Diagnosis and follow-up of infections in intensive care patients: value of C-reactive protein compared with other clinical and biological variables

OBJECTIVE: To evaluate diagnostic and prognostic values of C-reactive protein (CRP) dosage in critically ill patients. DESIGN: Prospective, observational study. SETTING: Medical intensive care unit (ICU) in a university hospital. PATIENTS: A consecutive series of 74 patients admitted to the ICU. INTERVENTION: CRP measurements at admission and every 4 days thereafter. MEASUREMENTS AND MAIN RESULTS: At admission, 28 patients (38%) had microbiologically proven infections. Compared with uninfected patients, their mean +/- SD CRP level was 191 +/- 123 vs. 83 +/- 91 mg/L (p < .0001), respectively, white blood cell count was 15.3 +/- 7.5 vs. 11.4 +/- 5.3 G/L (p = .01), and the systemic inflammatory response syndrome (SIRS) was present for 96% vs. 67% (p = .008). No threshold value could be identified to discriminate between these two populations. Multivariate analysis retained CRP and SIRS as the only variables independently associated with the presence of an infection. The combination of CRP > or = 50 mg/L with SIRS was identified as the best model to diagnose infection at admission. This multivariate model performed better than temperature, CRP alone, and white blood cell count. Among the 28 infected patients, 10 recovered; CRP values decreased significantly in this population as compared with patients with persistent infection (-130 +/- 110 vs. 12 +/- 97 mg/L, respectively; p = .004). A CRP decrease > or = 50 mg/L between admission and day 4 was the best cutoff value to diagnose recovery (sensitivity 89%, specificity 79%). CONCLUSION: CRP in combination with SIRS was useful to diagnose infection in ICU patients; a CRP decrease > or = 50 mg/L between admission and day 4 was the best predictor of recovery.     

Ontogenesis of the in vitro response of rat testis to gonadotropin-releasing hormone.

The age-related evolution of the in vitro effects of a gonadotropin releasing hormone agonist ([D-Trp6]-GnRH) on the secretion of testosterone by the testis, cultured during 3 days on a Millipore filter floating on M199 medium, was studied during the perinatal period in the rat. The basal and luteinizing hormone (LH)-stimulated secretions by testes explanted on fetal day 14.5 were unaffected by the agonist. With fetal testes explanted on days 16.5 and 18.5 post-conception, the agonist inhibited, in a concentration-dependent manner, both basal and LH-stimulated secretions from the second or the third day of treatment onwards. With fetal and neonatal testes explanted on days 20.5, 21.5 and 31.5 post-conception, the GnRH agonist also had a long-term inhibitory effect on LH-stimulated secretion, but increased basal secretion. This stimulatory effect was already observed after 4 h of culture, and was maintained for 3 days. These results suggest that, during fetal development, the cellular mechanisms involved in the negative testicular response to GnRH are differentiated 3-5 days before those involved in the positive response. Lastly, after 3 days of preculture in hormone-free medium, fetal testes explanted on day 14.5 displayed long-term GnRH agonist inhibition of in vitro basal secretion of testosterone. This observation points out a spontaneous differentiation of the negative responsiveness to GnRH in the cultured fetal testis.     

Localization of transforming growth factor-β 1 precursor and latent TGF-β 1 binding protein in colorectal adenomas

