Amniotic Fluid Infection Syndrome and Abruptio Placentae

The incidence of amniotic fluid infection syndrome, as assessed by the presence of an acute inflammatory infiltrate of the placenta, umbilical cord, and membranes at birth, was 23.3% in pregnancies complicated by severe abruptio placentae. This was not significantly higher than that noted in uncomplicated pregnancies. These data therefore fail to support the proposal that amniotic fluid infection predisposes to placental abruption.     

Amniotic Infection Syndrome: Nosology and Reproducibility of Placental Reaction Patterns

Clinically responsive placental examination seeks to provide useful information regarding the etiology, prognosis, and recurrence risk of pregnancy disorders. The purpose of this study was to assemble and validate a complete set of the placental reaction patterns seen with amniotic fluid infection in the hope that this might provide a standardized diagnostic framework useful for practicing pathologists. Study cases (14 with amniotic fluid infection, 6 controls) were reviewed blindly by six pathologists after agreement on a standard set of diagnostic criteria. After analysis of initial results, criteria were refined and a second, overlapping set of cases were reviewed. Majority vote served as the gold standard. Grading and staging of maternal and fetal inflammatory responses was found to be more reproducible using a two- versus three-tiered grading system than a three- versus five-tiered staging system (overall agreement 81% vs. 71%). Sensitivity, specificity, and efficiency for individual observations ranged from 67–100% (24/30 > 90%). Reproducibility was measured by unweighted kappa values and interpreted as follows: < 0.2, poor; 0.2–0.6, fair/moderate; > 0.6, substantial. Kappa values for the 12 lesions evaluated in 20 cases by the six pathologists were: acute chorioamnionitis/maternal inflammatory response (any, 0.93; severe 0.76; advanced stage, 0.49); chronic (subacute) chorioamnionitis (0.25); acute chorioamnionitis/fetal inflammatory response (any, 0.90; severe, 0.55; advanced stage, 0.52); chorionic vessel thrombi (0.37); peripheral funisitis (0.84); acute villitis (0.90); acute intervillositis/intervillous abscesses (0.65), and decidual plasma cells (0.30). Adoption of this clearly defined, clinically relevant, and pathologically reproducible terminology could enhance clinicopathologic correlation and provide a framework for future clinical research.     

Aspirin Treatment for Neonatal Infectious Endocarditis

We describe a term female neonate with Serratia marcescens endocarditis. Despite adequate antibiotic therapy for 8 days, the bacteremia persisted and there was an increase in vegetation size. Treatment with aspirin was initiated, with resolution of the bacteremia and a gradual decrease in vegetation size. We conclude that in neonatal endocarditis, aspirin may be beneficial additional treatment.     

Neonatal Cytomegalovirus Infection with Pancreatic Cystadenoma and Nephrotic Syndrome

An infant with microcephaly and generalized cytomegalovirus infection presented with two unusual complications: cystadenoma of the pancreas and minimal change nephrotic syndrome (MCN). Possible pathogenetic mechanisms of these conditions are discussed.     

Pediatric Renal Cell Carcinomas with Xp11.2 Rearrangements Are Immunoreactive for hMLH1 and hMSH2 Proteins

Alveolar soft part sarcoma and pediatric renal cell carcinoma share a similar chromosomal abnormality, t(X;17)(p11.2;q25). Recently, it has been suggested that the inactivation of DNA mismatch repair genes hMLH1 and hMSH2 may play an additional role in the pathogenesis of alveolar soft part sarcoma. Immunohistochemical expression of the proteins hMLH1 and hMSH2 is indicative of the activation status of the corresponding genes. We performed immunohistochemistry for hMLH1 and hMSH2 in 4 cases of pediatric renal cell carcinomas with Xp11.2 rearrangements. All cases showed nuclear immunoreactivity for both proteins, although the staining was patchy. Our study demonstrates that inactivation of the DNA mismatch repair genes hMLH1 and hMSH2 does not appear to play a role in the tumorigenesis of pediatric renal cell carcinomas with Xp11.2 rearrangements.     

