Demographics, natural history and treatment outcomes of non-molar gestational choriocarcinoma: a UK population study.

OBJECTIVE: To investigate the demographics, natural history and treatment outcomes of non-molar gestational choriocarcinoma. DESIGN: A retrospective national population-based study. SETTING: UK 1995-2015. POPULATION: A total of 234 women with a diagnosis of gestational choriocarcinoma, in the absence of a prior molar pregnancy, managed at the UKs two gestational trophoblast centres in London and Sheffield. METHODS: Retrospective review of the patient's demographic and clinical data. Comparison with contemporary UK birth and pregnancy statistics. MAIN OUTCOMES: Incidence statistics for non-molar choriocarcinoma across the maternal age groups. Cure rates for patients by FIGO prognostic score group. RESULTS: Over the 21-year study period, there were 234 cases of non-molar gestational choriocarcinoma, giving an incidence of 1:66 775 relative to live births and 1:84 226 to viable pregnancies. For women aged under 20, the incidence relative to viable pregnancies was 1:223 494, for ages 30-34, 1:80 227, and for ages 40-45, 1:41 718. Treatment outcomes indicated an overall 94.4% cure rate. Divided by FIGO prognostic groups, the cure rates were low-risk group 100%, high-risk group 96% and ultra-high-risk group 80.5%. CONCLUSIONS: Non-molar gestational choriocarcinoma is a very rare diagnosis with little prior detailed information on the demographics and natural history. The data in this study give age-related incidence data based on a large national population study. The results also demonstrated the widely varying natural history of this rare malignancy and the marked correlation of disease incidence with rising maternal age. TWEETABLE ABSTRACT: National gestational choriocarcinoma database indicates a close association between increasing maternal age and incidence.

Gene editing in the context of an increasingly complex genome.

The reporting of the first draft of the human genome in 2000 brought with it much hope for the future in what was felt as a paradigm shift toward improved health outcomes. Indeed, we have now mapped the majority of variation across human populations with landmark projects such as 1000 Genomes; in cancer, we have catalogued mutations across the primary carcinomas; whilst, for other diseases, we have identified the genetic variants with strongest association. Despite this, we are still awaiting the genetic revolution in healthcare to materialise and translate itself into the health benefits for which we had hoped. A major problem we face relates to our underestimation of the complexity of the genome, and that of biological mechanisms, generally. Fixation on DNA sequence alone and a 'rigid' mode of thinking about the genome has meant that the folding and structure of the DNA molecule -and how these relate to regulation- have been underappreciated. Projects like ENCODE have additionally taught us that regulation at the level of RNA is just as important as that at the spatiotemporal level of chromatin.In this review, we chart the course of the major advances in the biomedical sciences in the era pre- and post the release of the first draft sequence of the human genome, taking a focus on technology and how its development has influenced these. We additionally focus on gene editing via CRISPR/Cas9 as a key technique, in particular its use in the context of complex biological mechanisms. Our aim is to shift the mode of thinking about the genome to that which encompasses a greater appreciation of the folding of the DNA molecule, DNA- RNA/protein interactions, and how these regulate expression and elaborate disease mechanisms.Through the composition of our work, we recognise that technological improvement is conducive to a greater understanding of biological processes and life within the cell. We believe we now have the technology at our disposal that permits a better understanding of disease mechanisms, achievable through integrative data analyses. Finally, only with greater understanding of disease mechanisms can techniques such as gene editing be faithfully conducted.

Oil residue contamination of continental shelf sediments of the Gulf of Mexico.

We have investigated the distribution of a heavy oil residue in the coastal sediments of the Gulf of Mexico. The amount of the contamination was determined by high-temperature pyrolysis coupled with the Gas Chromatography-Mass Spectrometry (GCMS) of air-dried sediments. The pyrolysis products contain straight-chain saturated and unsaturated hydrocarbons, such as dodecane and 1-dodecene, resulting in a very characteristic pattern of double peaks in the GCMS. Hydrocarbons containing 8 to 23 carbon atoms were detected in the pyrolysis products. Using thermal pyrolysis we have found that the sediment samples collected along Texas, Louisiana, and Mississippi shores contain no detectable traces of oil residue, but most of the samples collected along Alabama and Florida shores contain ~200ppm of heavy oil residue.

Improving efficiency in robotic theatres in the Royal Wolverhampton NHS Trust: a gynaecology theatres perspective.

