Human metapneumovirus infection is associated with a substantial morbidity and mortality burden in adult inpatients.

Background: Human metapneumovirus (hMPV) is one of the leading respiratory viruses. This prospective observational study aimed to describe the clinical features and the outcomes of hMPV-associated lower respiratory tract infections in adult inpatients. Methods: Consecutive adult patients admitted to one of the 31 participating centers with an acute lower respiratory tract infection and a respiratory multiplex PCR positive for hMPV were included. A primary composite end point of complicated course (hospital death and/or the need for invasive mechanical ventilation) was used. Results: Between March 2018 and May 2019, 208 patients were included. The median age was 74 [62-84] years. Ninety-seven (47 %) patients were men, 187 (90 %) had at least one coexisting illness, and 67 (31 %) were immunocompromised. Median time between first symptoms and hospital admission was 3 [2-7] days. The two most frequent symptoms were dyspnea (86 %) and cough (85 %). The three most frequent clinical diagnoses were pneumonia (42 %), acute bronchitis (20 %) and acute exacerbation of chronic obstructive pulmonary disease (16 %). Among the 52 (25 %) patients who had a lung CT-scan, the most frequent abnormality was ground glass opacity (41 %). While over four-fifths of patients (81 %) received empirical antibiotic therapy, a bacterial coinfection was diagnosed in 61 (29 %) patients. Mixed flora (16 %) and enterobacteria (5 %) were the predominant documentations. The composite criterion of complicated course was assessable in 202 (97 %) patients, and present in 37 (18 %) of them. In the subpopulation of pneumonia patients (42 %), we observed a more complicated course in those with a bacterial coinfection (8/24, 33 %) as compared to those without (5/60, 8 %) (p = 0.02). Sixty (29 %) patients were admitted to the intensive care unit. Among them, 23 (38 %) patients required invasive mechanical ventilation. In multivariable analysis, tachycardia and alteration of consciousness were identified as risk factors for complicated course. Conclusion: hMPV-associated lower respiratory tract infections in adult inpatients mostly involved elderly people with pre-existing conditions. Bacterial coinfection was present in nearly 30 % of the patients. The need for mechanical ventilation and/or the hospital death were observed in almost 20 % of the patients.

From Exosome Biogenesis to Absorption: Key Takeaways for Cancer Research.

Exosomes are mediators of intercellular communication in normal physiology and diseases. While many studies have emerged on the function of exosomal cargoes, questions remain regarding the origin of these exosomes. The packaging and secretion of exosomes in different contexts modify exosomal composition, which may in turn impact delivery, uptake and cargo function in recipient cells. A mechanistic understanding of exosome biology is therefore crucial to investigating exosomal function in complex biological systems and to the development of novel therapeutic approaches. Here, we outline the steps in exosome biogenesis, including endosome formation, MVB formation, cargo sorting and extracellular release, as well as exosome absorption, including targeting, interaction with recipient cells and the fate of internalized exosomes. In addition to providing a framework of exosome dynamics, we summarize current evidence on major pathways and regulatory mechanisms. We also highlight the various mechanisms observed in cancer and point out directions to improve study design in exosome biology. Further research is needed to illuminate the relationship between exosome biogenesis and function, which will aid the development of translational applications.

The Role of Arginine Metabolism in Oral Tongue Squamous Cell Carcinoma.

Early diagnosis and treatment do not prevent the high morbidity and poor prognosis of oral tongue squamous cell carcinoma (TSCC). Earlier studies have shown that ARG1 signaling is deregulated in TSCC. Here, we investigated the complexity of ARG1 metabolism in this cancer subsite to appreciate the therapeutic potential of this potential biological vulnerability. Various functional studies show that ARG1 overexpression in oral cancer cells inhibits cell proliferation and invasion compared with controls. Further, RNA-sequencing revealed numerous differentially expressed genes (DEGs) and associated networks were dysregulated by ARG1 overexpression, including hypoxia-inducible factor (HIFα) signaling, the natural killer cell signaling pathway and interferon signaling. Our work provides a foundation for understanding the mechanism of action of disrupted arginine metabolism in oral tongue squamous cell carcinoma. This may impact the community for developing further therapeutic approaches.

