On May 23 and 24, 2013, the First PANS Consensus Conference was convened at Stanford University, calling together a geographically diverse group of clinicians and researchers from complementary fields of pediatrics: General and developmental pediatrics, infectious diseases, immunology, rheumatology, neurology, and child psychiatry. Participants were academicians with clinical and research interests in pediatric autoimmune neuropsychiatric disorder associated with streptococcus (PANDAS) in youth, and the larger category of pediatric acute-onset neuropsychiatric syndrome (PANS). The goals were to clarify the diagnostic boundaries of PANS, to develop systematic strategies for evaluation of suspected PANS cases, and to set forth the most urgently needed studies in this field. Presented here is a consensus statement proposing recommendations for the diagnostic evaluation of youth presenting with PANS.
Male fetal gender is associated with singleton preterm birth, an effect most evident in white women, particularly if married. Among preterm white twins, there is also a male excess, limited to gestations under 34 weeks. The excess of males in selected groups suggests the existence of a mechanism of preterm birth influenced by fetal gender. Preterm births in blacks and in twin gestations greater than 33 weeks may be more often due to alternative mechanisms that are independent of fetal gender.
The limulus gelation assay was utilized to investigate endotoxin inactivation by a number of antibiotics in vitro. Endotoxin activity was sharply reduced by polymyxin B and sodium colistimethate. The effect of the polymyxin was not significantly inhibited by 0.001 M calcium or 90% serum. Crude endotoxins from a variety of aerobic gram-negative bacteria, including several not previously studied, could be inactivated 1 or more logs by as little as 1 Og of polymyxin B per ml, whereas Bacteroides fragilis endotoxin was poorly detoxified. A 10,000-fold range in the relative susceptibility of different endotoxins to inactivation by polymyxin B was found. The endotoxin most susceptible to polymyxin B was derived from an organism resistant to polymyxin B by disk sensitivity testing, suggesting that the bacteriocidal and endotoxin detoxifying properties of polymyxin need not be directly related.Recent studies have demonstrated the capacity of polymyxin B to protect animals from a variety of toxic effects of endotoxin, including the generalized Schwartzman reaction (5, 23), diffuse intravascular coagulation (6, 7), renal cortical necrosis (6, 7), leukopenia (6, 7), and death (6,12,21,23). The limulus gelation test, developed by Levin and others (13,14), has provided a useful in vitro means to assess an endotoxin activity which corresponds with in vivo indices of toxicity (3,15,24). We have previously found this assay to be useful in evaluating endotoxin inactivation processes (4). The present study was designed to evaluate the effect of polymyxin B and other antibiotics upon endotoxin, the conditions of the reaction, and the relative polymyxin susceptibility of endotoxins from a variety of gram-negative bacteria.
MATERIALS AND METHODS
In a whole genome-based phylogeny, clinical and fecal isolates of Escherichia coli sequence type 131 (H30R1 and H30Rx subclones) from six households formed household-specific clusters, interspersed among reference ST131 genomes. This supported the fecal-urethral hypothesis and confirmed within-household strain sharing.
A fluoroquinolone-resistant Escherichia coli strain of sequence type ST131 caused severe septic arthritis and contiguous osteomyelitis in an 8-month-old girl, and colonized the girl's healthy mother, who shared a different fecal E. coli strain with the father. Within-household transmission can contribute to the dissemination of the emerging, multidrug-resistant ST131 clonal group, which has evident invasive potential for otherwise-healthy children.
Objective: This retrospective study examined whether changes in patient pre-and post-treatment symptoms correlated with changes in anti-neuronal autoantibody titers and the neuronal cell stimulation assay in the Cunningham Panel in patients with Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection (PANDAS), and Pediatric Acute-onset Neuropsychiatric Syndrome (PANS). Methods: In an analysis of all tests consecutively performed in Moleculera Labs' clinical laboratory from April 22, 2013 to December 31, 2016, we identified 206 patients who were prescribed at least one panel prior to and following treatment, and who met the PANDAS/PANS diagnostic criteria. Patient follow-up was performed to collect symptoms and treatment or medical intervention. Of the 206 patients, 58 met the inclusion criteria of providing informed consent/assent and documented pre-and post-treatment symptoms. Clinician and parentreported symptoms after treatment or medical intervention were categorized as "Improved/Resolved" (n = 34) or "Not-Improved/Worsened" (n = 24). These were analyzed for any association between changes in clinical status and changes in Cunningham panel test results. Clinical assay performance was also evaluated for reproducibility and reliability. Results: Comparison of pre-and post-treatment status revealed that the Cunningham Panel results correlated with changes in patient's neuropsychiatric symptoms. Based upon the change in the number of positive tests, the overall accuracy was 86%, the sensitivity and specificity were 88% and 83% respectively, and the Area Under the Curve (AUC) was 93.4%. When evaluated by changes in autoantibody levels, we observed an overall accuracy of 90%, a sensitivity of 88%, a specificity of 92% and an AUC of 95.7%. Assay reproducibility for the calcium/calmodulin-dependent protein kinase II (CaMKII) revealed a correlation coefficient of 0.90 10 −6 ) and the ELISA assays demonstrated test-retest reproducibility comparable with other ELISA assays. Conclusion: This study revealed a strong positive association between changes in neuropsychiatric symptoms and changes in the level of anti-neuronal antibodies and antibody-mediated CaMKII human neuronal cell activation. These results suggest there may be clinical utility in monitoring autoantibody levels and stimulatory activity against these five neuronal antigen targets as an aid in the diagnosis and treatment of infection-triggered autoimmune neuropsychiatric disorders. Future prospective studies should examine the feasibility of predicting antimicrobial and immunotherapy responses with the Cunningham Panel.
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