Osteosclerotic bone dysplasia in siblings with a Fam20C mutation.

Raine syndrome is an autosomal recessive disorder caused by mutations in the FAM20C gene. FAM20C codes for the human homolog of DMP4, a dentin matrix protein highly expressed in odontoblasts and moderately in bone. DMP4 is probably playing a role in the mineralization process. Since the first case reported in 1989 by Raine et al. 21 cases have been published delineating a phenotype which associates dysmorphic features, cerebral calcifications, choanal atresia or stenosis and thoracic/pulmonary hypoplasia. Kan and Kozlowski suggested the name of Raine syndrome to describe this new lethal osteosclerotic bone dysplasia. All the cases described were lethal during the neonatal period except for the last two reported patients aged 8 and 11 years who presented severe mental retardation. Here we describe two sisters, with an attenuated phenotype of Raine syndrome, who present an unexpectedly normal psychomotor development at ages 4 and 1, respectively. Identification of a homozygous mutation in the FAM20C gene confirmed the Raine syndrome diagnosis, thus contributing to the expansion of the Raine syndrome phenotype. This case report also prompted us to revisit the FAM20 gene classification and allowed us to highlight the ancestral status of Fam20C.

Hippocampal dysgenesis and variable neuropsychiatric phenotypes in patients with Bardet-Biedl syndrome underline complex CNS impact of primary cilia.

The Bardet-Biedl syndrome (BBS) is a rare ciliopathy clinically defined by the association of retinitis pigmentosa, polydactyly, obesity, kidney disease and cognitive impairment. The cognitive functioning, behavioral phenotype, prevalence of psychiatric diseases and memory performances of a cohort of 34 patients with BBS were evaluated and a systemic brain magnetic resonance imaging (MRI) was performed. The patients' cognitive functioning was of marked variable efficiency ranging from normal to disabling performances. Neuropsychological disorders such as slow thought process, attention difficulties and obsessive-compulsive traits were observed. Our main finding was hippocampal dysgenesis, diagnosed by MRI, found in 42.31% of the patients in this cohort. Moreover, we show that BBS proteins are expressed in the human hippocampus and in the human brain in the normal subject. Recent literature in the murine model shows that hippocampal neurogenesis, in particular in the adult mouse, requires an intact primary cilia. These results encourage us to further investigate the possible role of BBS proteins in the hippocampus and related central nervous system structures.

Value of (18)F-FDG-PET/CT in patients with fever of unknown origin and unexplained prolonged inflammatory syndrome: a single centre analysis experience.

OBJECTIVE: The aim of our study was to evaluate the diagnostic contribution of (18)F-fluoro-deoxyglucose ((18)F-FDG)-positron emission tomography (PET)/computed tomography (CT) in patients with fever of unknown origin (FUO) or unexplained prolonged inflammatory syndrome (UPIS) in real life. PATIENTS AND METHODS: We performed a retrospective study including 14 patients with FUO or UPIS hospitalised in our institution (Strasbourg University Hospital, France) between January 2005 and July 2006. (18)F-FDG-PET/CT was considered helpful when abnormal results allowed an accurate diagnosis. RESULTS: (18)F-FDG-PET/CT was helpful in half the patients (7/14) for final diagnosis. A diagnosis was reached in 87.5% of the patients (7/8) with an abnormal (18)F-FDG-PET/CT but only in 50% of the patients (3/6) with a normal (18)F-FDG-PET/CT. Conventional chest and abdominal CT was performed in 13 patients before ordering (18)F-FDG-PET/CT. We considered that (18)F-FDG-PET/CT was essential to establish the final diagnosis in only 23% of the patients (3/13) since neither chest nor abdominal CT identified abnormalities consistent with the final diagnosis. However, among the three patients, two were diagnosed with large vessel vasculitis and one patient with local prosthetic infection. CONCLUSIONS: Our study supports the potential interest of (18)F-FDG-PET/CT in the diagnostic workup of FUO and UPIS as it helped establish a fine diagnosis in half of the cases. However, (18)F-FDG-PET/CT appeared to be essential to the final diagnosis in only 23% of the cases. In our opinion, this protocol should be performed as a second level test, especially when conventional CT is normal or is unable to discriminate between active and silent lesions.