Infection of a lateral cervical cyst with Propionibacterium propionicum,Fusobacterium nucleatum,and Capnocytophaga sp.

A recurrent infection of the left cervical area dorsal to the sternocleidomastoid muscle with actinomycosis in a 6-year-old girl is presented. Several antibiotic regimens failed, and repeated surgical treatments were necessary. The existence of a lateral cervical cyst and subsequent infection with agents of actinomycosis may have been the route of infection in this case.     

MyD88和TICAM1基因多态性及其交互作用与儿童社区获得性肺炎的关联研究

目的 探讨髓样分化因子88(myeloid differentiation factor 88,MyD88)和Toll样受体衔接分子1(Toll-like receptor adaptor molecule 1,TICAM1)基因的单核苷酸多态性及其交互作用与儿童社区获得性肺炎（community-acquired pneumonia,CAP）的相关性。方法 前瞻性采用改良多重高温连接酶检测反应技术对2015年8月—2017年9月在延安大学医学院第二附属医院儿科就诊的375例CAP患儿和306例健康体检儿童的MyD88和TICAM1基因的9个标签位点进行分型,并采用logistic回归分析评价各位点基因型及其交互作用与儿童CAP的关联。结果 TICAM1基因rs11466711T/C位点多态性与儿童CAP易感性密切相关（P<0.05）;rs35747610G/A位点AA基因型可显著降低CAP患儿并发脓毒症的风险（P<0.05）;rs6510826G/A位点AA基因型与CAP患儿急性期C反应蛋白水平的增高显著关联（P<0.05）。MyD88基因rs7744A/G位点GG...     

Fungal Endocarditis in Neonates and Children

Fungal endocarditis in the neonate and pediatric population is associated with a high degree of morbidity and mortality, with diagnosis in the majority of cases made postmortem. The aim of this article is to review published literature on fungal endocarditis in children and to discuss the incidence due to a wide range of fungi, primarily Aspergillus and Candida species, as well as its diagnosis, including the importance of molecular-based approaches and various treatment regimes.     

Antibiotic resistance patterns among respiratory pathogens at a german university children’s hospital over a period of 10 years

Growing antimicrobial resistance among Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis is raising major concern worldwide. Strains of S. pneumoniae, H. influenzae and M. catarrhalis isolated from children with respiratory tract as well as invasive infection in a South-Western region of Germany between 1993 and 2002 were tested for susceptibility to common antibiotics including penicillins, cephalosporins and macrolides. A total of 2,362 S. pneumoniae, 2,501 H. influenzae, and 1,982 M. catarrhalis isolates were tested. Only two S. pneumoniae strains were found to be highly resistant to penicillin. The overall rate of intermediate resistance to penicillin was 3.5%. There was a significant increase in erythromycin resistance from 5% in 1993 to 12.2% in 2002 ( P =0.001). No increase in ampicillin resistance was observed for H. influenzae over time. The rate of cefaclor resistance, however, increased from 4.5% to 11.8% ( P <0.0001). Furthermore, a massive increase in erythromycin resistance from 26% to 40% was observed ( P <0.0001). The vast majority of M. catarrhalis isolates were -lactamase positive, the minimal inhibitory concentration to ampicillin, however, exceeded only in 3% of all strains the cut-off of 1.5 mg/l. The erythromycin resistance rate of M. catarrhalis was 0.3%. Conclusion:There is still a low rate of penicillin/ampicillin resistance in S. pneumoniae, and H. influenzae, but an alarming increase in resistance to erythromycin, and in H. influenzae a significant increase in cefaclor resistance was observed over the 10-year period in South-Western Germany.     

