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Relapse at the central nervous system (CNS) in acute myeloid leukemia (AML) carries a dismal prognosis. Treatment options are limited to intrathecal therapy, high-dose cytarabine, high-dose methotrexate, and radiotherapy. Novel strategies are needed. Venetoclax has recently been approved by the FDA, in combination with hypomethylating agents or low-dose cytarabine, for elderly adults or patients ineligible for intensive chemotherapy affected by AML. However, little is known on its efficacy in patients with leptomeningeal involvement. Here, we present a case of a 52-year-old patient affected by AML relapsed at CNS after allogeneic bone marrow transplantation who was treated with venetoclax. We evaluated the concentration of the drug in cerebrospinal fluid (CSF) by HPLC MS/MS method on three different occasions to verify the penetration of the drug through the brain-blood barrier and we observed that the concentration in CSF was similar to the IC50 established in vitro.

Transcatheter aortic valve implantation (TAVI) is relatively contraindicated in the bicuspid aortic valve, and to our knowledge has not been tried where the true native annulus is of a size far in excess of current device capabilities. We present here a case of a successful emergency TAVI of a 73-year-old previously healthy man, who presented with cardiogenic shock, ventricular tachycardia storm and severe left ventricular dysfunction because of the underlying critical bicuspid aortic stenosis with aortic annulus area of 991.9 mm2 and associated moderate aortic incompetence (the Society of Thoracic Surgeons (STS) risk score; score mortality of 40.9%). Despite the critical condition of the patient and technically challenging anatomy, successful TAVI was performed and the patient remains well with near-normal left ventricle (LV) function at 6 months follow-up.

The E/e' ratio has an established role in the assessment of left ventricular filling pressure (LVFP) in stable patients, but its accuracy in acute myocardial ischemia is less well established. The aim of this study was to validate the relation between the E/e' ratio and invasively measured LVFP in patients with non-ST elevation myocardial infarction (NSTEMI). A total of 120 unselected patients with NSTEMI underwent cardiac catheterization with measurement of left ventricular end-diastolic pressure (LVEDP; elevated ≥15 mm Hg) and Doppler echocardiography with either simultaneous (n = 30) or same-day (n = 90) measurement of E/e'. Patients were aged 64.1 ± 11.8 years, 72% were male and mean left ventricular ejection fraction was 48.0 ± 20.9%. Septal, lateral, and average E/e' ratios all showed a significant correlation with LVEDP (Pearson's r: 0.42, 0.43, 0.48, respectively [all p0.001]). Receiver operating characteristics curves showed an area under the curve of 0.72, 0.72, and 0.75 (all p0.001) for septal, lateral, and average E/e', respectively. The sensitivity, specificity, positive (PPV), and negative (NPV) predictive values for the guideline-recommended threshold of average E/e'14 for elevated LVEDP was 27%, 93%, 79%, and 44%, respectively. Utilizing lower E/e' boundaries of 6, 7, and 8 for lateral, average, and medial E/e', respectively, improved the NPV to ≥80% for each parameter. In conclusion, the E/e' ratio is a robust measure of LVFP during acute NSTEMI using upper and lower thresholds to achieve a high PPV and NPV, respectively, with the use of adjunctive guideline-recommend measures required in patients with nonconclusive E/e'.

Gupta et al. investigate forces generated during cell division in confining epithelial monolayers. In addition to finding that cells generate forces during mitotic rounding, they find that cells generate protrusive forces along the division axis that drive elongation and outward forces that facilitate postdivision spreading., Epithelial cells undergo striking morphological changes during division to ensure proper segregation of genetic and cytoplasmic materials. These morphological changes occur despite dividing cells being mechanically restricted by neighboring cells, indicating the need for extracellular force generation. Beyond driving cell division itself, forces associated with division have been implicated in tissue-scale processes, including development, tissue growth, migration, and epidermal stratification. While forces generated by mitotic rounding are well understood, forces generated after rounding remain unknown. Here, we identify two distinct stages of division force generation that follow rounding: (1) Protrusive forces along the division axis that drive division elongation, and (2) outward forces that facilitate postdivision spreading. Cytokinetic ring contraction of the dividing cell, but not activity of neighboring cells, generates extracellular forces that propel division elongation and contribute to chromosome segregation. Forces from division elongation are observed in epithelia across many model organisms. Thus, division elongation forces represent a universal mechanism that powers cell division in confining epithelia., Graphical Abstract

This expert Position Statement is a description of the requirements for Accreditation for transcatheter mitral valve therapy (TMVT) in Australia. The requirements include the need for a multidisciplinary Heart Team review of individual cases, mandatory reporting of outcome data to a national TMVT Registry, and accreditation of individuals and institutions by the Conjoint Accreditation Committee, the assigned accreditation authority.

