Protection against infectious bronchitis virus by spike ectodomain subunit vaccine

Publication date: Available online 9 September 2017
Source:Vaccine
Author(s): Fatma Eldemery, Kellye S. Joiner, Haroldo Toro, Vicky L. van Santen
The avian coronavirus infectious bronchitis virus (IBV) S1 subunit of the spike (S) glycoprotein mediates viral attachment to host cells and the S2 subunit is responsible for membrane fusion. Using IBV Arkansas-type (Ark) S protein histochemistry, we show that extension of S1 with the S2 ectodomain improves binding to chicken tissues. Although the S1 subunit is the major inducer of neutralizing antibodies, vaccination with S1 protein has been shown to confer inadequate protection against challenge. The demonstrated contribution of S2 ectodomain to binding to chicken tissues suggests that vaccination with the ectodomain might improve protection compared to vaccination with S1 alone. Therefore, we immunized chickens with recombinant trimeric soluble IBV Ark-type S1 or S-ectodomain protein produced from codon-optimized constructs in mammalian cells. Chickens were primed at 12days of age with water-in-oil emulsified S1 or S-ectodomain proteins, and then boosted 21days later. Challenge was performed with virulent Ark IBV 21days after boost. Chickens immunized with recombinant S-ectodomain protein showed statistically significantly (P<0.05) reduced viral loads 5days post-challenge in both tears and tracheas compared to chickens immunized with recombinant S1 protein. Consistent with viral loads, significantly reduced (P<0.05) tracheal mucosal thickness and tracheal lesion scores revealed that recombinant S-ectodomain protein provided improved protection of tracheal integrity compared to S1 protein. These results indicate that the S2 domain has an important role in inducing protective immunity. Thus, including the S2 domain with S1 might be promising for better viral vectored and/or subunit vaccine strategies.



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Cost-effectiveness of HPV vaccination in the context of high cervical cancer incidence and low screening coverage

Publication date: Available online 9 September 2017
Source:Vaccine
Author(s): Triin Võrno, Katrin Lutsar, Anneli Uusküla, Lee Padrik, Terje Raud, Rainer Reile, Oliver Nahkur, Raul-Allan Kiivet
BackgroundEstonia has high cervical cancer incidence and low screening coverage. We modelled the impact of population-based bivalent, quadrivalent or nonavalent HPV vaccination alongside cervical cancer screening.MethodsA Markov cohort model of the natural history of HPV infection was used to assess the cost-effectiveness of vaccinating a cohort of 12-year-old girls with bivalent, quadrivalent or nonavalent vaccine in two doses in a national, school-based vaccination programme. The model followed the natural progression of HPV infection into subsequent genital warts (GW); premalignant lesions (CIN1–3); cervical, oropharyngeal, vulvar, vaginal and anal cancer. Vaccine coverage was assumed to be 70%. A time horizon of 88years (up to 100years of age) was used to capture all lifetime vaccination costs and benefits. Costs and utilities were discounted using an annual discount rate of 5%.ResultsVaccination of 12-year-old girls alongside screening compared to screening alone had an incremental cost-effectiveness ratio (ICER) of €14,007 (bivalent), €14,067 (quadrivalent) and €11,633 (nonavalent) per quality-adjusted life-year (QALY) in the base-case scenario and ranged between €5367–21,711, €5142–21,800 and €4563–18,142, respectively, in sensitivity analysis. The results were most sensitive to changes in discount rate, vaccination regimen, vaccine prices and cervical cancer screening coverage.ConclusionVaccination of 12-year-old girls alongside current cervical cancer screening can be considered a cost-effective intervention in Estonia. Adding HPV vaccination to the national immunisation schedule is expected to prevent a considerable number of HPV infections, genital warts, premalignant lesions, HPV related cancers and deaths. Although in our model ICERs varied slightly depending on the vaccine used, they generally fell within the same range. Cost-effectiveness of HPV vaccination was found to be most dependent on vaccine cost and duration of vaccine immunity, but not on the type of vaccine used.



http://ift.tt/2xSV99m

Bioreactor culture duration of engineered constructs influences bone formation by mesenchymal stem cells

