Kuhn P.,University of Strasbourg |
Dheu C.,University of Strasbourg |
Dheu C.,Center Hospitalier Of Colmar |
Bolender C.,Center Hospitalier Of Haguenau |
And 7 more authors.
Paediatric and Perinatal Epidemiology | Year: 2010
In 2001 France issued a new set of guidelines for the use of antenatal antibiotics (AA). These guidelines recommended intrapartum antimicrobial prophylaxis (IAP) to prevent group B streptococcal (GBS) disease and AA to prolong pregnancy in the event of preterm premature rupture of membranes (AA for PPROM). This study aims to determine the effects of AA, recommended by national guidelines, on the incidence and distribution of pathogens in early-onset neonatal sepsis (EONS). We performed a population-based, prospective, observational study of level II and III perinatal centres throughout the region of Alsace, a northeastern area of France, between March 2004 and February 2005. The study population included all neonates with confirmed or probable EONS, who were treated with antibiotics for at least 5 days. We analysed exposure to AA, as well as clinical and microbiological data obtained from medical records. A total of 20 131 neonates were born during the study period, and 217 were included in the study. Of these, 24 subjects had confirmed sepsis, 140 had probable sepsis and 53 had possible EONS. The overall incidence of confirmed EONS was 1.19 per 1000 births. The infecting bacteria was GBS in 15 of 24 (62.5%) confirmed EONS cases (incidence: 0.75 per 1000 births) and in 81 of 140 (58%) probable sepsis cases. Escherichia coli was identified in 6 of 24 (25%) cases of confirmed EONS (incidence: 0.3 per 1000 births) and in 30 of 140 (21%) cases of clinical sepsis. Among E. coli infections (n = 36), amoxicillin resistance (n = 18) was statistically linked with AA use (P = 0.045). This link was significant in cases of PPROM (P = 0.015), but not when IAP was administered to prevent GBS disease (P = 0.264). IAP was not performed in 18 of 60 (30%) cases and 32 of 93 (34%) cases, despite positive screening or the presence of risk factors for EONS, respectively. Group B streptococcus remains the predominant pathogen in the era of AA. Aminopenicillin-resistant E. coli infections seem to be linked to prolonged AA in cases of PPROM and appear to preferentially affect preterm infants. Therefore, postnatal treatment strategies should consider this possible effect. Our data indicate that the current policy of GBS maternal prophylaxis is not associated with an excessive risk of pathogen resistance. Considering the high incidence of GBS EONS in our region, possible progress could result from better observance of guidelines. These results strengthen the need for continuation of surveillance. © 2010 Blackwell Publishing Ltd.
Didier C.,University of Strasbourg |
Streicher M.-P.,Center Hospitalier Of Haguenau |
Chognot D.,Center Hospitalier Of Colmar |
Campagni R.,Center Hospitalier Of Mulhouse |
And 7 more authors.
European Journal of Pediatrics | Year: 2012
Widespread use of intrapartum antimicrobial prophylaxis has significantly reduced the incidence of earlyonset neonatal infection (EONI); however, little is known about the effects of increased maternal exposure to antibiotics on late-onset neonatal infection (LONI). This study aims to evaluate LONI epidemiology in our region after the application of French recommendations and to determine whether LONI-causing organisms and their antibiotic susceptibility are influenced by peripartum antibiotic exposure. We performed a prospective epidemiologic study of 139 confirmed and possible cases of bacterial LONI in patients treated with antibiotics for at least 5 days of the 22,458 infants born in our region in the year 2007. The overall incidence of LONI caused by all pathogens, Group B streptococcus (GBS) and Escherichia coli (E. coli) were 6.19, 0.36 and 2.72, respectively, per 1,000 live births. Our findings revealed three major types of LONI: E. coli-induced urinary tract infection (UTI) among term infants, coagulase negative Staphylococcus septicemia affecting preterm infants, and GBS infections with severe clinical presentation. Univariable analysis revealed that maternal antibiotic exposure was significantly associated with the risk of amoxicillin-resistant E. coli infection (p00.01). Postnatal antibiotic exposure was associated with an increased risk of E. coli LONI (p00.048). This link persisted upon multivariable analysis; however, no additional risk factors were identified for LONI caused by antibiotic-resistant E. coli. Conclusion Our findings confirm that despite the benefits of antenatal antibiotics, this treatment can increase the risk of antibiotic-resistant cases of LONI. National and international surveillance of LONI epidemiology is essential to assess benefits and potential negative consequences of perinatal antibiotic exposure. © Springer-Verlag 2011.
