Fatal fat embolism after above knee amputation in a child

We report a fatal pulmonary fat embolism syndrome arising consequent to an above knee amputation in a child. Pre-existing poor respiratory reserves, as a result of severe scoliosis, may have contributed to the fatal outcome

Combining mathematical modelling with in vitro experiments to predict in vivo drug-eluting stent performance

In this study, we developed a predictive model of in vivo stent based drug release and distribution that is capable of providing useful insights into performance. In a combined mathematical modelling and experimental approach, we created two novel sirolimus-eluting stent coatings with quite distinct doses and release kinetics. Using readily measurable in vitro data, we then generated parameterised mathematical models of drug release. These were then used to simulate in vivo drug uptake and retention. Finally, we validated our model predictions against data on drug kinetics and efficacy obtained in a small in vivo evaluation. In agreement with the in vivo experimental results, our mathematical model predicted consistently higher sirolimus content in tissue for the higher dose stents compared with the lower dose stents. High dose stents resulted in statistically significant improvements in three key efficacy measures, providing further evidence of a basic relationship between dose and efficacy within DES. However, our mathematical modelling suggests a more complex relationship is at play, with efficacy being dependent not only on delivering an initial dose of drug sufficient to achieve receptor saturation, but also on the consequent drug release rate being tuned to ensure prolonged saturation. In summary, we have demonstrated that our combined in vitro experimental and mathematical modelling framework may be used to predict in vivo DES performance, opening up the possibility of an in silico approach to optimising the drug release profile and ultimately the effectiveness of the device

Non-union following bilateral simultaneos Ganz trochanteric osteotomy

Between January 2003 and December 2004, 13 patients underwent bilateral resurfacing arthroplasty via a Ganz trochanteric osteotomy. This bilateral group was mobilised fully weight-bearing with crutches. During the same period 139 Ganz trochanteric osteotomies were performed for unilateral hip resurfacing. These patients were mobilised with crutches, weight-bearing up to 10 kg on the operated leg. Nine osteotomies (32%) in the bilateral group subsequently developed a symptomatic non-union requiring revision of fixation. This compares with 10 patients (7%) in the unilateral group. Applying the Fisher's exact test, the difference reached significance (P=0.0004). In two patients a second revision was required to achieve union. In one patient, revision of trochanteric fixation precipitated a deep infection. Protected weight-bearing following a Ganz trochanteric osteotomy is important to the success of the procedure. Simultaneous bilateral hip arthroplasty through a Ganz approach should be avoided. If it is undertaken, we recommend that patients should be non weight-bearing for 6 weeks following surgery. Non-union following a Ganz trochanteric osteotomy for arthroplasty carries a significant morbidity

Speeding up ecological and evolutionary computations in R; essentials of high performance computing for biologists

Computation has become a critical component of research in biology. A risk has emerged that computational and programming challenges may limit research scope, depth, and quality. We review various solutions to common computational efficiency problems in ecological and evolutionary research. Our review pulls together material that is currently scattered across many sources and emphasizes those techniques that are especially effective for typical ecological and environmental problems. We demonstrate how straightforward it can be to write efficient code and implement techniques such as profiling or parallel computing. We supply a newly developed R package (aprof) that helps to identify computational bottlenecks in R code and determine whether optimization can be effective. Our review is complemented by a practical set of examples and detailed Supporting Information material (S1–S3 Texts) that demonstrate large improvements in computational speed (ranging from 10.5 times to 14,000 times faster). By improving computational efficiency, biologists can feasibly solve more complex tasks, ask more ambitious questions, and include more sophisticated analyses in their research

The role of peri-hepatic drain placement in liver surgery: a prospective analysis

