Genome-based typing reveals rare events of patient contamination with Pseudomonas aeruginosa from other patients and sink traps in a medical intensive care unit.

AIM: We used genome-based typing data with the aim of identifying the routes of acquisition of Pseudomonas aeruginosa by patients hospitalized in a medical intensive care unit (MICU) over a long period in a non-epidemic context. METHODS: This monocentric prospective study took place over 10 months in 2019 in a 15-bed MICU that applies standard precautions of hygiene. Lockable sink traps installed at all water points of use were bleach disinfected twice a week. We sampled all sink traps weekly to collect 404 P. aeruginosa environmental isolates and collected all P. aeruginosa isolates (N = 115) colonizing or infecting patients (N = 65). All isolates had their phenotypic resistance profile determined and their genome sequenced, from which we identified resistance determinants and assessed the population structure of the collection at the nucleotide level to identify events of P. aeruginosa transmission. FINDINGS: All sink traps were positive for P. aeruginosa, each sink trap being colonized for several months by one or more clones. The combination of genomic and spatiotemporal data identified one potential event of P. aeruginosa transmission from a sink trap to a patient (1/65, 1.5%) and six events of patient cross-transmission, leading to the contamination of five patients (5/65, 7.7%). All transmitted isolates were fully susceptible to ß-lactams and aminoglycosides. CONCLUSIONS: Genome-based typing revealed the contamination of patients by P. aeruginosa originating from sink traps to be infrequent (1.5%) in an MICU with sink trap-bleaching measures, and that only 7.7% of the patients acquired P. aeruginosa originating from another patient.

Investigation of the value of precipitins in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients with a positive marker for Aspergillus species.

Although a high prevalence of COVID-19-associated pulmonary aspergillosis has been reported, it is still difficult to distinguish between colonization with Aspergillus fumigatus and infection. Concomitantly, similarities between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and hypersensitivity pneumonitis were suggested. The objective of this study was to investigate retrospectively if precipitin assays targeting A. fumigatus could have been useful in the management of SARS-CoV-2 patients hospitalized in an Intensive Care Unit (ICU) in 2020. SARS-CoV-2 ICU patients were screened for Aspergillus co-infection using biomarkers (galactomannan antigen, qPCR) and culture of respiratory samples (tracheal aspirates and bronchoalveolar lavage). For all these patients, clinical data, ICU characteristics and microbial results were collected. Electrosyneresis assays were performed using commercial A. fumigatus somatic and metabolic antigens. ELISA were performed using in-house A. fumigatus purified antigen and recombinant antigens.Our study population consisted of 65 predominantly male patients, with a median ICU stay of 22 days, and a global survival rate of 62%. Thirty-five patients had at least one positive marker for Aspergillus species detection. The number of arcs obtained by electrosyneresis using the somatic A. fumigatus antigen was significantly higher for these 35 SARS-CoV-2 ICU patients (P 0.01, Welch's t-test). Our study showed that SARS-CoV-2 ICU patients with a positive marker for Aspergillus species detection more often presented precipitins towards A. fumigatus. Serology assays could be an additional tool to assess the clinical relevance of the Aspergillus species in respiratory samples of SARS-CoV-2 ICU patients. LAY SUMMARY: This study showed retrospectively that precipitin assays, such as electrosyneresis, could be helpful to distinguish between colonization and infection with Aspergillus fumigatus during the management of severe acute respiratory syndrome Coronavirus-2 (SARS CoV-2) patients in an intensive care unit.

Comparison of high-flow nasal oxygen therapy and non-invasive ventilation in ICU patients with acute respiratory failure and a do-not-intubate orders: a multicentre prospective study OXYPAL.