Improving efficiency within the operating theatre is always a key concern when running a successful operating list. However, with robotic surgery, this can become paramount. Robotic procedures require a more technical set up, additional planning, and good solid communication within the multidisciplinary team. Efficiency needs to be at the forefront of everyone's mind. Forward planning requires knowledge of the procedures being carried out and adequate training with the robot. Trouble shooting will also improve efficiency in robotic surgery, as being able to expect the unexpected can be a major advantage. This article looks at the hurdles encountered by the theatre team at Royal Wolverhampton Trust at the implementation of the robotic programme, and how the theatre team made adjustments to working practice in order to minimise disruption and maximise efficiency.

'Being there' for women with metastatic breast cancer: a pan-European patient survey.

BACKGROUND: Understanding their experiences of diagnosis is integral to improving the quality of care for women living with advanced/metastatic breast cancer. METHODS: A survey, initiated in March 2011, was conducted in two stages. First, the views of 47 breast cancer-related patient groups in eight European countries were sought on standards of breast cancer care and unmet needs of patients. Findings were used to develop a patient-centric survey to capture personal experiences of advanced breast cancer to determine insights into the 'trade-off' between extending overall survival and side effects associated with its treatment. The second online survey was open to women with locally advanced or metastatic breast cancer, or their carers, and responders were recruited through local patient groups. Data were collected via anonymous local language questionnaires. RESULTS: The online stage II survey received a total of 230 responses from 17 European countries: 94% of respondents had locally advanced or metastatic breast cancer and 6% were adult carers. Although the overall experience of care was generally good/excellent (77%), gaps were still perceived in terms of treatment choice and information provision. Treatment choice for patients was felt to be lacking by 32% of responders. In addition, 68% of those who responded would have liked more information about future medical treatments and research, with 57% wishing to receive this information from their oncologist. Two-thirds (66%) of women with advanced breast cancer, or their carers, believed life-extending treatment to be important so that they can spend more time with family and friends, and 67% said that the treatment was worthwhile, despite potential associated side effects. CONCLUSION: These findings show a continuing need to provide women with advanced breast cancer with better information and emphasise the importance that these patients often place on prolonging survival.

Safety, cost-effectiveness and feasibility of daycase paracentesis in the management of malignant ascites with a focus on ovarian cancer.

BACKGROUND: Paracentesis for malignant ascites is usually performed as an in-patient procedure, with a median length of stay (LoS) of 3-5 days, with intermittent clamping of the drain due to a perceived risk of hypotension. In this study, we assessed the safety of free drainage and the feasibility and cost-effectiveness of daycase paracentesis. METHOD: Ovarian cancer admissions at Hammersmith Hospital between July and October 2009 were audited (Stage 1). A total of 21 patients (Stage 2) subsequently underwent paracentesis with free drainage of ascites without intermittent clamping (October 2010-January 2011). Finally, 13 patients (19 paracenteses, Stage 3), were drained as a daycase (May-December 2011). RESULTS: Of 67 patients (Stage 1), 22% of admissions and 18% of bed-days were for paracentesis, with a median LoS of 4 days. In all, 81% of patients (Stage 2) drained completely without hypotension. Of four patients with hypotension, none was tachycardic or symptomatic. Daycase paracentesis achieved complete ascites drainage without complications, or the need for in-patient admission in 94.7% of cases (Stage 3), and cost £954 compared with £1473 for in-patient drainage. CONCLUSIONS: Free drainage of malignant ascites is safe. Daycase paracentesis is feasible, cost-effective and reduces hospital admissions, and potentially represents the standard of care for patients with malignant ascites.

Uterine artery pulsatility index: a predictor of methotrexate resistance in gestational trophoblastic neoplasia.

BACKGROUND: Neo-angiogenesis is a hallmark of cancer. The aim of this study was to test the hypothesis, in a prospective patient cohort, that in low-risk gestational trophoblastic neoplasia (LR-GTN) the uterine artery pulsatility index (UAPI), a measure of tumour vascularity, can predict resistance to methotrexate chemotherapy (MTX-R). METHODS: 286 LR-GTN patients (Charing Cross Hospital (CXH) score 0-8, or FIGO score 0-6) were treated with methotrexate between January 2008 and June 2011 at CXH. During staging investigations, patients underwent a Doppler ultrasound to assess the UAPI. RESULTS: 239 patients were assessable for both UAPI and MTX-R. The median UAPI was lower (higher vascularity) in MTX-R compared with MTX-sensitive patients (0.8 vs 1.4, P<0.0001). In multivariate logistic regression, UAPI≤1 predicted MTX-R, independent of both CXH and FIGO scores. The risk of MTX-R in patients with a FIGO score of 6 and UAPI≤1 was 100% vs 20% in patients with UAPI>1 (χ(2) P<0.0001). CONCLUSION: UAPI represents an independently validated clinically useful predictor of MTX-R in LR-GTN. Further, consideration of whether to incorporate UAPI into the FIGO scoring system is now warranted so that patients with a score of 6 and a UAPI ≤1 might be upstaged and offered combination chemotherapy rather than MTX.

