The Binding of Pseudomonas aeruginosa to Cystic Fibrosis Bronchial Epithelial Model Cells Alters the Composition of the Exosomes They Produce Compared to Healthy Control Cells.

Cystic fibrosis (CF) is a genetic disease that causes dehydration of the surface of the airways, increasing lung infections, most frequently caused by Pseudomonas aeruginosa. Exosomes are nanovesicles released by cells that play an essential role in intercellular communication, although their role during bacterial infections is not well understood. In this article, we analyze the alterations in exosomes produced by healthy bronchial epithelial and cystic fibrosis cell lines caused by the interaction with P. aeruginosa. The proteomic study detected alterations in 30% of the species analyzed. In healthy cells, they mainly involve proteins related to the extracellular matrix, cytoskeleton, and various catabolic enzymes. In CF, proteins related to the cytoskeleton and matrix, in addition to the proteasome. These differences could be related to the inflammatory response. A study of miRNAs detected alterations in 18% of the species analyzed. The prediction of their potential biological targets identified 7149 genes, regulated by up to 7 different miRNAs. The identification of their functions showed that they preferentially affected molecules involved in binding and catalytic activities, although with differences between cell types. In conclusion, this study shows differences in exosomes between CF and healthy cells that could be involved in the response to infection.

Cytologic features of a pleural effusion after silicone breast implant rupture.

Pleural effusion is an extremely rare complication of ruptured breast silicone implants. Rupture may be related to a recent trauma or occur spontaneously, making its diagnosis more difficult. In the few reported cases, cytology did not play a relevant role in its diagnosis. We describe and illustrate a silicone foreign body reaction in a pleural effusion. Cytologic findings were so remarkable as to permit a specific diagnosis. The patient, a 37-year-old female with a history of previous bilateral breast implant surgery was admitted because of a pleural effusion. Computed tomography scan showed a left effusion with secondary atelectasis and bilateral breast rupture with lymph node "siliconomas." Cytologic analysis of the effusion showed well-defined droplets or globules of transparent material, in addition to a microvacuolized background. Where abundant silicone droplets induced a staining artifact of the smears. These were cellular with numerous macrophages containing large vacuoles displacing the nuclei to the periphery. Some had a signet cell ring appearance, while others showed multinucleation. Flow cytometry revealed a predominant macrophagic cell population. With the increasing use of silicone breast implants, rare complications such as pleural effusion may become more common. The pathologist must consider this possibility when extracellular transparent droplets or evidence of a foreign body-type reaction are present. The artifact appearance of the smears may help to suspect it. This rare complication must be always considered when evaluating effusions in patients with silicone breast implants.

Glycosaminoglycans are differentially involved in bacterial binding to healthy and cystic fibrosis lung cells.

BACKGROUND: Glycosaminoglycans (GAGs) are essential in many infections, including recurrent bacterial respiratory infections, the main cause of mortality in cystic fibrosis (CF) patients. METHODS: Using a cellular model of healthy and CF lung epithelium, a comparative transcriptomic study of GAG encoding genes was performed using qRT-PCR, and their differential involvement in the adhesion of bacterial pathogens analyzed by enzymatic degradation and binding competition experiments. RESULTS: Various alterations in gene expression in CF cells were found which affect GAG structures and seem to influence bacterial adherence to lung epithelium cells. Heparan sulfate appears to be the most important GAG species involved in bacterial binding. CONCLUSIONS: Adherence to lung epithelial cells of some of the main pathogens involved in CF is dependent on GAGs, and the expression of these polysaccharides is altered in CF cells, suggesting it could play an essential role in the development of infectious pathology.

Desaturations During 6-Minute Walk Test and Predicting Nocturnal Desaturations in Adult Subjects With Cystic Fibrosis.