INTRODUCTION: A palliative approach to intensive care unit (ICU) patients with acute respiratory failure and a do-not-intubate order corresponds to a poorly evaluated target for non-invasive oxygenation treatments. Survival alone should not be the only target; it also matters to avoid discomfort and to restore the patient's quality of life. We aim to conduct a prospective multicentre observational study to analyse clinical practices and their impact on outcomes of palliative high-flow nasal oxygen therapy (HFOT) and non-invasive ventilation (NIV) in ICU patients with do-not-intubate orders. METHODS AND ANALYSIS: This is an investigator-initiated, multicentre prospective observational cohort study comparing the three following strategies of oxygenation: HFOT alone, NIV alternating with HFOT and NIV alternating with standard oxygen in patients admitted in the ICU for acute respiratory failure with a do-not-intubate order. The primary outcome is the hospital survival within 14 days after ICU admission in patients weaned from NIV and HFOT. The sample size was estimated at a minimum of 330 patients divided into three groups according to the oxygenation strategy applied. The analysis takes into account confounding factors by modelling a propensity score. ETHICS AND DISSEMINATION: The study has been approved by the ethics committee and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03673631.

Abdominal compartment syndrome and intra-abdominal hypertension in critically ill patients: diagnostic value of computed tomography.

AIMS: The aims of the present work were to reevaluate, prospectively, the diagnostic value of already-described computed tomography (CT) landmarks of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) and to study the diagnostic value of some undescribed CT signs for the diagnosis of IAH and ACS. MATERIALS AND METHODS: Consecutive patients admitted to the intensive care unit (ICU) in shock for whom an abdominal CT was clinically indicated were included. CT examinations were reviewed and scored by two reviewers for the 12 proposed CT features of IAH and ACS. Intravesical pressure (IVP) was measured for each patient. Imaging features and clinical data of patients with IAH (IVP ≥ 12 mmHg) were compared to those of patients with normal intra-abdominal pressure (IVP < 12 mmHg). RESULTS: Forty-one patients were included. Twenty-one patients (51%) presented IAH with an IVP value ≥ 12 mmHg. Four patients (10%) were considered to have ACS (10%). Only an increased peritoneal-to-abdominal height ratio (PAR) was associated with the presence of IAH (PAR = 0.45 [0.40-0.49] in patients with IVP < 12 mmHg and PAR = 0.52 [0.48-0.53] in patients with IVP ≥ 12 mmHg; p < 0.001). Increased PAR ≥ 0.52 had a specificity of 85% for IAH diagnosis. CONCLUSION: The present study suggests that a PAR ≥ 0.52 could help radiologists to identify IAH on abdominal CT scan and could lead to adequate identification and/or treatment, even at early stages of IAH. KEY POINTS: • CT is an efficient first-intention procedure to evaluate and follow up underlying conditions in critically ill patients at risk of IAH and ACS overcome. • Raising the possibility of an IAH on a CT examination is relevant information for the clinician. • The only factors associated with intra-abdominal hypertension were the peritoneal-to-abdominal height ratio (PAR) and the ratio of maximal anteroposterior to transverse abdominal diameter (which define the round belly sign when > 0.8).

Rapid Discovery of De Novo Deleterious Mutations in Cattle Enhances the Value of Livestock as Model Species.

In humans, the clinical and molecular characterization of sporadic syndromes is often hindered by the small number of patients and the difficulty in developing animal models for severe dominant conditions. Here we show that the availability of large data sets of whole-genome sequences, high-density SNP chip genotypes and extensive recording of phenotype offers an unprecedented opportunity to quickly dissect the genetic architecture of severe dominant conditions in livestock. We report on the identification of seven dominant de novo mutations in CHD7, COL1A1, COL2A1, COPA, and MITF and exploit the structure of cattle populations to describe their clinical consequences and map modifier loci. Moreover, we demonstrate that the emergence of recessive genetic defects can be monitored by detecting de novo deleterious mutations in the genome of bulls used for artificial insemination. These results demonstrate the attractiveness of cattle as a model species in the post genomic era, particularly to confirm the genetic aetiology of isolated clinical case reports in humans.

Echography for nasogastric tube placement verification.

