The origins of the mesenchymal cells participating in tissue repair and pathological processes, notably tissue fibrosis, tumor invasiveness, and metastasis, are poorly understood. However, emerging evidence suggests that epithelial-mesenchymal transitions (EMTs) represent one important source of these cells. As we discuss here, processes similar to the EMTs associated with embryo implantation, embryogenesis, and organ development are appropriated and subverted by chronically inflamed tissues and neoplasias. The identification of the signaling pathways that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes and possible therapeutic interventions.

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The basics of epithelial-mesenchymal transition

Objective. To describe antimicrobial resistance patterns for healthcare-associated infections (HAIs) reported to the National Healthcare Safety Network (NHSN) during 2009-2010. Methods. Central line-associated bloodstream infections, catheter-associated urinary tract infections, ventilator-associated pneumonia, and surgical site infections were included. Pooled mean proportions of isolates interpreted as resistant (or, in some cases, nonsusceptible) to selected antimicrobial agents were calculated by type of HAI and compared to historical data. Results. Overall, 2,039 hospitals reported 1 or more HAIs; 1,749 (86%) were general acute care hospitals, and 1,143 (56%) had fewer than 200 beds. There were 69,475 HAIs and 81,139 pathogens reported. Eight pathogen groups accounted for about 80% of reported pathogens: Staphylococcus aureus (16%), Enterococcus spp. (14%), Escherichia coli (12%), coagulase-negative staphylococci (11%), Candida spp. (9%), Klebsiella pneumoniae (and Klebsiella oxytoca; 8%), Pseudomonas aeruginosa (8%), and Enterobacter spp. (5%). The percentage of resistance was similar to that reported in the previous 2-year period, with a slight decrease in the percentage of S. aureus resistant to oxacillins (MRSA). Nearly 20% of pathogens reported from all HAIs were the following multidrug-resistant phenotypes: MRSA (8.5%); vancomycin-resistant Enterococcus (3%); extended-spectrum cephalosporin-resistant K. pneumoniae and K. oxytoca (2%), E. coli (2%), and Enterobacter spp. (2%); and carbapenem-resistant P. aeruginosa (2%), K. pneumoniae/oxytoca (<1%), E, coli (<1%), and Enterobacter spp. (<1%). Among facilities reporting HAIs with 1 of the above gram-negative bacteria, 20%-40% reported at least 1 with the resistant phenotype. Conclusion. While the proportion of resistant isolates did not substantially change from that in the previous 2 years, multidrug-resistant gram-negative phenotypes were reported from a moderate proportion of facilities.

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Antimicrobial-Resistant Pathogens Associated with Healthcare- Associated Infections: Summary of Data Reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2009-2010

ObjectiveTo evaluate the use of the Sequential Organ Failure Assessment (SOFA) score in assessing the incidence and severity of organ dysfunction in critically ill patients.DesignProspective, multicenter study.SettingForty intensive care units (ICUs) in 16 countries.PatientsPatients admitted to the

Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: Results of a multicenter, prospective study

Context Infection is a major cause of morbidity and mortality in intensive care units (ICUs) worldwide. However, relatively little information is available about the global epidemiology of such infections. Objective To provide an up-to-date, international picture of the extent and patterns of infection in ICUs. Design, Setting, and Patients The Extended Prevalence of Infection in Intensive Care (EPIC II) study, a 1-day, prospective, point prevalence study with follow-up conducted on May 8, 2007. Demographic, physiological, bacteriological, therapeutic, and outcome data were collected for 14 414 patients in 1265 participating ICUs from 75 countries on the study day. Analyses focused on the data from the 13 796 adult (>18 years) patients. Results On the day of the study, 7087 of 13 796 patients (51%) were considered infected; 9084 (71%) were receiving antibiotics. The infection was of respiratory origin in 4503 (64%), and microbiological culture results were positive in 4947 (70%) of the infected patients; 62% of the positive isolates were gram-negative organisms, 47% were gram-positive, and 19% were fungi. Patients who had longer ICU stays prior to the study day had higher rates of infection, especially infections due to resistant staphylococci, Acinetobacter, Pseudomonas species, and Candida species. The ICU mortality rate of infected patients was more than twice that of noninfected patients (25% [1688/6659] vs 11% [ 682/6352], respectively; P  Conclusions Infections are common in patients in contemporary ICUs, and risk of infection increases with duration of ICU stay. In this large cohort, infection was independently associated with an increased risk of hospital death.