Patients with a true porcelain aorta and a failed mechanical aortic valve prosthesis have limited treatment options. Using a hybrid of an open trans-ventricular approach with peripheral cardiopulmonary bypass and integration of transcatheter techniques this challenge can be overcome. Trans-ventricular mechanical valve extraction (with transcatheter endovascular occlusion and cardioplegia) followed by direct ante-grade transcatheter heart valve implantation offers a potential solution to this conundrum. The procedure described is a novel technique that allows for the effective treatment of patients with failed mechanical surgical aortic valve prostheses in the setting of an inoperable porcelain aorta. In addition, a collaborative integrated multi-disciplinary heart team environment is required for the management of these complex patients.

Background: The present study is a prospective observational single arm clinical investigation, with parallel bench test interrogation, aimed at investigating the technical feasibility, safety and clinical outcomes with the cone flare crush modified-T (CFCT) bifurcation stenting technique. Bifurcation percutaneous coronary intervention (PCI) remains an area of ongoing procedural evolution. More widely applicable and reproducible techniques are required. Methods: From April 2018 until March 2019, 20 consecutive patients underwent bifurcation PCI using the CFCT technique with a Pt-Cr everolimus drug-eluting stent with a bioresorbable polymer. Exercise stress echocardiography was performed at 12-month follow-up. The primary outcome was a composite of cardiac related mortality, myocardial infarction, target lesion/vessel revascularization and stroke. Safety secondary endpoints included bleeding, all-cause mortality and stent thrombosis. Results: All patients underwent a successful CFCT bifurcation procedure with no complications to 30-day follow-up. One patient met the primary endpoint requiring target lesion revascularization at 9 months for stable angina. There were no other primary or secondary outcome events in the cohort. There were no strokes, deaths, stent thrombosis or myocardial infarction during the follow-up period. The mean CCS score improved from 2.25 to 0.25 (p

Assays of cytokines in the plasma at the onset of graft-vs. -host disease (GVHD) can predict disease severity and treatment-related mortality (TRM); however, the optimal time during which cytokines should be tested and the specific panel of cytokines with the highest predictive ability remain unknown. We chose a predefined time point, 18 days after hematopoietic stem cell transplantation (HSCT), to measure the levels of six cytokines in the plasma: soluble interleukin-2 receptor alpha (sIL2-Rα), T-cell immunoglobulin domain and mucin domain-3 (TIM-3), suppression of tumorigenicity-2 (ST-2), intercellular adhesion molecule (ICAM-1), interferon-gamma (IFN-γ), and interleukin-6 (IL-6). The study included 95 patients, who underwent allogeneic hematopoietic transplantation at our institution. Plasma levels of sIL2-Rα and TIM-3, measured as continuous data, had predictive value for overall survival (sIL2-Rα, p = 0.002; TIM-3, p = 0.0007), while TRM could be predicted by sIL2-Rα (p = 0.0005), IFN-gamma (p = 0.01), and IL-6 (p = 0.0001). No cytokine was associated with the risk of relapse. Patients were categorized into groups, according to cytokine thresholds determined by receiver operating characteristic curve analysis (sIL2-Rα ≤ or > 8,100 pg/ml; TIM-3 ≤ or > 950 pg/ml) and multivariate analysis was conducted. High levels of both TIM-3 and sIL2-Rα were significant predictors of poor survival [TIM-3 > 950 pg/ml: hazard ratio (HR) = 6.214 (95% CI 1.939–19.910), p = 0.002 and sIL2-Rα > 8.100 pg/ml: HR = 2.644 (95% CI 1.308–5.347), p = 0.006]. Using these cutoff thresholds, we constructed a composite scoring system that could distinguish three different groups of patients with varying rates of TRM: high risk, 41.7%; intermediate risk, 10.8%; and low risk, 7.1% (Gray's test: p = 0.001). If confirmed in a validation cohort, this composite scoring system could be used to guide the modulation of post-transplant immune suppressive therapy.