To report the interest of abdominal ultrasonography for confirming the appropriate location of nasogastric tube (NGT) in the stomach using a new dynamic test, and to illustrate the aspect of this test at ultrasonography. Clinical observation of a patient, images of abdominal ultrasonography and video of the stomach visualized by ultrasonography. We describe the video of a critically ill patient in whom, immediately after NGT insertion, aspiration of gastric liquid and instillation within the NGT was associated with ultrasonographic evidence of turbulences in the stomach. In addition to the direct visualization of the NGT in the stomach, ultrasonographic visualization of turbulences after aspiration and instillation of gastric liquid may allow to assess the appropriate positioning of the NGT.

The respiratory DC/macrophage network at steady-state and upon influenza infection in the swine biomedical model.

Human and mouse respiratory tracts show anatomical and physiological differences, which will benefit from alternative experimental models for studying many respiratory diseases. Pig has been recognized as a valuable biomedical model, in particular for lung transplantation or pathologies such as cystic fibrosis and influenza infection. However, there is a lack of knowledge about the porcine respiratory immune system. Here we segregated and studied six populations of pig lung dendritic cells (DCs)/macrophages (Mθs) as follows: conventional DCs (cDC) 1 and cDC2, inflammatory monocyte-derived DCs (moDCs), monocyte-derived Mθs, and interstitial and alveolar Mθs. The three DC subsets present migratory and naive T-cell stimulation capacities. As observed in human and mice, porcine cDC1 and cDC2 were able to induce T-helper (Th)1 and Th2 responses, respectively. Interestingly, porcine moDCs increased in the lung upon influenza infection, as observed in the mouse model. Pig cDC2 shared some characteristics observed in human but not in mice, such as the expression of FCɛRIα and Langerin, and an intra-epithelial localization. This work, by unraveling the extended similarities of the porcine and human lung DC/Mθ networks, highlights the relevance of pig, both as an exploratory model of DC/Mθ functions and as a model for human inflammatory lung pathologies.

Identification of differentially expressed genes in spontaneously regressing melanoma using the MeLiM swine model.

Partial and some few cases of complete spontaneous regression have been observed in cutaneous melanoma patients but little is known about the molecular mechanisms involved. The Melanoblastoma-bearing Libechov Minipig (MeLiM) is a suitable animal model to study the phenomenon of spontaneous regression because MeLiM pigs exhibit naturally occurring melanomas which regress completely 6 months after birth. In this study, we used suppression subtractive hybridization (SSH) to identify molecular determinants of melanoma regression within swine melanoma tissues and melanoma cell cultures. Several markers involved in cell-adhesion, -communication, -motility, signal transduction, negative regulation of cell proliferation, transport and immune response were identified that correlated with melanoma regression whereas the main genes involved in melanin synthesis showed a strong downregulation. For the most differentially expressed genes, we validated the results obtained by SSH with qRT-PCR and with immunohistochemistry for some of them (CD9, MITF, RARRES1). Most notable, for the first time in melanoma, we identified the retinoic acid responder 1 gene (RARRES1) as a main actor of the regression process in melanoma. This first gene expression study in swine melanoma regression, may contribute to the finding of new therapeutic targets for human melanoma treatment.

Severe systemic cytomegalovirus infections in patients with steroid-refractory ulcerative colitis treated by an oral microemulsion form of cyclosporine: report of two cases.

CMV reactivation is frequently observed in acute flares of ulcerative colitis (UC), particularly those which do not respond to intravenous steroids. Several recent series have suggested that, in most cases, CMV reactivation does not lead to severe complications and resolves spontaneously with the UC flare and discontinuation of immunosuppression. In the present paper, we describe two patients with active UC who developed a severe systemic CMV infection during a treatment with an oral microemulsion form of cyclosporine. This is of concern, particularly in a context of increasing use of immunosuppressive drugs in UC. We propose a prophylactic and curative approach to decrease morbidity related to CMV infection in active UC.