AbstractBackgroundThe standard use of an intra-operative perihepatic drain (IPD) in liver surgery is controversial and mainly supported by retrospective data. The aim of this study was to evaluate the role of IPD in liver surgery.MethodsAll patients included in a previous, randomized trial were analysed to determine the association between IPD placement, post-operative complications (PC) and treatment. A multivariate analysis identified predictive factors of PC.ResultsOne hundred and ninety-nine patients were included in the final analysis of which 114 (57%) had colorectal liver metastases. IPD (n = 87, 44%) was associated with pre-operative biliary instrumentation (P = 0.023), intra-operative bleeding (P < 0.011), Pringle's manoeuver(P < 0.001) and extent of resection (P = 0.001). Seventy-seven (39%) patients had a PC, which was associated with pre-operative biliary instrumentation (P = 0.048), extent of resection (P = 0.002) and a blood transfusion (P = 0.001). Patients with IPD had a higher rate of high-grade PC (25% versus 12%, P = 0.008). Nineteen patients (9.5%) developed a post-operative collection [IPD (n = 10, 11.5%) vs. no drains (n = 9, 8%), P = 0.470]. Seven (8%) patients treated with and 9(8%) without a IPD needed a second drain after surgery, P = 1. Resection of ≥3 segments was the only independent factor associated with PC [odds ratio (OR) = 2, P = 0.025, 95% confidence interval (CI) 1.1–3.7].DiscussionIn spite of preferential IPD use in patients with more complex tumours/resections, IPD did not decrease the rate of PC, collections and the need for a percutaneous post-operative drain. IPD should be reserved for exceptional circumstances in liver surgery

Long term cost effectiveness of interventions for obesity:A Mendelian randomisation study

Background The prevalence of obesity has increased in the United Kingdom, and reliably measuring the impact on quality of life and the total healthcare cost from obesity is key to informing the cost-effectiveness of interventions that target obesity, and determining healthcare funding. Current methods for estimating cost-effectiveness of interventions for obesity may be subject to confounding and reverse causation. The aim of this study is to apply a new approach using mendelian randomisation for estimating the cost-effectiveness of interventions that target body mass index (BMI), which may be less affected by confounding and reverse causation than previous approaches. Methods and findings We estimated health-related quality-adjusted life years (QALYs) and both primary and secondary healthcare costs for 310,913 men and women of white British ancestry aged between 39 and 72 years in UK Biobank between recruitment (2006 to 2010) and 31 March 2017. We then estimated the causal effect of differences in BMI on QALYs and total healthcare costs using mendelian randomisation. For this, we used instrumental variable regression with a polygenic risk score (PRS) for BMI, derived using a genome-wide association study (GWAS) of BMI, with age, sex, recruitment centre, and 40 genetic principal components as covariables to estimate the effect of a unit increase in BMI on QALYs and total healthcare costs. Finally, we used simulations to estimate the likely effect on BMI of policy relevant interventions for BMI, then used the mendelian randomisation estimates to estimate the cost-effectiveness of these interventions. A unit increase in BMI decreased QALYs by 0.65% of a QALY (95% confidence interval [CI]: 0.49% to 0.81%) per year and increased annual total healthcare costs by £42.23 (95% CI: £32.95 to £51.51) per person. When considering only health conditions usually considered in previous cost-effectiveness modelling studies (cancer, cardiovascular disease, cerebrovascular disease, and type 2 diabetes), we estimated that a unit increase in BMI decreased QALYs by only 0.16% of a QALY (95% CI: 0.10% to 0.22%) per year. We estimated that both laparoscopic bariatric surgery among individuals with BMI greater than 35 kg/m2, and restricting volume promotions for high fat, salt, and sugar products, would increase QALYs and decrease total healthcare costs, with net monetary benefits (at £20,000 per QALY) of £13,936 (95% CI: £8,112 to £20,658) per person over 20 years, and £546 million (95% CI: £435 million to £671 million) in total per year, respectively. The main limitations of this approach are that mendelian randomisation relies on assumptions that cannot be proven, including the absence of directional pleiotropy, and that genotypes are independent of confounders. Conclusions Mendelian randomisation can be used to estimate the impact of interventions on quality of life and healthcare costs. We observed that the effect of increasing BMI on health-related quality of life is much larger when accounting for 240 chronic health conditions, compared with only a limited selection. This means that previous cost-effectiveness studies have likely underestimated the effect of BMI on quality of life and, therefore, the potential cost-effectiveness of interventions to reduce BMI

Central Line-Associated Bloodstream Infection Risk Factors in a Pediatric Population