Publication date: November 2017
Source:Biomaterials, Volume 146
Author(s): Debika Mitra, Jacklyn Whitehead, Osamu W. Yasui, J. Kent Leach
Perfusion culture of mesenchymal stem cells (MSCs) seeded in biomaterial scaffolds provides nutrients for cell survival, enhances extracellular matrix deposition, and increases osteogenic cell differentiation. However, there is no consensus on the appropriate perfusion duration of cellular constructs in vitro to boost their bone forming capacity in vivo. We investigated this phenomenon by culturing human MSCs in macroporous composite scaffolds in a direct perfusion bioreactor and compared their response to scaffolds in continuous dynamic culture conditions on an XYZ shaker. Cell seeding in continuous perfusion bioreactors resulted in more uniform MSC distribution than static seeding. We observed similar calcium deposition in all composite scaffolds over 21 days of bioreactor culture, regardless of pore size. Compared to scaffolds in dynamic culture, perfused scaffolds exhibited increased DNA content and expression of osteogenic markers up to 14 days in culture that plateaued thereafter. We then evaluated the effect of perfusion culture duration on bone formation when MSC-seeded scaffolds were implanted in a murine ectopic site. Human MSCs persisted in all scaffolds at 2 weeks in vivo, and we observed increased neovascularization in constructs cultured under perfusion for 7 days relative to those cultured for 1 day within each gender. At 8 weeks post-implantation, we observed greater bone volume fraction, bone mineral density, tissue ingrowth, collagen density, and osteoblastic markers in bioreactor constructs cultured for 14 days compared to those cultured for 1 or 7 days, and acellular constructs. Taken together, these data demonstrate that culturing MSCs under perfusion culture for at least 14 days in vitro improves the quantity and quality of bone formation in vivo. This study highlights the need for optimizing in vitro bioreactor culture duration of engineered constructs to achieve the desired level of bone formation.



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Extracellular matrix-derived extracellular vesicles promote cardiomyocyte growth and electrical activity in engineered cardiac atria

Publication date: November 2017
Source:Biomaterials, Volume 146
Author(s): Minae An, Kihwan Kwon, Junbeom Park, Dong-Ryeol Ryu, Jung-A. Shin, Jihee Lee Kang, Ji Ha Choi, Eun-Mi Park, Kyung Eun Lee, Minna Woo, Minsuk Kim
Extracellular matrix (ECM) plays a critical role in the provision of the necessary microenvironment for the proper regeneration of the cardiac tissue. However, specific mechanisms that lead to ECM-mediated cardiac regeneration are not well understood. To elucidate the potential mechanisms, we investigated ultra-structures of the cardiac ECM using electron microscopy. Intriguingly, we observed large quantities of micro-vesicles from decellularized right atria. RNA and protein analyses revealed that these contained exosomal proteins and microRNAs (miRNAs), which we referred to herein as ECM-derived extracellular vesicles (ECM-EVs). One particular miRNA from ECM-EVs, miR-199a-3p, promoted cell growth of isolated neonatal cardiomyocytes and sinus nodal cells by repressing homeodomain-only protein (HOPX) expression and increasing GATA-binding 4 (Gata4) acetylation. To determine the mechanisms, we knocked down Gata4 and showed that miR-199a-3p actions required Gata4 for cell proliferation in isolated neonatal cardiomyocytes and sinus nodal cells. To further explore the role of this miRNA, we isolated neonatal cardiac cells and recellularized into atrial ECM, referred here has engineered atria. Remarkably, miR-199a-3p mediated the enrichment of cardiomyocyte and sinus nodal cell population, and enhanced electrocardiographic signal activity of sinus nodal cells in the engineered atria. Importantly, antisense of miRNA (antagomir) against miR-199a-3p was capable of abolishing these actions of miR-199a-3p in the engineered atria. We further showed in Ang II-infused animal model of sinus nodal dysfunction that miR-199-3p-treated cardiac cells remarkably ameliorated and restored the electrical activity as shown by normalization of the ECG, in contrast to untreated cells, which did not show electrical recovery. In conclusion, these results provide clear evidence of the critical role of ECM, in not only providing a scaffold for cardiac tissue growth, but also in promoting atrial electrical function through ECM-derived miR-199a-3p.



