Epidemiology of invasive early-onset neonatal infection in a French administrative district: A 10-year population-based study.

BACKGROUND: In light of the pending update of the French guidelines for the management of neonatal infections, knowing the current epidemiology of early-onset neonatal infection (EONI) is essential. OBJECTIVES: The aim of this study was to assess the current epidemiology of a French administrative district population of proven EONI, including umbilical cord blood procalcitonin levels. METHODS: We conducted a retrospective population-based study in the Nantes metropolitan area. We included all infants treated for proven EONI in the maternity, neonatology, and intensive care wards between 1 January 2006 and 31 December 2015 in the Nantes University Hospital. RESULTS: Among the 140,502 children born during the study period, 61 cases of EONI were documented. The overall incidence of confirmed EONI was 0.43/1000 live births, with 0.23/1000 GBS (group B streptococcus) infections and 0.08/1000 Escherichia coli infections. The majority of infected newborns were full-term or late-preterm infants (67% were≥34 weeks of gestation), 88% had symptoms of EONI in the first 24h of life, most of which were respiratory. The mortality rate was 8% (in premature infants). Available in 51% of the population, the cord blood PCT value could contribute to an earlier diagnostic screening in 10% of cases but with a very low sensitivity. CONCLUSIONS: The incidence of confirmed EONI is low in this French district. The diagnostic value of PCT umbilical blood cord should be assessed based on further studies before confirming its value. We suggest that a national registry of these rare but serious cases of EONI could contribute to monitoring the epidemiological progression as well as to optimizing our diagnostic and therapeutic strategies.

Surgical and medical antibiotic prophylaxis.

Surgical site infections are the leading cause of perioperative morbidity and mortality as well as increased costs following surgery. Among preventive measures, antibiotic prophylaxis, when indicated, significantly decreases these risks. Adult and pediatric guidelines have recently been published (1,2). Specific pediatric data are scarce, but adult recommendations can be used by extrapolation except for neonates. For procedures that may warrant antimicrobial prophylaxis, agents of choice are frequently first-generation cephalosporins such as cefazolin, that are not currently used in curative treatment, with an appropriate dosage. Administration of an antimicrobial agent within 1 hour before surgery is often sufficient. Continuation for more than 24 hours is exceptionally advised.

Preoperative Staphylococcus aureus Carriage and Risk of Surgical Site Infection After Cardiac Surgery in Children Younger than 1 year: A Pilot Cohort Study.

Surgical site infections (SSI) increase length of stay, morbidity, mortality and cost of hospitalization. Staphylococcus aureus (SA) carriage is a known risk factor of SSI in adults, but its role in pediatrics remains uncertain. The main objective of this pilot prospective monocentric cohort study was to describe the prevalence of SA colonization in children under 1 year old before cardiac surgery. The secondary objectives were to compare the incidence of SSI and other nosocomial infections (NI) between preoperative carriers and non-carriers. From May 2012 to November 2013, all children <1 year old undergoing cardiac surgery under cardiopulmonary bypass underwent preoperative methicillin-resistant (MRSA) and methicillin-sensitive SA (MSSA) screening using real-time PCR. The only exclusion criterion was invalid PCR. All patients were followed up to 1 year after the surgery regarding SSI and other nosocomial infections. Among the 68 studied patients, SA colonization prevalence was 26.5%, comprising 23.5% MSSA and 2.9% MRSA. There was no significant difference between colonized and non-colonized children regarding SSI rate (16.7 vs 20%; p = 0.53), but ventilator-associated pneumonia rate was significantly higher among the SA carriers (22.2 vs 2%; p < 0.05). The colonization rate was different depending on the age of the patients (p < 0.05). This pilot study highlights that colonization with MSSA is frequent whereas MRSA prevalence is low in our population. In this cohort, there was no association between SA colonization and SSI incidence but further studies are needed to analyze this association.

[Diagnosis and management of chronic kidney disease in children: Guidelines of the French Society of Pediatric Nephrology]. / Diagnostic et prise en charge de la maladie rénale chronique de l'enfant : recommandations de la Société de néphrologie pédiatrique (SNP).