Background Central venous line (CVL) placement in children is often necessary for treatment and may be complicated by central line-associated bloodstream infection (CLABSI). We hypothesize that line type and clinical and demographic factors at line placement impact CLABSI rates. Methods This is a single-institution case-control study of pediatric patients (≤18 years old) admitted between January 1, 2015, and December 31, 2019. Case patients had a documented CLABSI. Control patients had a CVL placed during the study period and were matched by sex and age in a 2:1 ratio. Bivariate and multivariate logistic regression analysis was performed. Results We identified 78 patients with a CLABSI and 140 patients without a CLABSI. After controlling for pertinent covariates, patients undergoing tunneled or non-tunneled CVL had higher odds of CLABSI than those undergoing PICC (OR 2.51, CI 1.12-5.64 and OR 3.88, CI 1.06-14.20 respectively), and patients undergoing port placement had decreased odds of CLABSI compared to PICC (OR .05, CI 0.01-.51). There were lower odds of CLABSI when lines were placed for intravenous medications compared to those placed for solid tumor malignancy (OR .15, CI .03-.79). Race and age were not statistically significant risk factors. Discussion Central lines placed for medication administration compared to solid tumors, PICC compared to tunneled and non-tunneled central lines, and ports compared to PICC were associated with lower odds of CLABSI. Future improvement efforts should focus on PICC and port placement in appropriate patients to decrease CLABSI rates

The adequacy of Hepato‐Pancreato‐Biliary training: how closely do perceptions of fellows and programme directors align?

BackgroundHepatopancreatobiliary fellowship programmes have recently undergone significant changes with regards to training standards, case‐volume thresholds and multimodality educational platforms. The goals of this study were to compare the perspectives of fellows and programme directors (PDs) on perceptions of readiness to enter practice and identify core Hepato‐Pancreato‐Biliary (HPB) procedures that require increased emphasis during training.MethodsThis survey targeted PDs and trainees participating in the Fellowship Council/AHPBA pathway. Data related to demographics, education and career plans were collected. Analysis of PD and fellow opinions regarding their confidence to perform core HPB procedures was completed.ResultsThe response rate was 88% for both fellows (21/24) and PDs (23/26). There was good agreement between PDs and fellows in the perception of case volumes. Select differences where PDs ranked higher perceptions included major hepatectomies (PDs: 87% versus fellows: 57%, P = 0.04), pancreaticoduodenectomies (100% versus 81%, P = 0.04) and laparoscopic distal pancreatectomies (78% versus 43%, P = 0.03). ‘Good or excellent’ case volumes translated into increased fellow readiness, except for some pancreatitis procedures, laparoscopic distal pancreatectomies and potentially major hepatectomies.ConclusionsThis study provides insight into content domains that may require additional attention to achieve an appropriate level of proficiency and confidence upon completion of training.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113116/1/hpb12457.pd

A genomics-informed, SNP association study reveals FBLN1 and FABP4 as contributing to resistance to fleece rot in Australian Merino sheep

<p>Abstract</p> <p>Background</p> <p>Fleece rot (FR) and body-strike of Merino sheep by the sheep blowfly <it>Lucilia cuprina </it>are major problems for the Australian wool industry, causing significant losses as a result of increased management costs coupled with reduced wool productivity and quality. In addition to direct effects on fleece quality, fleece rot is a major predisposing factor to blowfly strike on the body of sheep. In order to investigate the genetic drivers of resistance to fleece rot, we constructed a combined ovine-bovine cDNA microarray of almost 12,000 probes including 6,125 skin expressed sequence tags and 5,760 anonymous clones obtained from skin subtracted libraries derived from fleece rot resistant and susceptible animals. This microarray platform was used to profile the gene expression changes between skin samples of six resistant and six susceptible animals taken immediately before, during and after FR induction. Mixed-model equations were employed to normalize the data and 155 genes were found to be differentially expressed (DE). Ten DE genes were selected for validation using real-time PCR on independent skin samples. The genomic regions of a further 5 DE genes were surveyed to identify single nucleotide polymorphisms (SNP) that were genotyped across three populations for their associations with fleece rot resistance.</p> <p>Results</p> <p>The majority of the DE genes originated from the fleece rot subtracted libraries and over-representing gene ontology terms included defense response to bacterium and epidermis development, indicating a role of these processes in modulating the sheep's response to fleece rot. We focused on genes that contribute to the physical barrier function of skin, including keratins, collagens, fibulin and lipid proteins, to identify SNPs that were associated to fleece rot scores.</p> <p>Conclusions</p> <p>We identified FBLN1 (fibulin) and FABP4 (fatty acid binding protein 4) as key factors in sheep's resistance to fleece rot. Validation of these markers in other populations could lead to vital tests for marker assisted selection that will ultimately increase the natural fleece rot resistance of Merino sheep.</p