PubMed | Hopitaux Universitaires Of Strasbourg, Nancy University Hospital Center, University of Strasbourg, Pole de Medecine et de Chirurgie Bucco dentaire and 19 more.
Type: Journal Article | Journal: Journal of medical genetics | Year: 2016
Orodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders.We designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption.We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases.We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease.NCT01746121 and NCT02397824.
PubMed | Brest University Hospital Center, Clermont Ferrand University Hospital, Hopital La Pitie Salpetriere, University of Nantes and 32 more.
Type: Journal Article | Journal: JAMA | Year: 2016
One-third of patients with rheumatoid arthritis show inadequate response to tumor necrosis factor (TNF-) inhibitors; little guidance on choosing the next treatment exists.To compare the efficacy of a non-TNF-targeted biologic (non-TNF) vs a second anti-TNF drug for patients with insufficient response to a TNF inhibitor.A total of 300 patients (conducted between 2009-2012) with rheumatoid arthritis, with persistent disease activity (disease activity score in 28 joints-erythrocyte sedimentation rate [DAS28-ESR] 3.2 [range, 0-9.3]) and an insufficient response to anti-TNF therapy were included in a 52-week multicenter, pragmatic, open-label randomized clinical trial. The final follow-up date was in August 2013.Patients were randomly assigned (1:1) to receive a non-TNF-targeted biologic agent or an anti-TNF that differed from their previous treatment. The choice of the biologic prescribed within each randomized group was left to the treating clinician.The primary outcome was the proportion of patients with good or moderate response according to the European League Against Rheumatism (EULAR) scale at week 24. Secondary outcomes included the EULAR response at weeks 12 and 52; at weeks 12, 24, and 52; DAS28ESR, low disease activity (DAS28 3.2), remission (DAS28 2.6); serious adverse events; and serious infections.Of the 300 randomized patients (243 [83.2%] women; mean [SD] age, 57.1 [12.2] years; baseline DAS28-ESR, 5.1 [1.1]), 269 (89.7%) completed the study. At week 24, 101 of 146 patients (69%) in the non-TNF group and 76 (52%) in the second anti-TNF group achieved a good or moderate EULAR response (OR, 2.06; 95% CI, 1.27-3.37; P=.004, with imputation of missing data; absolute difference, 17.2%; 95% CI, 6.2% to 28.2%). The DAS28-ESR was lower in the non-TNF group than in the second anti-TNF group (mean difference adjusted for baseline differences, -0.43; 95% CI, -0.72 to -0.14; P=.004). At weeks 24 and 52, more patients in the non-TNF group vs the second anti-TNF group showed low disease activity (45% vs 28% at week 24; OR, 2.09; 95% CI, 1.27 to 3.43; P=.004 and 41% vs 23% at week 52; OR, 2.26; 95% CI, 1.33 to 3.86; P=.003).Among patients with rheumatoid arthritis previously treated with anti-TNF drugs but with inadequate primary response, a non-TNF biologic agent was more effective in achieving a good or moderate disease activity response at 24 weeks than was the second anti-TNF medication.clinicaltrials.gov Identifier: NCT01000441.
