Pancreatic cancer is detected late in the disease process and has an extremely poor prognosis. A blood-based biomarker that can enable early detection of disease, monitor response to treatment, and ...potentially allow for personalized treatment would be of great benefit. This review analyzes the literature regarding two potential biomarkers, circulating tumor cells (CTCs) and cell-free DNA (cfDNA), with regard to pancreatic ductal adenocarcinoma. The origin of CTCs and the methods of detection are discussed and a decade of research examining CTCs in pancreatic cancer is summarized, including both levels of CTCs and analyzing their molecular characteristics and how they may affect survival in both advanced and early disease and allow for treatment monitoring. The origin of cfDNA is discussed, and the literature over the past 15 years is summarized. This includes analyzing cfDNA for genetic mutations and methylation abnormalities, which have the potential to be used for the detection and prognosis of pancreatic ductal adenocarcinoma. However, the research certainly remains in the experimental stage, warranting future large trials in these areas.
An in vitro zymosan-activation of the Complement system, through the lectin and alternative pathways, was performed in pooled human serum over a 24h time-course. Activation was quantitatively ...monitored by measuring the concentration of the upper Complement pathway fragment, C3a and the terminal pathway fragment, C5a. Upper Complement showed a maximum activation of 39% and the time-to-maximum activation reduced 8-fold, as a highly non-linear function of the zymosan dose. The C3a:C5a molar ratio rose to a maximum of 1100:1, before terminal pathway activation was initiated; indicating a flux threshold. This threshold appears to be exceeded once more than 31% of C3 molecules are activated. Above this threshold, significant activation of terminal pathway was observed; reducing the molar ratio to 17:1. The C5a/C3a molar ratio was used to determine the terminal pathway activation relative to total Complement activation and ranged from 0.1–0.8%. This depicts upper Complement activation to be 49-fold larger than terminal activation, a figure consistent with the observed density of the membrane attack complex in the membrane of cells. Our results thus indicate that the relative activity of opsonisation is ~50-fold greater than membrane attack complex formation, in vitro, in the pooled serum phenotype. The results suggest a potential clinical application, where an in vitro analysis of a patient on admission, or prior to a surgical procedure, would indicate their upper Complement activation capacity, with activation of C3 measured thereafter, or post-operatively. A patient with an exhausted upper Complement capacity may be vulnerable to infections and complications, such as sepsis.
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•Serum C3a and C5a concentrations were assayed as markers of upper and terminal Complement activation.•Upper Complement activation peaked as 39% of C3 molecules were converted to C3a.•More than 31% upper Complement activation triggered significant activation of the terminal pathway.•The molar ratio of C3a:C5a decreased from ~1000:1 to 17:1 once the terminal pathway was activated.•Upper Complement (opsonisation) is 49-fold more active than the terminal pathway (cell lysis).
The identification of the make and model of a total knee replacement (TKR) is a necessary step prior to revision surgery for periprosthetic fracture, loosening, wear or infection. Current methods may ...fail to correctly identify the implant up to 10% of the time. This study presents the training of a Convolutional Neural Network (CNN) to automatically identify the make and model of seven TKR implants or the absence of a TKR on plain-film radiographs. Our dataset consists of 588 anteroposterior (AP) X-rays of the knee. They were randomly divided into a train, validation and testing sets with a 50:25:25 split. A CNN based on the ResNet-18 architecture was trained with the best model selected using validation results. The final model was tested on the hold-out test dataset.
The trained network demonstrated perfect accuracy in classifying a hold-out test dataset of X-rays to one of the eight labelled classes. Saliency maps demonstrated the outlines of the implants are key to a given prediction.
Further research will benefit from larger datasets with more complete coverage of the possible implants. The ability to recognize that implants are outside the networks trained distribution is essential to such an algorithm operating safely in clinical practice. With these issues and limitations addressed there is potential that such an algorithm could save clinicians time and reduce instances where implants are not identified pre-operatively, simplifying re-operative cases and improving clinical outcomes.