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Engineered, axially-vascularized osteogenic grafts from human adipose-derived cells to treat avascular necrosis of bone in a rat model

Publication date: Available online 8 September 2017
Source:Acta Biomaterialia
Author(s): Tarek Ismail, Rik Osinga, Atanas Todorov Jr., Alexander Haumer, Laurent A. Tchang, Christian Epple, Nima Allafi, Nadia Menzi, René D. Largo, Alexandre Kaempfen, Ivan Martin, Dirk J. Schaefer, Arnaud Scherberich
BackgroundAvascular necrosis of bone (AVN) leads to sclerosis and collapse of bone and joints. The standard of care, vascularized bone grafts, is limited by donor site morbidity and restricted availability. The aim of this study was to generate and test engineered, axially vascularized SVF cells-based bone substitutes in a rat model of AVN.MethodsSVF cells were isolated from lipoaspirates and cultured onto porous hydroxyapatite scaffolds within a perfusion-based bioreactor system for 5 days. The resulting constructs were inserted into devitalized bone cylinders mimicking AVN-affected bone. A ligated vascular bundle was inserted upon subcutaneous implantation of constructs in nude rats. After 1 and 8 weeks in vivo, bone formation and vascularization were analyzed.ResultsNewly-formed bone was found in 80% of SVF-seeded scaffolds after 8 weeks but not in unseeded controls. Human ALU+ cells in the bone structures evidenced a direct contribution of SVF cells to bone formation. A higher density of regenerative, M2 macrophages was observed in SVF-seeded constructs. In both experimental groups, devitalized bone was revitalized by vascularized tissue after 8 weeks.ConclusionSVF cells-based osteogenic constructs revitalized fully necrotic bone in a challenging AVN rat model of clinically-relevant size. SVF cells contributed to accelerated initial vascularization, to bone formation and to recruitment of pro-regenerative endogenous cells.Statement of SignificanceAvascular necrosis (AVN) of bone often requires surgical treatment with autologous bone grafts, which is surgically demanding and restricted by significant donor site morbidity and limited availability. This paper describes a de novo engineered axially-vascularized bone graft substitute and tests the potential to revitalize dead bone and provide efficient new bone formation in a rat model.The engineering of an osteogenic/vasculogenic construct of clinically-relevant size with stromal vascular fraction of human adipose, combined to an arteriovenous bundle is described. This construct revitalized and generated new bone tissue. This successful approach proposes a novel paradigm in the treatment of AVN, in which an engineered, vascularized osteogenic graft would be used as a germ to revitalize large volumes of necrotic bone.

Graphical abstract

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SI-traceable calibration-free analysis for the active concentration of G2-EPSPS protein using surface plasmon resonance

Publication date: 1 February 2018
Source:Talanta, Volume 178
Author(s): Ping Su, Zhangjing He, Liqing Wu, Liang Li, Kangle Zheng, Yi Yang
Active proteins play important roles in the function regulation of human bodies and attract much interest for use in pharmaceuticals and clinical diagnostics. However, the lack of primary methods to analyze active proteins means there is currently no metrology standard for active protein measurement. In recent years, calibration-free concentration analysis (CFCA), which is based on surface plasmon resonance (SPR) technology, has been proposed to determine the active concentration of proteins that have specific binding activity with a binding partner without any higher order standards. The CFCA experiment observes the changes of binding rates at totally different two flow rates and uses the known diffusion coefficient of an analyte to calculate the active concentration of proteins, theoretically required, the binding process have to be under diffusion-limited conditions. Measuring the active concentration of G2-EPSPS protein by CFCA was proposed in this study. This method involves optimization of the regeneration buffer and preparation of chip surfaces for appropriate reaction conditions by immobilizing ligands (G2-EPSPS antibodies) on sensor chips (CM5) via amine coupling. The active concentration of G2-EPSPS was then determined by injection of G2-EPSPS protein samples and running buffer over immobilized and reference chip surfaces at two different flow rates (5 and 100μLmin⁻¹). The active concentration of G2-EPSPS was obtained after analyzing these sensorgrams with the 1:1 model. Using the determined active concentration of G2-EPSPS, the association, dissociation, and equilibrium constants of G2-EPSPS and its antibody were determined to be 2.18 ± 0.03 × 10⁶M⁻¹s⁻¹, 5.79 ± 0.06 ×10⁻³s⁻¹, and 2.65 ± 0.06 × 10⁻⁹M, respectively. The performance of the proposed method was evaluated. The within-day precisions were from 3.26% to 4.59%, and the between-day precision was 8.36%. The recovery rate of the method was from 97.46% to 104.34% in the concentration range of 1.5–8nM. The appropriate concentration range of G2-EPSPS in the proposed method was determined to be 1.5–8nM. The active G2-EPSPS protein concentration determined by our method was only 17.82% of that obtained by isotope dilution mass spectrometry, showing the active protein was only a small part of the total G2-EPSPS protein. The measurement principle of the proposed method can be clearly described by equations and the measurement result can be expressed in SI units. Therefore, the proposed method shows promise to become a primary method for active protein concentration measurement, which can benefit the development of certified reference materials for active proteins.