Beck M.,Center Hospitalier Of Mulhouse |
Bodin F.,University of Strasbourg |
Lutz J.C.,University of Strasbourg |
Bruant-Rodier C.,University of Strasbourg
European Journal of Plastic Surgery | Year: 2012
As an indication for the treatment of sequelae of conservative breast cancer surgery, fat transfer in the breast raises two questions: the efficiency of the procedure in terms of volume and curve, and its impact on both breast imaging and oncological evolution. From April 2005 to April 2009, our prospective study included ten consecutive patients. They underwent one-step lipostructure according to Coleman's technique for the treatment of the sequelae of conservative surgery for breast cancer. We studied the patients' overall treatment satisfaction graded from 0 to 10 at the first and third months, and 3 years post-intervention. Patients evaluated the rate of fat resorbed in their breast at 1, 3, and 9 months and 3 years post-intervention. They were submitted to mammary computed tomography (CT) scan before lipofilling and 3 and 9 months later and after 3 years in order to obtain an objective evaluation of fat resorption by a three-dimensional (3D) approach. All patients underwent mammography before lipofilling and 3 years after. The patients were asked if lipofilling had been a significant surgical procedure and if they would accept another one. We noticed that patients' long-term satisfaction remained constantly good. Seventy percent were satisfied with the total treatment after 3 years. Average fat resorption values evaluated by the patients and by CT scan were quite close, which suggests a reliability of subjective patient evaluation. The experience of the average fat resorption shows that surgeons can repeat the procedure after 9 months thanks to the stabilization of fat resorption. Long term fat resorption after 3 years was estimated to be on average 44% on CT scan evaluation and 53% on patients; this confirms the usually agreed concept in clinical practice, which advises an overcorrection of 30 to 50% in order to offset for future fat resorption. All patients considered lipofilling to be a minimally invasive technique. We encountered no difficulty in patient follow-up post-lipofilling. Thanks to mammography, ultrasonography and RMI for suspect images, radiological follow-up allowed 90% of the cases to distinguish post-lipofilling images from radiological abnormality due to breast cancer. Lipofilling provides an elegant technique to treat the sequelae of conservative breast surgery. It is a less invasive technique that results in a high level of patient satisfaction and satisfactory follow-up attendance. Nevertheless this procedure may require further injections to obtain fully satisfying results. © 2011 Springer-Verlag.
Koscinski I.,University of Strasbourg |
Elinati E.,University of Strasbourg |
Fossard C.,University of Strasbourg |
Redin C.,University of Strasbourg |
And 11 more authors.
American Journal of Human Genetics | Year: 2011
Globozoospermia, characterized by round-headed spermatozoa, is a rare (< 0.1% in male infertile patients) and severe teratozoospermia consisting primarily of spermatozoa lacking an acrosome. Studying a Jordanian consanguineous family in which five brothers were diagnosed with complete globozoospermia, we showed that the four out of five analyzed infertile brothers carried a homozygous deletion of 200 kb on chromosome 12 encompassing only DPY19L2. Very similar deletions were found in three additional unrelated patients, suggesting that DPY19L2 deletion is a major cause of globozoospermia, given that 19% (4 of 21) of the analyzed patients had such deletion. The deletion is most probably due to a nonallelic homologous recombination (NAHR), because the gene is surrounded by two low copy repeats (LCRs). We found DPY19L2 deletion in patients from three different origins and two different breakpoints, strongly suggesting that the deletion results from recurrent events linked to the specific architectural feature of this locus rather than from a founder effect, without fully excluding a recent founder effect. DPY19L2 is associated with a complete form of globozoospermia, as is the case for the first two genes found to be associated with globozoospermia, SPATA16 or PICK1. However, in contrast to SPATA16, for which no pregnancy was reported, pregnancies were achieved, via intracytoplasmic sperm injection, for two patients with DPY19L2 deletion, who then fathered three children. © 2011 The American Society of Human Genetics.
Lohmann C.,Center Hospitalier Of Mulhouse |
Sabou M.,University of Strasbourg |
Moussaoui W.,University of Strasbourg |
Prevost G.,University of Strasbourg |
And 4 more authors.