We here report final results of a phase II/III prospective study that evaluated in Multiple Myeloma the use of on-demand plerixafor (PLX) added to mobilizing chemotherapy for patients showing predictive signs of mobilization failure. A total of 111 patients with MM were registered, all received cyclophosphamide 4 g/m2 and granulocyte colony-stimulating factor (G-CSF). Overall, a successful CD34+ cell mobilization was achieved in 97.2% (108/111) of patients. Minimum harvest (≥2.0 × 106 CD34+ cells/kg) was achieved in 97.2% (108/111) and optimal harvest success (≥4.0 × 106 CD34+ cells/kg) was achieved in 84.6% (94/111). Multivariate analysis showed that patients who received on-demand PLX treatment had significantly higher likelihoods of successfully achieving both the minimal (p = .006) and optimal harvest (p = .05) in respect to a historical control group mobilized without any PLX. The incremental cost-effectiveness ratio, for each 1% increase in probability of achieving a successful minimal harve...

Influenza is a highly contagious, acute, febrile respiratory infection that can have fatal consequences particularly in individuals with chronic illnesses. Sporadic reports suggest that intravenous immunoglobulin (IVIg) may be efficacious in the influenza setting. We investigated the potential of human IVIg to ameliorate influenza infection in ferrets exposed to either the pandemic H1N1/09 virus (pH1N1) or highly pathogenic avian influenza (H5N1). IVIg administered at the time of influenza virus exposure led to a significant reduction in lung viral load following pH1N1 challenge. In the lethal H5N1 model, the majority of animals given IVIg survived challenge in a dose dependent manner. Protection was also afforded by purified F(ab′)2 but not Fc fragments derived from IVIg, supporting a specific antibody-mediated mechanism of protection. We conclude that pre-pandemic IVIg can modulate serious influenza infection-associated mortality and morbidity. IVIg could be useful prophylactically in the event of a pandemic to protect vulnerable population groups and in the critical care setting as a first stage intervention., Highlights • Intravenous immunoglobulin (IVIg), prepared prior to a pandemic, prevents pandemic influenza disease in ferrets. • IVIg effectively reduced viral levels of pandemic H1N1 influenza and prevented disease due to avian influenza H5N1. • This work has implications for preventing and treating pandemic influenza infections with IVIg before a vaccine is available. Influenza pandemics cause large numbers of infections and deaths. There is a lag between the identification of a pandemic and the development of vaccines. Future pandemics may be caused by influenza strains resistant to current anti-influenza drugs. New treatments are needed for future pandemic influenza outbreaks. We show that a readily available product (intravenous immunoglobuling – pooled antibodies from human donors) can prevent viral replication and disease caused by 2 strains of pandemic influenza viruses (“swine-flu” and “bird-flu”) in an appropriate animal model of influenza. This could form the basis of future treatments for severe influenza caused by pandemic strains.

Coronary occlusion (immediate or delayed) is an uncommon but potentially devastating complication of transcatheter aortic valve replacement/implantation (TAVR/TAVI). Several patient-related, anatomical, device and procedural risk factors can be assessed to risk-stratify patients and assist in procedural planning. In patients at high risk for coronary occlusion, coronary protection measures should be employed. In the highest risk patients, consideration should be given to prophylactic techniques to prevent coronary occlusion. This how-to-do-it report provides a framework for risk assessment for coronary occlusion followed by a step-wise description of the emerging chimney snorkel coronary stenting technique as a predictable procedural approach for the management of this potentially challenging clinical scenario.

PURPOSE: To describe a new and simple technique of glaucoma tube extension that carries several advantages over previously described techniques. PATIENTS AND METHODS: A retrospective noncomparative case series of 3 patients (1 adult and 2 pediatric cases) with glaucoma tube retraction managed by the "tube-in-tube" technique. The follow-up duration ranges from 1 month to 3 years. RESULTS: Adequate tube position and length were seen in all cases throughout the follow-up period. No tube migration was seen. The intraocular pressures were significantly reduced and maintained in all cases. There was no visual loss as a result of the procedure. CONCLUSIONS: This new "tube-in-tube" glaucoma drainage device tube extension technique is safe and simple to perform, and has many advantages over previously reported techniques. It can be used in both the adult and pediatric glaucoma population, and is not limited to the type of drainage implants.