Graphical abstract

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Growth of Escherichia coli on the GaAs (001) surface

Publication date: 1 February 2018
Source:Talanta, Volume 178
Author(s): Elnaz Nazemi, Walid M. Hassen, Eric H. Frost, Jan J. Dubowski
Detection of pathogenic bacteria and monitoring their susceptibility to antibiotics are of great importance in the fields of medicine, pharmaceutical research, as well as water and food industries. In order to develop a photonic biosensor for detection of bacteria by taking advantage of photoluminescence (PL) of GaAs-based devices, we have investigated the capture and growth of Escherichia coli K12 on bare and biofunctionalized surfaces of GaAs (001) – a material of interest for capping different semiconductor microstructures. The results were compared with the capture and growth of Escherichia coli K12 on Au surfaces that have commonly been applied for studying a variety of biological and biochemical reactions. We found that neither GaAs nor Au-coated glass wafers placed in Petri dishes inoculated with bacteria inhibited bacterial growth in nutrient agar, regardless of the wafers being bare or biofunctionalized. However, the capture and growth of bacteria on biofunctionalized surfaces of GaAs and Au wafers kept in a flow cell and exposed to different concentrations of bacteria and growth medium revealed that the initial surface coverage and the subsequent bacterial growth were dependent on the biofunctionalization architecture, with antibody-coated surfaces clearly being most efficient in capturing bacteria and offering better conditions for growth of bacteria. We have observed that, as long as the GaAs wafers were exposed to bacterial suspensions at concentrations of at least 10⁵ CFU/mL, bacteria could grow on the surface of wafers, regardless of the type of biofunctionalization architecture used to capture the bacteria. These results provide important insight towards the successful development of GaAs-based devices designed for photonic monitoring of bacterial reactions to different biochemical environments.

Graphical abstract

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The prognostic value of derived neutrophil to lymphocyte ratio in oesophageal cancer treated with definitive chemoradiotherapy

Publication date: Available online 8 September 2017
Source:Radiotherapy and Oncology
Author(s): Samantha Cox, Christopher Hurt, Tal Grenader, Somnath Mukherjee, John Bridgewater, Thomas Crosby
Background and purposeThe derived neutrophil–lymphocyte ratio (dNLR) is a validated prognostic biomarker for cancer survival but has not been extensively studied in locally-advanced oesophageal cancer treated with definitive chemoradiotherapy (dCRT). We aimed to identify the prognostic value of dNLR in patients recruited to the SCOPE1 trial.Materials and methods258 patients were randomised to receive dCRT±cetuximab. Kaplan–Meier's curves and both univariable and multivariable Cox regression models were calculated for overall survival (OS), progression free survival (PFS), local PFS inside the radiation volume (LPFSi), local PFS outside the radiation volume (LPFSo), and distant PFS (DPFS).ResultsAn elevated pre-treatment dNLR≥2 was significantly associated with decreased OS in univariable (HR 1.74 [95% CI 1.29–2.35], p<0.001) and multivariable analyses (HR 1.64 [1.17–2.29], p=0.004). Median OS was 36months (95% CI 27.8–42.4) if dNLR<2 and 18.4months (95% CI 14.1–24.9) if dNLR≥2. All measures of PFS were also significantly reduced with an elevated dNLR. dNLR was prognostic for OS in cases of squamous cell carcinoma with a non-significant trend for adenocarcinoma/undifferentiated tumours.ConclusionsAn elevated pre-treatment dNLR may be an independent prognostic biomarker for OS and PFS in oesophageal cancer patients treated with definitive CRT. dNLR is a simple, inexpensive and readily available tool for risk-stratification and should be considered for use in future oesophageal cancer clinical trials.The SCOPE1 trial was an International Standard Randomised Controlled Trial [number 47718479].



