Treatment with plasma exchange of a pregnant woman with anti-PP1Pk alloimmunization: A case report.

The histo-blood group antigens P, P1 and Pk are a closely related set of glycosphingolipid structures expressed by red blood cells and other tissues. None of these three characters is expressed on p cells, a null phenotype that arises in the context of homozygous mutation of the A4GALT gene. Subjects with p phenotype spontaneously develop a natural alloantibody named anti-PP1Pk, which is a mixture of IgG and IgM against P1, P and Pk. While anti-P1 is a weak cold antibody with poor clinical significance, anti-P and anti-Pk antibodies are potent haemolysins responsible for severe hemolytic transfusion reactions. The rare anti-PP1Pk alloantibodies are associated with recurrent spontaneous abortion in the first trimester of gestation. P and Pk antigens are expressed at high levels on the placenta and antibodies directed against both these structures are deleterious to placental trophoblasts. Here we describe the use of plasma exchange (PEX) in a nulliparous 39-year-old woman with anti-PP1Pk antibodies and a history of repeated spontaneous early abortions and hypofertility. The patient underwent apheresis starting from the third week throughout the pregnancy and a healthy child was delivered by cesarean section at 35 WG. The newborn required only phototherapy within a few days of life. We can state that an early treatment with the only PEX has proven to be effective and safe in the management of a fetomaternal P-incompatibility caused by a high anti-PP1Pk titer (256).

Distinguishable DNA methylation defines a cardiac-specific epigenetic clock.

BACKGROUND: The present study investigates whether epigenetic differences emerge in the heart of patients undergoing cardiac surgery for an aortic valvular replacement (AVR) or coronary artery bypass graft (CABG). An algorithm is also established to determine how the pathophysiological condition might influence the human biological cardiac age. RESULTS: Blood samples and cardiac auricles were collected from patients who underwent cardiac procedures: 94 AVR and 289 CABG. The CpGs from three independent blood-derived biological clocks were selected to design a new blood- and the first cardiac-specific clocks. Specifically, 31 CpGs from six age-related genes, ELOVL2, EDARADD, ITGA2B, ASPA, PDE4C, and FHL2, were used to construct the tissue-tailored clocks. The best-fitting variables were combined to define new cardiac- and blood-tailored clocks validated through neural network analysis and elastic regression. In addition, telomere length (TL) was measured by qPCR. These new methods revealed a similarity between chronological and biological age in the blood and heart; the average TL was significantly higher in the heart than in the blood. In addition, the cardiac clock discriminated well between AVR and CABG and was sensitive to cardiovascular risk factors such as obesity and smoking. Moreover, the cardiac-specific clock identified an AVR patient's subgroup whose accelerated bioage correlated with the altered ventricular parameters, including left ventricular diastolic and systolic volume. CONCLUSION: This study reports on applying a method to evaluate the cardiac biological age revealing epigenetic features that separate subgroups of AVR and CABG.

Intrathecal antibody kinetics in neuroborreliosis: A report on three cases and a literature review.

Borreliosis is a common affliction in northern countries and its neurological manifestations often mislead trained clinicians. We present three cases of Lyme neuroborreliosis, with intrathecal synthesis of specific antibodies, lymphocytic meningitis and magnetic-resonance imaging (MRI) findings. Our description aims at illustrating the natural history of the infection, highlighting persistent intrathecal synthesis of anti-Borrelia antibodies months after treatment completion, and its clinical significance. We then review the literature on MRI findings in neuroborreliosis and the kinetics of intrathecal synthesis of specific anti-Borrelia antibodies.

Intracranial Arterial Tortuosity in Marfan Syndrome and Loeys-Dietz Syndrome: Tortuosity Index Evaluation Is Useful in the Differential Diagnosis.