Background A strength of Drosophila as a model system is its utility as a tool to screen for novel regulators of various functional and developmental processes. However, the utility of Drosophila as a screening tool is dependent on the speed and simplicity of the assay used. Methods Here, we use larval locomotion as an assay to identify novel regulators of skeletal muscle function. We combined this assay with muscle-specific depletion of 82 genes to identify genes that impact muscle function by their expression in muscle cells. The data from the screen were supported with characterization of the muscle pattern in embryos and larvae that had disrupted expression of the strongest hit from the screen. Results With this assay, we showed that 12/82 tested genes regulate muscle function. Intriguingly, the disruption of five genes caused an increase in muscle function, illustrating that mechanisms that reduce muscle function exist and that the larval locomotion assay is sufficiently quantitative to identify conditions that both increase and decrease muscle function. We extended the data from this screen and tested the mechanism by which the strongest hit, fascin, impacted muscle function. Compared to controls, animals in which fascin expression was disrupted with either a mutant allele or muscle-specific expression of RNAi had fewer muscles, smaller muscles, muscles with fewer nuclei, and muscles with disrupted myotendinous junctions. However, expression of RNAi against fascin only after the muscle had finished embryonic development did not recapitulate any of these phenotypes. Conclusions These data suggest that muscle function is reduced due to impaired myoblast fusion, muscle growth, and muscle attachment. Together, these data demonstrate the utility of Drosophila larval locomotion as an assay for the identification of novel regulators of muscle development and implicate fascin as necessary for embryonic muscle development. Electronic supplementary material The online version of this article (10.1186/s13395-018-0159-9) contains supplementary material, which is available to authorized users.

Amblyopia is a common cause of reduced vision in children. The clinical diagnosis is complicated and requires consideration of the severity of vision loss relative to the characteristics of the disrupting amblyogenic factor. Added to the challenge of a thorough examination of very young children, is the weight of consequence if the amblyogenic factor is not identified and treated appropriately within clinically recommended time frames. Further, the poor visual function may be a symptom of more sinister underlying pathology impacting the visual pathway. This review presents an evidence-based, pragmatic approach to the diagnosis of amblyopia, as a means for guiding best practice for the care of children who present with reduced vision.

Background Revascularisation of left main coronary artery (LMCA) disease can be potentially managed with percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG). Recent randomised controlled trial (RCT) data have added to the literature on this subject and this meta-analysis aims to assess the state of the data to assist in guiding patient treatment decisions. Methods A systematic literature search of Cochrane Library, Embase, OVID, and PubMed MEDLINE was performed. Randomised controlled trials of patients with LMCA disease undergoing PCI with drug eluting stents or CABG were included. Clinical outcomes and adverse events were assessed and analysed. Results Four suitable RCTs of adequate quality and follow-up were identified. The incidence of major adverse cardiac and cerebrovascular events (MACCE) at 3 to 5 years of follow-up was significantly increased with PCI compared to CABG (23.3% vs 18.2%, OR 1.37; 95% CI: 1.18–1.58; p = 2 = 0%) and was largely driven by more repeat revascularisation procedures among patients treated with PCI. There was no statistically significant difference in rates of mortality, myocardial infarction or stroke (either individually or when these outcomes were combined as a composite endpoint). Conclusions Coronary artery bypass grafting and PCI both represent reasonable treatment modalities for LMCA disease in appropriately selected patients. However, where CABG is feasible it offers superior long-term freedom from repeat revascularisation. Longer-term follow-up is required to further clarify the durability of mortality outcomes, especially in patients treated with PCI.

Aims Survivors of out-of-hospital cardiac arrest (OHCA) have a high rate of morbidity and mortality. Invasive cardiac assessment with coronary angiography offers the potential for improving outcomes by facilitating early revascularization. The aim of the present study was to review the published data on early coronary angiography for survivors of OHCA, and its impact on survival and neurological outcomes. Methods Medline, Embase and PubMed were searched with a structured search query. The primary outcome was in-hospital (or if not available, 30 day or 6 month) survival. Rates of survival with good neurological outcome were a secondary endpoint. The time period of the search was from 1 January 1980 to 1 January 2014. Data was pooled with means and 95% CI interval calculated. Meta-analysis of the main outcomes was performed using a weighted random effects model. Results Following review of all identified records, 105 relevant full text articles were retrieved. Fifty had adequate outcome information stratified by the use of coronary angiography for analysis. In studies where a control group was available for comparison, the overall survival in the acute angiography group was 58.8% versus 30.9% in the control group (Odds ratio 2.77, 95% CI 2.06–3.72). Survival with good neurological outcome (as per the Utstein framework) in the early angiography group was 58% versus 35.8% in the control group (Odds ratio 2.20, 95% CI 1.46–3.32). Conclusions Early coronary angiography in patients following OHCA is associated with improved outcome and better survival.