Placental Findings after Laser Ablation of Communicating Vessels in Twin-to-Twin Transfusion Syndrome

As laser ablation of placental vascular communications gains acceptance as treatment option for severe twin-to-twin transfusion syndrome (TTTS), pathologists are increasingly confronted with the interpretation of laser-treated placentas. We present our preliminary institutional experience with the gross and microscopic analysis of these specimens. Patients underwent selective ablation for severe TTTS (Quintero stages II to V) between 16 and 25 wk gestation and the placentas were examined between < 24 h and 19 wk postoperatively. The placental vasculature was injected with gelatin-dye mixtures. The type and number of vascular anastomoses were recorded, followed by routine histopathological analysis of the placenta. Foci of laser impact were identified in all placentas examined within 1 month after laser coagulation. Located along the recipient side of the dividing membrane, the laser-treated vessels appeared hemorrhagic and showed a characteristic abrupt interruption of dye filling after vascular injection. In placentas examined more than 1 month after intervention, the most frequent gross finding was the absence or relative paucity of intertwin anastomoses, associated with subchorionic fibrin deposition. Microscopically, laser-treated vessels showed varying degrees of necrosis, associated with focal hemorrhage, avascular villi, and fibrin deposition in the underlying parenchyma. In some cases of intrauterine fetal demise or placental disruption, no definite laser scars were identified. As expected, the number of residual anastomoses (all types) was significantly smaller in laser-treated placentas than in control monochorionic placentas (2.4 ± 2.2 [n = 10] vs. 6.2 ± 3.2 [n = 70], P < 0.01). Velamentous cord insertion was noted in 50% of cases; markedly uneven placental sharing in 60%. Detailed analysis of laser-treated placentas and clinicopathological correlation may lead to a better understanding of the pathophysiology of TTTS and continued refinement of therapeutic approaches for this often lethal condition.     

Increased level of N-acetylaspartylglutamate (NAAG) in the CSF of a patient with Pelizaeus-Merzbacher-like disease due to mutation in the GJA12 gene

Autosomal recessive Pelizaeus-Merzbacher-like disease 1 (PMLD1) is a hypomyelinating disorder of the central nervous system (CNS) with virtually identical phenotype to Pelizaeus-Merzbacher disease (PMD). PMLD1 is caused by mutations in GJA12 gene, PMD is due to mutations in PLP1 gene. Elevated levels of N-acetylaspartylglutamate (NAAG), the most abundant peptide neuromodulator in the human brain, have been recently reported in cerebral spinal fluid (CSF) of patients with PMD. Using capillary electrophoresis, we analyzed for the first time, the CSF from a girl with PMLD1 and detected high concentrations of NAAG. This finding confirms the hypothesis that NAAG may be involved in myelination-related processes and can be considered as a useful diagnostic marker not only for patients with the PLP1 related disorder, but also in those with Pelizaeus-Merzbacher like hypomyelinating disease due to other defined genetic causes, such as PMLD1.     

Colostrum from healthy Brazilian women inhibits adhesion and contains IgA antibodies reactive with Shiga toxin-producing <Emphasis Type="Italic"> Escherichia coli</Emphasis>

Although Shiga toxin-producing Escherichia coli (STEC) has been isolated in Brazil, severe manifestations of the infection, such as haemorrhagic colitis and haemolytic-uraemic syndrome, are extremely rare in our population. Enteropathogenic Escherichia coli (EPEC) is the main aetiological agent of acute infantile diarrhoea in Brazil. There are many similarities between STEC and EPEC, such as the ability to produce attaching and effacing (A/E) lesions and some virulence-associated factors. Our aim was to investigate the presence of anti-STEC antibodies in healthy people living in an EPEC endemic area. Colostrum samples collected from 51 women living in low socio-economic conditions were analysed. Two STEC strains: O111:H- (Stx1) and O157:H7 (Stx2), and one EPEC strain (O111:H-) were used in the bacterial adhesion assays to HEp-2 cells, in the Stx1 and Stx2 cytotoxicity assays on Vero cells, in immunoblotting and in ELISA assays. All the samples strongly inhibited the adhesion of the three strains and contained SIgA antibodies reactive with antigens of EPEC O111:H-, STEC O111:H- and STEC O157:H7, mainly STEC and EPEC 94 kDa adhesin intimin. High titres of anti-LPS O111 antibodies were found in many samples. Nevertheless, the cytotoxic effect of both Stx1 and Stx2 on Vero cells was not neutralised by any sample. Conclusion: Our results suggest that Brazilian people may be exposed to Shiga toxin-producing Escherichia coli more frequently than previously thought or alternatively there may be a cross reactive immunity between enteropathogenic Escherichia coli and Shiga toxin-producing Escherichia coli.     