BACKGROUND AND PURPOSE: The association of arterial tortuosity and connective tissue diseases is widely reported in the literature, but only a few studies were based on a quantitative evaluation of this arterial phenotype, and none of the latter examined the intracranial vasculature. The aim of this study was to evaluate the degree of intracranial arterial tortuosity in patients with Marfan syndrome and those with Loeys-Dietz syndrome, and to assess its usefulness in the differential diagnosis. MATERIALS AND METHODS: We performed a retrospective analysis of 68 patients with genetically confirmed Marfan syndrome (n = 36) or Loeys-Dietz syndrome (n = 32), who underwent at least 1 MRA of the brain at our institution. Fifty-two controls were randomly selected among patients who presented with headache and without any known comorbidity. Tortuosity indexes of 4 intracranial arterial segments were measured on a 3D volume-rendered angiogram by using the following formula: [Formula: see text]. RESULTS: Both Marfan syndrome and Loeys-Dietz syndrome showed a significantly higher tortuosity index compared with controls in all examined vessels. The tortuosity index of the vertebrobasilar system showed an excellent interrater reliability (intraclass correlation coefficient, 0.99) and was the strongest independent predictor of Loeys-Dietz syndrome in patients with connective tissue disease (P = .002), with a 97% specificity for this pathology when its value was > 60. CONCLUSIONS: The tortuosity index of intracranial arteries is an easily calculated and highly reproducible measure, which shows a high specificity for Marfan syndrome and Loeys-Dietz syndrome and may be useful in differentiating these 2 entities.

Epidemiology of Lyme borreliosis through two surveillance systems: the national Sentinelles GP network and the national hospital discharge database, France, 2005 to 2016.

BACKGROUND: Lyme borreliosis (LB) is the most frequent vector-borne disease in France. Since 2009, surveillance of LB is conducted by a sentinel network of general practitioners (GPs). This system, in conjunction with the national hospitalisation database was used to estimate the incidence and describe the characteristics of LB in France. AIM: To describe the estimated incidence and trends in GP consultations and hospital admissions for LB in France and identify risk groups and high-incidence regions. RESULTS: From 2011 to 2016, the mean yearly incidence rate of LB cases was 53 per 100,000 inhabitants (95% CI: 41-65) ranging from 41 in 2011 to 84 per 100 000 in 2016. A mean of 799 cases per year were hospitalised with LB associated diagnoses 2005-16. The hospitalisation incidence rate (HIR) ranged from 1.1 cases per 100,000 inhabitants in 2005 to 1.5 in 2011 with no statistically significant trend. We observed seasonality with a peak during the summer, important inter-regional variations and a bimodal age distribution in LB incidence and HIR with higher incidence between 5 and 9 year olds and those aged 60 years. Erythema migrans affected 633/667 (95%) of the patients at primary care level. Among hospitalised cases, the most common manifestation was neuroborreliosis 4,906/9,594 (51%). CONCLUSION: Public health strategies should focus on high-incidence age groups and regions during the months with the highest incidences and should emphasise prevention measures such as regular tick checks after exposure and prompt removal to avoid infection.

Yeasts and moulds contaminants of food ice cubes and their survival in different drinks.

AIMS: To evaluate the levels of unicellular and filamentous fungi in ice cubes produced at different levels and to determine their survival in alcoholic beverages and soft drinks. METHODS AND RESULTS: Sixty samples of ice cubes collected from home level (HL) productions, bars and pubs (BP) and industrial manufacturing plants (MP) were investigated for the presence and cell density of yeasts and moulds. Moulds were detected in almost all samples, while yeasts developed from the majority of HL and MP samples. Representative colonies of microfungi were subjected to phenotypic and genotypic characterization. The identification was carried out by restriction fragment length polymorphism (RFLP) analysis of the region spanning the internal transcribed spacers (ITS1 and ITS2) and the 5·8S rRNA gene. The process of yeast identification was concluded by sequencing the D1/D2 region of the 26S rRNA gene. The fungal biodiversity associated with food ice was represented by nine yeast and nine mould species. Strains belonging to Candida parapsilosis and Cryptococcus curvatus, both opportunistic human pathogens, and Penicillium glabrum, an ubiquitous mould in the ice samples analysed, were selected to evaluate the effectiveness of the ice cubes to transfer pathogenic microfungi to consumers, after addition to alcoholic beverages and soft drinks. All strains retained their viability. CONCLUSIONS: The survival test indicated that the most common mode of consumption of ice cubes, through its direct addition to drinks and beverages, did not reduce the viability of microfungi. SIGNIFICANCE AND IMPACT OF THE STUDY: This study evidenced the presence of microfungi in food ice and ascertained their survival in soft drinks and alcoholic beverages.

[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.

A foot tumour as late cutaneous Lyme borreliosis: a new entity?