[MRSA bacteremia: recent epidemiological and therapeutical trends]. / Bactériémies à Staphylococcus aureus résistant à la méthicilline: aspects épidémiologiques et thérapeutiques récents.

PURPOSE: Staphylococcus aureus is the first agent responsible for nosocomial bacteremia in France. About 40% of the strains are resistant to methicillin (MRSA). The epidemiology of these infections has changed in the last fifteen years whereas therapeutics options have slightly progressed. CURRENT KNOWLEDGE AND KEY POINTS: Hospital-acquired MRSA bacteremia are more and more frequent while community-acquired strains recently appeared. Factors influencing the emergence of these infections were identified thanks to numerous clinical studies, as well as patients risk factors for developing these infections and their complications. At the same time, intermediate sensitive and resistant MRSA strains to glycopeptides appeared. Conversely, the best antibiotic strategy is still unclear in absence of good clinical studies. The interest of antibiotics combinations and of glycopeptides serum-concentrations control is still a matter of debate. Finally, the number of new active molecules remains limited. PERSPECTIVES: The frequency and severity of MRSA bacteremia are quite worrying in our country. The epidemiology of these infections must be known by every clinicians in order to prevent them. The therapeutic strategy has to be better define and need for new anti-infectious agents is critic.

[Lyme borreliosis: follow up criteria after antibiotherapy?]. / Borréliose de Lyme: quel est le suivi nécessaire après le traitement?

The post therapeutic follow-up of Lyme borreliosis is managed according to clinical and serological data. The evolution of antibody rates is such that it doesn't constitute the best element to rely on for follow-up. Indeed, after a sometimes transitory increase of this rate during or after antibiotherapy, the decrease is very slow, sometimes several months, and often incomplete. The follow-up should thus be made according to clinical symptoms and their resolution. Resolution of some but not all symptoms must lead to discussing two options. The first is that of administrating a complementary antibiotherapy with a different mode of action than the first antibiotic used. The second is that this may be due to recontamination, especially in highly endemic zones, given that antibodies present have no protecting effect. In this case, a new antibiotherapy must of course be initiated.

[Mucocutaneous leishmaniasis in Brazilian Amazonia]. / Leishmaniose cutanéomuqueuse en Amazonie brésilienne.

BACKGROUND: This study had for aim to describe the clinical aspects and favoring factors of mucosal Leishmaniasis in an Amazonian population of 30,000 habitants in Guajara-Mirim (Rondonia-Brazil). MATERIAL AND METHOD: A descriptive study was made of 16 patients with mucosal Leishmaniasis among 170 patients infected by Leishmania. Inclusion criteria were a mucosal lesion and positivity of direct microscopic examination. The patients were investigated retrospectively. RESULTS: Patients with mucosal Leishmaniasis were young and mostly male The absence of treatment and the number of cutaneous lesions were probably responsible for the mucosal form, as well as the host immune response and maybe, the parasite species or vector characteristics. CONCLUSION: The mucosal form of leishmaniasis affects more often young male patients and this form must be detected early to avoid destructing lesions.

[Invasive Streptococcus agalactiae infections in non-pregnant adults]. / Les infections invasives à Streptococcus agalactiae chez l'adulte (femme enceinte exclue).

OBJECTIVES: Streptococcus agalactiae (Group B streptococcus) is a major cause of invasive diseases in non-pregnant adults, particularly in the elderly and those with underlying conditions. We describe these conditions and clinical characteristics of patients followed in our teaching hospital. METHODS: We retrospectively reviewed clinical records of 64 patients with S. agalactiae-related invasive infection, hospitalized between January 1997 and January 2006. RESULTS: The mean age of patients was 59 (+/-17 years). The H:F sex ratio was 1.06. At least one underlying condition was found in 90.6%. Diabetes mellitus (43.7%), peripheral vascular disease (34.4%), myocardial ischemia (20.3%) and malignant neoplasms (20.3%) were among the most frequent conditions. The mean index of comorbidity (Charlson) was 2.5 (+/-2). Common clinical manifestations included infection of the urinary tract (32.8%), skin and soft-tissue (25%), and osteoarthritis (21.9%). Bacteremia occurred in 31.2% with no identified source in 2 patients. During the first month, 2 cases of endocarditis, 1 case of meningitis, and 4 deaths occurred. CONCLUSION: We confirm the importance of underlying diseases in the emergence of S. agalactiae infections.