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International Study of the Prevalence and Outcomes of Infection in Intensive Care Units

Ventilator-associated pneumonia (VAP) continues to complicate the course of 8 to 28% of patients receiving mechanical ventilation (MV). In contrast to infections of more frequently involved organs (e.g., urinary tract and skin), for which mortality is low, ranging from 1 to 4%, the mortality rate for VAP ranges from 24 to 50% and can reach 76% in some specific settings or when lung infection is caused by high-risk pathogens. The predominant organisms responsible for infection are Staphylococcus aureus, Pseudomonas aeruginosa, and Enterobacteriaceae, but etiologic agents widely differ according to the population of patients in an intensive care unit, duration of hospital stay, and prior antimicrobial therapy. Because appropriate antimicrobial treatment of patients with VAP significantly improves outcome, more rapid identification of infected patients and accurate selection of antimicrobial agents represent important clinical goals. Our personal bias is that using bronchoscopic techniques to obtain protected brush and bronchoalveolar lavage specimens from the affected area in the lung permits physicians to devise a therapeutic strategy that is superior to one based only on clinical evaluation. When fiberoptic bronchoscopy is not available to physicians treating patients clinically suspected of having VAP, we recommend using either a simplified nonbronchoscopic diagnostic procedure or following a strategy in which decisions regarding antibiotic therapy are based on a clinical score constructed from seven variables. Selection of the initial antimicrobial therapy should be based on predominant flora responsible for VAP at each institution, clinical setting, information provided by direct examination of pulmonary secretions, and intrinsic antibacterial activities of antimicrobial agents and their pharmacokinetic characteristics. Further trials will be needed to clarify the optimal duration of treatment and the circumstances in which monotherapy can be safely used.

Ventilator-associated pneumonia.

Objective. —To determine the prevalence of intensive care unit (ICU)—acquired infections and the risk factors for these infections, identify the predominant infecting organisms, and evaluate the relationship between ICU-acquired infection and mortality. Design. —A 1-day point-prevalence study. Setting. —Intensive care units in 17 countries in Western Europe, excluding coronary care units and pediatric and special care infant units. Patients. —All patients (>10 years of age) occupying an ICU bed over a 24-hour period. A total of 1417 ICUs provided 10 038 patient case reports. Main Outcome Measures. —Rates of ICU-acquired infection, prescription of antimicrobials, resistance patterns of microbiological isolates, and potential risk factors for ICU-acquired infection and death. Results. —A total of 4501 patients (44.8%) were infected, and 2064 (20.6%) had ICU-acquired infection. Pneumonia (46.9%), lower respiratory tract infection (17.8%), urinary tract infection (17.6%), and bloodstream infection (12%) were the most frequent types of ICU infection reported. Most frequently reported microorganisms were Enterobacteriaceae (34.4%),Staphylococcus aureus(30.1%; [60% resistant to methicillin]),Pseudomonas aeruginosa(28.7%), coagulase-negative staphylococci (19.1%), and fungi (17.1%). Seven risk factors for ICU-acquired infection were identified: increasing length of ICU stay (>48 hours), mechanical ventilation, diagnosis of trauma, central venous, pulmonary artery, and urinary catheterization, and stress ulcer prophylaxis. ICU-acquired pneumonia (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.6 to 2.29), clinical sepsis (OR, 3.50; 95% CI, 1.71 to 7.18), and bloodstream infection (OR, 1.73; 95% CI, 1.25 to 2.41) increased the risk of ICU death. Conclusions. —ICU-acquired infection is common and often associated with microbiological isolates of resistant organisms. The potential effects on outcome emphasize the importance of specific measures for infection control in critically ill patients. (JAMA. 1995;274:639-644)

The prevalence of nosocomial infection in intensive care units in Europe. Results of the European Prevalence of Infection in Intensive Care (EPIC) Study. EPIC International Advisory Committee.

In Reply. —We agree with Dr Langer and colleagues that prevalence studies have their limitations and that the EPIC study may have overestimated the magnitude of ICU-acquired infections. Unfortunately, we did not have access to the data sources cited by Langer et al. They refer to one study reported in abstract form for a local meeting held 10 years ago (their reference 2) and a second study for which preliminary results were published only recently (their reference 3). They also focused on the incidence of sepsis without specific presentation of the relevant data on nosocomial infections. Nevertheless, the methods used in the EPIC study were identical for the various countries, so any comparisons between or among countries remain appropriate. As we discussed in our article, the differences observed among the European countries may well be explained by different severities of illness of the patients included, as reflected by higher Acute

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=jama&articleId=395571&pdfFileName=jama_275_5_032.pdf

Nosocomial Infections in Intensive Care Units

Infertility is an increasing problem all over the world, and it has been estimated that 10-15% of couples in fertile age have fertility problems. Likewise induced unsafe abortion is a serious threat to women's health. Despite advances made in assisted reproduction techniques, little progress has been made in increasing the success rate during fertility treatment. This document describes a wide range of projects carried out to increase the understanding in the field of embryo implantation research. The 'Fruitful' research network was created to encourage collaborations within the consortium and to describe our different research potentials to granting agencies or private sponsors.

Jane White

Papers

The prevalence of nosocomial infection in intensive care units in Europe. Results of the European Prevalence of Infection in Intensive Care (EPIC) Study. EPIC International Advisory Committee.

Nosocomial Infections in Intensive Care Units

Implantation of the human embryo: research lines and models. From the implantation research network 'Fruitful'.