Fecal metabolite profiling identifies liver transplant recipients at risk for postoperative infection.

Metabolites produced by the intestinal microbiome modulate mucosal immune defenses and optimize epithelial barrier function. Intestinal dysbiosis, including loss of intestinal microbiome diversity and expansion of antibiotic-resistant pathobionts, is accompanied by changes in fecal metabolite concentrations and increased incidence of systemic infection. Laboratory tests that quantify intestinal dysbiosis, however, have yet to be incorporated into clinical practice. We quantified fecal metabolites in 107 patients undergoing liver transplantation (LT) and correlated these with fecal microbiome compositions, pathobiont expansion, and postoperative infections. Consistent with experimental studies implicating microbiome-derived metabolites with host-mediated antimicrobial defenses, reduced fecal concentrations of short- and branched-chain fatty acids, secondary bile acids, and tryptophan metabolites correlate with compositional microbiome dysbiosis in LT patients and the relative risk of postoperative infection. Our findings demonstrate that fecal metabolite profiling can identify LT patients at increased risk of postoperative infection and may provide guideposts for microbiome-targeted therapies.

Bifidobacteria metabolize lactulose to optimize gut metabolites and prevent systemic infection in patients with liver disease.

Progression of chronic liver disease is precipitated by hepatocyte loss, inflammation and fibrosis. This process results in the loss of critical hepatic functions, increasing morbidity and the risk of infection. Medical interventions that treat complications of hepatic failure, including antibiotic administration for systemic infections and lactulose treatment for hepatic encephalopathy, can impact gut microbiome composition and metabolite production. Here, using shotgun metagenomic sequencing and targeted metabolomic analyses on 847 faecal samples from 262 patients with acute or chronic liver disease, we demonstrate that patients hospitalized for liver disease have reduced microbiome diversity and a paucity of bioactive metabolites, including short-chain fatty acids and bile acid derivatives, that impact immune defences and epithelial barrier integrity. We find that patients treated with the orally administered but non-absorbable disaccharide lactulose have increased densities of intestinal bifidobacteria and reduced incidence of systemic infections and mortality. Bifidobacteria metabolize lactulose, produce high concentrations of acetate and acidify the gut lumen in humans and mice, which, in combination, can reduce the growth of antibiotic-resistant bacteria such as vancomycin-resistant Enterococcus faecium in vitro. Our studies suggest that lactulose and bifidobacteria serve as a synbiotic to reduce rates of infection in patients with severe liver disease.

Reduced immunomodulatory metabolite concentrations in peri-transplant fecal samples from heart allograft recipients.

Background: Emerging evidence is revealing the impact of the gut microbiome on hematopoietic and solid organ transplantation. Prior studies postulate that this influence is mediated by bioactive metabolites produced by gut-dwelling commensal bacteria. However, gut microbial metabolite production has not previously been measured among heart transplant (HT) recipients. Methods: In order to investigate the potential influence of the gut microbiome and its metabolites on HT, we analyzed the composition and metabolite production of the fecal microbiome among 48 HT recipients at the time of HT. Results: Compared to 20 healthy donors, HT recipients have significantly reduced alpha, i.e. within-sample, microbiota diversity, with significantly lower abundances of key anaerobic commensal bacteria and higher abundances of potentially pathogenic taxa that have been correlated with adverse outcomes in other forms of transplantation. HT recipients have a wide range of microbiota-derived fecal metabolite concentrations, with significantly reduced levels of immune modulatory metabolites such as short chain fatty acids and secondary bile acids compared to healthy donors. These differences were likely due to disease severity and prior antibiotic exposures but were not explained by other demographic or clinical factors. Conclusions: Key potentially immune modulatory gut microbial metabolites are quantifiable and significantly reduced among HT recipients compared to healthy donors. Further study is needed to understand whether this wide range of gut microbial dysbiosis and metabolite alterations impact clinical outcomes and if they can be used as predictive biomarkers or manipulated to improve transplant outcomes.