These guidelines are intended to assist physicians in the care of children with chronic kidney disease (CKD), defined in children as in adults, regardless of its cause. Often silent for a long time, CKD can evolve to chronic renal failure or end-stage renal disease. Its management aims at slowing disease progression and treating CKD complications as soon as they appear. The different aspects of pediatric CKD care are addressed in these guidelines (screening, treatment, monitoring, diet, quality of life) as proposed by the French Society of Pediatric Nephrology. Highly specialized care provided in the hospital setting by pediatric nephrologists is not detailed.

Cervicofacial non-tuberculous mycobacteria: A report of 30 cases.

BACKGROUND: Mycobacterial infection is the most common cause of cervical granuloma, implicating either a tuberculous or a non-tuberculous mycobacterium (NTM). NTM is a ubiquitous organism, found in soil, water, food, etc. The most frequently implicated is Mycobacterium avium-intracellular. Most authors agree that NTM is increasingly isolated, due to a decrease in vaccination rates. Initial diagnosis is difficult and management is not clearly codified. METHODS: A retrospective study conducted in the University Hospital of Nantes, France, between 2005 and 2014, included all patients treated for head and neck NTM lymphadenitis. The research was conducted on the database of the institution's bacteriology department. Population, history, symptoms and diagnostic features were noted. Treatment, surgical complications, adverse reactions to antibiotics, patient adherence, antibiotic therapy duration, time to remission and prognosis were analyzed. RESULTS: Between 2005 and 2014, 30 patients were diagnosed with head and neck NTM lymphadenitis: 17 female, 13 male; mean age at diagnosis, 4.5 years. Locations were submandibular (n=16), parotid, (n=7), cervical (n=5), parapharyngeal (n=4) and, for 1 patient, in the auricle concha. Eight patients received first-line surgical treatment, which was effective in 75% of cases, 2 patients requiring additional antibiotic therapy. Twenty-two patients were treated with first-line antibiotherapy, which was effective in 90% of cases. There were no relapses at a mean 32 weeks' follow-up. CONCLUSIONS: Total resection of all affected nodes and infiltrated subcutaneous fatty tissue is the treatment of choice. Drug therapy (including at least a macrolide) seems indicated only in case of incomplete resection or if surgery would entail functional and/or esthetic risk. Increased incidence, since BCG vaccination was stopped, will continue to confront the practitioner with an infantile disease in which management must be multidisciplinary.

Diagnostic and medical strategy for renovascular hypertension: report from a monocentric pediatric cohort.

UNLABELLED: Renovascular hypertension accounts for 5-10 % of hypertension cases in children; there is currently no consensus on treatment. Here, we report on our clinical experience with this disease and outline the different pathways in which to investigate it. We report retrospectively on ten children diagnosed with renovascular hypertension at the University Hospital of Nantes from 2001 to 2012. The main findings were obtained by fortuitous screening of children aged 2 months to 14 years old with neurofibromatosis (n = 2) and fibromuscular dysplasia (n = 8). The hypertension was always severe yet asymptomatic. Lesions were complicated in nine out of ten cases and included bilateral, multiple, mid-aortic syndrome and aneurysm. Doppler ultrasound associated with computed tomography allowed for a precise diagnosis in seven out of ten cases. Where ambiguities persisted, they were highlighted by arteriography, the gold standard investigation. Medical treatment was insufficient, leading to invasive procedures in nine out of ten children: 2 nephrectomies, 2 autotransplantations, and 21 repetitive percutaneous transluminal angioplasties. After invasive procedures, blood pressure control improved in four cases and was resolved in three. CONCLUSION: Arteriography remains to be the gold standard technique for renovascular hypertension in children and can be combined with angioplasty when medical treatment is rendered obsolete. The role of computed tomography is controversial. Despite the heterogeneity of the children studied, we present a general medical and therapeutic management pathway for the treatment of this disease.

[Antibioprophylaxis in pediatric surgery: how to harmonize practices?]. / Antibioprophylaxie chirurgicale : les grands principes, état des lieux et exemple d'harmonisation des pratiques.

Surgical antibiotic prophylaxis has demonstrated its effectiveness in reducing surgical site infections. Existing recommendations for adults are however subject to poor compliance. Surgical antibiotic representing a significant proportion of antibiotic prescriptions, it is then important to respect its general principles (narrow spectrum, short duration, choosing molecules different than the ones used in therapeutics, etc.) to limit its impact on the bacterial ecology. A brief survey of pediatric practices in five French university hospitals has allowed us to highlight some significant changes in terms of choice of molecule or duration. Through the experience of harmonizing practices at the University Hospital of Nantes, we showed that the development of national guidelines is a prerequisite to harmonize practices but must be accompanied by a multidisciplinary reflexion within each hospital in order to improve their acceptability and application.