Journal of Clinical Microbiology | Year: 2013
Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is emerging in laboratories as a new diagnostic tool for microorganism identification. We prospectively compared the performances of the Biflex III-Biotyper (Bruker Daltonics) and the Axima (Shimadzu)-SARAMIS (AnagnosTec) systems for the identification of 312 yeasts isolated from clinical specimens (249 Candida spp., including 19 C. albicans and 230 non-albicans species and 63 isolates belonging to different species of the genera Saccharomyces [20 isolates], Rhodotorula [8 isolates], Cryptococcus [8 isolates], Trichosporon [7 isolates], Pichia [7 isolates], Geotrichum [12 isolates], and Sporopachydermia cereana [1 isolate]). Species were identified by using routine conventional phenotypical methods and internal transcribed spacer (ITS) sequencing in case of discrepancy. We used expanded thresholds for species identification (log score of >1.7 with 3 identical consecutive propositions and no discrepancy between the duplicates for the Bruker Daltonics system and similitude of <40% with 5 successive identical propositions and no discrepancy between the duplicates for the Shimadzu system). Of the 312 isolates, 272 (87.2%) and 258 (82.7%) were successfully identified by the Bruker Daltonics and Shimadzu systems, respectively. All isolates were successfully identified within the most frequent and clinically relevant Candida species by the two systems. Nonvalid results corresponded mainly to species not or poorly represented in the databases. Major misidentifications were observed for 2 isolates (0.6%) by the Bruker Daltonics system and 4 isolates (1.3%) by the Shimadzu system. In conclusion, the performances of the Bruker Daltonics and the Shimadzu systems for yeast identification were good and comparable under routine clinical conditions, despite their differences in sample preparation, database content, and spectrum analysis. © 2013, American Society for Microbiology.
Boyer O.,French Institute of Health and Medical Research |
Boyer O.,University of Paris Descartes |
Woerner S.,French Institute of Health and Medical Research |
Yang F.,Novartis |
And 20 more authors.
Journal of the American Society of Nephrology | Year: 2013
LMX1B encodes a homeodomain-containing transcription factor that is essential during development. Mutations in LMX1B cause nail-patella syndrome, characterized by dysplasia of the patellae, nails, and elbows and FSGS with specific ultrastructural lesions of the glomerular basement membrane (GBM). By linkage analysis and exome sequencing, we unexpectedly identified an LMX1B mutation segregating with disease in a pedigree of five patients with autosomal dominant FSGS but without either extrarenal features or ultrastructural abnormalities of the GBM suggestive of nail-patella-like renal disease. Subsequently, we screened 73 additional unrelated families with FSGS and found mutations involving the same amino acid (R246) in 2 families. An LMX1B in silico homology model suggested that themutated residue plays an important role in strengthening the interaction between the LMX1B homeodomain and DNA; both identified mutations would be expected to diminish such interactions. In summary, these results suggest that isolated FSGS could result from mutations in genes that are also involved in syndromic forms of FSGS. This highlights the need to include these genes in all diagnostic approaches to FSGS that involve next-generation sequencing. Copyright © 2013 by the American Society of Nephrology.
Rostoker G.,Service Route |
Hummel A.,Service de Nephrologie et de Dialyse Adultes |
Chantrel F.,Center Hospitalier Of Mulhouse |
Ryckelynck J.-P.,Caen University Hospital Center
Nephrologie et Therapeutique | Year: 2014
The Kidney Disease Improving Global Outcomes (KDIGO)-2012 on the treatment of anemia emit suggestions (which differ from recommendations) based on a scientific evidence of low level. The first rule is no harm; physicians must take into account the profile of the patient and its associated morbidities and remember on the potential risks to begin a treatment by erythropoiesis stimulating agents (ESA) (thrombosis of arteriovenous fistula, hypertension, stroke). All correctable causes of anemia other than erythropoietin deficiency should be actively sought. It is necessary to individualize the treatment by ESA and assess the clinical improvement expected. The ESA will be used in the following way: initiate at 10 g/dL of hemoglobin level with the aim of 11.5 g/dL, without exceeding 13 g/dL. In case of ESA resistance, it seems suitable to assess the risks and benefits of ESA versus blood transfusion. The ERBP-2013 have endorsed the KDIGO-2012 except the proposals dealing with the treatment by IV iron. The use of intravenous iron must be more cautious in the future taking into account the results of a recent French study published in the American Journal of Medicine showing the high frequency of iron overload at quantitative hepatic MRI among haemodialysis patients receiving iron IV following the current guidelines. It is appropriate to use oral iron in first intention as recommended by the ANSM (French Drug Agency) in a recent information note and respect the dosage regimen of the label. The realization of a quantitative hepatic MRI to evaluate iron overload and monitor the treatment by iron IV must also be considered on a case by case basis. © 2014 Association Socié té de né phrologie. Publié par Elsevier Masson SAS. Tous droits ré servé s.