[Neurosyphilis: A retrospective study of 13 cases at Strasbourg University Hospital]. / La neurosyphilis, étude rétrospective de 13 cas survenus aux hôpitaux universitaires de Strasbourg.

OBJECTIVE: After a decade of constant decline, the number of syphilis cases has been steadily increasing since the 2000s, particularly in HIV infected patients. Neurosyphilis is a rare manifestation of this sexually transmitted disease for which we performed a retrospective study and analyzed clinical manifestations. PATIENTS AND METHODS: We reviewed retrospectively all the neurosyphilis cases admitted to Strasbourg University Hospital between 2004 and 2014. We included and analyzed 13 patients admitted during this period who met the diagnostic criteria for neurosyphilis. RESULTS: Nine of 13 patients had isolated visual manifestations; three (23.1%) experienced posterior uveitis, two (15.4%), panuveitis, and 4 (30.8%) had papillitis. Out of five patients (38.5%) who were HIV positive, three (60%) had a CD4 cell count above 400/mm3 at the time of diagnosis of neurosyphilis. All patients received parenteral penicillin G or cephalosporin, and 5/13 (38.5%) received systemic corticotherapy. CONCLUSION: Ophthalmologists appear as key players in the identification, management and follow-up of neurosyphilis, since ocular findings are key diagnostic features in these patients.

VISLISI trial, a prospective clinical study allowing identification of a new metalloprotease and putative virulence factor from Staphylococcus lugdunensis.

OBJECTIVE: Staphylococcus lugdunensis is a coagulase-negative staphylococcus that displays an unusually high virulence rate close to that of Staphylococcus aureus. It also shares phenotypic properties with S. aureus and several studies found putative virulence factors. The objective of the study was to describe the clinical manifestations of S. lugdunensis infections and investigate putative virulence factors. METHOD: We conducted a prospective study from November 2013 to March 2016 at the University Hospital of Strasbourg. Putative virulence factors were investigated by clumping factor detection, screening for proteolytic activity, and sequence analysis using tandem nano-liquid chromatography-mass spectrometry. RESULTS: In total, 347 positive samples for S. lugdunensis were collected, of which 129 (37.2%) were from confirmed cases of S. lugdunensis infection. Eighty-one of these 129 patients were included in the study. Bone and prosthetic joints (PJI) were the most frequent sites of infection (n=28; 34.6%) followed by skin and soft tissues (n=23; 28.4%). We identified and purified a novel protease secreted by 50 samples (61.7%), most frequently associated with samples from deep infections and PJI (pr 0.97 and pr 0.91, respectively). Protease peptide sequencing by nano-liquid chromatography-mass spectrometry revealed a novel protease bearing 62.42% identity with ShpI, a metalloprotease secreted by Staphylococcus hyicus. CONCLUSION: This study confirms the pathogenicity of S. lugdunensis, particularly in bone and PJI. We also identified a novel metalloprotease called lugdulysin that may contribute to virulence.

An outbreak of Pneumococcal pneumonia among residents of a retirement home in France during October 2003.

We describe an outbreak of pneumonia due to Streptococcus pneumoniae in a French retirement home. Eleven residents developed pneumonia. Eight patients had positive results of urinary antigen tests. There were no further cases after the implementation of control measures, which involved isolation of and receipt of antibiotic therapy by symptomatic residents. No risk factors for transmission of S. pneumoniae were identified in this population.

Impact of the use of aminoglycosides in combination antibiotic therapy on septic shock and mortality due to Staphylococcus aureus bacteremia.

