Matrix metalloproteinase-9, -10, and tissue inhibitor of matrix metalloproteinases-1 blood levels as biomarkers of severity and mortality in sepsis

Introduction

Matrix metalloproteinases (MMPs) play a role in infectious diseases through extracellular matrix (ECM) degradation, which favors the migration of immune cells from the bloodstream to sites of inflammation. Although higher levels of MMP-9 and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) have been found in small series of patients with sepsis, MMP-10 levels have not been studied in this setting. The objective of this study was to determine the predictive value of MMP-9, MMP-10, and TIMP-1 on clinical severity and mortality in a large series of patients with severe sepsis.

Methods

This was a multicenter, observational, and prospective study carried out in six Spanish Intensive Care Units. We included 192 (125 surviving and 67 nonsurviving) patients with severe sepsis and 50 age- and sex-matched healthy controls in the study. Serum levels of MMP-9, MMP-10, TIMP-1, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-10 were measured in patients with severe sepsis at the time of diagnosis and in healthy controls.

Results

Sepsis patients had higher levels of MMP-10 and TIMP-1, higher MMP-10/TIMP-1 ratios, and lower MMP-9/TIMP-1 ratios than did healthy controls (P < 0.001). An association was found between MMP-9, MMP-10, TIMP-1, and MMP-9/TIMP-1 ratios and parameters of sepsis severity, assessed by the SOFA score, the APACHE-II score, lactic acid, platelet count, and markers of coagulopathy. Nonsurviving sepsis patients had lower levels of MMP-9 (P = 0.037), higher levels of TIMP-1 (P < 0.001), lower MMP-9/TIMP-1 ratio (P = 0.003), higher levels of IL-10 (P < 0.001), and lower TNF-α/IL-10 ratio than did surviving patients. An association was found between MMP-9, MMP-10, and TIMP-1 levels, and TNF-α and IL-10 levels. The risk of death in sepsis patients with TIMP-1 values greater than 531 ng/ml was 80% higher than that in patients with lower values (RR = 1.80; 95% CI = 1.13 to 2.87;P = 0.01; sensitivity = 0.73; specificity = 0.45).

Conclusions

The novel findings of our study on patients with severe sepsis (to our knowledge, the largest series reporting data about MMP levels in sepsis) are that reduced MMP-9/TIMP-1 ratios and increased MMP-10 levels may be of great pathophysiologic significance in terms of severity and mortality, and that TIMP-1 levels may represent a biomarker to predict the clinical outcome of patients with sepsis.     

Mechanisms of antimicrobial resistance in Stenotrophomonas maltophilia: a review of current knowledge

ABSTRACT

Introduction: Stenotrophomonas maltophilia is a prototype of bacteria intrinsically resistant to antibiotics. The reduced susceptibility of this microorganism to antimicrobials mainly relies on the presence in its chromosome of genes encoding efflux pumps and antibiotic inactivating enzymes. Consequently, the therapeutic options for treating S. maltophilia infections are limited.

Areas covered: Known mechanisms of intrinsic, acquired and phenotypic resistance to antibiotics of S. maltophilia and the consequences of such resistance for treating S. maltophilia infections are discussed. Acquisition of some genes, mainly those involved in co-trimoxazole resistance, contributes to acquired resistance. Mutation, mainly in the regulators of chromosomally-encoded antibiotic resistance genes, is a major cause for S. maltophilia acquisition of resistance. The expression of some of these genes is triggered by specific signals or stressors, which can lead to transient phenotypic resistance.

Expert opinion: Treatment of S. maltophilia infections is difficult because this organism presents low susceptibility to antibiotics. Besides, it can acquire resistance to antimicrobials currently in use. Particularly problematic is the selection of mutants overexpressing efflux pumps since they present a multidrug resistance phenotype. The use of novel antimicrobials alone or in combination, together with the development of efflux pumps’ inhibitors may help in fighting S. maltophilia infections.     

The placenta growth factor in skin angiogenesis

The placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family that has been shown to play an important role in promoting adult pathological angiogenesis. Besides inducing its own signaling in endothelial cells, PlGF exerts its angiogenic action by synergising with VEGF. In the skin, PlGF expression is upregulated during wound healing and PlGF-deficient mice show delayed wound closure, indicating that this factor promotes angiogenesis during skin repair. Moreover, PlGF expression by melanoma cells has been linked to tumor growth. The analysis of a transgenic mouse model constitutively expressing high levels of PlGF in basal keratinocytes has shown that this factor has strong angiogenic properties in the skin during both embryonic and post-natal life. Furthermore, PlGF delivery to the skin via an adenoviral vector induces the formation of large and stable blood vessels, but contrary to VEGF application, does not affect lymphatic vessel functionality. Such evidence opens the possibility of employing PlGF for therapeutic modulation of skin angiogenesis.     