[Antibioprophylaxis in pediatric orthopedic surgery]. / Antibioprophylaxie en chirurgie orthopédique pédiatrique.

The pediatric osteo-articular surgery has certain characteristics that justify specific recommendations (spine surgery, reconstruction after tumorectomy). The children with the higher risks of surgical site infection are children with comorbidities or undergoing prolonged surgery. Bacteria targeted by antibioprophylaxis are those of the skin flora, most particularly Staphylococcus aureus. Cefazolin is the antibiotic of choice for osteoarticular surgery. Detection and decontamination of Staphylococcus aureus can be discussed especially in centers with strong incidence of surgical site infection caused by MRSA. The adaptation of the antibioprophylaxis to the urinary flora of patients with neuromuscular disease can also be justified on a case before spine surgery.

[Neonatal surgical antibioprophylaxis: which target? which propositions?]. / Antibioprophylaxie en chirurgie néonatale : quelle est la cible ? quelles propositions ?

Neonatal surgical antibioprophylaxis must take into account the specificities of this life period, as immunological immaturity, microbiotal implantation and antibiotic treatment pharmacokinetics properties. Very few data are available, but it seems that coagulase negative Staphylococcus (CNS) is the most reported bacteria, in intestinal tract at the time of surgery as well as in surgical site infections. Usual vertical transmission bacteria as S. agalactiae or E. coli K1 are rarely documented. The antibioprophylaxis treatment must consider the age and the environmental context of the newborn; first or second generation cephalosporins sometimes in association with vancomycin seem appropriate in this context. It is now urgent to conduct clinical trials in order to validate theses propositions.

Failure of bortezomib to cure acute antibody-mediated rejection in a non-compliant renal transplant patient.

Bortezomib has appeared recently as a potential active treatment for acute AMR for few years. We reported a patient who received two courses of bortezomib for the treatment of an acute AMR associated with de novo HLA DSA that occurred 18 months after renal transplantation because of non-compliance. Graft biopsy revealed features of acute humoral rejection with plasmocyte infiltration and C4d staining. Bortezomib was associated with corticosteroid pulses, IVIgs, and PP. Despite this rapid management, the patient lost his graft and carried on dialysis. Bortezomib therapy in addition to current therapy of AMR is not always effective in the treatment for late acute AMR in renal transplantation. We discuss on the place of such a treatment and other therapeutic strategies in this indication.

The MLL recombinome of acute leukemias in 2013.

Chromosomal rearrangements of the human MLL (mixed lineage leukemia) gene are associated with high-risk infant, pediatric, adult and therapy-induced acute leukemias. We used long-distance inverse-polymerase chain reaction to characterize the chromosomal rearrangement of individual acute leukemia patients. We present data of the molecular characterization of 1590 MLL-rearranged biopsy samples obtained from acute leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and novel TPGs identified. All patients were classified according to their gender (852 females and 745 males), age at diagnosis (558 infant, 416 pediatric and 616 adult leukemia patients) and other clinical criteria. Combined data of our study and recently published data revealed a total of 121 different MLL rearrangements, of which 79 TPGs are now characterized at the molecular level. However, only seven rearrangements seem to be predominantly associated with illegitimate recombinations of the MLL gene (≈ 90%): AFF1/AF4, MLLT3/AF9, MLLT1/ENL, MLLT10/AF10, ELL, partial tandem duplications (MLL PTDs) and MLLT4/AF6, respectively. The MLL breakpoint distributions for all clinical relevant subtypes (gender, disease type, age at diagnosis, reciprocal, complex and therapy-induced translocations) are presented. Finally, we present the extending network of reciprocal MLL fusions deriving from complex rearrangements.

[Therapeutics strategies for the management of urinary tract infection in children]. / Stratégies thérapeutiques dans les infections urinaires du nourrisson et de l'enfant.