BACKGROUND: The purpose of this study was to evaluate the possible impact of antimicrobial combination regimens containing an aminoglycoside (AG) on morbidity and mortality associated with S. aureus bacteremia. METHODS: All inpatients over 18 years of age with S. aureus bacteremia were prospectively enrolled in three tertiary care hospitals in France and Ireland. Patients were included in the group "treated with AG" if they received at least 24 h of aminoglycoside therapy within 7 days after a positive blood culture in combination with an effective antimicrobial against the S. aureus. A Cox's proportional hazard model was used in univariate and multivariate survival analysis, the covariate "treatment with AG" being introduced as a time-dependent covariate. RESULTS: Nine percent of the 90 patients who received AG died because of infection versus 13% in the group that did not receive a combination including an AG (p>0.05). In the multivariate Cox model, stratified by septic shock and controlling for age and Charlson-weighted index of comorbidity, the adjusted odds ratio for death due to S. aureus infection associated with the use of AG was 0.6 [95% CI: (0.2-1.9); p=0.4]. However, AG was found to have a protective effect on septic shock occurrence [OR=0.3; 95% CI: (0.1-0.7), p=0.004], controlling for age, portal of entry not related to catheter infection, and diabetes. CONCLUSION: Although there was no decrease in mortality due to S. aureus infection in patients treated with AG therapy, we found a significant benefit of AG in preventing septic shock. This data argues for the early use of AG in patients with S. aureus bacteremia.

Suspected SARS patients hospitalised in French isolation units during the early SARS epidemic: The French experience.

During the SARS epidemic, many patients were screened according to WHO criteria but never went on to develop SARS. In May 2003, early in the epidemic, we conducted a retrospective study to describe suspected SARS patients hospitalised in France and compared them with documented cases of patients with SARS to evaluate the screening strategy. A total of 117 patients were studied. Only 3.4% had been in close contact with a SARS patient but 73.5% came from an affected area. 67.5% had fever and respiratory symptoms on their admission to hospital. 49.6% had fever and non specific symptoms. Clinical symptoms that were significantly more common among patients with SARS were fever, myalgia, dyspnoea, and nausea or vomiting. Presumed viral fever and respiratory tract infection were the most common diagnosis. Symptoms cannot be distinguished from an early stage of SARS confirming the usefulness of the WHO case definitions in isolation decision to avoid further transmission.

Suspected SARS patients hospitalised in French isolation units during the early SARS epidemic: the French experience.

During the SARS epidemic, many patients were screened according to WHO criteria but never went on to develop SARS. In May 2003, early in the epidemic, we conducted a retrospective study to describe suspected SARS patients hospitalised in France and compared them with documented cases of patients with SARS to evaluate the screening strategy. A total of 117 patients were studied. Only 3.4% had been in close contact with a SARS patient but 73.5% came from an affected area. 67.5% had fever and respiratory symptoms on their admission to hospital. 49.6% had fever and non specific symptoms. Clinical symptoms that were significantly more common among patients with SARS were fever, myalgia, dyspnoea, and nausea or vomiting. Presumed viral fever and respiratory tract infection were the most common diagnosis. Symptoms cannot be distinguished from an early stage of SARS confirming the usefulness of the WHO case definitions in isolation decision to avoid further transmission.

[Cogan's syndrome revealed by haemorrhagic glairous diarrhoea]. / Syndrome de Cogan révélé par une diarrhée glairo-sanglante.

INTRODUCTION: Cogan's syndrome is defined by the combination of non syphilitic interstitial keratitis and inner ear dysfunction, similar to Meniere's disease. OBSERVATION: Cogan's syndrome was revealed by haemorrhagic glaireous diarrhoea in a 21 year-old woman whose medical history included Hirschsprung's disease. Cerebral MRI revealed viral-like bilateral neuritis of the eighth cranial nerve, never described in the literature before. The auditory and visual disorders regressed after treatment with corticosteroids. CONCLUSION: The early diagnosis of Cogan's syndrome permits the cure of the visual and auditory and notably inner ear symptoms with corticosteroid therapy.

