collecting daily leachate samples to quantify leaching rates of six hormones, eight pharmaceuticals, and seven per- and polyfluoroalkyl substances (PFAS). Detection of hormones and pharmaceuticals was rare, suggesting that compost amendments are likely not a major source of these contaminants to groundwater resources. In contrast, we detected three of the seven PFAS compounds in leachate samples throughout the study. Perfluorohexanoic acid (PFHxA) was more likely to leach from biosolids-based compost treatments than other treatments (p < 0.05) and perfluorobutane sulfonate (PFBS) was only detected in biosolids-based treatments (although PFBS concentrations did not significantly differ among treatments). In contrast, perfluorooctanoic acid (PFOA) was commonly detected across all treatments (including controls), suggesting potential PFOA experimental contamination. Overall, these results demonstrate that commercially available composted biosolids amendments are likely not a major source of hormone and pharmaceutical contamination. The detection of PFHxA at significantly higher concentrations in biosolids treatments suggests that biosolids-based composts may act as sources of PFHxA to the environment. However, concentrations of multiple PFAS compounds found in leachate in this study were lower than concentrations found in known PFAS hotspots. Therefore, there is potential for environmental contamination from PFAS leaching from composted biosolids, but leachate concentrations are low which should be considered in risk-benefit analyses when considering whether or not to use composted biosolids as an organic amendment to enhance residential soil health.

Isavuconazole plasma concentrations in critically ill patients during extracorporeal membrane oxygenation.

BACKGROUND: Isavuconazole is an antifungal drug used for treatment of invasive fungal infections. Critically ill COVID-19 and influenza patients require extracorporeal membrane oxygenation (ECMO) in cases with severe acute respiratory distress syndrome and have risk factors for invasive pulmonary aspergillosis. Little is known about isavuconazole plasma concentrations during ECMO. OBJECTIVES: To determine isavuconazole plasma concentrations in seven patients treated with intravenous isavuconazole under ECMO and the influence of the ECMO circuit immediately after the first isavuconazole dose. METHODS: Critically ill patients treated with isavuconazole (standard doses) and ECMO were included in this study. Sixty-four blood samples used for measurement of isavuconazole concentrations were collected at several timepoints starting 2 h after the first isavuconazole dose up to 168 h. An additional 27 blood samples were drawn from the inflow and outflow line of the membrane oxygenator to assess any potential isavuconazole clearance effect of the ECMO oxygenation device and the lines. RESULTS: Median isavuconazole trough levels above 1 µg/mL (min. 0.83, max. 1.73) or 2 µg/mL (min. 0.84, max. 2.97) were achieved 24 h or 96 h after the first dose of isavuconazole. The isavuconazole plasma concentrations pre (inflow line) and post (outflow line) the membrane oxygenator were directly correlated (ρ = 0.987, R2 = 0.994, P < 0.001). Post membrane oxygenator isavuconazole concentrations were directly correlated to contemporaneous samples obtained from the arterial lines of patients (ρ = 0.942, R2 = 0.945, P < 0.001). CONCLUSIONS: Isavuconazole concentrations might be influenced by the higher volume of distribution due to ECMO therapy, but were not altered by the ECMO oxygenator and achieved median plasma concentrations >1 µg/mL 24 h after the first loading dose.

Red urine and a red herring - diagnosing rare diseases in the light of the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has occupied the time and resources of health care professionals for more than 1 year. The risk of missed diagnoses has been discussed in the medical literature, mainly for common diseases such as cancer and cardiovascular events. However, rare diseases also need appropriate attention in times of a pandemic. CASE REPORT: We report a 34-year-old woman with fever, pinprick sensation in her chest and thoracic spine, and dizziness after receiving the first dose of ChAdOx1 nCoV-19 vaccination. The patient's condition worsened with abdominal pain, red urine, and hyponatremia, needing intensive care admission. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) was diagnosed. Vaccine-induced thrombocytopenia and thrombosis were ruled out. Acute hepatic porphyria was finally diagnosed, and the patient recovered completely after treatment with hemin. CONCLUSION: Currently, the focus of physicians is on COVID-19 and associated medical problems, such as vaccine side effects. However, it is important to be vigilant for other uncommon medical emergencies in medically exceptional situations that may shift our perception.