Urinary tract infections is one of the most common bacterial infections in pediatrics The increasing involvement of multiresistant bacteria including E. coli producing extended spectrum ß-lactamase (ESBL) makes its management difficult. The purpose of this article is to evaluate the state of the art and to propose ways of thinking about the management of E. coli urinary tract infection in children. The current percentage (less than 10%) of E. coli strains resistant to third generation cephalosporins and the relative efficiency of the latter, should not led to an immediate change of our protocols. Nevertheless, we should verify as soon as possible susceptibility of E. coli responsible for urinary tract infections and consider other therapeutic options for initial therapy and adaptation after obtaining antibiogram. The use of an aminoglycosid as initial treatment seems very interesting. Aminoglycosides have a very good distribution in the renal parenchyma and are still working on the majority of ESBL-producing bacteria. A rapid oral relay after 48 to 72 hours may be proposed according to the results of the susceptibility with either cotrimoxazole, cefixime, ciprofloxacin or an association cefixime-amoxicilline/clavulanate. The treatment of cystitis due to ESBL E. coli is much less problematic given the good urinary beta-lactam antibiotics diffusion. If clinical improvement occurs, even if antibiogram shows that the strain is resistant to the antibiotic prescribed, it is usually unnecessary to change treatment.

[Comparison of two protocols of febrile urinary tract infection management in children]. / Comparaison de deux protocoles de prise en charge des infections urinaires fébriles de l'enfant.

PURPOSE: To compare two first febrile urinary tract infection (UTI) management protocols with regards to the diagnosis of high-grade vesicoureteral reflux (VUR) and cost. METHODS: This study compared two cohorts of children under 16 years of age, admitted for a first episode of febrile UTI. The first group (in 2005) was managed according to previous recommendations (IV treatment and cystography performed for all children under 3 years of age). The second group (in 2006) was managed according to age and procalcitonin level. High-grade VUR frequency, UTI recurrence, hospitalization rate, and cost were compared between the two cohorts. RESULTS: A total of 225 children were included in 2005 and 116 in 2006. High-grade VUR was found in 6.2 and 9.5% of the patients in 2005 and 2006, respectively (P=0.274). There was no statistically significant difference in the UTI recurrence rate between the two cohorts (5.3% in 2005 and 8.6% in 2006; P=0.237). The mean cost of an episode of febrile UTI was not significantly different in 2005 and 2006 (€2235 in 2005, €2256 in 2006; P=0.902), but was lower for children older than 6 months in 2006 (€1292 versus €1882 in 2005; P=0.0042). CONCLUSION: Our management protocol for a first febrile UTI episode in children based on procalcitonin levels seems to be suitable for the diagnosis of high-grade VUR. The hospitalization rate and the mean cost of management for children older than 6 months of age was significantly reduced in 2006. The management guidelines for a first occurrence of febrile UTI in children should be reconsidered.

Mortality in pediatric renal transplantation: a study of the French pediatric kidney database.

OBJECTIVE AND METHODS: To assess patient survival in pediatric renal transplantation, we retrospectively reviewed 573 transplants in 553 patients, registered from 1995 to 2005. RESULTS: Mean age at transplantation was 9.9 years. Patient survival at 1, 5 and 10 years was respectively 99%, 97% and 96%. Death occurred at a median time of 2.6 years after transplantation. Long-term patient survival was significantly lower in recipients younger than 5 years old. Seventeen patients (3.1%) died. Two deaths occurred while under maintenance dialysis. Among the remaining patients, the two main causes of death were infections (33%) and malignancies (27%). Interestingly, initial disease-related complications were a major cause of death (34%). CONCLUSION: A low mortality rate was observed, with the majority of deaths due to malignancies and infections, and with a notable participation of complications related to the initial disease. No impact of cardiovascular disease was noted with the given follow-up period. Improvements in managing immunosuppression may contribute to reducing mortality in pediatric renal transplantation.

Specific cytogenetic abnormalities are associated with a significantly inferior outcome in children and adolescents with mature B-cell non-Hodgkin's lymphoma: results of the FAB/LMB 96 international study.