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Transcriptional-mediated effects of radiation on the expression of immune susceptibility markers in melanoma

Publication date: Available online 8 September 2017
Source:Radiotherapy and Oncology
Author(s): Lauryn R. Werner, Jasdeep S. Kler, Monica M. Gressett, Maureen Riegert, Lindsey K. Werner, Clinton M. Heinze, Joseph G. Kern, Mahyar Abbariki, Amy K. Erbe, Ravi B. Patel, Raghava N. Sriramaneni, Paul M. Harari, Zachary S. Morris
Background and purposeWe recently reported a time-sensitive, cooperative, anti-tumor effect elicited by radiation (RT) and intra-tumoral-immunocytokine injection in vivo. We hypothesized that RT triggers transcriptional-mediated changes in tumor expression of immune susceptibility markers at delayed time points, which may explain these previously observed time-dependent effects.Materials and methodsWe examined the time course of changes in expression of immune susceptibility markers following in vitro or in vivo RT in B78 murine melanoma and A375 human melanoma using flow cytometry, immunoblotting, and qPCR.ResultsFlow cytometry and immunoblot revealed time-dependent increases in expression of death receptors and T cell co-stimulatory/co-inhibitory ligands following RT in murine and human melanoma. Using high-throughput qPCR, we observed comparable time courses of RT-induced transcriptional upregulation for multiple immune susceptibility markers. We confirmed analogous changes in B78 tumors irradiated in vivo. We observed upregulated expression of DNA damage response markers days prior to changes in immune markers, whereas phosphorylation of the STAT1 transcription factor occurred concurrently with changes following RT.ConclusionThis study highlights time-dependent, transcription-mediated changes in tumor immune susceptibility marker expression following RT. These findings may help in the design of strategies to optimize sequencing of RT and immunotherapy in translational and clinical studies.



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1-Hydroxypyrido[2,3-d]pyrimidin-2(1H)-ones as Novel Selective HIV Integrase Inhibitors Obtained via Privileged Substructure-Based Compound Libraries

Publication date: Available online 8 September 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Ping Gao, Lingzi Zhang, Lin Sun, Tianguang Huang, Jing Tan, Jian Zhang, Zhongxia Zhou, Tong Zhao, Luis Menéndez-Arias, Christophe Pannecouque, Erik De Clercq, Peng Zhan, Xinyong Liu
A small library containing 3-hydroxyquinazoline-2,4(1H,3H)-dione and 1-hydroxypyrido[2,3-d]pyrimidin-2(1H)-one scaffolds was obtained via the copper(I)-catalyzed azidealkyne cycloaddition (CuAAC) reaction and evaluated for their anti-HIV activity in MT-4 cells. Among the synthesized compounds, several 1-hydroxypyrido[2,3-d]pyrimidin-2(1H)-one derivatives showed remarkable anti-HIV potency with EC50 values ranging from 0.92 to 26.85 µM. The most active one, IIA-2, also showed remarkable and selective potency against HIV type 1 integrase (IN). To the best of our knowledge, this is the first report showing that 1-hydroxypyrido[2,3-d]pyrimidin-2(1H)-ones are selective HIV IN inhibitors. Preliminary structure-activity relationship (SAR) studies suggested that the divalent metal ion chelators and the nature and position of substituents around the core are important for antiviral potency. Molecular modeling has been used to predict the binding site of the pyrido[2,3-d]pyrimidin-2(1H)-one core in HIV type 1 IN and suggestions are made for improvement of its inhibitory activity.



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Control of multidrug-resistant Acinetobacter baumannii in Hong Kong: Role of environmental surveillance in communal areas after a hospital outbreak