Immunomodulatory fecal metabolites are associated with mortality in COVID-19 patients with respiratory failure.

Respiratory failure and mortality from COVID-19 result from virus- and inflammation-induced lung tissue damage. The intestinal microbiome and associated metabolites are implicated in immune responses to respiratory viral infections, however their impact on progression of severe COVID-19 remains unclear. We prospectively enrolled 71 patients with COVID-19 associated critical illness, collected fecal specimens within 3 days of medical intensive care unit admission, defined microbiome compositions by shotgun metagenomic sequencing, and quantified microbiota-derived metabolites (NCT #04552834). Of the 71 patients, 39 survived and 32 died. Mortality was associated with increased representation of Proteobacteria in the fecal microbiota and decreased concentrations of fecal secondary bile acids and desaminotyrosine (DAT). A microbiome metabolic profile (MMP) that accounts for fecal secondary bile acids and desaminotyrosine concentrations was independently associated with progression of respiratory failure leading to mechanical ventilation. Our findings demonstrate that fecal microbiota composition and microbiota-derived metabolite concentrations can predict the trajectory of respiratory function and death in patients with severe SARS-Cov-2 infection and suggest that the gut-lung axis plays an important role in the recovery from COVID-19.

Translating Microbiome Research From and To the Clinic.

Extensive research has elucidated the influence of the gut microbiota on human health and disease susceptibility and resistance. We review recent clinical and laboratory-based experimental studies associating the gut microbiota with certain human diseases. We also highlight ongoing translational advances that manipulate the gut microbiota to treat human diseases and discuss opportunities and challenges in translating microbiome research from and to the bedside.

Cancer, transplant, and immunocompromising conditions were not significantly associated with severe illness or death in hospitalized COVID-19 patients.

OBJECTIVE: Patients with cancer, transplant, and other immunocompromising conditions are at uncertain risk of severe COVID-19 illness. This study aimed to clarify whether patients with immunocompromising conditions were more likely to develop severe COVID-19 illness in a single urban academic medical center. METHODS: A retrospective chart review and electronic data extraction of the first 401 patients at the University of Chicago Hospitals with SARS-CoV-2 infection was performed. Patients met criteria for severe COVID-19 illness if they required ICU level care, high flow oxygen, positive pressure support, helmet non-invasive ventilation, mechanical ventilation, or ECMO, developed ARDS, or died. RESULTS: The mean age was 60 years, 52% were women, 90% were African American, and mortality at 30 days post discharge was 13%. Severe COVID-19 illness was found in 168 (40%) patients. Of the 56 patients with past or current cancer, 25 (45%) had severe illness (p=0.76). Of the 55 patients with other immunocompromised conditions, 24 (44%) had severe illness (p=0.89) After controlling for age, sex, and race, neither cancer (p=0.73) nor immunocompromised conditions (p=0.64) were associated with severe illness. CONCLUSION: No association was found between severe COVID-19 illness and cancer, transplant, and other immunocompromising conditions in a cohort of mostly African American patients.

Community-acquired Coinfection in Coronavirus Disease 2019: A Retrospective Observational Experience.

Community-acquired coinfection in coronavirus disease 2019 (COVID-19) is not well defined. Current literature describes coinfection in 0-40% of COVID-19 patients. In this retrospective report, coinfection was identified in 3.7% of patients and 41% of patients admitted to intensive care (P < .005). Despite infrequent coinfection, antibiotics were used in 69% of patients.

Author Correction: Global and regional trends of atmospheric sulfur.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Global and regional trends of atmospheric sulfur.