VA-ECMO and thrombus aspiration in a pulmonary embolism patient with cardiac arrest and contraindications to thrombolytic therapy.

A 57-year-old male patient with a history of proximal deep vein thrombosis on vitamin K antagonist therapy, suffered a recent hypertensive intracranial hemorrhage without significant neurological deficit. Three weeks later he presented with bilateral central pulmonary embolism. He had witnessed cardiac arrest and was put on veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Endovascular thrombectomy with an Aspirex device led to a significant improvement of hemodynamics. VA-ECMO was terminated after one day, an IVC filter was inserted, and he was discharged from ICU after 15 days. In conclusion, VA-ECMO and endovascular therapy are rescue strategies in patients with contraindications for thrombolysis.

Dosing the Coast: Leaking Sewage Infrastructure Delivers Large Annual Doses and Dynamic Mixtures of Pharmaceuticals to Urban Rivers.

Pharmaceuticals are commonly detected at low concentrations in surface waters, where they disrupt biological and ecological processes. Despite their ubiquity, the annual mass of pharmaceuticals exported from watersheds is rarely quantified. We used liquid chromatography-mass spectroscopy to screen for 92 pharmaceuticals in weekly samples from an urban stream network in Baltimore, MD, USA, that lacks wastewater treatment effluents. Across the network, we detected 37 unique compounds, with higher concentrations and more compounds in streams with higher population densities. We also used concentrations and stream discharge to calculate annual pharmaceutical loads at the watershed outlet, which range from less than 1 kg to ∼15 kg and are equivalent to tens of thousands of human doses. By calculating annual watershed mass balances for eight compounds, we show that ∼0.05 to ∼42% of the pharmaceuticals consumed by humans in this watershed are released to surface waters, with the importance of different pathways (leaking sewage vs treated wastewater effluent) differing among compounds. These results demonstrate the importance of developing, maintaining, and improving sewage infrastructure to protect water resources from pharmaceutical contamination.

Antifungal prophylaxis for prevention of COVID-19-associated pulmonary aspergillosis in critically ill patients: an observational study.

BACKGROUND: Coronavirus disease 19 (COVID-19)-associated pulmonary aspergillosis (CAPA) emerged as important fungal complications in patients with COVID-19-associated severe acute respiratory failure (ARF). Whether mould active antifungal prophylaxis (MAFP) can prevent CAPA remains elusive so far. METHODS: In this observational study, we included all consecutive patients admitted to intensive care units with COVID-19-associated ARF between September 1, 2020, and May 1, 2021. We compared patients with versus without antifungal prophylaxis with respect to CAPA incidence (primary outcome) and mortality (secondary outcome). Propensity score adjustment was performed to account for any imbalances in baseline characteristics. CAPA cases were classified according to European Confederation of Medical Mycology (ECMM)/International Society of Human and Animal Mycoses (ISHAM) consensus criteria. RESULTS: We included 132 patients, of whom 75 (57%) received antifungal prophylaxis (98% posaconazole). Ten CAPA cases were diagnosed, after a median of 6 days following ICU admission. Of those, 9 CAPA cases were recorded in the non-prophylaxis group and one in the prophylaxis group, respectively. However, no difference in 30-day ICU mortality could be observed. Thirty-day CAPA incidence estimates were 1.4% (95% CI 0.2-9.7) in the MAFP group and 17.5% (95% CI 9.6-31.4) in the group without MAFP (p = 0.002). The respective subdistributional hazard ratio (sHR) for CAPA incidence comparing the MAFP versus no MAFP group was of 0.08 (95% CI 0.01-0.63; p = 0.017). CONCLUSION: In ICU patients with COVID-19 ARF, antifungal prophylaxis was associated with significantly reduced CAPA incidence, but this did not translate into improved survival. Randomized controlled trials are warranted to evaluate the efficacy and safety of MAFP with respect to CAPA incidence and clinical outcomes.

Influence of Water Resource Recovery Facility Effluents on the Presence of Selected Trace Organic Contaminants (TOrCs) in the Reedy River, South Carolina.