Publication date: Available online 8 September 2017
Source:American Journal of Infection Control
Author(s): Vincent C.C. Cheng, Shuk-Ching Wong, Jonathan H.K. Chen, Simon Y.C. So, Sally C.Y. Wong, Pak-Leung Ho, Kwok-Yung Yuen
BackgroundEnvironmental reservoir is an important source of multidrug-resistant Acinetobacter baumannii (MRAB) outbreaks. The role of postoutbreak environmental surveillance for guiding sustained infection control effort has not been examined.MethodsEnhanced environmental disinfection and regular environmental surveillance of ward communal areas after an outbreak were performed in a university-affiliated hospital. To assess the usefulness of environmental culture in predicting patients with MRAB, weekly surveillance of communal areas was continued for 3 months after the outbreak in intervention wards. The incidence of MRAB in intervention and nonintervention wards (control) was compared, whereas the other infection control measures remained identical.ResultsPostoutbreak weekly surveillance of communal areas showed that identification of newly diagnosed MRAB patients was significantly correlated with preceding environmental contamination with MRAB (P = .001). The incidence of nosocomial MRAB infection was significantly lower in the intervention compared with nonintervention wards (0.55 vs 2.28 per 1,000 patient days, respectively; P = .04). All MRAB isolated from the environmental and patients' samples belonged to multilocus sequence typing ST457 and were blaOXA23-like positive.ConclusionsEnvironmental surveillance may serve as a surrogate marker for the presence of MRAB carriers. Implementation of timely infection control measures should be guided by environmental culture for MRAB to minimize the risk of MRAB outbreak.



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Depositional histories of faunal remains from the Neolithic cultic site of Kfar HaHoresh, Israel

Publication date: December 2017
Source:Journal of Anthropological Archaeology, Volume 48
Author(s): Jacqueline S. Meier, A. Nigel Goring-Morris, Natalie D. Munro




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Can predicting transfusion in cardiac surgery help patients?

In this issue of the British Journal of Anaesthesia, Klein and colleagues¹ describe the ACTA-PORT, a new score for predicting the risk of one or more red blood cell transfusions in patients undergoing cardiac surgery. The authors' desire to provide a simple, accurate tool to help predict the risk of transfusion in patients undergoing cardiac surgery is commendable, but does it help our patients?

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Beyond availability: the importance of routine videolaryngoscopy and institution-based rescue methods of difficult videolaryngoscopy

Editor—We appreciate the fabulous work of Cook and Kelly on the national survey of videolaryngoscopy (VL) in the UK.¹ According to the Difficult Airway Society's 2015 guidelines² videolaryngoscopes should be immediately available at all times and all anaesthetists should be trained and skilled in their use. We are glad to see the main finding that VL is available in >90% of UK hospital, though only one in seven hospitals have VL available in all relevant clinical areas. Beyond the availability of videolaryngoscopes, whether to be skilled in VL remains an important issue.

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Lack of benefit of near-infrared spectroscopy monitoring for improving patient outcomes. Case closed?

Near-infrared spectroscopy (NIRS) monitoring of regional cerebral oxygen saturation (rSco2) during cardiac surgery has been available to clinicians for more than three decades.¹² This monitoring is attractive because it is non-invasive, requires minimal user technical expertise, provides an intuitively important end point (oxygenation of the superficial cerebral cortex), and has a continuous output. As a result of these features, NIRS monitoring overcomes many of the limitations of existing monitors for judging adequacy of cerebral perfusion during surgery [(particularly, throughout cardiopulmonary bypass (CPB)], such as electroencephalography, transcranial Doppler monitoring, and jugular bulb venous oxygen saturation. Early reports showing the value of bilateral rSco2 monitoring for early detection of CPB oxygenator malfunction, arterial or venous cannula malposition, and occult aortic dissection, in addition to utility during aortic arch surgery, fuelled enthusiasm for its adoption in cardiac surgery.² This enthusiasm was broadened with publication of non-randomized, observational studies showing a link between reduction from baseline rSco2 (i.e. 'desaturations') during CPB and a variety of neurological end points, including postoperative cognition dysfunction (POCD) and stroke.² Interpretation of these data, however, are confounded by many methodological limitations.

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Response to: Go/no-go decision in anaesthesia: wide variation in risk tolerance amongst anaesthetists

Editor—The work by Greig and colleagues¹ brings to light conflicting organizational and management practices for the operating theatre. A majority of the confusion and tension in this high-pressure environment can be traced back to the fundamental misunderstanding of high-reliability organizations (HRO) and ultra-safe systems (USS). In fact, the authors state that "health care providers aspire to become high-reliability organizations, but this practice contrasts with existing high-reliability organizations, such as aviation, where decision-making aids and standardized operating procedures are widely used."¹ However, the aviation industry is predominantly an ultra-safe system, not a high-reliability organization.

