BackgroundPrevious work has demonstrated a strong association between lung injury in African American children with pneumonia and a polymorphic (TG)mTn region in cystic fibrosis transmembrane conductance (CFTR) involved in the generation of a nonfunctional CFTR protein lacking exon 9. A number of splicing factors that regulate the inclusion/exclusion of exon 9 have been identified. The objective of this study was to determine whether genetic variants in these splicing factors were associated with acute respiratory distress syndrome (ARDS) in children with pneumonia.MethodsThis is a prospective cohort genetic association study of lung injury in African American and non-Hispanic Caucasian children with community-acquired pneumonia evaluated in the emergency department or admitted to the hospital. Linkage-disequilibrium-tag single nucleotide polymorphisms (LD-tag SNPs) in genes of the following splicing factors (followed by gene name) involved in exon 9 skipping PTB1 (PTBP1), SRp40 (SFRS1), SR2/ASF (SFRS5), TDP-43 (TARDBP), TIA-1 (TIA1), and U2AF65 (U2AF2) were genotyped. SNPs in the gene of the splicing factor CELF2 (CELF2) were selected by conservation score. Multivariable analysis was used to examine association between genotypes and ARDS.ResultsThe African American cohort (n = 474) had 29 children with ARDS and the non-Hispanic Caucasian cohort (n = 304) had 32 children with ARDS. In the African American group multivariable analysis indicated that three variants in CELF2, rs7068124 (p = 0.004), rs3814634 (p = 0.032) and rs10905928 (p = 0.044), and two in TIA1, rs2592178 (p = 0.005) and rs13402990 (p = 0.018) were independently associated with ARDS. In the non-Hispanic Caucasian group, a single variant in CELF2, rs2277212 (p = 0.014), was associated with increased risk of developing ARDS.ConclusionsThe data indicate that SNPs in CELF2 may be associated with the risk of developing ARDS in both African American and non-Hispanic Caucasian children with pneumonia and suggest that the potential role of the splicing factor CELF2 in ARDS should be explored further.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1454-7) contains supplementary material, which is available to authorized users.
Key Clinical MessageIntravenous immunoglobulin therapy should be considered in pediatric acute hemorrhagic leukoencephalitis that is refractory to steroid and plasmapheresis.
Acute ischemic stroke (AIS) in children is rare with almost 40% diagnosed as cryptogenic. One possible mechanism associated with AIS is an elevated Lipoprotein (a) [Lp(a)] level. Here, we discuss the case of an 11-year old boy who presented with multiple thrombotic strokes secondary to elevated Lp(a), which was identified as the only risk factor and immediately treated with lipoprotein apheresis (LA). Eighteen months post-AIS, he is still receiving LA treatments and has made remarkable progress in his recovery without another cerebrovascular event.
serum Na+ 191 mmol/l, BUN 245 mg/dl, Glucose 161 mg/dl, calculated serum osmolality 479 mOsm/l) complicated with prerenal AKI (serum Cr 4.1 mg/dl, and K+ 6.3 mmol/l), anuria, ATN, serum non-conjugated bilirubin of 27 mg/ dl, DIC (INR 2.3, PTT 55 s), and thrombocytopenia (platelet count 33,000/μl). Patient's weight on admission was 2.2 kg, with an estimated weight loss of 43% since birth. She had grayish skin discoloration with surprisingly normal vital signs, lactatemia and normal neurological status. Density of the dural venous sinuses was prominent on brain CT scan, likely reflecting hemoconcentration (Hg 22.5 g/dl). Current literature does not provide clear recommendations for correction of extreme hypertonic dehydration with co-existing life threatening complications. This clinical situation represents a very challenging scenario with potential for severe risks in case of too rapid or slow correction of fluid and electrolyte imbalance, including exacerbation of systemic hypoperfusion with hemodynamic instability, brain edema, dysrhythmias, irreversible kidney injury, cerebral sinus venous thrombosis, and kernicterus. Our therapeutic interventions included two 20-ml/kg NS boluses for peripheral perfusion optimization and then a third 20-ml/kg bolus for anuria. Patient was placed on D5 ½ NS (1.5 maintenance rate based on actual patient's weight), and oral rehydration with pedialyte. Double phototherapy was implemented for the first 12 hrs. No attempt was made at correcting DIC during the first 48 hrs. Patient diuresis was restored during first 5 hrs of therapy. Serum Na+, BUN and Cr levels steadily normalized over the next 96 hrs. Patient neurological status remained intact and she was discharged from the PICU after 7 days of treatment fully recovered.
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