BACKGROUND: Nocturnal desaturation in cystic fibrosis (CF) may have prognostic implications because a significant and maintained nocturnal desaturation can contribute to the development and progression of pulmonary hypertension with cor pulmonale. Its relation with the desaturation in exercise has not been sufficiently studied. We aimed to determine whether desaturation during 6MWT can be an indicator of nocturnal desaturation in adult subjects with CF. METHODS: 57 subjects were included: 50.9% male, 27.5 ± 7.7 y old, mean FEV1 = 2.37 ± 0.74 L, and %FEV1 67 ± 18.1%. Desaturation during 6MWT was defined as oxygen saturation (SpO2 ) ≤ 90% or a decline of > 4 points in SpO2 from baseline, and nocturnal desaturation as a desaturation index > 4 or > 5% of sleep time with SpO2 ≤ 90%. RESULTS: Desaturation observed during 6MWT in adult subjects with CF did not correlate with nocturnal desaturation (P = .27). Subjects with %FEV1 ≤ 55% and diffusion capacity of carbon monoxide (DLCO) ≤ 50 mmol/min/mm Hg were at higher risk of 6MWT desaturation. Nocturnal desaturation was more frequent in males, with PaO2 ≤ 71 mm Hg in blood gas analysis. CONCLUSIONS: Desaturation observed in 6MWT cannot predict desaturation at night in adults with CF. Other parameters were identified as predictors of desaturation.

A multicentre, randomized controlled trial of telehealth for the management of COPD.

BACKGROUND: Evidence is needed to determine the role of telehealth (TH) in COPD management. METHODS: PROMETE II was a multicentre, randomized, 12-month trial. Severe COPD patients in stable condition were randomized to a specific monitoring protocol with TH or routine clinical practice (RCP). The primary objective was to reduce the number of COPD exacerbations leading to ER visits/hospital admissions between groups. RESULTS: Overall, 237 COPD patients were screened, and 229 (96.6%) were randomized to TH (n = 115) or RCP (n = 114), with age of 71 ±â€¯8 years and 80% were men. Overall, 169 completed the full follow-up period. There were no statistical differences at one year between groups in the proportion of participants who had a COPD exacerbation (60% in TH vs. 53.5% in RCP; p = 0.321). There was, however, a marked but non-significant trend towards a shorter duration of hospitalization and days in ICU in the TH group (18.9 ±â€¯16.0 and 6.0 ±â€¯4.6 days) compared to the RCP group (22.4 ±â€¯19.5 and 13.3 ±â€¯11.1 days). The number of all-cause deaths was comparable between groups (12 in TH vs. 13 in RCP) as was total resource utilization cost (7912€ in TH vs. 8918€ in RCP). Telehealth was evaluated highly positively by patients and doctors. CONCLUSIONS: Remote patient management did not reduce COPD-related ER visits or hospital admissions compared to RCP within 12 months.

Glycosaminoglycans are involved in bacterial adherence to lung cells.

BACKGROUND: Lower respiratory infections are among the top ten causes of death worldwide. Since pathogen to cell adhesion is a crucial step in the infection progress, blocking the interaction between eukaryotic receptors and bacterial ligands may enable the pathogenesis process to be stopped. Cell surface glycosaminoglycans (GAGs) are known to be mediators in the adhesion of diverse bacteria to different cell types, making it of interest to examine their involvement in the attachment of various pathogenic bacteria to lung cells, including epithelial cells and fibroblasts. METHODS: The function of cell surface GAGs in bacterial adhesion was studied by reducing their levels through inhibiting their biosynthesis and enzymatic degradation, as well as in binding competition experiments with various species of GAGs. The participation of the different bacterial adhesins in attachment was evaluated through competition with two peptides, both containing consensus heparin binding sequences. Blocking inhibition assays using anti-syndecans and the enzymatic removal of glypicans were conducted to test their involvement in bacterial adhesion. The importance of the fine structure of GAGs in the interaction with pathogens was investigated in competition experiments with specifically desulfated heparins. RESULTS: The binding of all bacteria tested decreased when GAG levels in cell surface of both lung cells were diminished. Competition experiments with different types of GAGs showed that heparan sulfate chains are the main species involved. Blocking or removal of cell surface proteoglycans evidenced that syndecans play a more important role than glypicans. The binding was partially inhibited by peptides including heparin binding sequences. Desulfated heparins also reduced bacterial adhesion to different extents depending on the bacterium and the sulfated residue, especially in fibroblast cells. CONCLUSIONS: Taken together, these data demonstrate that the GAG chains of the cell surface are involved in the adhesion of bacterial adhesins to lung cells. Heparan sulfate seems to be the main species implicated, and binding is dependent on the sulfation pattern of the molecule. These data could facilitate the development of new anti-infective strategies, enabling the development of new procedures for blocking the interaction between pathogens and lung cells more effectively.