The profound changes in global SO2 emissions over the last decades have affected atmospheric composition on a regional and global scale with large impact on air quality, atmospheric deposition and the radiative forcing of sulfate aerosols. Reproduction of historical atmospheric pollution levels based on global aerosol models and emission changes is crucial to prove that such models are able to predict future scenarios. Here, we analyze consistency of trends in observations of sulfur components in air and precipitation from major regional networks and estimates from six different global aerosol models from 1990 until 2015. There are large interregional differences in the sulfur trends consistently captured by the models and observations, especially for North America and Europe. Europe had the largest reductions in sulfur emissions in the first part of the period while the highest reduction came later in North America and East Asia. The uncertainties in both the emissions and the representativity of the observations are larger in Asia. However, emissions from East Asia clearly increased from 2000 to 2005 followed by a decrease, while in India a steady increase over the whole period has been observed and modelled. The agreement between a bottom-up approach, which uses emissions and process-based chemical transport models, with independent observations gives an improved confidence in the understanding of the atmospheric sulfur budget.

Preventable Adverse Drug Events Among Inpatients: A Systematic Review.

: media-1vid110.1542/5799876436001PEDS-VA_2018-0805Video Abstract CONTEXT: Patient harm resulting from medication errors drives prevention efforts, yet harm associated with medication errors in children has not been systematically reviewed. OBJECTIVE: To review the incidence and severity of preventable adverse drug events (pADEs) resulting from medication errors in pediatric inpatient settings. DATA SOURCES: Data sources included Cumulative Index of Nursing and Allied Health Literature, Medline, Scopus, the Cochrane Library, and Embase. STUDY SELECTION: Selected studies were published between January 2000 and December 2017, written in the English language, and measured pADEs among pediatric hospital inpatients by chart review or direct observation. DATA EXTRACTION: Data extracted were medication error and harm definitions, pADE incidence and severity rates, items required for quality assessment, and sample details. RESULTS: Twenty-two studies were included. For children in general pediatric wards, incidence was at 0 to 17 pADEs per 1000 patient days or 1.3% of medication errors (of any type) compared with 0 to 29 pADEs per 1000 patient days or 1.5% of medication errors in ICUs. Hospital-wide studies contained reports of up to 74 pADEs per 1000 patient days or 2.6% of medication errors. The severity of pADEs was mainly minor. LIMITATIONS: Limited literature on the severity of pADEs is available. Additional study will better illuminate differences among hospital wards and among those with or without health information technology. CONCLUSIONS: Medication errors in pediatric settings seldom result in patient harm, and if they do, harm is predominantly of minor severity. Implementing health information technologies was associated with reduced incidence of harm.

RETRACTED: Trends in bromide wet deposition concentrations in the contiguous United States, 2001-2016.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the authors due to the results of a detailed investigation of the data quality conducted by the Central Analytical Laboratory (CAL) after relocation to the University of Wisconsin (UW) ­ Wisconsin State Laboratory of Hygiene. Using a subset of the 30 samples with the highest bromide ion (Br-) concentrations, the CAL at UW found 6 samples that could not be verified or were incorrect. Because the extent of the incorrect data is unknown, the NADP Executive Committee voted unanimously in May 2019 to discontinue public access to these data, and they decided to sequester all Br- data prior to June 2018. These issues were not obvious to the authors when the paper was written. The authors apologize for the inconvenience caused.

Apical Lung Herniation Associated with Continuous Positive Airway Pressure in a 4-Year-Old Girl.

ABSTRACT: We report a case of apical lung herniation through the superior thoracic aperture of an obese child using nocturnal CPAP. Lung herniation has been described in association with congenital thoracic abnormalities and elevated intra-thoracic pressure, such as trauma. This patient was hospitalized with community acquired pneumonia and required nocturnal CPAP for treatment of concurrent obstructive sleep apnea. Her lung hernia was discovered incidentally on routine follow-up chest radiography and resolved with cessation of CPAP treatment. Lung herniation in association with the use of continuous positive airway pressure (CPAP) has not been previously described.

Evaluation of the Impact of National HIV Testing Day - United States, 2011-2014.