Congenital and opportunistic infections: Ureaplasma species and Mycoplasma hominis

There is strong evidence from clinical and experimental animal studies that ureaplasmas can invade the amnionic sac and induce an inflammatory response resulting in chorioamnionitis, preterm labor and neonatal lung injury. The ability of Ureaplasma spp. and Mycoplasma hominis to cause pneumonia, bacteremia, and meningitis in newborns can no longer be questioned. The association of Ureaplasma spp. with bronchopulmonary dysplasia has been supported by the majority of observational studies, but proof of causality is still lacking. The availability of molecular diagnostic technologies has enabled the designation of the two Ureaplasma biovars as individual species, but additional work must be done to establish whether there is differential pathogenicity between the Ureaplasma spp. or among their respective serovars. Future investigations to prevent prematurity should be directed toward identification and localization of specific micro-organisms combined with targeted antibiotic trials to determine whether such interventions can improve long-term infant outcomes.     

Halofantrine efficacy in non-immune children with imported acute Plasmodium falciparum malaria Infection

A rising incidence of imported acute malaria has been observed in non-immune traveller children returning from the tropics to France. Halofantrine efficacy has been poorly assessed in non-immune children. In order to assess halofantrine efficacy in non-immune children with acute uncomplicated Plasmodium falciparum malaria, we collected data of children with positive blood smears in an open prospective study. Children with neurological manifestations, vomiting and congenital long QT were excluded. All children were hospitalised and received halofantrine (24 mg/kg divided into three doses per day) on an empty stomach. Persistent fever after day 3 defined failure. Relapse was defined by a positive blood smear with or without systemic symptoms within a 1 month follow-up period. In total, 52 children were enrolled. No failure was observed, but relapses occurred in 14/52. On univariate analysis, the mean age of children with relapse was significantly lower (P<0.05). Moreover, diarrhoea was more frequently associated with relapses (P<0.04). Age and diarrhoea were significant independent factors contributing to relapses. Conclusion:this study shows that with a relapse rate of 27%, this regimen with a 1-day course of halofantrine is not to be recommended.     

Failure of voriconazole to cure disseminated zygomycosis in an immunocompromised child

Voriconazole is increasingly used as a first-line agent for empirical antifungal therapy of prolonged febrile neutropenia in paediatric cancer patients. We describe the case of a 9-year-old patient with stage IV Burkitt lymphoma, who developed pulmonary and splenic zygomycosis while receiving voriconazole for persistent febrile neutropenia. The causative agent, Absidia corymbifera, was identified by broad-range fungal PCR in a lung biopsy sample. The patient was successfully treated with a combination of partial resection of the left upper lobe and antifungal therapy with high-dose liposomal amphotericin B followed by oral itraconazole as demonstrated by resolving pulmonary infiltrates on serial high resolution CT scans. Conclusion:This case emphasises that the lack of in vitro activity of voriconazole against zygomycetes is clinically relevant. Failure of voriconazole in suspected fungal infection should be investigated for the possibility of zygomycosis. Broad-range polymerase chain reaction may be able to identify the causative organism when cultures remain sterile.