North Bristol NHS Trust

About: North Bristol NHS Trust is a healthcare organization based out in Bristol, United Kingdom. It is known for research contribution in the topics: Population & Medicine. The organization has 2204 authors who have published 2811 publications receiving 61110 citations.

Quantitative analysis of ERG expression and its splice isoforms in formalin-fixed, paraffin-embedded prostate cancer samples: association with seminal vesicle invasion and biochemical recurrence.

Abstract: Objectives: The proto-oncogene ETS-related gene ( ERG ) is consistently overexpressed in prostate cancer. Alternatively spliced isoforms of ERG have variable biological activities; inclusion of exon 11 (72 base pairs [bp]) is associated with aggressiveness and progression of disease. Exon 10 (81 bp) has also been shown to be alternatively spliced. Within this study, we assess whether ERG protein, messenger RNA (mRNA), and ERG splice isoform mRNA expression is altered as prostate cancer progresses. Methods: Detection of the TMPRSS2-ERG fusion was done using direct methods (reverse transcription polymerase chain reaction [PCR] and fluorescence in situ hybridization) and indirect methods for ERG mRNA and protein expression using quantitative PCR and immunohistochemistry, respectively. A linear equation method was used to quantitatively determine relative proportions of ERG variants ( ERG72/Δ72 , ERG81/Δ81 ) for each sample. Results: ERG mRNA and protein expression is increased in patients with advanced prostate cancer, with higher levels of ERG expression significantly associated with seminal vesicle invasion (stage pT3b) and biochemical recurrence. Genes involved in cell migration and invasiveness (matrix metalloproteinase 7, osteopontin, and septin 9) are increased in prostate cancers that overexpress ERG . In addition, there is a clear indication of increased retention of exons 10 and 11 in prostate cancer. Conclusions: Analysis of ERG and its variants may be valuable in determining prognosis and development of prostate cancer.

Comparative Effectiveness in Perioperative Outcomes of Robotic versus Open Radical Cystectomy: Results from a Multicenter Contemporary Retrospective Cohort Study

Abstract: Background The comparative effectiveness of robotic-assisted radical cystectomy (RARC) versus open radical cystectomy (ORC) in terms of perioperative outcomes is still a matter of debate affecting payors, physicians, and patients. Objective To evaluate comparative perioperative and longer-term morbidity of RARC versus ORC in a multicenter contemporary retrospective cohort of patients. Design, setting, and participants This retrospective multicenter study included patients with bladder cancer treated with radical cystectomy at 10 academic centers between 2000 and 2017. Outcome measurements and statistical analysis Intraoperative outcomes including blood loss and operative time as well as postoperative outcomes including time to discharge, complication, readmission, reoperation, and mortality rates at 30 and 90 d were assessed. Multiple imputation and inverse probability of treatment weighting (IPTW) were used. IPTW-multivariable-adjusted regression and logistic analyses were performed to evaluate the associations of RARC versus ORC with perioperative outcomes at 30 and 90 d. Results and limitations Overall, 1887 patients (1197 RARC and 690 ORC) were included in the study. After IPTW-adjusted analysis, no differences between the groups in terms of preoperative characteristics were observed. RARC was associated with lower blood loss (p Conclusions While RARC was associated with less blood loss and shorter hospital stay, it also led to longer operation times and more readmissions. There were no differences in 30- and 90-d complications. Because there are no apparent differences in safety between ORC and RARC in expert centers, differences in oncologic and cost-effectiveness outcomes are likely to drive decision making regarding RARC utilization. Patient summary In this study we investigated the differences between RARC and ORC in terms of perioperative outcomes. We found no difference in early and late complications. We concluded that, to date, differences in oncologic and cost-effectiveness outcomes should drive decision making regarding RARC utilization.

Luteinizing hormone/chorionic gonadotrophin receptor overexpressed in granulosa cells from polycystic ovary syndrome ovaries is functionally active

Abstract: Polycystic ovarian syndrome (PCOS) is associated with anovulatory infertility. Luteinizing hormone/chorionic gonadotrophin receptor (LHCGR), which is critical for ovulation, has been suggested to be expressed prematurely in the ovarian follicles of women with PCOS. This study aimed to analyse the expression and activity of LHCGR in ovarian granulosa cells from PCOS patients and the involvement of ARF6 small GTPase in LHCGR internalization. Granulosa cells (GC) isolated from follicular fluid collected during oocyte retrieval from normal women (n = 19) and women with PCOS (n = 17) were used to study differences in LHCGR protein expression and activity between normal and PCOS patients. LHCGR expression is up-regulated in GC from PCOS women. LHCGR in PCOS GC is functionally active, as shown by increased cAMP production upon human gonadotrophin (HCG)-stimulation. Moreover, ARF6 is highly expressed in GC from PCOS patients and HCG-stimulation increases the concentrations of active ARF6. The inhibition of ARF6 activation attenuates HCG-induced LHCGR internalization in both normal and PCOS GC, indicating that there are no alterations in LHCGR internalisation in GC from PCOS. In conclusion, the expression and activation of LHCGR and ARF6 are up-regulated in GC from PCOS women but the mechanism of agonist-induced LHCGR internalization is unaltered.

Use of Intraosseous Needles in Neonates: A Systematic Review.

Abstract: Background: The use of intraosseous (IO) access during resuscitation is widely accepted and promoted in paediatric medicine but features less prominently in neonatal training. Whilst umbilical venous catheterization (UVC) is a reliable method of delivering emergency drugs and fluids, it is not always achievable in a timely manner. IO access warrants exploration as an alternative. Aim: Conduct a systematic review of existing literature to examine the evidence for efficacy and safety of IO devices in neonatal patients, from birth to discharge. Method: A search of PubMed, Ovid, Medline, and Embase was carried out. Abstracts were screened for relevance to focus on neonatal-specific literature and studies which carried out separate analyses for neonates (infants <28 days of age or resident on a neonatal unit). Results: One case series and 12 case reports describe IO device insertion into 41 neonates, delivering a variety of drugs, including adrenaline (epinephrine) and volume resuscitation. Complications range from none to severe. Cadaveric studies show that despite a small margin for error, IO devices can be correctly sited in neonates. Simulation studies suggest that IO devices may be faster and easier to site than UVC, even in experienced hands. Conclusion: IO access should be available on neonatal units and considered for early use in neonates where other access routes have failed. Appropriate training should be available to staff in addition to existing life support and UVC training. Further studies are required to assess the optimal device, position, and whether medication can be delivered IO as effectively as by UVC. If IO devices provide a faster method of delivering adrenaline effectively than UVC, this may lead to changes in neonatal resuscitation practice.