Lumbar Spinal Stenosis: Therapeutic Options Review

Lumbar spinal stenosis (LSS) functionally impacts significant numbers of Americans per year. Current estimates place the number of Americans suffering from senescent lumbar spinal stenosis at 400,000. The prevalence of this disorder in patients ranging from 60 to 69 years of age is very high. Forty‐seven percent of this age group have mild to moderate stenosis, and 19.7% have severe stenosis. As the baby boomer generation gets older, 10,000 individuals attain the age of 65 years every day in United States. LSS is becoming very common and will be a major healthcare issue as the population ages. Although LSS is not life threatening, it can cause substantial disability with limitations to performing daily activities, and thus, the associated negative impact on quality of life (QOL). This article reviews the pathophysiology and current treatment options for LSS, focusing on evidence‐based treatment options.     

MQSA update

Since the MQSA regulations took effect in 1999, several amendments have been enacted, most notably new stringent equipment guidelines that became effective on October 28, 2002. After reading this review of the amended final regulations, readers will: Be familiar with the amended final equipment and quality assurance regulations. Understand policy guidance help regarding the new regulations. Understand new policy guidance for radiologic technologists. Know the basics of MQSA's impact on providers, patients and mammography quality and reasons for facility citations since release of the final regulations. Know where to go for MQSA information and guidance resources.     

Combined test + inhibin A at week 13 in contingent sequential testing: an interesting alternative for first-trimester prenatal screening for Down syndrome

OBJECTIVE: To analyze various possibilities of using dimeric inhibin A (DIA) as a first-trimester marker, during week 13, for diverse sequential strategies together with the combined test (CT) [which uses pregnancy-associated plasma protein A, free beta-human chorionic gonadotrophin and nuchal translucency]. METHOD: We analyzed three sequential strategies (nondisclosure, stepwise and contingent) for measuring DIA in week 13. Multivariate Gaussian modelling was used to estimate second-trimester, false-positive and detection rates. Model parameters were taken from the Serum, Urine and Ultrasound Screening Study (SURUSS) assay. RESULTS: The three sequential strategies provided high and comparable levels of effectiveness, with false-positive rate for fixed detection rate of 85% and detection rate for fixed false-positive rate of 5% values of about 91 and 2%, respectively. The contingent strategy (with two CT risk cutoffs, of 1 in 50 and 1 in 2000) produced a screening-positive rate of 0.8% with CT, while only 23% of the women needed subsequent DIA measurement. CONCLUSIONS: First-trimester sequential screening using CT together with DIA measurement in week 13 is capable of producing results that are comparable with those of the integrated test, with the additional advantage that the final result is obtained earlier. It is recommended that this strategy be evaluated in large-scale prospective studies. Copyright (c) 2008 John Wiley & Sons, Ltd.     

Colposacropexia por laparoscopia en el tratamiento del prolapso genital

Objectives

To analyze the results of laparoscopic colposacropexy and to achieve a long-lasting support system without recurrences.

Material and methods

From March 2001 to March 2007, we performed laparoscopic colposacropexy in 42 patients. The mean age was 56 years (42-70 years).Patients with prior hysterectomy showed complex vaginal vault prolapse while those without hysterectomy showed prolapse affecting more than one compartment. The 28 women with pelvic uterine prolapse underwent hysterectomy (supracervical hysterectomy in 15 and total hysterectomy in 13). The transperitoneal Burch procedure was carried out in eight patients with stress urinary incontinence.

Results

The mean length of follow-up was 3.5 years (range: 1-6). Surgery was successful in 39 patients (92.8%). Anterior compartment recurrence was observed in one patient and severe lumbar pain associated with postoperative spondylodiscitis in another patient. A third patient required posterior trachelectomy. The mean operating time was 180 min (range: 120-240). The mean length of hospital stay was 2.5 days (range: 2-3).

Conclusions

Laparoscopic colposacropexy is a safe and constantly evolving procedure with longterm durability. This procedure provides similar results to laparotomy but produces fewer vaginal complications.     

Evaluation and management of dysmenorrhea in adolescents

Chronic pelvic pain is defined by the American College of Obstetricians and Gynecologists (ACOG) as noncyclic pelvic pain of at least 3 months duration or cyclic pain of 6-month duration, either of which interferes with one's normal activities of daily living. Dysmenorrhea, or painful menses, is the most common gynecologic complaint among adolescent and young adult females and is the leading cause of recurrent short-term school or work absenteeism. This chapter reviews the assessment, diagnosis, and treatment of some of the most common causes of pelvic pain in adolescents.