Campylobacter infection after prosthetic joint surgery

Few cases of Campylobacter prosthetic joint infection (PJI) have been reported so far. We describe the demographic characteristics, underlying conditions, clinical features, treatment, and outcome of 8 patients with Campylobacter PJI in our hospital. All strains were confirmed at the French National Reference Center for Campylobacter and Helicobacter. Seven patients were infected with C. fetus and 1 with C. jejuni. Most patients were elderly and immunocompromised. Four had bacteremia, one of these with a pacemaker endocarditis. All the patients received at least 3 months of antibiotic treatment and 6 were treated surgically. The outcome was favorable at 2 years of follow-up in all except for 1 patient. Campylobacter PJI cases are rare but likely to become more frequent. C. fetus bacteremia should motivate physicians to look for a secondary localization such as a Campylobacter PJI

Sensitive molecular detection of small nodal metastasis in uterine cervical cancer using HPV16-E6/CK19/MUC1 cancer biomarkers

International audienceMetastatic nodal involvement is a critical prognostic factor in uterine cervical cancer (UCC). To improve current methods of detecting UCC metastases in lymph nodes (LNs), we used quantitative PCR (qPCR) to assess mRNA expression of potential metastatic biomarkers. We found that expression of HPV16-E6, cytokeratin19 (CK19), and mucin1 (MUC1) is consistently upregulated in tumors and metastatic tissues, supporting a role for these genes in UCC progression. These putative biomarkers were able to predict the presence of histologically positive metastatic LNs with respective sensitivities and specificities of 82% and 99% (CK19), 76% and 95% (HPV16-E6), and 76% and 78% (MUC1). While the biomarkers failed to detect 1.7% to 2.2% of the histologically positive LNs when used individually, combining CK19 and HPV16-E6 enhanced sensitivity and specificity to 100% and 94%, respectively. To explore the sensitivity of qPCR-based detection of varying proportions of invading HPV16-positive UCC cells, we designed a LN metastasis model that achieved a fresh cell detection limit of 0.008% (1:12500 HPV16-positive to HPV16-negative cells), and a paraffin-embedded, formalin-fixed (PEFF) detection limit of 0.02% (1:5000 HPV16-positive to HPV16-negative cells), both of which are within the theoretical detection limit for micrometastasis. Thus, HPV E6/E7 oncogenes may be useful targets for the ultrasensitive detection of nodal involvements like micrometastases in fresh or archived tissue samples. Moreover, our results suggest that the biomarker combination of CK19/HPV-E6 could support a real-time intraoperative strategy for the detection of small, but potentially lethal, metastatic nodal involvements in fresh UCC tissues

Messenger RNA expression of leptin and leptin receptors and their prognostic value in 322 human primary breast cancers

International audienc

Continuous Cefazolin Infusion To Treat Bone and Joint Infections: Clinical Efficacy, Feasibility, Safety, and Serum and Bone Concentrations▿

Cefazolin has been used for many years to treat bone and joint infections. Because of its time-dependent antimicrobial activity, continuous infusion would potentially be beneficial. We report on the feasibility, safety, and efficacy of prolonged continuous intravenous cefazolin therapy in a cohort of 100 patients, their serum cefazolin levels, and the concomitant bone cefazolin concentrations in 8 of them. This retrospective cohort study included all the patients treated for bone or joint infection with a continuous cefazolin infusion administered over a 12-h period twice daily for ≥2 weeks. Drug monitoring was performed at least twice for all the patients. Serum and bone cefazolin concentrations were determined by standardized disk diffusion microbiological assays. The absence of clinical, biological, and radiological signs of infection after 2 years of follow-up and the same criteria after 1 year of follow-up defined cures and probable cures, respectively. The median treatment duration was 42 days, and the median daily cefazolin dose was 6 g. Half of the patients received parenteral antibiotic therapy on an outpatient basis. Two moderate-grade adverse events were observed. The median serum cefazolin concentrations were 63 μg/ml (range, 13 to 203 μg/ml) and 57 μg/ml (range, 29 to 128 μg/ml) on days 2 to 10 and days 11 to 21, respectively. The median bone cefazolin concentration reached 13.5 μg/g (range, 3.5 to 29 μg/g). The median bone concentration/serum concentration ratio was 0.25 (range, 0.06 to 0.41). Among 88 patients with a median follow-up of 25 months (range, 12 to 53 months), 52 were considered cured and 29 were considered probably cured. Thus, the treatment of bone and joint infections with a prolonged continuous intravenous cefazolin infusion was feasible, effective, well-tolerated, safe, and convenient, making it a strong candidate for home therapy

