Measurement of C1-Inhibitor function alone is sufficient for diagnosis of hereditary angioedema

The World Allergy Organisiation/European Academy of Allergy and Clinical Immunology (WAO/EAACI) 2017/2018 guidelines recommend measuring complement4 levels, followed by C1-inhibitor level and function for diagnosis of hereditary angioedema (HAE). We analysed 6 months’ worth of data generated in our laboratory which is a specialist regional immunology service and also provides laboratory service for the Barts Health immunology department, which is a GA2LEN/HAEi-Angioedema Centre of Excellence and Reference (ACARE) and hence, investigates a large number of patients for HAE. We found that an efficient and sensitive approach for laboratory diagnosis of HAE is to only test the C1-inhibitor function. This approach had a sensitivity of 100% and reduced the cost of laboratory investigations for HAE diagnosis by 45%

Genomic diversity of Escherichia coli isolates from backyard chickens and guinea fowl in the Gambia

Chickens and guinea fowl are commonly reared in Gambian homes as affordable sources of protein. Using standard microbiological techniques, we obtained 68 caecal isolates of Escherichia coli from 10 chickens and 9 guinea fowl in rural Gambia. After Illumina whole-genome sequencing, 28 sequence types were detected in the isolates (4 of them novel), of which ST155 was the most common (22/68, 32 %). These strains span four of the eight main phylogroups of E. coli, with phylogroups B1 and A being most prevalent. Nearly a third of the isolates harboured at least one antimicrobial resistance gene, while most of the ST155 isolates (14/22, 64 %) encoded resistance to ≥3 classes of clinically relevant antibiotics, as well as putative virulence factors, suggesting pathogenic potential in humans. Furthermore, hierarchical clustering revealed that several Gambian poultry strains were closely related to isolates from humans. Although the ST155 lineage is common in poultry from Africa and South America, the Gambian ST155 isolates belong to a unique cgMLST cluster comprising closely related (38-39 alleles differences) isolates from poultry and livestock from sub-Saharan Africa - suggesting that strains can be exchanged between poultry and livestock in this setting. Continued surveillance of E. coli and other potential pathogens in rural backyard poultry from sub-Saharan Africa is warranted

Availability of Food Preparation Supplies among Pregnant Women: Preliminary Results from the Decision Making, Eating, and Weight Gain during Pregnancy (DEW) Study

Background: Lack of cooking supplies may be a potential barrier to preparing healthy meals at home. We examined the availability of food preparation supplies among pregnant women in relation to sociodemographic characteristics. Methods: We used preliminary data (N=59) from an ongoing study which enrolled English-speaking women aged 18+ years, pregnant with singleton gestation \u3c36\u3eweeks, pre-pregnancy BMI 18.5-40 kg/m2, and planning to deliver at UMMHC. Women completed the Food Preparation Checklist (FPC) at home. The FPC asks women if 41 specific food preparation items; scores reflect number of items present in the home. Other variables were self-reported. Pearson’s correlation, t-tests, and ANOVAs provided comparisons. We constructed an adjusted linear regression model to explore FPC by sociodemographic characteristics. Results: Women were aged 30.3 (SD=4.1) years, 64.4% were non-Hispanic White, 84.8% were married or living with a partner, and 30.5% reported difficulty paying for basic expenses. Women were enrolled at 22.7 (SD=5.6) weeks gestation; 30.5% were primigravid. Mean pre-pregnancy BMI was 25.0 (SD=4.6) kg/m2; 25.4% were overweight and 17.0% obese. Average FPC score was 32.3 (SD=6.1; range:14-39). FPC scores were higher among Non-Hispanic White women (34.6±3.5 vs. 28.1±7.5, p\u3c0.0001), those with higher education (28.3±7.0 high school/GED or less, 31.0±6.2 some/college degree, vs. 34.7±4.6 some/degree graduate, p\u3c0.01), those married or living with a partner (33.3±5.7 vs. 26.9±5.7, p\u3c0.01), with lower pre-pregnancy BMI (r=-0.38, p\u3c0.01), and who had no difficulty paying for basic expenses (34.0±5.0 vs. 28.4±6.6, p\u3c0.001). In a model that additionally adjusted for pre-pregnancy BMI, non-Hispanic White women had on average 5.7 more food preparation items (95% CI: 3.2, 8.3) and those reporting difficulty paying for basic expenses 3.8 fewer items (95% CI: -6.8, -0.9). Conclusions: Understanding the food preparation supplies available to pregnant women may be useful when designing interventions to improve diet quality and promote healthy weight gain during pregnancy

Evolution of Salmonella enterica serotype Typhimurium driven by anthropogenic selection and niche adaptation