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Viscoelastometric testing, fibrinogen and transfusion during post-partum haemorrhage

Editor—Many readers will recognize the pleasure of a new pair of glasses (Fig. 1). They are perfectly tailored to our own visual defect, and wearing them gives one a feeling of clarity and brightness that is comparable with opening the curtains after a good night's sleep. In an era of evidence-based medicine, should we question the evidence base for eyeglasses? Might this be unnecessary when there is a palpable association between a specific intervention and an intended outcome such that we are easily convinced of the causal nature of that association? There will certainly be an effect of using viscoelastometric testing on plasma transfusion if practice changes from giving plasma 'blindly' to giving plasma based on the coagulation testing. The real question is whether this change in practice will lead to better outcomes. In this issue of the BritishJournalof Anaesthesia, Collins and colleagues¹² provide new information on monitoring and managing haemostasis in patients with post-partum haemorrhage.

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Influence of deep neuromuscular block on the surgeonś assessment of surgical conditions during laparotomy: a randomized controlled double blinded trial with rocuronium and sugammadex

Abstract

Background. During laparotomy, surgeons may experience difficult surgical conditions if the patient's abdominal wall or diaphragm is tense. Deep neuromuscular block (NMB), defined as a post-tetanic-count (PTC) between 0-1, paralyses the abdominal wall muscles and the diaphragm. We hypothesized that deep NMB (PTC 0-1) would improve subjective ratings of surgical conditions during upper laparotomy as compared with standard NMB.Methods. This was a double blinded, randomized study. A total of 128 patients undergoing elective upper laparotomy were randomized to either continuous deep NMB (infusion of rocuronium 2 mg ml⁻¹) or standard NMB (bolus of rocuronium 10 mg or increased depth of anaesthesia). Surgical conditions were evaluated using a 5-point subjective rating scale (1: extremely poor, 5: optimal) every 30 min. Primary outcome was the average of scores for a patient's surgical conditions. Other outcomes were surgical rating score during fascial closure, episodes of a need to optimize surgical conditions, occurrence of wound dehiscence, and wound infection.Results. Deep compared with standard NMB resulted in better ratings of surgical conditions; median 4.75 (range 3–5) compared with 4.00 (range 1–5) (P<0.001), respectively. Deep compared with standard NMB resulted in better ratings of surgical conditions during fascial closure (P<0.001), fewer episodes of need to optimize surgical conditions (P<0.001), and fewer incidents with sudden movements (P<0.001). No differences in operating time, occurrence of wound infection, and wound dehiscence were found.Conclusions. Deep NMB compared with standard NMB resulted in better subjective ratings of surgical conditions during laparotomy.Clinical trial registration: NCT02140593.

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Videolaryngoscopy and obstetric anaesthesia

Editor—We congratulate Professor Cook and Dr Kelly on their important national survey of videolaryngoscopy in the UK.¹ They highlighted that while videolaryngoscopes (VLs) are widely available in main operating theatres, availability in other areas where tracheal intubation is undertaken is much lower, being around only 50% of intensive care units and obstetric theatres. We would suggest that this figure is a particular concern to obstetric anaesthesia, where the risk of failed intubation is greater than the general population. In 2011, we conducted a national Obstetric Anaesthetists' Association approved survey of the availability of VLs in UK obstetric units. This survey (response rate 72%) found that only 42% of obstetric units had a dedicated VL with widespread variation in the type of device available.²

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Theseus, the Labyrinth, and the Minotaur of anaesthetic-induced developmental neurotoxicity

When Theseus set sail to slay the mighty Minotaur, he likely spared a thought for the difficulty in navigating the Labyrinth that surrounded his foe. The search for therapies for anaesthetic-induced developmental neurotoxicity shares a similar mythical context. In our version of these events, Prince Theseus is the cure (potentially played by dexmedetomidine), the Minotaur is sevoflurane-induced neurotoxicity and the Labyrinth (a maze of confounding factors) is represented by physiological aberrations. In this issue of the British Journal of Anaesthesia, two reports¹² appear to arrive at contradictory conclusions regarding the success of dexmedetomidine in combating sevoflurane-induced developmental neurotoxicity in neonatal rat pups. The two research teams are to be congratulated for reporting the results in a manner that enables the reader to appreciate the entire gamut from protection against organ toxicity to toxicity to the entire organism because of the clarity and detail in their reports. However, the physiological derangements observed in these studies, and their contradictory findings, lead to labyrinthine interpretation. Readers should also refer to the accompanying editorial on the same studies by Vutskits and Sall³ when considering these issues.

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