Acrodermatitis chronica atrophicans (ACA) is the late cutaneous form of Lyme borreliosis. The early inflammatory phase manifests with a bluish-red discoloration and doughy swelling of the skin. The atrophic phase represents a late-phase process with red discoloration, and a thin and wrinkled appearance of the skin. We present a patient who exhibited a previously undescribed form of late cutaneous Lyme borreliosis (LCLB) with a foot tumour. A 64-year-old woman had a large tumorous lesion on the right sole. The tumour size and deformation of the feet made wearing shoes difficult. On skin histology, a granulomatous lymphohistiocytic infiltrate with plasma cells was noticed. In fact, the patient recalled tick bites 2 or 3 years before. Borrelia burgdorferi (Bb) serology was highly positive and a polymerase chain reaction analysis on the skin biopsy detected Bb sensu lato, genospecies B. afzelii. We diagnosed LCLB and antibiotics were prescribed. On the more recent examination, the tumour had totally disappeared; the skin was atrophic and dry with only few scales. We report an atypical case of European LCLB, suggesting that ACA is not the only possible presentation of LCLB. The diagnosis of ACA is often clinically missed for months or years, and may be mistaken at the inflammation phase for vascular disorders, erysipelas or bursitis/arthritis, and at the atrophic phase for lichen sclerosus atrophicus, morphoea or anetoderma. To our knowledge, no such tumorous LCLB has previously been described.

Impact of serodiagnosis on the management of Lyme borreliosis at Angers University Hospital.

INTRODUCTION: Lyme borreliosis (LB) is an emerging arthropod-borne disease the diagnosis of which is made on clinical and biological data. We assessed the Angers University Hospital physicians' management of LB, in case of positive serology, and estimated their compliance to European recommendations (EUCALB). METHODS: We retrospectively included 75 cases with positive ELISA serologies confirmed by Western-Blot, performed at the Angers University Hospital between 2008 and 2012. RESULTS AND DISCUSSION: There were 4 cases of early localized phase, 26 of early-disseminated phase (including 17 cases of neuroborreliosis), and one case of late phase. The curative management complied with EUCALB guidelines in 28 cases out of 31. CONCLUSION: Serology remains a reference diagnostic tool for LB, as long as the practitioner is aware of the main clinical and biological criteria.

[Prospective assessment of children with pervasive developmental disorder after 2 years of day-hospital treatment]. / Évaluation prospective d'enfants atteints d'un trouble envahissant du développement après deux ans de prise en charge en hôpital de jour.

The treatment of children with pervasive developmental disorders (PDD) has not been systematically assessed in French day-care units. In this prospective study, 11 children with a diagnosis of PDD were followed up for 2years in a day-care unit in the Marseille university hospital. The treatment they received is based on an initial assessment by the "Centre Ressources Autisme" (CRA PACA) and further included a continued observation of the child and an assessment of the child's abilities and needs. This treatment used various therapeutic approaches 10h weekly and also included parental counseling and coordinated work with schools. Treatment in our day-care unit can be categorized as eclectic, non-intensive therapy. It is based on methods such as TEACCH (Treatment and Education of Autistic and related Communication handicapped Children), Floor Time Play, speech and language therapy, developmental therapy, and psychotherapy. International studies on intensive behavioral therapies suggest that this treatment is superior to non-behavioral and/or non-intensive treatment. They suggest its efficiency is due both to the nature of the treatment (behavioral) and to its intensity (more than 25h a week). In this study, the CRA diagnosed children using the ADI and ADOS. The 11 children (mean age, 3years 5months) were tested twice, with the Vineland and CARS scales. The first assessment was on admission to the day hospital and the second was 2years later. The results showed developmental progress with a mean increase of 13.5 months at the Vineland Scale, and a decrease of the autism severity score on the CARS. The treatment presented here proves to be efficient; if compared to similar results in international studies, we obtained better results than their eclectic intensive or non-intensive treatment comparison group.

[Cognitive profiles in pervasive developmental disorders]. / Les profils cognitifs dans les troubles envahissants du développement.