Transforming growth factor- ₁ (TGF- ₁) is a multifunctional cytokine and is thought to be involved in colorectal tumorigenesis as a regulator of cell growth and differentiation. This role is mainly supported byin vitro studies while its rolein vivo remains unclear. The aim of the present study was to investigate whether the TGF- ₁ precursor ( ₁-LAP) and the latent TGF- ₁ binding protein (LTBP) are expressed in colorectal adenomas, the presumed precursors of most of colorectal adenocarcinomas. TGF- ₁ precursor and LTBP were examined in 35 adenomas and 10 normal colonic mucosa specimens by immunohistochemistry, using specific polyclonal antibodies. In normal colonic mucosa, ₁-LAP was moderately expressed in epithelial crypt cells and in the stromal cells in the lamina propria. In adenomas, ₁-LAP was localized in epithelial cells with an heterogeneous pattern and was also present in stromal cells around the adenomatous glands. LTBP was not detected in epithelial cells but was observed in stromal cells and in the extracellular matrix (ECM). ₁-LAP expression in epithelial cells did not correlate with the grade of dysplasia, while LTBP localized in stromal cells and ECM appeared to be closely associated with areas of higher grade of dysplasia. This study is the first demonstration of both ₁-LAP and LTBP in colorectal adenomas with different dysplasia grades. Our results suggest that TGF- ₁ might be involved in the mechanisms controllingin vivo colorectal tumorigenesis and support a role for the stromal-associated TGF- ₁.J.-L. Van Laethem is supported by a grant of the Fondation Erasme (Brussels, Belgium).     

Biomechanics-based graph matching for augmented CT-CBCT

Purpose

Augmenting intraoperative cone beam computed tomography (CBCT) images with preoperative computed tomography data in the context of image-guided liver therapy is proposed. The expected benefit is an improved visualization of tumor(s), vascular system and other internal structures of interest.

Method

An automatic elastic registration based on matching of vascular trees extracted from both the preoperative and intraoperative images is presented. Although methods dedicated to nonrigid graph matching exist, they are not efficient when large intraoperative deformations of tissues occur, as is the case during the liver surgery. The contribution is an extension of the graph matching algorithm using Gaussian process regression (GPR) (Serradell et al. in IEEE Trans Pattern Anal Mach Intell 37(3):625–638, 2015): First, an improved GPR matching is introduced by imposing additional constraints during the matching when the number of hypothesis is large; like the original algorithm, this extended version does not require a manual initialization of matching. Second, a fast biomechanical model is employed to make the method capable of handling large deformations.

Results

The proposed automatic intraoperative augmentation is evaluated on both synthetic and real data. It is demonstrated that the algorithm is capable of handling large deformations, thus being more robust and reliable than previous approaches. Moreover, the time required to perform the elastic registration is compatible with the intraoperative navigation scenario.

Conclusion

A biomechanics-based graph matching method, which can handle large deformations and augment intraoperative CBCT, is presented and evaluated.

     

Interventional cardiologists and risk of radiation-induced cataract: Results of a French multicenter observational study

Background

Interventional cardiologists (ICs) are exposed to X-rays and may be at risk to develop cataract earlier than common senile cataract. Excess risk of posterior subcapsular cataract, known as radiation-induced, was previously observed in samples of ICs from Malaysia, and Latin America. The O'CLOC study (Occupational Cataracts and Lens Opacities in interventional Cardiology) was performed to quantify the risk at the scale of France.

Methods

This cross-sectional multicenter study included an exposed group of ICs from different French centers and an unexposed control group of non-medical workers. Individual information was collected about cataract risk factors and past and present workload in catheterization laboratory. All participants had a clinical eye examination to classify the lens opacities (nuclear, cortical, or posterior subcapsular) with the international standard classification LOCS III.

Results

The study included 106 ICs (mean age = 51 ± 7 years) and 99 unexposed control subjects (mean age = 50 ± 7 years). The groups did not differ significantly in the prevalence of either nuclear or cortical lens opacities (61% vs. 69% and 23% vs. 29%, respectively). However, posterior subcapsular lens opacities, were significantly more frequent among ICs (17% vs. 5%, p = 0.006), for an OR = 3.9 [1.3–11.4]. The risk increased with duration of activity but no clear relationship with workload was observed. However, the risk appeared lower for regular users of protective lead glasses (OR = 2.2 [0.4–12.8]).

Conclusions

ICs, in France as elsewhere, are at high risk of posterior subcapsular cataracts. Use of protective equipment against X-rays, in particular lead glasses, is strongly recommended to limit this risk.     