Prognostic value of ERM gene expression in human primary breast cancers

We measured the expression of ERM gene, a nuclear transcription factor belonging to the ets family, in a series of 364 unselected primary breast cancers from patients who underwent locoregional surgery in the Centre Oscar Lambret between May 1989 and December 1991. The expression of ERM was quantified with a real-time one-step reverse transcription-PCR assay based on the 5′-nuclease activity of the TaqDNA polymerase and with an Abi Prism 7700 Sequence Detector System (Applied Biosystems, Courtaboeuf, France). ERM was positively correlated (Spearman test) to epidermal growth factor receptor (EGFR; P < 0.001, r = 0.296) and to histoprognostic grading (P = 0.044, r = 0.112), whereas it was negatively correlated to estradiol receptors (P = 0.019, r = -0.124), HER3 (c-erbB-3; P = 0.01, r = -0.135), and HER4 (c-erbB-4; P = 0.003, r = -0.154). Using the χ2 test, a positive relationship was found between the expression of ERM and EGFR (χ2 = 7.795, P = 0.007). In overall survival studies, Cox univariate analyses demonstrated a prognostic value of ERM (P = 0.006; risk ratio, 2.95) besides the classical prognostic factors histoprognostic grading, node involvement, tumor size, estradiol receptors, progesterone receptors, EGFR, HER3, and HER4. In multivariate analyses, ERM preserved its prognostic value (P = 0.004; risk ratio, 3.779) together with histoprognostic grading, tumor size, estradiol receptors, and progesterone receptors. In relapse-free survival studies, univariate analyses demonstrated that histoprognostic grading, node involvement, tumor size, and HER4 were prognostic factors. These parameters, except histoprognostic grading, retained their prognostic value in multivariate analyses. This study demonstrates for the first time that ERM gene expression is an independent adverse prognostic factor for overall survival in breast cancer patients.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Leptin gene in rabbit: cloning and expression in mammary epithelial cells during pregnancy and lactation

International audienceLeptin is known as a cytokine mostly produced by fat cells and implicated in regulation of energy metabolism and food intake but has also been shown to be involved in many physiological mechanisms such as tissue metabolism and cell differentiation and proliferation. In particular, leptin influences the development of mammary gland. Although leptin expression in mammary gland has been studied in several species, no data are available in the rabbit. Leptin transcripts in this species have been described as being encoded by only two exons rather than three as in other species. Our focus was to clone and sequence the rabbit leptin cDNA and to prepare the recombinant biologically active protein for validation of the proper sequence and then to describe leptin expression in rabbit mammary gland during different stages of pregnancy and lactation. The leptin sequence obtained was compared with those of other species, and genome alignment demonstrated that the rabbit leptin gene is also encoded by three exons. Additionally, we analyzed the expression of leptin during pregnancy and lactation. Leptin mRNA was weakly expressed throughout pregnancy, whereas mRNA levels were higher during lactation, with a significant increase between days 3 and 16. Leptin transcripts and protein were localized in luminal epithelial cells, thus indicating that leptin synthesis occurs in this compartment. Therefore, mammary synthesized leptin may constitute a major regulator of mammary gland development by acting locally as an autocrine and/or paracrine factor. Furthermore, our results support the possible physiological role of leptin in newborns through consumption of milk