Wastewater reclamation facilities are known sources of emerging contaminants associated with human health and sanitation. This study evaluated the contribution of trace organic contaminants to a previously unmonitored river by water resource reclamation facilities. Six sampling events were conducted on the Reedy River in South Carolina. Sampling locations included sites upstream and downstream of two WRRFs located on the river to examine potential contributions under drought conditions where WRRF effluents comprise a large proportion of total stream flow. Five target analytes were monitored including atrazine, carbamazepine, 17ß-estradiol, perfluorooctanoic acid, and sulfamethoxazole. On a mass basis, the WRRFs contributed additional loadings of carbamazepine ranging from 5.4 g/d to 7.2 g/d (mean: 6.3 ± 0.4 g/d), PFOA ranging from 8.6 to 31.9 g/d (mean: 20.0 ± 4.9), and sulfamethoxazole ranging from 49.4 g/d to 75.1 g/d (mean: 62.1 ± 4.8). 17ß-estradiol was detected once and atrazine was not detected.

Disease severity and proton pump inhibitor use impact strongest on faecal microbiome composition in liver cirrhosis.

BACKGROUND & AIMS: Compositional changes of the faecal microbiome in cirrhosis are well described and have been associated with complications and prognosis. However, it is less well known, which disease or treatment-related factors affect microbiome composition most distinctively. METHODS: 16S rDNA sequencing data of 88 cirrhotic outpatients were investigated. Factors influencing microbiome composition were analysed by univariate and multivariate redundancy analysis. The association of the identified factors with changes in diversity and taxonomic composition was studied in depth using analysis of composition of microbiome, LDA-effect size and least absolute shrinkage and selection operator regularized regression. RESULTS: Disease severity and aetiology, proton pump inhibitor (PPI) use, nutritional status, age and C-reactive protein are significant explanatory variables for faecal microbiome composition in liver cirrhosis. Despite some taxonomic overlaps especially between disease severity and PPI use, we could show that the effects of disease severity, aetiology, PPI use and age are independent factors influencing microbiome composition also in subgroup analyses. CONCLUSION: Our cross sectional system biology study identifies disease severity, aetiology, PPI use and age as independent factors that influence microbiome composition in liver cirrhosis. In chronic diseases with high morbidity, such as liver cirrhosis, precise patient metadata documentation is of utmost importance in microbiome analysis. Further studies with a higher sample size are necessary to validate this finding. TRIAL REGISTRATION NUMBER: NCT01607528.

Diagnosis of acute intoxications in critically ill patients: focus on biomarkers - part 2: markers for specific intoxications.

In medical intensive care units, acute intoxications contribute to a large proportion of all patients. Epidemiology and a basic overview on this topic were presented in part one. The purpose of this second part regarding toxicological biomarkers in the ICU setting focuses on specific poisons and toxins. Following the introduction of anion and osmol gap in part one, it's relevance in toxic alcohols and other biomarkers for these poisonings are presented within this publication. Furthermore, the role of markers in the blood, urine and cerebrospinal fluid for several intoxications is evaluated. Specific details are presented, amongst others, for cardiovascular drug poisoning, paracetamol (acetaminophen), ethanol, pesticides, ricin and yew tree intoxications. Detailed biomarkers and therapeutic decision tools are shown for carbon monoxide (CO) and cyanide (CN-) poisoning. Also, biomarkers in environmental toxicological situations such as mushroom poisoning and scorpion stings are presented.

Diagnosis of acute intoxications in critically ill patients: focus on biomarkers - part 1: epidemiology, methodology and general overview.

Acute intoxications account for a significant proportion of the patient population in intensive care units and sedative medications, ethanol, illicit drugs, inhalable poisons and mixed intoxications are the most common causes. The aim of this article is to describe biomarkers for screening and diagnosis of acute intoxications in critically ill patients. For this purpose, a survey of the relevant literature was conducted, and guidelines, case reports, expert assessments, and scientific publications were reviewed. In critical care, it should always be attempted to identify and quantify the poison or toxin with the assistance of enzyme immunoassay (EIA), chromatography, and mass spectrometry techniques and this section is critically appraised in this publication. The principles for anion gap, osmol gap and lactate gap and their usage in intoxications is shown. Basic rules in test methodology and pre-analytics are reviewed. Biomarkers in general are presented in part one and biomarkers for specific intoxications including ethanol, paracetamol, cardiovascular drugs and many others are presented in part two of these publications.

Seeing the light: urban stream restoration affects stream metabolism and nitrate uptake via changes in canopy cover.