Background— Remote ischemic preconditioning may result in reduction in infarct size during percutaneous coronary intervention (PCI). It is unclear whether remote ischemic postconditioning (RIPost) will reduce the incidence of myocardial injury after PCI, and whether ischemic conditioning of a larger remote organ (thigh versus arm) would provide further myocardial protection. Methods and Results— We randomized 360 patients presenting with stable or unstable angina (28% of patients) and negative Troponin T at baseline to 3 groups: 2 groups received RIPost (induced by ischemia to upper or lower limb), and a third was the control group. RIPost was applied during PCI immediately after stent deployment, by three 5-minute cycles of blood pressure cuff inflation to >200 mm Hg in the arm or thigh (20 mm Hg in the control) with 5-minute breaks between each cycle. The primary end-point was the proportion of patients with Troponin T levels >3×ULN postprocedure (at 6 or 18–24 hours), where ULN stands for upper limit of normal. A total of 120 patients were randomized to each group. There were no differences in baseline characteristics between the 3 groups. The primary outcome occurred in 30%, 35%, and 35% of the arm, thigh, and control groups, respectively ( P =0.64). There were no differences in creatine kinase or high sensitivity C-reactive protein levels after PCI or in the incidence of acute kidney injury between the groups. Conclusions— RIPost during PCI did not reduce the incidence of periprocedural myocardial injury. Similar effect was obtained when remote ischemia was induced to the upper or lower limb. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00970827.

Time to reperfusion is among the strongest predictors of clinical outcome in patients who present with ST elevation acute myocardial infarction. When time to access is equivalent, primary percutaneous coronary intervention has demonstrated superior outcomes to fibrinolysis. However, where significant delays exist in accessing percutaneous intervention, fibrinolysis has an important role. The potential for fibrinolysis delivery in the pre-hospital setting means that delays to primary percutaneous intervention need to be considered from the time that the patient becomes eligible for fibrinolysis in the field. This can be particularly challenging in patients with symptom duration ofless than two hours, as some evidence suggests fibrinolysis may be particularly beneficial in this early phase. Additionally, access to primary percutaneous intervention provided by an experienced operator, in a timely manner at any time of the day or night, is not an available option in many healthcare settings. This review focuses on the current evidence and practice of pre-hospital fibrinolysis and assesses potential roles for this therapy in the future.

The induction of neutralising antibodies to the viral surface glycoprotein, haemagglutinin (HA) is considered the cornerstone of current seasonal and pandemic influenza vaccines. Mapping of neutralising epitopes using monoclonal antibodies (mAbs) helps define mechanisms of antigenic drift, neutralising escape and facilitates pre-pandemic vaccine design. In the present study we reverse engineered the antigenic structure of the HAs of two highly pathogenic H5N1 vaccine strains representative of currently circulating clade 1 and 2.2 H5N1 viruses. The HA sequence of the A/Vietnam/1194/04 clade 1 virus was progressively mutated into the HA sequence of the clade 2.2 virus, A/Bar-headed Goose/Qinghai/1A/05. Fine mapping of clade-specific neutralising epitopes was performed by examining the cross-reactivity of mAbs raised against the native HA of each parent virus. The reactivity across all clade specific mAbs centred around a constellation of mutations at positions 140, 145, 171 and 172, all of which are proximal to the receptor binding site on the membrane distal globular head of the HA. Overlapping cross-reactivity of these antigenic sites suggests that these amino acid positions relate to the antigenic evolution of the H5 clade 1 and 2.2 viruses. This finding may prove useful for the design of vaccines with broader neutralising cross-reactivity against the different H5 HA sublineages currently in circulation. These findings provide important information about the amino acid changes involved in the cross-clade evolution of H5N1 viruses and their potential for human to human transmission; and facilitates a greater understanding of the pandemic potential of H5N1 isolates.

Intravenous loop diuretics remain a first-line component in the management of acute heart failure and suggestions to the contrary are not based on sound evidence nor supported by internationally recognised guidelines on the subject.