A 49-year-old diabetic male was admitted to a hospital in 2018 following a 3-week history of worsening dyspnoea and pedal oedema. Early review and investigations indicated acute heart failure. ...Transthoracic echocardiogram (TTE) revealed mitral regurgitation (MR), aneurysmal change of the ventricles, a ventricular septal defect (VSD) and systolic dysfunction. Coronary angiogram demonstrated a significant left anterior descending and right coronary artery disease. He was diagnosed with a late presenting myocardial infarction (MI) with secondary mechanical complications. Mechanical complications of MI frequently require surgical intervention. The patient underwent a repair of VSD, mitral valve repair, excision of aneurysmal segment and coronary artery bypass grafting. Post-operative recovery was complicated by a sternal wound infection managed in conjunction with the plastic surgeons. A post-operative TTE showed a repaired ventricular septum and no residual MR. Early recognition and appropriate medical optimisation are required to achieve good patient outcomes.
•Invasive coronary angiography was performed in high risk transplant candidates.•Multidisciplinary decision on listing for transplant and coronary revascularisation.•169 patients listed underwent ...coronary angiography, 73 had coronary artery disease.•Coronary artery disease did not affect 5-year survival post-transplant.
Cardiovascular assessment is central to evaluation of liver transplant (LT) candidates. However, there is a lack of consensus on the diagnostic algorithm for screening for coronary artery disease (CAD), and the place for invasive coronary angiography (ICA) remains undefined.
We retrospectively analysed 1201 adults who underwent elective LT assessment over a 5-year period. For patients who underwent LT, survival data to 5 years post-LT was collected.
ICA was performed in 259 (21.6%): 134 no CAD, 58 mild, 33 moderate, and 34 severe. Detection of CAD was associated with age (OR 1.08, P < 0.01), current smoking (OR 4.92, P < 0.01) and prior CAD (OR 8.93, P < 0.001). Poor performance on cardiopulmonary exercise test (CPET) was associated with age (OR 1.02, P < .05) and diabetes mellitus (OR 1.54, P < 0.05). 122 (10.2%) patients were declined due to severity of cardiovascular disease.
169/779 (21.7%) patients listed for LT had undergone ICA, and CAD was present in 73/169 (43.2%). The non-risk-adjusted all-cause post-LT 5-year survival was 82.6%, with no difference in survival in those with and without CAD on ICA. In patients with CAD, diabetes was associated with reduced survival (OR 3.78, P < 0.05).
Multi-modality cardiac evaluation is useful in high-risk patients undergoing LT assessment. ICA can be used with non-invasive assessments and risk factors to delineate candidacy. In selected patients with CAD, LT has been undertaken with comparable post-LT survival.
Optimization of the operating factors to achieve the maximum yield of biodiesel through transesterification reaction was performed by using face-centered central composite design (FCCD) approach of ...response surface methodology. A total of 29 independent batch experiments were considered in this model to carefully observe the effect of operating factors, such as the volume ratio of methanol/oil, catalyst (KOH) weight percent, reaction temperature, and reaction time. The FCCD model predicted that a maximum yield of 99.5% biodiesel would be achieved from flaxseed oil at a reaction temperature of 59 °C, 0.51% catalyst, the reaction time of 33 min, and a molar ratio of methanol to flaxseed oil of 5.9:1. Experimental verification of the predicted yield under the optimum conditions gave a maximum yield of 98 ± 2%, which is in very good agreement with the predicted value of the model. The physicochemical properties of the flaxseed oil-derived biodiesel were compared with those of standard biodiesel to identify and verify the quality of the produced biodiesel. All observed physicochemical parameters of the flaxseed oil-derived biodiesel were closely in agreement with those of standard biodiesel. Thus, demonstrating that the production of high-quality biodiesel from flaxseed oil is a viable option.
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•Potassium hydroxide was used as catalyst for the transesterification of flax seed oil.•Optimization of the biodiesel production from flax seed oil was conducted.•The optimized conditions for biodiesel production was methanol/oil molar ratio (5.9:1), catalyst weight (0.51%), temperature (59 °C), reaction time (33 min).•At optimized conditions the yield was experimentally found to be 98.6%.•The produced flax seed biodiesel was closely in agreement with those of standard biodiesel specification.
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