National Early Warning Score and New-Onset Atrial Fibrillation for Predicting In-Hospital Mortality or Transfer to the Intensive Care Unit in Emergency Department Patients with Suspected Bacterial Infections.

Purpose: There are conflicting data regarding the role of the National Early Warning Score 2 (NEWS2) in predicting adverse outcomes in patients with infectious diseases. New-onset atrial fibrillation (NO-AF) has been suggested as a sepsis-defining sign of organ dysfunction. This study aimed to examine the prognostic accuracy of NEWS2 and whether NO-AF can provide prognostic information in emergency department (ED) patients with suspected bacterial infections. Patients and Methods: Secondary analyses of data from a prospective observational cohort study of adults admitted in a 6-month period with suspected bacterial infections. We used the composite endpoint of in-hospital mortality or transfer to the intensive care unit as the primary outcome. The prognostic accuracy of NEWS2 and quick sequential organ failure assessment (qSOFA) and covariate-adjusted area under the receiver operating curves (AAUROC) were used to describe the performance of the scores. Logistic regression analysis was used to examine the association between NO-AF and the composite endpoint. Results: A total of 2055 patients were included in this study. The composite endpoint was achieved in 198 (9.6%) patients. NO-AF was observed in 80 (3.9%) patients. The sensitivity and specificity for NEWS2 ≥5 were 70.2% (63.3-76.5) and 60.2% (57.9-62.4), respectively, and those for qSOFA ≥2 were 26.3% (20.3-33.0) and 91.0% (89.6-92.3), respectively. AAUROC for NEWS2 and qSOFA were 0.68 (0.65-0.73) and 0.63 (0.59-0.68), respectively. The adjusted odds ratio for achieving the composite endpoint in 48 patients with NO-AF who fulfilled the NEWS2 ≥5 criteria was 2.71 (1.35-5.44). Conclusion: NEWS2 had higher sensitivity but lower specificity and better, albeit poor, discriminative ability to predict the composite endpoint compared to qSOFA. NO-AF can provide important prognostic information.

Evidence for a shift in placental HLA-G allelic dominance and the HLA-G isoform profile during a healthy pregnancy and preeclampsia†.

Human leukocyte antigen (HLA)-G, which belongs to a nonclassical class Ib major histocompatibility complex gene family expressed by placental trophoblast cells, plays a central role in establishing tolerance to the semiallogeneic fetus and in placentation. HLA-G exists in different soluble or membrane-bound isoforms. Preeclampsia, a major cause of fetal and maternal morbidity and mortality, has been linked to insufficient placentation and an altered immune response in pregnancy, including altered HLA-G expression. The 14 bp insertion/deletion polymorphism in the 3' untranslated region of the gene and the isoform profile may affect HLA-G expression. The aim of the current pilot study was to characterize the expression patterns of HLAG mRNA, protein, and isoform profile in uncomplicated term pregnancies and in cases of preeclampsia. Maternal sHLA-G mRNA and protein levels were slightly reduced in preeclampsia. No difference was found for placental blood, and no correlation between peripheral and placental sHLA-G levels was found. We observed no association between neither fetal nor maternal HLA-G 14 bp insertion/deletion genotypes and preeclampsia, nor a significant difference in isoform profiles. However, in HLA-G 14 bp insertion/deletion heterozygous placental samples, we observed abundant HLA-G1 14 bp insertion allele expression in the term placentae, which is contrary to previous findings in first trimester trophoblast. Increased HLA-G1 14 bp insertion allele expression in the placenta was associated with reduced levels of placental sHLA-G and an altered isoform profile with increased relative levels of HLA-G1 and -G5 and reduced levels of HLA-G3. The results indicate that an allelic shift in heterozygous individuals could represent a novel regulatory pathway.

Maternal HLA Ib Polymorphisms in Pregnancy Allo-Immunization.

During pregnancy the formation of alloreactive anti-human leukocyte antigen (HLA) antibodies are a major cause of acute rejection in organ transplantation and of adverse effects in blood transfusion. The purpose of the study was to identify maternal HLA class Ib genetic factors associated with anti-HLA allo-immunization in pregnancy and the degree of tolerance estimated by IgG4 expression. In total, 86 primiparous women with singleton pregnancies were included in the study. Maternal blood samples and umbilical cord samples were collected at delivery. Clinical data were obtained. Maternal blood serum was screened for HLA class I and II antibodies, identification of Donor Specific Antibody (DSA), activation of complement measured by C1q and IgG4 concentrations. Mothers were genotyped for HLA class Ib (HLA-E, -F and -G). Anti-HLA class I and II antibodies were identified in 24% of the women. The maternal HLA-E*01:06 allele was significantly associated with a higher fraction of anti-HLA I immunization (20.0% vs. 4.8%, p = 0.048). The maternal HLA-G 3'-untranslated region UTR4-HLA-G*01:01:01:05 haplotype and the HLA-F*01:03:01 allele were significantly associated with a low anti-HLA I C1q activation (16.7% vs. 57.1%, p = 0.028; 16.7% vs. 50.0%, p = 0.046; respectively). Both HLA­G and HLA-F*01:03:01 showed significantly higher levels of IgG4 compared with the other haplotypes. The results support an association of certain HLA class Ib alleles with allo-immunization during pregnancy. Further studies are needed to elucidate the roles of HLA-E*01:06, HLA-F*01:03 and HLA­G UTR4 in reducing the risk for allo-immunization.