Drosophila is used as a model system to show that the common phenotype of mispositioned nuclei occurs via distinct mechanisms in Emery–Dreifuss muscular dystrophy and centronuclear myopathy., Muscle cells are a syncytium in which the many nuclei are positioned to maximize the distance between adjacent nuclei. Although mispositioned nuclei are correlated with many muscle disorders, it is not known whether this common phenotype is the result of a common mechanism. To answer this question, we disrupted the expression of genes linked to Emery–Dreifuss muscular dystrophy (EDMD) and centronuclear myopathy (CNM) in Drosophila and evaluated the position of the nuclei. We found that the genes linked to EDMD and CNM were each necessary to properly position nuclei. However, the specific phenotypes were different. EDMD-linked genes were necessary for the initial separation of nuclei into distinct clusters, suggesting that these factors relieve interactions between nuclei. CNM-linked genes were necessary to maintain the nuclei within clusters as they moved toward the muscle ends, suggesting that these factors were necessary to maintain interactions between nuclei. Together these data suggest that nuclear position is disrupted by distinct mechanisms in EDMD and CNM.

Aortic valve replacement is indicated in patients with severe symptomatic aortic stenosis (AS). Transcatheter aortic valve replacement (TAVR) has evolved as a potential strategy in a growing proportion of patients in preference to surgical aortic valve replacement (SAVR). This meta-analysis aims to assess the differential outcomes of TAVR and SAVR in patients enrolled in published randomised controlled trials (RCTs).A systematic literature search of Cochrane Library, EMBASE, OVID, and PubMed MEDLINE was performed. Randomised controlled trials of patients with severe AS undergoing TAVR compared with SAVR were included. Clinical outcomes and procedural complications were assessed.Five RCTs with a total of 3,828 patients (1,928 TAVR and 1,900 SAVR) were analysed. There was no statistically significant difference in combined rates of all-cause mortality and stroke at 30-days for TAVR vs SAVR (6.3% vs 7.5%; OR 0.83; 95% CI: 0.64-1.08; P=0.17) or at 12 months (17.2% vs 19.2%; OR 0.87; 95% CI: 0.73-1.03; P=0.29). No statistically significant difference was seen for death or stroke separately at any time point although a numerical trend in favour of TAVR for both was recorded. Length of in-patient stay was significantly less with TAVR vs SAVR (9.6 +/- 7.7 days vs 12.2 +/- 8.8 days; OR -2.94; 95% CI: -4.64 to -1.24; P=0.0007). Major vascular complications were more frequent in patients undergoing TAVR vs SAVR (8.2% vs. 4.0%; OR 2.15; 95% CI: 1.62-2.86; P0.00001) but major bleeding was more common among SAVR patients (20.5% vs 44.2%; OR 0.34; 95% CI: 0.22-0.52; P=0.00001).Transcatheter aortic valve replacement and SAVR are associated with overall similar rates of death and stroke among patients in intermediate to high-risk cohorts but with reduced length of in-patient hospital stay.

Please cite this paper as: Verity et al. (2011) Rapid generation of pandemic influenza virus vaccine candidate strains using synthetic DNA. Influenza and Other Respiratory Viruses DOI:10.1111/j.1750-2659.2011.00273.x. Background Vaccination is considered the most effective means of reducing influenza burden. The emergence of H5N1 and pandemic spread of novel H1N1/2009 viruses reinforces the need to have strategies in place to rapidly develop seed viruses for vaccine manufacture. Methods Candidate pandemic vaccine strains consisting of the circulating strain haemagglutinin (HA) and neuraminidase (NA) in an A/PR/8/34 backbone were generated using alternative synthetic DNA approaches, including site-directed mutagenesis of DNA encoding related virus strains, and rapid generation of virus using synthetic DNA cloned into plasmid vectors. Results Firstly, synthetic A/Bar Headed Goose/Qinghai/1A/2005 (H5N1) virus was generated from an A/Vietnam/1194/2004 template using site-directed mutagenesis. Secondly, A/Whooper Swan/Mongolia/244/2005 (H5N1) and A/California/04/09 (H1N1) viruses were generated using synthetic DNA encoding the viral HA and NA genes. Replication and antigenicity of the synthetic viruses were comparable to that of the corresponding non-synthetic viruses. Conclusions In the event of an influenza pandemic, the use of these approaches may significantly reduce the time required to generate and distribute the vaccine seed virus and vaccine manufacture. These approaches also offer the advantage of not needing to handle wild-type virus, potentially diminishing biocontainment requirements.

Background: To review the use of electroretinography and identify common reasons for referral and diagnoses at a tertiary paediatric hospital.

