Baseline haemoglobin variability by measurement technique in pregnant people on the day of childbirth.

Point-of-care haemoglobin measurement devices may play an important role in the antenatal detection of anaemia in pregnant people and may be useful in guiding blood transfusion during resuscitation in obstetric haemorrhage. We compared baseline haemoglobin variability of venous and capillary HemoCue® haemoglobin, and Masimo® Rad-67 Pulse CO-Oximeter haemoglobin with laboratory haemoglobin in people on the day of their planned vaginal birth. A total of 180 people undergoing planned vaginal birth were enrolled in this prospective observational study. Laboratory haemoglobin was compared with HemoCue and Masimo Rad-67 Pulse CO-Oximeter measurements using Bland-Altman analysis, calculating mean difference (bias) and limits of agreement. Five (2.8%) people had anaemia (haemoglobin < 110 g.l-1 ). Laboratory haemoglobin and HemoCue venous haemoglobin comparison showed an acceptable bias (SD) 0.7 (7.54) g.l-1 (95%CI -0.43-1.79), with limits of agreement -14.10-15.46 g.l-1 and acceptable agreement range of 29.6 g.l-1 . Laboratory and HemoCue capillary haemoglobin comparison showed an unacceptable bias (SD) 13.3 (14.12) g.l-1 (95%CI 11.17-15.34), with limits of agreement - 14.42-40.93 g.l-1 and unacceptable agreement range of 55.3 g.l-1 . Laboratory and Masimo haemoglobin comparison showed an unacceptable bias (SD) -14.0 (11.15) g.l-1 (95%CI -15.63 to -12.34), with limits of agreement to -35.85 to 7.87 g.l-1 and acceptable agreement range of 43.7 g.l-1 . Venous HemoCue, with its acceptable bias and limits of agreement, should be applied more widely in the antenatal setting to detect, manage and risk stratify pregnant people with anaemia. HemoCue capillary measurement under-estimated haemoglobin and Masimo haemoglobin measurement over-estimated, limiting their clinical use. Serial studies are needed to determine if the accuracy of venous HemoCue haemoglobin measurement is sustained in other obstetric settings.

The rare C9 P167S risk variant for age-related macular degeneration increases polymerization of the terminal component of the complement cascade.

Age-related macular degeneration (AMD) is a complex neurodegenerative eye disease with behavioral and genetic etiology and is the leading cause of irreversible vision loss among elderly Caucasians. Functionally significant genetic variants in the alternative pathway of complement have been strongly linked to disease. More recently, a rare variant in the terminal pathway of complement has been associated with increased risk, Complement component 9 (C9) P167S. To assess the functional consequence of this variant, C9 levels were measured in two independent cohorts of AMD patients. In both cohorts, it was demonstrated that the P167S variant was associated with low C9 plasma levels. Further analysis showed that patients with advanced AMD had elevated sC5b-9 compared to those with non-advanced AMD, although this was not associated with the P167S polymorphism. Electron microscopy of membrane attack complexes (MACs) generated using recombinantly produced wild type or P167S C9 demonstrated identical MAC ring structures. In functional assays, the P167S variant displayed a higher propensity to polymerize and a small increase in its ability to induce hemolysis of sheep erythrocytes when added to C9-depleted serum. The demonstration that this C9 P167S AMD risk polymorphism displays increased polymerization and functional activity provides a rationale for the gene therapy trials of sCD59 to inhibit the terminal pathway of complement in AMD that are underway.

Primary External Ventricular Drains in the Management of Open Myelomeningocele Repairs in the Neonatal Setting in Ireland

Aim The aim of this study is to outline the role of primary external ventricular drains (EVD) in the management of open myelomeningoceles in the neonatal setting in Ireland. Methods Retrospective cohort study involving all infants who underwent open myelomeningocele repair in a teritary centre in Ireland between January 2009 and April 2016. Medical charts and laboratory data was reviewed on all infants meeting the inclusion criteria. Results One hundred and forty-three neonates underwent open myelomeningocele repair in the 6.5 year period. EVD were inserted at the time of primary wound closure in 19 cases (13%). EVD were used to aid in wound closure and as a primary method of cerebrospinal fluid (CSF) diversion. They remained in place for a median of 8 days, ranging from 1-22 days. All EVD, apart from one, in our series were replaced by a ventricular-peritoneal (VP) shunt at some stage. Conclusion EVD were used in 13% of cases of open myelomeningocele repairs from Jan 2009-Apr 2016 as a primary measure to aid in management. Compared to the cohort in whom an EVD was not inserted at the time of surgery, there was a decrease in the rate of infections. However, there was an increased rate of wound dehiscence/leak and a later need for VP shunt insertion.

Local and systemic effects of cat allergen nasal provocation.

BACKGROUND: Cat allergen is widely distributed in homes and schools; allergic sensitization is common. OBJECTIVE: To develop a model of cat allergen nasal challenge to establish dose-response and time-course characteristics and investigate local and systemic biomarkers of allergic inflammation. METHODS: Nineteen cat-allergic individuals underwent titrated nasal challenge, range 0.243 to 14.6 µg/mL Fel d1, and matched diluent-only provocation. Clinical response to 8 h was assessed by symptom scores and peak nasal inspiratory flow (PNIF). Nasal fluid was collected using polyurethane sponges and analysed by ImmunoCAP and multiplex assays. Whole blood flow cytometry for basophil surface CD63, CD107a, and CD203c was carried out at baseline and 6 h post-challenge. RESULTS: A dose-response to allergen was seen in symptom scores and PNIF, maximal at 10 000 BU/mL (4.87 µg/mL Fel d1), P < 0.0001 vs. diluent. Nasal fluid tryptase was elevated at 5 min after challenge (P < 0.05 vs. diluent); eotaxin, IL-4, -5, -9, and -13 were increased at 8 h (P < 0.05 to P < 0.0001 vs. diluent); TSLP was undetectable; IL-10, IL-17A, and IL-33 were unchanged compared to diluent challenge. Nasal fluid IL-5 and IL-13 correlated inversely with PNIF after challenge (IL-5, r = -0.79, P < 0.0001; IL-13, r = -0.60, P = 0.006). Surface expression of CD63 and CD107a was greater at 6 h than at baseline, both in the presence (both P < 0.05) and absence (CD63, P < 0.01; CD107a, P < 0.05) of in vitro allergen stimulation; no changes were seen on diluent challenge day. CONCLUSIONS: Cat allergen nasal challenge produces local and systemic Th2-driven inflammatory responses and has potential as a surrogate outcome measure in clinical trials.