Human immunodeficiency virus (HIV) testing is the first step in the continuum of HIV prevention, care, and treatment services, without which, gaps in HIV diagnosis cannot be addressed. National HIV testing campaigns are useful for promoting HIV testing among large numbers of persons. However, the impact of such campaigns on identification of new HIV-positive diagnoses is unclear. To assess whether National HIV Testing Day (NHTD, June 27) was effective in identifying new HIV-positive diagnoses, National HIV Prevention Program Monitoring and Evaluation (NHM&E) data for CDC-funded testing events conducted during 2011-2014 were analyzed. The number of HIV testing events and new HIV-positive diagnoses during June of each year were compared with those in other months by demographics and target populations. The number of HIV testing events and new HIV-positive diagnoses were also compared for each day leading up to and after NHTD in June and July of each year. New HIV-positive diagnoses peaked in June relative to other months and specifically on NHTD. During 2011-2014, NHTD had a substantial impact on increasing the number of persons who knew their HIV status and in diagnosing new HIV infections. NHTD also proved effective in reaching persons at high risk disproportionately affected by HIV, including African American (black) men, men who have sex with men (MSM), and transgender persons. Promoting NHTD can successfully increase the number of new HIV-positive diagnoses, including HIV infections among target populations at high risk for HIV infection.

Increasing importance of deposition of reduced nitrogen in the United States.

Rapid development of agriculture and fossil fuel combustion greatly increased US reactive nitrogen emissions to the atmosphere in the second half of the 20th century, resulting in excess nitrogen deposition to natural ecosystems. Recent efforts to lower nitrogen oxides emissions have substantially decreased nitrate wet deposition. Levels of wet ammonium deposition, by contrast, have increased in many regions. Together these changes have altered the balance between oxidized and reduced nitrogen deposition. Across most of the United States, wet deposition has transitioned from being nitrate-dominated in the 1980s to ammonium-dominated in recent years. Ammonia has historically not been routinely measured because there are no specific regulatory requirements for its measurement. Recent expansion in ammonia observations, however, along with ongoing measurements of nitric acid and fine particle ammonium and nitrate, permit new insight into the balance of oxidized and reduced nitrogen in the total (wet + dry) US nitrogen deposition budget. Observations from 37 sites reveal that reduced nitrogen contributes, on average, ∼65% of the total inorganic nitrogen deposition budget. Dry deposition of ammonia plays an especially key role in nitrogen deposition, contributing from 19% to 65% in different regions. Future progress toward reducing US nitrogen deposition will be increasingly difficult without a reduction in ammonia emissions.

A statistical comparison of active and passive ammonia measurements collected at Clean Air Status and Trends Network (CASTNET) sites.

Atmospheric concentrations of ammonia (NH3) are not well characterized in the United States due to the sparse number of monitors, the relatively short lifetime of NH3 in the atmosphere, and the difficulty in measuring non-point source emissions such as fertilized agricultural land. In this study, we compare measured weekly concentrations of NH3 collected by two denuder systems with a bi-weekly passive NH3 sampler used by the National Atmospheric Deposition Program's (NADP) Ammonia Monitoring Network (AMoN). The purpose of the study was to verify the passive samplers used by AMoN and characterize any uncertainties introduced when using a bi-weekly versus weekly sampling time period. The study was conducted for 1 year at five remote Clean Air Status and Trends Network (CASTNET) sites. Measured ambient NH3 concentrations ranged from 0.03 µg NH3 m(-3) to 4.64 µg NH3 m(-3) in upstate New York and northwest Texas, respectively, while dry deposition estimates ranged from 0.003 kg N ha(-1) wk(-1) to 0.47 kg N ha(-1) wk(-1). Results showed that the bi-weekly passive samplers performed well compared to annular denuder systems (ADS) deployed at each of the five CASTNET sites, while the MetOne Super SASS Mini-Parallel Plate Denuder System (MPPD) was biased low when compared to the ADS. The mean relative percent difference (MRPD) between the ADS and MPPD and the ADS and AMoN sampler was -38% and -9%, respectively. Precision of the ADS and MPPD was 5% and 13%, respectively, while the precision of the passive samplers was 5%. The results of this study demonstrate that the NH3 concentrations measured by AMoN are comparable to the ADS and may be used to supplement the high-time resolution measurements to gain information on spatial gradients of NH3, long-term trends and seasonal variations in NH3 concentrations.