Ninety-six AML patients in 1st CR were evaluated for peak CD34+ cell levels in peripheral blood (PB) during PBSC mobilization and harvest. Distribution of CD34+ cell peaks was determined and cases were grouped on the basis of 50th and 75th percentile: group A, those having a CD34+ cell peak ≤70 × 10(9)/L (n=48); group B, those having a CD34+ cell peak between 70 and 183 × 10(9)/L (n=24); group C, those having a CD34+ cell peak183 × 10(9)/L (n=24). Irrespective of post-remission treatment received, group A had a disease free survival (DFS) of 73%, group B a DFS of 51% and group C of 30% (P=0.0003). In intermediate cytogenetic risk patients, those treated by autologous transplantation had a DFS of 68, 33 and 14% in the groups A, B and C, respectively, (P=0.01) whereas after allogeneic transplantation DFS was 87% in group A+B vs 50% in group C (P=0.009). The peak of CD34+ cells in PB, was an independent predictor for DFS in multivariate analysis.

Wild type human influenza viruses do not usually grow well in embryonated hens' eggs, the substrate of choice for the production of inactivated influenza vaccine, and vaccine viruses need to be developed specifically for this purpose. In the event of a pandemic of influenza, vaccine viruses need to be created with utmost speed. At the onset of the current A(H1N1) pandemic in April 2009, a network of laboratories began a race against time to develop suitable candidate vaccine viruses. Two approaches were followed, the classical reassortment approach and the more recent reverse genetics approach. This report describes the development and the characteristics of current pandemic H1N1 candidate vaccine viruses.

Fibromuscular dysplasia (FMD) of the epicardial coronary arteries is an uncommon entity. We describe the first published case of this condition presenting as a transient ischaemic attack due to thromboembolism from intracardiac thrombus secondary to silent myocardial infarction. We also present the first published case of epicardial coronary FMD with sparing of the renal arteries. This case provides further evidence that FMD of the epicardial coronary arteries frequently involves the mid to distal segments of the left anterior descending artery. A brief review of the literature on FMD is presented.

The capacity of an adjuvant to reduce the amount of antigen required in vaccines would be beneficial in a variety of settings, including situations where antigen is difficult or expensive to manufacture, or in situations where demand exceeds production capacity, such as pandemic influenza. The ability to reduce antigen dose would also be a significant advantage in combination vaccines, and vaccines that by necessity must contain multiple antigens to accommodate variability between strains or genotypes. ISCOMATRIX™ adjuvant was compared to aluminium hydroxide adjuvant (Al(OH3)) for induction of antibody responses and dose sparing of a recombinant HIV gp120 vaccine. Neutralising antibody responses were significantly greater, at the same protein dose, when the gp120 protein was formulated with ISCOMATRIX™ adjuvant compared to Al(OH3). Moreover, strong responses were achieved with up to 100-fold lower doses of gp120 using ISCOMATRIX™ adjuvant. Therefore, ISCOMATRIX™ adjuvant has the potential to substantially reduce the dose of antigen required in human vaccines, without compromising the immune response.

We designed intermediate dose etoposide + G-CSF 16 microg/kg as a Peripheral Blood Stem Cell (PBSC) mobilization schedule suitable for outpatient administration. Forty-one Lymphoma patients received intermediate dose etoposide (200 mg/m(2) i.v. day +1, +2, +3) +G-CSF 16 microg/kg/day. Results of PBSC mobilization in these patients were compared with those of a group of 37 lymphoma patients mobilized using cyclophosphamide (CTX) at dosage of 4 g/m(2) + G-CSF 10 microg/kg/die. Mean peak of CD34+ cells achieved in P.B. and total CD34+ cells harvested were higher in patients mobilized with intermediate dose etoposide (p = 0.003 and p = 0.004, respectively). After transplantation recovery of polymorphonucleate neutrophils (PMN)0.5 x 10(9)/L did not differ significantly between groups: 11.7 days in intermediate dose etoposide group and 11.5 days in CTX group (p = 0.7). Intermediate dose etoposide + G-CSF 16 microg/kg resulted in a maximum length of neutropenia (PMN0.5 x 10(9)/L) of 2 days and neutropenic fever was registered during only 3/41 courses (7.3%). Intermediate dose etoposide + G-CSF 16 microg/kg is a highly effective mobilizing therapy, further, it has the advantage of low hematologic toxicity and can be easily administered as outpatient treatment.