OBJECTIVE: This study investigated the cognitive skills in pervasive developmental disorders (PDD). METHODOLOGY: Two groups of children participated in this study, 39 individuals with autism and 18 individuals with Asperger syndrome. Each participant was assessed by the Wechsler scales: WPPSI-III, WISC-III or WISC-IV. RESULTS: Children with Asperger syndrome have VIQ more than PIQ and the children with autism have VIQ less than PIQ. The performances in "block design" task vary according to the cognitive level and not according to the PDD type. The high-functioning autistic children show high performance in "block design" task. Children with Asperger syndrome revealed impairments in the "understanding of social situations" task. DISCUSSION: Individuals with autism have a verbal intelligence quotient lower than individuals with an Asperger syndrome. Several hypotheses have tried to explain verbal differences between children with autism and Asperger syndrome. A first hypothesis proposed a developmental convergence between these two groups. A second hypothesis suggested that communication and social interaction impairments could be implicated in verbal skills. A third hypothesis supported that individuals with Asperger syndrome could develop a specific cognitive style. Children with autism have spatial and perceptive capacities better than verbal capacities. These performances could be interpreted as the expression of a specific cognitive style based on the visual analysis of the detail. CONCLUSION: The low-functioning children with autism have a cognitive profile with PIQ more than VIQ and high skills in spatial organization. The high-level children with autism have a cognitive profile with PIQ more than VIQ and high skills in spatial abstraction. Children with Asperger syndrome have a profile VIQ more than PIQ profile, they are particularly good in verbal learning notably vocabulary.

Lyme endocarditis.

Lyme borreliosis is a common tick-borne disease with a wide variety of clinical manifestations. Cardiac involvement has been reported during both the acute phase (atrioventricular block, pericarditis) and the chronic stage (dilated cardiomyopathy), but is rare (<5%). Here we describe the first case of Borrelia afzelii Lyme endocarditis, in a 61-year-old man living in an endemic area of France. The diagnosis was confirmed by detection of B. afzelii DNA in the mitral valve by specific real-time PCR. He was treated empirically with amoxicillin for 6 weeks and remains well 12 months later.

Identification and genotyping of Mycobacterium tuberculosis complex species by use of a SNaPshot Minisequencing-based assay.

The aim of the present study was to investigate the use of the SNaPshot minisequencing method for the identification of Mycobacterium tuberculosis complex (MTBC) isolates to the species level and for further genotyping of M. tuberculosis isolates. We developed an innovative strategy based on two multiplex allele-specific minisequencing assays that allowed detection of eight species-specific and eight lineage-specific single nucleotide polymorphisms (SNPs). Each assay consisted of an eightplex PCR amplification, followed by an eightplex minisequencing reaction with the SNaPshot multiplex kit (Applied Biosystems) and, finally, analysis of the extension products by capillary electrophoresis. The whole strategy was developed with a panel of 56 MTBC strains and 15 negative controls. All MTBC strains tested except one M. africanum clinical isolate were accurately identified to the species level, and all M. tuberculosis isolates were successfully further genotyped. This two-step strategy based on SNaPshot minisequencing allows the simultaneous differentiation of closely related members of the MTBC, the distinction between principal genetic groups, and the characterization of M. tuberculosis isolates into one of the seven prominent SNP cluster groups (SCGs) and could be a useful tool for diagnostic and epidemiological purposes.

Species of Borrelia burgdorferi complex that cause borrelial lymphocytoma in France.

BACKGROUND: Only about 30 cases of borrelial lymphocytoma (BL) with identification of the causative species of Borrelia have been published to date, mainly from Eastern or Central European countries. OBJECTIVES: To identify the species of B. burgdorferi complex responsible for BL in France. METHODS: Nine patients with BL acquired in France and for whom skin samples were sent to the national reference centre laboratory between 1994 and 2007 were included in this retrospective study. Direct detection of Borrelia in skin samples was made by polymerase chain reaction targeting the fla gene. Culture was performed when technically possible, and identification of each species was made by hybridization of a fragment of the fla gene with a panel of species-specific oligonucleotides. RESULTS: Borrelia afzelii was identified in three cases, B. garinii and B. burgdorferi sensu stricto in one case each. Culture was positive in only one case (B. garinii). CONCLUSIONS: Borrelia afzelii seems to be the predominant species of Borrelia responsible for BL in France, as already reported in other European countries.

[Acute myelitis and Lyme disease]. / Myélite aiguë et neuroborréliose.

INTRODUCTION: Acute myelitis accounts for 4 to 5 percent of all cases of neuroborreliosis. In the literature, simultaneous spinal MRI and cerebrospinal fluid (CSF) investigations are presented for only 8 cases. We describe here 3 cases of acute Lyme myelitis. METHOD: In a cohort of 45 patients with neuroborreliosis, diagnosed between January 1998 and January 2005, 3 had acute myelitis. Clinical, biological and radiological data were studied. CASE REPORTS: The three patients had motor, sensorial and sphincter involvement. Extra-spinal involvement, such as fever and headache for one, facial nerve palsy for the second and subarachnoid hemorrhage for the third, was also noted. Pleocytosis varied from 10 to 520 white cells per mm3. Lyme serology was positive in CSF for all. Intrathecal anti-Borrelia antibody index was positive or intermediate for all three patients. Spinal cord MRI revealed a large hyperintense zone involving more than 3 vertebral segments. Myelitis was central, posterior or transverse in the axial plane. The clinical course was favorable after a three-week course of appropriate antibiotics. CONCLUSION: These 3 cases and the others from the literature show the diversity of the clinical and radiological features of acute myelitis: transverse, central or posterior myelitis. Thus, Lyme serology in CSF in indicated for patients presenting acute myelitis, particularly in endemic areas.