[Management of erysipelas in French hospitals: a post-consensus conference study]. / Prise en charge de l'érysipèle en milieu hospitalier.

INTRODUCTION: A prospective hospital-based survey on the management of bacterial dermal-hypodermal infections was conducted before the consensus conference "How should Erysipelas-Necrotic Fasciitis be managed?". The results of the survey were circulated early in 2001. To assess the eventual impact of the guidelines from the conference on hospital practices with regard to erysipelas, we conducted a new prospective survey at the end of 2002. PATIENTS AND METHODS: The questionnaire used was identical to that of the 2001 survey. It collected, anonymously, data on the clinical characteristics, supplementary examinations conducted (bacteriology, imaging), initial treatment and outcome. The questionnaire was mailed to the departments of dermatology, internal and/or infectious diseases and intensive care that had replied to the first survey (n = 124). The patients eligible for inclusion were those hospitalized between 09/01/2002 and 11/30/2002. Statistical analysis compared the results with those of the preceding survey. RESULTS: The files of 245 patients were collected that came from 41 departments (15 from university hospitals, 23 from general hospitals and 3 from military hospitals) and 235 of whom had erysipelas. For those with erysipelas, the mean age was of 65 +/- 2.5 years, the M/F sex ratio was of 0.66 and the localization was the leg in 89.5 p. 100 of cases. A Doppler of the legs was performed in 33 p. 100 of cases. The initial antibiotherapy was penicillin G in 38 p. 100 of cases and pristinamycine in 18 p. 100 (others: 44 p. 100). The route of administration was initially intravenous in 73 p. 100 of cases. An anti-coagulant was associated in 60 p. 100. The outcome was favorable in 94 p. 100 of cases, with a mean duration of hospitalization of 11.2 +/- 1.2 days and antibiotics of 17.7 +/- 1.3 days. Dopplers and the blood cultures were performed more frequently than before the consensus conference, but no difference was found in the antibiotics or adjuvant therapies. DISCUSSION: The follow-up survey showed the stability of hospital practices concerning erysipelas, notably with regard to treatment. In contrast, the clear tendency in limiting the supplementary examinations is in agreement with the consensus conference.

Human anaplasmosis presenting as atypical pneumonitis in France.

Human anaplasmosis is a febrile illness caused by Anaplasma phagocytophilum, an intracellular bacterium transmitted by Ixodes ticks in the United States and Europe. Although cough is reported in 30% of the American cases, interstitial pneumonitis has been noted only once. Of the 9 confirmed cases reported in Europe, 3 presented with atypical pneumonitis. A. phagocytophilum should be added to the list of agents responsible for interstitial pneumonitis, especially in areas where human anaplasmosis is endemic.

Double-blind randomised trial of the antiemetic efficacy and safety of ondansetron and metoclopramide in advanced breast cancer patients treated with epirubicin and cyclophosphamide.

Ondansetron was compared with metoclopramide for antiemetic efficacy in a randomised double-blind trial in 122 patients with advanced breast cancer. All patients were treated with epirubicin (greater than 50 mg/m2) and cyclophosphamide (greater than 500 mg/m2). 50 patients receiving ondansetron and 60 with metoclopramide were considered evaluable. Ondansetron was at least as effective as metoclopramide in the control of vomiting and nausea. The percentage of patients with complete plus major control was 72% (59-85%) vs. 61% (48-74%) on day 1 (P = 0.230) and 79% (67-91%) vs. 66% (53-78%) on days 2-3 after chemotherapy (P = 0.122). Over the 3-day study period, nausea was absent or mild in 60% of the patients treated with ondansetron, compared to 45% given metoclopramide (P = 0.064). No major drug-related side-effects were reported. 1 patient receiving ondansetron experienced gastrointestinal disturbance and headache. Episodes of diarrhoea, fever, hyperkinetic syndrome, fatigue, restlessness and migraine with vomiting were reported by 5 patients treated with metoclopramide. None of the changes in the biochemical or haematological parameters was attributed to the antiemetic treatments.