Randomized intubation with polyurethane or conical cuffs to prevent pneumonia in ventilated patients.

RATIONALE: The occurrence of ventilator-associated pneumonia (VAP) is linked to the aspiration of contaminated pharyngeal secretions around the endotracheal tube. Tubes with cuffs made of polyurethane rather than polyvinyl chloride or with a conical rather than a cylindrical shape increase tracheal sealing. OBJECTIVES: To test whether using polyurethane and/or conical cuffs reduces tracheal colonization and VAP in patients with acute respiratory failure. METHODS: We conducted a multicenter, prospective, open-label, randomized study in four parallel groups in four intensive care units between 2010 and 2012. A cohort of 621 patients with expected ventilation longer than 2 days was included at intubation with a cuff composed of cylindrical polyvinyl chloride (n = 148), cylindrical polyurethane (n = 143), conical polyvinyl chloride (n = 150), or conical polyurethane (n = 162). We used Kaplan-Meier estimates and log-rank tests to compare times to events. MEASUREMENTS AND MAIN RESULTS: After excluding 17 patients who secondarily refused participation or had met an exclusion criterion, 604 were included in the intention-to-treat analysis. Cumulative tracheal colonization greater than 10(3) cfu/ml at Day 2 was as follows (median [interquartile range]): cylindrical polyvinyl chloride, 0.66 (0.58-0.74); cylindrical polyurethane, 0.61 (0.53-0.70); conical polyvinyl chloride, 0.67 (0.60-0.76); and conical polyurethane, 0.62 (0.55-0.70) (P = 0.55). VAP developed in 77 patients (14.4%), and postextubational stridor developed in 28 patients (6.4%) (P = 0.20 and 0.28 between groups, respectively). CONCLUSIONS: Among patients requiring mechanical ventilation, polyurethane and/or conically shaped cuffs were not superior to conventional cuffs in preventing tracheal colonization and VAP. Clinical trial registered with clinicaltrials.gov (NCT01114022).

A case of daptomycin-induced immune thrombocytopenia.

We report a case of severe daptomycin-induced immune thrombocytopenia in a patient treated for methicillin-resistant Staphylococcus epidermidis and ampicillin-resistant Enterococcus faecalis bacteremia acquired in an intensive care unit. Serum antibodies bound to platelets in the presence of daptomycin on flow cytometry. There was no evidence of other causes of thrombocytopenia. The patient died of brain herniation complicating extensive cerebral hemorrhage. To our knowledge, this is the first described case of daptomycin-induced thrombocytopenia.

Overview of medical errors and adverse events.

Safety is a global concept that encompasses efficiency, security of care, reactivity of caregivers, and satisfaction of patients and relatives. Patient safety has emerged as a major target for healthcare improvement. Quality assurance is a complex task, and patients in the intensive care unit (ICU) are more likely than other hospitalized patients to experience medical errors, due to the complexity of their conditions, need for urgent interventions, and considerable workload fluctuation. Medication errors are the most common medical errors and can induce adverse events. Two approaches are available for evaluating and improving quality-of-care: the room-for-improvement model, in which problems are identified, plans are made to resolve them, and the results of the plans are measured; and the monitoring model, in which quality indicators are defined as relevant to potential problems and then monitored periodically. Indicators that reflect structures, processes, or outcomes have been developed by medical societies. Surveillance of these indicators is organized at the hospital or national level. Using a combination of methods improves the results. Errors are caused by combinations of human factors and system factors, and information must be obtained on how people make errors in the ICU environment. Preventive strategies are more likely to be effective if they rely on a system-based approach, in which organizational flaws are remedied, rather than a human-based approach of encouraging people not to make errors. The development of a safety culture in the ICU is crucial to effective prevention and should occur before the evaluation of safety programs, which are more likely to be effective when they involve bundles of measures.