Long-term safety and efficacy of tobramycin in the management of cystic fibrosis.

Cystic fibrosis (CF) is a fatal inherited disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene whose mortality is conditioned by a progressive decline in lung function. Bacterial infections play a key role in this decline. Chronic bacterial infection in CF patients varies over time and the presence of Pseudomonas aeruginosa in sputum is a marker of poor prognosis. P. aeruginosa is eradicated from the airways using inhaled antibiotics administered in various formulations and devices. Antipseudomonal antibiotics have extended the survival of CF patients to 40 years. Tobramycin is a bactericidal aminoglycoside antibiotic with demonstrated activity against gram-negative microorganisms. Initially, the drug was administered as an inhaled parenteral solution. Subsequently, a specific tobramycin inhalation solution was developed. PulmoSphere™ technology enables dry tobramycin powder to be formulated for inhalation (tobramycin inhalation powder) using a small and portable capsule-based breath-activated device (T-326). Chronic colonization by P. aeruginosa is the main indication for aerosol antibiotic therapy. The American Cystic Fibrosis Foundation, European guidelines, and Spanish consensus guidelines provide different recommendations for eradication.

Non-invasive ventilation in an elderly population admitted to a respiratory monitoring unit: causes, complications and one-year evolution.

OBJECTIVE: To determine the usefulness of non-invasive ventilation (NIV) in elderly patients (≥75) admitted to a respiratory monitoring unit (RMU) during hospitalization and 1 year later in comparison with the results from the younger age group (<75). MATERIAL AND METHODS: Ours is a prospective observational study carried out at the Hospital Universitario La Princesa (Madrid, Spain). We recruited all patients who were ≥75 years old and were admitted to our RMU during the period 2008-2009 with respiratory acidosis (pH<7.35 and PaCO(2)>45 mmHg) requiring NIV. We gathered data for basic variables as well as sociodemographics, history of previous pathologies, reason for hospitalization and severity, analysis upon admission and the evolution of blood gases at the start of NIV (within the first hour and after 24 h), complications and evolution at the 1-year follow-up. RESULTS: Mean age of the sample was 80.6. The Charlson index was 3.27. About half of the patients had some limitation for performing daily activities. The main reasons for admission were COPD exacerbation and heart failure. There were complications in 36% of the cases (11 renal failure and 6 atrial fibrillation). The survival rate at the 1-year follow-up was 63.21%. CONCLUSIONS: NIV is a good alternative in elderly patients admitted to the hospital with respiratory acidosis. We did not detect differences in mortality during admission between the two groups. The elderly patients were more frequently re-admitted than the younger group in the 6-12 months after hospital discharge. This could be due to their poorer functional state after hospitalization requiring NIV.

[Evaluation of hand hygiene guidelines and protocols used in Spain]. / Evaluación de la calidad de las guías y protocolos de lavado de manos existentes en España.

The aim of this study was to evaluate, through a retrospective and external study, the quality of Spanish hand hygiene guidelines and protocols. None of the guidelines achieved a score of 100% in all areas. The mean score was only 43.9%, ranging from 23.8% for rigorous design to 69.4% for clarity and presentation. None of the protocols achieved a score of 100% in all areas; 100% clearly named the health problem dealt with in the protocol, which was reflected in its contents, and complied with length specifications and absence of formal defects; 80% had a paginated index and 66.7% a definition of compliance, while only 6.7% contained information on organization and functioning, the necessary resources, procedures and evaluation period. In general, the average compliance was less than 50%, except in one guideline, which met 87.5% of the requirements Problems with references were found in 77.7%. In view of the problems detected, a new guide for the drafting of hand hygiene guidelines and protocols is proposed.