Salmonella enterica serotype Typhimurium (S. Typhimurium) is a leading cause of gastroenteritis and bacteraemia worldwide, and a model organism for the study of host-pathogen interactions. Two S. Typhimurium strains (SL1344 and ATCC14028) are widely used to study host-pathogen interactions, yet genotypic variation results in strains with diverse host range, pathogenicity and risk to food safety. The population structure of diverse strains of S. Typhimurium revealed a major phylogroup of predominantly sequence type 19 (ST19) and a minor phylogroup of ST36. The major phylogroup had a population structure with two high order clades (α and β) and multiple subclades on extended internal branches, that exhibited distinct signatures of host adaptation and anthropogenic selection. Clade α contained a number of subclades composed of strains from well characterized epidemics in domesticated animals, while clade β contained multiple subclades associated with wild avian species. The contrasting epidemiology of strains in clade α and β was reflected by the distinct distribution of antimicrobial resistance (AMR) genes, accumulation of hypothetically disrupted coding sequences (HDCS), and signatures of functional diversification. These observations were consistent with elevated anthropogenic selection of clade α lineages from adaptation to circulation in populations of domesticated livestock, and the predisposition of clade β lineages to undergo adaptation to an invasive lifestyle by a process of convergent evolution with of host adapted Salmonella serotypes. Gene flux was predominantly driven by acquisition and recombination of prophage and associated cargo genes, with only occasional loss of these elements. The acquisition of large chromosomally-encoded genetic islands was limited, but notably, a feature of two recent pandemic clones (DT104 and monophasic S. Typhimurium ST34) of clade α (SGI-1 and SGI-4)

Evening Snacking in Relation to Self-reported Declines in Sleep Quality during Pregnancy: Preliminary Results from the Decision-Making, Eating, and Weight Gain During Pregnancy (DEW) Study

Background: Poor sleep in non-pregnant adults has been associated with increased evening snacking, which may contribute to weight gain. Sleep disturbances are common during pregnancy. Objective: To examine the association between changes in sleep quality from pre-pregnancy and evening snacking. Methods: In an ongoing prospective cohort study, pregnant women were recruited from UMMHC obstetric practices and the community. Participants are 18+ years, with singleton gestationweeks, pre-pregnancy BMI 18.5-40 kg/m2, English-speaking, and with plans to deliver at UMMHC. Participants were asked “compared to the three months before you became pregnant, how is your sleep quality now?”; we combined responses of “about the same”/“a little better”/“a lot better” versus “a little worse”/“much worse”. Participants completed three 24-hour dietary recalls (2 weekdays, 1 weekend day). Evening snacks were defined as eating occasions after dinner but before bedtime during which food items other than water was consumed. Fisher’s Exact tests and t-tests provided comparisons for evening snacking (yes/no), number of snacks, and energy intake. Results: Women with complete data (n=55) were 58% non-Hispanic White and aged 30.0 (SD:4.3) years; gestational age at study visit was 23.0 (SD:5.9) weeks. Of 866 meals reported, 94 were evening snacks. 71% (n=39) reported that their current sleep quality was worse than before pregnancy. Evening snacks were reported by 90% of women reporting worse sleep and 69% same/better (p=0.1028). While the number of snacks among snackers did not differ by change in sleep quality (M[SD]: 2.2[1.2] versus 1.6[0.8], p=0.2372), energy intake from these snacks was higher among women whose sleep quality had declined (M[SD]: 630[488] versus 309[331] kcal, p=0.0480). Conclusions: Declines in sleep quality during pregnancy may be linked to evening snacking. More research is needed to understand the role of sleep quality, eating behavior, and weight gain during pregnancy

Mechanisms involved in acquisition of blaNDM genes by IncA/C2 and IncFIIY plasmids

blaNDM genes confer carbapenem resistance and have been identified on transferable plasmids belonging to different incompatibility (Inc) groups. Here we present the complete sequences of four plasmids carrying a blaNDM gene, pKP1-NDM-1, pEC2-NDM-3, pECL3-NDM-1, and pEC4-NDM-6, from four clinical samples originating from four different patients. Different plasmids carry segments that align to different parts of the blaNDM region found on Acinetobacter plasmids. pKP1-NDM-1 and pEC2-NDM-3, from Klebsiella pneumoniae and Escherichia coli, respectively, were identified as type 1 IncA/C2 plasmids with almost identical backbones. Different regions carrying blaNDM are inserted in different locations in the antibiotic resistance island known as ARI-A, and ISCR1 may have been involved in the acquisition of blaNDM-3 by pEC2-NDM-3. pECL3-NDM-1 and pEC4-NDM-6, from Enterobacter cloacae and E. coli, respectively, have similar IncFIIY backbones, but different regions carrying blaNDM are found in different locations. Tn3-derived inverted-repeat transposable elements (TIME) appear to have been involved in the acquisition of blaNDM-6 by pEC4-NDM-6 and the rmtC 16S rRNA methylase gene by IncFIIY plasmids. Characterization of these plasmids further demonstrates that even very closely related plasmids may have acquired blaNDM genes by different mechanisms. These findings also illustrate the complex relationships between antimicrobial resistance genes, transposable elements, and plasmids and provide insights into the possible routes for transmission of blaNDM genes among species of the Enterobacteriaceae family

Global dissemination of a multidrug resistant Escherichia coli clone.