Phthalates Impair Germ Cell Development in the Human Fetal Testis in Vitro without Change in Testosterone Production

Background

Several studies have described an increasing frequency of male reproductive disorders, which may have a common origin in fetal life and which are hypothesized to be caused by endocrine disruptors. Phthalate esters represent a class of environmental endocrine-active chemicals known to disrupt development of the male reproductive tract by decreasing testosterone production in the fetal rat.

Objectives

Using the organ culture system we developed previously, we investigated the effects on the development of human fetal testis of one phthalate—mono-2-ethylhexyl phthalate (MEHP)—an industrial chemical found in many products, which has been incriminated as a disruptor of male reproductive function.

Methods

Human fetal testes were recovered during the first trimester (7–12 weeks) of gestation, a critical period for testicular differentiation, and cultured for 3 days with or without MEHP in basal conditions or stimulated with luteinizing hormone (LH).

Results

Whatever the dose, MEHP treatment had no effect on basal or LH-stimulated testosterone produced by the human fetal testis in vitro, although testosterone production can be modulated in our culture system. MEHP (10⁻⁴ M) did not affect proliferation or apoptosis of Sertoli cells, but it reduced the mRNA expression of anti-Müllerian hormone. MEHP (10⁻⁴ M) reduced the number of germ cells by increasing their apoptosis, measured by the detection of caspase-3–positive germ cells, without modification of their proliferation.

Conclusions

This is the first experimental demonstration that phthalates alter the development of the germ cell lineage in humans. However, in contrast to results observed in the rat, phthalates did not affect steroidogenesis.     

Use of the bioMérieux VIDAS troponin I ultra assay for the diagnosis of myocardial infarction and detection of adverse events in patients presenting with symptoms suggestive of acute coronary syndrome

BACKGROUND: We demonstrate the performance of the bioMérieux VIDAS Troponin I Ultra assay for diagnostic accuracy for detection of myocardial infarction (MI) and risk stratification. METHOD: cTnI was measured in 545 patients from 2 clinical centers with symptoms suggestive of ACS at admission, with an additional specimen at 4-12 h (453 patients). The 99th percentile value (0.01 microg/l) was used to assess clinical accuracy for diagnosis of acute MI. Primary endpoint for risk stratification was first of cardiac event or death in 302 patients (one center) followed for 60 days. RESULTS: 157 (28.8%) patients ruled in for an MI during index hospitalization. Sensitivities and specificities were 88.1% (95% CI 81.9 to 92.4%) and 79.9% (CI 75.5 to 83.6%) for baseline and 100% (CI 96.5 to 100%) and 79.4% (CI 74.4 to 83.4%) for follow-up specimens. ROC curve areas increased from 0.912 (CI 0.879 to 0.944) at baseline to 0.994 (CI 0.988 to 0.999) at second sampling (n=453, p<0.01); with no differences between sites. Primary endpoint rate for the 223 patients (74%) with normal cTnI on presentation was lower than the 79 patients (26%) with cTnI>0.01 ug/l (5.9% vs. 42.3%, p<0.0001). The relative risk for the >0.01 ug/l group was 8.9 (CI 4.6 to 17). CONCLUSION: The VIDAS cTnI assay is a sensitive diagnostic method for the early detection of MI and predicts increased risk for adverse events in patients with symptoms suggestive of ACS.     

Progressive loss of dopaminergic neurons in the ventral midbrain of adult mice heterozygote for Engrailed1: a new genetic model for Parkinson's disease?

Engrailed1 is a developmental gene of the homeogene family that controls the survival of midbrain dopaminergic neurons throughout life. Since these neurons have been crucially implicated in Parkinson's disease (PD), transgenic mice lacking one En1 allele could be of particular interest for the development of an animal model for PD. We showed in En1+/- mice, some traits reminiscent of PD such as (1) a progressive loss of mesencephalic dopaminergic (DA) neurons, and (2) motor deficits, anhedonia, decreased social interactions and depression-like behaviours. Further validation is needed, but these first results suggest that En1+/- mice could provide a promising model for the study of PD.