Relevance of the antibody index to diagnose Lyme neuroborreliosis among seropositive patients.

BACKGROUND: No consensual criteria exist to diagnose neuroborreliosis. The intrathecal anti-Borrelia antibody index (AI) is a necessary criterion to diagnose neuroborreliosis in Europe, but not in the United States. Previous studies to determine the diagnostic value of the AI found a sensitivity ranging from 55% to 80%. However, these studies included only typical clinical cases of meningitis or meningoradiculitis, and none had a control group with CSF anti-Borrelia antibodies. METHODS: We studied a sample of 123 consecutive patients with clinical signs of neurologic involvement and CSF anti-Borrelia antibodies. We determined the AI for all patients and a final diagnosis was made. Patients were then divided into three groups (neuroborreliosis, possible neuroborreliosis, control). RESULTS: Thirty of the 40 patients with neuroborreliosis had a positive AI (AI sensitivity = 75%). Two of the 74 patients with another neurologic diagnosis had a positive AI (AI specificity = 97%). CONCLUSION: The antibody index has a very good specificity but only moderate sensitivity. Given the lack of consensual criteria for neuroborreliosis and the absence of a "gold standard" diagnostic test, we propose pragmatic diagnostic criteria for neuroborreliosis, namely the presence of four of the following five items: no past history of neuroborreliosis, positive CSF ELISA serology, positive anti-Borrelia antibody index, favorable outcome after specific antibiotic treatment, and no differential diagnosis. These new criteria will need to be tested in a larger, prospective cohort.

[Role of biological assays in the diagnosis of Lyme borreliosis presentations. What are the techniques and which are currently available?]. / Place des méthodes biologiques dans le diagnostic des différentes manifestations de la borréliose de Lyme. Quelles sont les techniques? Quelles sont celles disponibles actuellement?

The biological diagnosis of Borrelia burgdorferi sensu lato infection is usually made by antibody detection in patient sera. Thus, serological testing (Elisa, immunoblotting) is essential for a biological diagnosis. Specific antibody detection is usually done in serum and CSF of patients suspected of Lyme borreliosis. Laboratories must follow European recommendations to validate these assays in routine practice. Antibody detection lacks sensitivity in the early cutaneous phase of the infection. Therefore, serological testing is not recommended for the diagnosis of erythema migrans. The interpretation of serology must take into account the variability of Elisa sensitivity and specificity and the lack of standardization for Western-blotting in Europe. Besides these indirect diagnosis techniques, there is also direct detection of spirochetes by culture or by in vitro DNA amplification but these require adequate samples. These molecular tests must not be performed routinely, but only for specific clinical situations and in specialized laboratories only.

[Autism and mental retardation: a study of the early social communication]. / Autisme et retard mental: étude de la communication sociale précoce.

OBJECTIVE: To determine developmental communication profiles in young autistic children with mental retardation. METHODS: A group of 19 autistic children (mean age=43 months) were matched with a group of 11 mentally retarded children (mean age=39 months) on mental age (17,6 months). All of these children were without speech (less than 5 words of vocabulary). Communication skills were assessed with the Guidetti-Tourrette scales (ECSP), French adaptation of the Seibert-Hogan scales. RESULTS: Autistic children displayed a much lower score than mentally retarded children in the 3 functions of early social communication (behavior regulation, social interaction and joint attention). The developmental communication profiles was the same in the 2 groups. DISCUSSION: The results showed evidence of distortion in autistic children development: they displayed important deficits in communication skills, in comparison with cognitive skills. Autistic children mainly displayed requesting gestures: they used adults to help them to reach a goal, instead of regarding them as social partners. However, young children who have mental age less than 18 months mainly use the same functions of communication, with or without autistic trouble. CONCLUSIONS: There is a same developmental sequence in communication skills in young children, with or without autistic trouble.