Escherichia coli sequence type 131 (ST131) is a globally disseminated, multidrug resistant (MDR) clone responsible for a high proportion of urinary tract and bloodstream infections. The rapid emergence and successful spread of E. coli ST131 is strongly associated with several factors, including resistance to fluoroquinolones, high virulence gene content, the possession of the type 1 fimbriae FimH30 allele, and the production of the CTX-M-15 extended spectrum β-lactamase (ESBL). Here, we used genome sequencing to examine the molecular epidemiology of a collection of E. coli ST131 strains isolated from six distinct geographical locations across the world spanning 2000-2011. The global phylogeny of E. coli ST131, determined from whole-genome sequence data, revealed a single lineage of E. coli ST131 distinct from other extraintestinal E. coli strains within the B2 phylogroup. Three closely related E. coli ST131 sublineages were identified, with little association to geographic origin. The majority of single-nucleotide variants associated with each of the sublineages were due to recombination in regions adjacent to mobile genetic elements (MGEs). The most prevalent sublineage of ST131 strains was characterized by fluoroquinolone resistance, and a distinct virulence factor and MGE profile. Four different variants of the CTX-M ESBL-resistance gene were identified in our ST131 strains, with acquisition of CTX-M-15 representing a defining feature of a discrete but geographically dispersed ST131 sublineage. This study confirms the global dispersal of a single E. coli ST131 clone and demonstrates the role of MGEs and recombination in the evolution of this important MDR pathogen

Thirty‐day mortality with andexanet alfa compared with prothrombin complex concentrate therapy for life‐threatening direct oral anticoagulant‐related bleeding

Objective Compare 30-day mortality among patients receiving the specific reversal agent andexanet alfa versus replacement prothrombin complex concentrate (PCC) in the management of direct-acting oral anticoagulant (DOAC)–related bleeds. Methods Two patient-level datasets were used: ANNEXA-4, a prospective, single-arm trial of patients taking apixaban or rivaroxaban who received andexanet alfa and ORANGE, a prospective, observational study of anticoagulated patients in UK hospitals, some of whom received PCC. Patients were propensity score matched based on demographic and clinical characteristics. Subgroup analyses were performed by bleed type (intracranial hemorrhage [ICH], gastrointestinal [GI], other). Relative risk (RR) of all-cause 30-day mortality was calculated. Results 322 ANNEXA-4 patients treated with andexanet alfa (mean age = 77.7 years; 64.9% ICH) were matched with 88 ORANGE patients treated with PCC (mean age = 74.9 years, 67.1% ICH). Adjusted 30-day mortality for patients treated with andexanet alfa (14.6%) was lower than patients treated with PCC (34.1%; RR, 0.43; 95% CI, 0.29–0.63). In the ICH subgroup, patients treated with andexanet alfa had lower mortality (15.3%) than patients treated with PCC (48.9%; RR, 0.31; 95% CI, 0.20–0.48). Mortality risk was lowest for patients in the GI subgroup but did not differ significantly by treatment (12.2% for andexanet alfa vs 25.0% for PCC; RR, 0.49; 95% CI, 0.21–1.16). Conclusions In this propensity score–matched comparison across 2 independent datasets, adjusted 30-day mortality rates were lower for patients treated with andexanet alfa than in matched patients receiving PCC. This indirect comparison was limited in that it could not account for several highly predictive variables including GCS score, hematoma volume, and expected survival. Further research is warranted to confirm the mortality differences between reversal/replacement agents for DOAC-related bleeding

Heparin based prophylaxis to prevent venous thromboembolic events and death in patients with cancer - a subgroup analysis of CERTIFY

<p>Abstract</p> <p>Background</p> <p>Patients with cancer have an increased risk of VTE. We compared VTE rates and bleeding complications in 1) cancer patients receiving LMWH or UFH and 2) patients with or without cancer.</p> <p>Methods</p> <p>Acutely-ill, non-surgical patients ≥70 years with (n = 274) or without cancer (n = 2,965) received certoparin 3,000 UaXa o.d. or UFH 5,000 IU t.i.d. for 8-20 days.</p> <p>Results</p> <p>1) Thromboembolic events in cancer patients (proximal DVT, symptomatic non-fatal PE and VTE-related death) occurred at 4.50% with certoparin and 6.03% with UFH (OR 0.73; 95% CI 0.23-2.39). Major bleeding was comparable and minor bleedings (0.75 vs. 5.67%) were nominally less frequent. 7.5% of certoparin and 12.8% of UFH treated patients experienced serious adverse events. 2) Thromboembolic event rates were comparable in patients with or without cancer (5.29 vs. 4.13%) as were bleeding complications. All cause death was increased in cancer (OR 2.68; 95%CI 1.22-5.86). 10.2% of patients with and 5.81% of those without cancer experienced serious adverse events (OR 1.85; 95% CI 1.21-2.81).</p> <p>Conclusions</p> <p>Certoparin 3,000 UaXa o.d. and 5,000 IU UFH t.i.d. were equally effective and safe with respect to bleeding complications in patients with cancer. There were no statistically significant differences in the risk of thromboembolic events in patients with or without cancer receiving adequate anticoagulation.</p> <p>Trial Registration</p> <p>clinicaltrials.gov, <a href="http://www.clinicaltrials.gov/ct2/show/NCT00451412">NCT00451412</a></p