Clinical studies showed that advanced stage, high LDH, poor response to reduction therapy and combined bone marrow and central nervous system disease are significantly associated with a decreased event-free survival (EFS) in pediatric mature B-cell non-Hodgkin's lymphoma (B-NHL) treated on FAB/LMB96. Although rearranged MYC/8q24 (R8q24) is characteristic of Burkitt lymphoma (BL), little information is available on other cytogenetic abnormalities and their prognostic importance. We performed an international review of 238 abnormal karyotypes in childhood mature B-NHL treated on FAB/LMB96: 76% BL, 8% Burkitt-like lymphoma, 13% diffuse large B-cell lymphoma (DLBCL). The main BL R8q24-associated chromosomal aberrations were +1q (29%), +7q and del(13q) (14% each). The DLBCL appeared heterogeneous and more complex. Incidence of R8q24 (34%) was higher than reported in adult DLBCL. The prognostic value of cytogenetic abnormalities on EFS was studied by Cox model controlling for the known risk factors: R8q24, +7q and del(13q) were independently associated with a significant inferior EFS (hazard ratio: 6.1 (P=0.030), 2.5 (P=0.015) and 4.0 (P=0.0003), respectively). The adverse prognosis of R8q24 was observed only in DLBCL, whereas del(13q) and +7q had a similar effect in DLBCL and BL. These results emphasize the significant biological heterogeneity and the development of cytogenetic risk-adapted therapy in childhood mature B-NHL.

Hypokalaemic periodic paralysis type 2 caused by mutations at codon 672 in the muscle sodium channel gene SCN4A.

Hypokalaemic periodic paralysis (hypoPP) is an autosomal dominant muscle disorder characterized by episodic attacks of muscle weakness associated with a decrease in blood potassium levels. Mutations in the gene encoding the skeletal muscle voltage-gated calcium channel alpha-1 subunit (CACNL1A3) account for the majority of cases. Recently, mutations in the gene coding for the skeletal muscle voltage-gated sodium channel alpha subunit (SCN4A) have been reported in a small number of hypoPP families. In order to determine the relative frequency of the CANCL1A3 and SCN4A mutations in a large population of hypoPP patients, and to specify the clinical and pathological features associated with each of them, we searched for mutations in 58 independent hypoPP index cases. We detected the causative mutation in 45 cases: 40 were linked to the CACNL1A3 gene and five to the SCN4A gene. One mutation has not been described before. Some remarkable clinical features were observed in a large hypoPP family carrying an SCN4A mutation: a complete penetrance in men and women, an early age at onset, postcritic myalgias and an increased number and severity of attacks induced by acetazolamide. A muscle biopsy, performed in two members of this family, revealed a peculiar myopathy characterized by tubular aggregates. In contrast, vacuoles were predominant in muscles from hypoPP patients carrying CACNL1A3 mutations. Our findings point to the usefulness of a molecular characterization of hypoPP patients in clinical practice. They also provide new clues for understanding the mechanisms behind functional and structural alterations of the skeletal muscle in hypoPP.

Multiple lymphomatous polyposis of the gastrointestinal tract. An extensive histopathologic and immunohistochemical study of 12 cases.

BACKGROUND: Multiple lymphomatous polyposis (LP) is a rare entity, characterized by multiple polypoid tumors involving several segments of the gastrointestinal tract. METHODS: In this large retrospective series of 12 patients with LP, histologic and immunohistochemical features were investigated from patients with multiple biopsy samples from each site (500 gastrointestinal biopsies). Immunohistochemistry was performed on paraffin embedded biopsies from 12 patients and on frozen tissue biopsies from 8 patients, for each of whom at least two different anatomic sites were studied. RESULTS: Histologic features always were characterized by nodules located in mucosa and submucosa composed of lymphomatous, small cleaved cells. B-cell phenotype of the neoplastic cells was the same phenotype as adult mantle-zone cells or fetal follicle cells (frequent coexpression of surface IgM and surface IgD, and weak expression of CD5, CD35+, CDw32+, and CD23-). Tested cases expressed bcl-2. Five to 20% of LP cells were positive for the monoclonal antibody Ki-67. Five patients died within 5-32 months after diagnosis. Frequent extradigestive sites were also identified. There were two unique findings: five cases with digestive tract lymphoepithelial lesions (LEL), and one secondary transformation to large B-cell malignant lymphoma. CONCLUSIONS: To the authors' knowledge, this is the largest series so far of LP studied with immunohistochemistry on frozen sections. Mantle-cell B cell phenotype of the nodular monotonous, small cleaved cells is confirmed. This entity may be classified as mantle-cell lymphoma with a similar aggressive clinical course, and treated as a high grade B-cell lymphoma. The authors know of no such LEL that has been reported previously, and secondary transformation has been described only briefly in one case.