The continually increasing global population residing in urban landscapes impacts numerous ecosystem functions and services provided by urban streams. Urban stream restoration is often employed to offset these impacts and conserve or enhance the various functions and services these streams provide. Despite the assumption that "if you build it, [the function] will come," current understanding of the effects of urban stream restoration on stream ecosystem functions are based on short term studies that may not capture variation in restoration effectiveness over time. We quantified the impact of stream restoration on nutrient and energy dynamics of urban streams by studying 10 urban stream reaches (five restored, five unrestored) in the Baltimore, Maryland, USA, region over a two-year period. We measured gross primary production (GPP) and ecosystem respiration (ER) at the whole-stream scale continuously throughout the study and nitrate (NO3- -N) spiraling rates seasonally (spring, summer, autumn) across all reaches. There was no significant restoration effect on NO3- -N spiraling across reaches. However, there was a significant canopy cover effect on NO3- -N spiraling, and directly comparing paired sets of unrestored-restored reaches showed that restoration does affect NO3- -N spiraling after accounting for other environmental variation. Furthermore, there was a change in GPP : ER seasonality, with restored and open-canopied reaches exhibiting higher GPP : ER during summer. The restoration effect, though, appears contingent upon altered canopy cover, which is likely to be a temporary effect of restoration and is a driver of multiple ecosystem services, e.g., habitat, riparian nutrient processing. Our results suggest that decision-making about stream restoration, including evaluations of nutrient benefits, clearly needs to consider spatial and temporal dynamics of canopy cover and trade-offs among multiple ecosystem services.

High mortality in aquatic predators of mosquito larvae caused by exposure to insect repellent.

In the face of mosquito-borne disease outbreaks, effective mosquito control is a primary goal for public health. Insect repellents, containing active compounds such as DEET and picaridin, are a first defence against biting insects. Owing to widespread use and incomplete sewage treatment, these compounds are frequently detected in surface waters, but their effects on aquatic taxa such as mosquito larvae or their naturally occurring aquatic predators are poorly understood. We investigated the effects of environmentally realistic concentrations of commercial products containing DEET and picaridin on survivorship of mosquito larvae, and their potential indirect effects on survival of larval salamanders, a major predator of mosquito larvae. Larval mosquitos were not affected by exposure to repellents containing DEET or picaridin. We found no larval salamander mortality in control and DEET treatments, but mortality rates in picaridin treatments ranged from 45 to 65% after 25 days of exposure. Salamander larvae exposed to repellents containing picaridin began to display tail deformities and impaired development four days after the experiment began. Our findings suggest the possibility that environmentally realistic concentrations of picaridin-containing repellents in surface waters may increase the abundance of adult mosquitos owing to decreased predation pressure.

Critical care management of acute intoxications, dynamics and changes over time: a cohort study.

Acute intoxications and poisonings are a relevant cause for ICU admission of critically ill patients. This study aimed to determine the characteristics of intoxicated patients in a tertiary center medical ICU in Austria over time and to investigate parameters associated with ICU mortality. This study was a retrospective data analysis including adult ICU patients from the years 2007 to 2021. In addition to ICU documentation, pre-hospital, and emergency department documents as well as autopsy reports were utilized. In an exploratory subanalysis, we compared these findings to a historical dataset from our facility from 1992 to 1996. We identified 581 cases admitted to the medical ICU because of acute poisoning (2007-2021), of which 45% were female and 46.6% were mixed intoxications. Suicidal intent was the primary cause of intoxication (48.2%) and ICU length of stay was median 1.2 days. The majority of deceased patients received pre-hospital mechanical CPR. Primary and secondary poison/toxin removal modalities were used in 29.9% and 11.7% of cases, whereas antidotes were administered in 54.4%. Comparing the data with a historical cohort (n = 168), we found a shift in primary detoxification away from gastric lavage and an increase in alternative secondary poison/toxin removal techniques. The ICU mortality was 4.1% and 4.2% in the present and historic cohort, respectively. Pre-existing psychiatric illnesses increased from 49% in the historic to 69% in the present cohort. Psychiatric illness predisposes patients to severe intoxications necessitating ICU care, thus increasing prevention measures seems warranted. Females did present with a different spectrum of intoxications compared to males. ICU mortality remained low over time and most deceased patients had a grim prognosis already on ICU arrival.