Factors in perioperative care that determine blood loss in liver surgery

AbstractObjectivesExcessive blood loss during liver surgery contributes to postoperative morbidity and mortality and the minimizing of blood loss improves outcomes. This study examines pre- and intraoperative factors contributing to blood loss and identifies areas for improvement.MethodsAll patients who underwent elective hepatic resection between June 2007 and June 2009 were identified. Detailed information on the pre- and perioperative clinical course was analysed. Univariate and multivariate analyses were used to identify factors associated with intraoperative blood loss.ResultsA total of 175 patients were studied, of whom 95 (54%) underwent resection of three or more segments. Median blood loss was 782ml. Greater blood loss occurred during major resections and prolonged surgery and was associated with an increase in postoperative complications (P= 0.026). Peak central venous pressure (CVP) of >10cm H2O was associated with increased blood loss (P= 0.01). Although no differences in case mix were identified, blood loss varied significantly among anaesthetists, as did intraoperative volumes of i.v. fluids and transfusion practices.ConclusionsThis study confirms a relationship between CVP and blood loss in hepatic resection. Intraoperative CVP values were higher than those described in other studies. There was variation in the intraoperative management of patients. Collaboration between surgical and anaesthesia teams is required to minimize blood loss and the standardization of intraoperative anaesthesia practice may improve outcomes following liver surgery

Strategies to Support Recruitment of Patients With Life-Limiting Illness for Research: The Palliative Care Research Cooperative Group

The Palliative Care Research Cooperative group (PCRC) is the first clinical trials cooperative for palliative care in the United States

Prostate cancer detection through unbiased capture of methylated cell-free DNA

Funding: Cancer Research UK, CRUK Career Development Fellowship, University of Cambridge W.D. Armstrong Trust Fund, John Black Prostate Cancer Foundation Young Investigator Award. This research was also supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014).Prostate cancer screening using prostate-specific antigen (PSA) has been shown to reduce mortality but with substantial overdiagnosis, leading to unnecessary biopsies. The identification of a highly specific biomarker using liquid biopsies, represents an unmet need in the diagnostic pathway for prostate cancer. In this study, we employed a method that enriches for methylated cell-free DNA fragments coupled with a machine learning algorithm which enabled the detection of metastatic and localized cancers with AUCs of 0.96 and 0.74, respectively. The model also detected 51.8% (14/27) of localized and 88.7% (79/89) of patients with metastatic cancer in an external dataset. Furthermore, we show that the differentially methylated regions reflect epigenetic and transcriptomic changes at the tissue level. Notably, these regions are significantly enriched for biologically relevant pathways associated with the regulation of cellular proliferation and TGF-beta signaling. This demonstrates the potential of circulating tumor DNA methylation for prostate cancer detection and prognostication.Peer reviewe

Effectiveness of epidural analgesia following open liver resection

AbstractObjectivesEpidural analgesia is often considered the reference standard for pain relief following major abdominal surgery; however, the provision of analgesia in the context of liver surgery raises unique challenges. This study investigated the effectiveness of analgesia and the postoperative course of patients who did or did not receive epidural analgesia following liver resection.MethodsData were collected retrospectively on 177 patients who underwent open liver resection between June 2007 and June 2009. Patients were divided into two groups consisting, respectively, of those who received epidural analgesia (Epidural group, n= 148) and those who did not (No-Epidural group, n= 29).ResultsIn the Epidural group, 27 patients (18%) required i.v. opiate analgesia on the day of surgery (DoS) or the first postoperative day (POD1). The Epidural group received significantly more i.v. colloid solution on the DoS (median: 1500ml vs. 750ml, range: 0–12000ml vs. 0–3500ml; P= 0.004) and POD1 (median: 0ml vs. 0ml, range: 0–5000ml vs. 0–1000ml; P= 0.018), and total fluid on the DoS and POD1 combined (median: 6522ml vs. 5453ml, range: 2150–21300ml vs. 2875–15886ml; P= 0.032).ConclusionsEpidural analgesia provided inadequate postoperative pain relief in approximately 20% of liver resection patients and was associated with the administration of significantly greater volumes of i.v. colloid solution

Effects of Subthalamic Nucleus Lesions and Stimulation upon Corticostriatal Afferents in the 6-Hydroxydopamine-Lesioned Rat

Abnormalities of striatal glutamate neurotransmission may play a role in the pathophysiology of Parkinson's disease and may respond to neurosurgical interventions, specifically stimulation or lesioning of the subthalamic nucleus (STN). The major glutamatergic afferent pathways to the striatum are from the cortex and thalamus, and are thus likely to be sources of striatal neuronally-released glutamate. Corticostriatal terminals can be distinguished within the striatum at the electron microscopic level as their synaptic vesicles contain the vesicular glutamate transporter, VGLUT1. The majority of terminals which are immunolabeled for glutamate but are not VGLUT1 positive are likely to be thalamostriatal afferents. We compared the effects of short term, high frequency, STN stimulation and lesioning in 6-hydroxydopamine (6OHDA)-lesioned rats upon striatal terminals immunolabeled for both presynaptic glutamate and VGLUT1. 6OHDA lesions resulted in a small but significant increase in the proportions of VGLUT1-labeled terminals making synapses on dendritic shafts rather than spines. STN stimulation for one hour, but not STN lesions, increased the proportion of synapses upon spines. The density of presynaptic glutamate immuno-gold labeling was unchanged in both VGLUT1-labeled and -unlabeled terminals in 6OHDA-lesioned rats compared to controls. Rats with 6OHDA lesions+STN stimulation showed a decrease in nerve terminal glutamate immuno-gold labeling in both VGLUT1-labeled and -unlabeled terminals. STN lesions resulted in a significant decrease in the density of presynaptic immuno-gold-labeled glutamate only in VGLUT1-labeled terminals. STN interventions may achieve at least part of their therapeutic effect in PD by normalizing the location of corticostriatal glutamatergic terminals and by altering striatal glutamatergic neurotransmission

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Using High-Performance Liquid Chromatography to Assess Genetic Susceptibility to Gestational and Lactational Benzo[a]pyrene Exposure

"Traffic-related air pollution is a complex mixture that includes the neurotoxic polycyclic aromatic hydrocarbon benzo[a]pyrene. We use mice to model human genetic variation in genes related to BaP metabolism to identify those at higher risk from early life exposure. Following behavioral testing of mice exposed to BaP during pregnancy and breast-feeding, we measure neurotransmitter levels in multiple brain regions. We found significant differences in levels of both dopamine and serotonin and their metabolites. The greatest changes were in the hippocampus which has a critical role in learning and memory and the prefrontal cortex which is required for normal cognitive function."2021 Celebration of Student Research and Creativity presentationhttps://youtu.be/8Bh_jwIxTO

Intersectionality Policymaking Toolkit

Grounded in core tenets of intersectionality, the Intersectionality Policymaking Toolkit (IPT) was developed to help policymakers, practitioners, and other stakeholders with their health equity work in the area of maternal and child health.