Cardiac beta ARK1 inhibition prolongs survival and augments beta blocker therapy in a mouse model of severe heart failure.

Chronic human heart failure is characterized by abnormalities in beta-adrenergic receptor (betaAR) signaling, including increased levels of betaAR kinase 1 (betaARK1), which seems critical to the pathogenesis of the disease. To determine whether inhibition of betaARK1 is sufficient to rescue a model of severe heart failure, we mated transgenic mice overexpressing a peptide inhibitor of betaARK1 (betaARKct) with transgenic mice overexpressing the sarcoplasmic reticulum Ca(2+)-binding protein, calsequestrin (CSQ). CSQ mice have a severe cardiomyopathy and markedly shortened survival (9 +/- 1 weeks). In contrast, CSQ/betaARKct mice exhibited a significant increase in mean survival age (15 +/- 1 weeks; P < 0.0001) and showed less cardiac dilation, and cardiac function was significantly improved (CSQ vs. CSQ/betaARKct, left ventricular end diastolic dimension 5.60 +/- 0.17 mm vs. 4.19 +/- 0.09 mm, P < 0.005; % fractional shortening, 15 +/- 2 vs. 36 +/- 2, P < 0.005). The enhancement of the survival rate in CSQ/betaARKct mice was substantially potentiated by chronic treatment with the betaAR antagonist metoprolol (CSQ/betaARKct nontreated vs. CSQ/betaARKct metoprolol treated, 15 +/- 1 weeks vs. 25 +/- 2 weeks, P < 0.0001). Thus, overexpression of the betaARKct resulted in a marked prolongation in survival and improved cardiac function in a mouse model of severe cardiomyopathy that can be potentiated with beta-blocker therapy. These data demonstrate a significant synergy between an established heart-failure treatment and the strategy of betaARK1 inhibition.

Inpatient vs. outpatient pain management: results of a randomised controlled trial.

Inpatient and outpatient cognitive behavioural pain management programmes for mixed chronic pain patients were compared. Patients were randomly allocated to the 4 week inpatient programme or to the 8 half day per week outpatient programme, or to a waiting list control group. Staff, teaching materials, and setting were the same for the two treatment groups. Patients were assessed pre-treatment, and at 1 month after discharge, and treated patients also at 6 months and 1 year after discharge, by assessors blind to treatment group; assessments included physical, functional and psychological measures, and medication use. In total, 121 mixed chronic pain patients (mean age 50 years; mean chronicity 8.1 years) were included in the study, following medical examination to ensure that no further medical treatment was appropriate. There was no change in the control group; inpatients and outpatients, comparable before treatment, both made significant improvements in physical performance and psychological function, and reduced medication use. Inpatients made greater gains, and maintained them better at 1 year; they also used less health care than outpatients. There were no outstanding predictors of improvement other than treatment group.

Sheep pancreatic microsomes as an alternative to the dog source for studying protein translocation.

A procedure is described for the preparation of rough membrane vesicles of endoplasmic-reticular origin from the pancreas of sheep. These isolated membranes translocate, process and glycosylate in vitro-translated heterologous proteins in a manner comparable with that exhibited by dog pancreatic microsomes.

Closing the audit loop: a patient satisfaction survey.

A patient satisfaction survey was carried out in a nuclear medicine department of a large acute hospital. Surveys were initially carried out by interview and postal techniques, with approximately 100 responders in each category. The responses to each question were not significantly different for the two types of survey, although overall there was a significantly larger number of dissatisfied responses in the postal survey (22%) compared with the interview study (12%). The postal survey was repeated after 1 year, thus completing the audit loop. A significant reduction in dissatisfied responses has occurred in those areas which had been addressed following the criticisms revealed by the first survey.