Quality assurance in surgical trials of arteriovenous grafts for haemodialysis: A systematic review, a narrative exploration and expert recommendations.

BACKGROUND: Introducing new procedures and challenging established paradigms requires well-designed randomised controlled trials (RCT). However, RCT in surgery present unique challenges with much of treatment tailored to the individual patient circumstances, refined by experience and limited by organisational factors. There has been considerable debate over the outcomes of arteriovenous grafts (AVG) compared to AVF, but any differences may reflect differing practice and potential variability. It is essential, therefore, when considering an RCT of a novel surgical procedure or device that quality assurance (QA) is defined for both the new approach and the comparator. The aim of this systematic review was to evaluate the QA standards performed in RCT of AVG using a multi-national, multi-disciplinary approach and propose an approach for future RCT. METHOD: The methods of this have been previously registered (PROSPERO: CRD420234284280) and published. In summary, a four-stage review was performed: identification of RCT of AVG, initial review, multidisciplinary appraisal of QA methods and reconciliation. QA measures were sought in four areas - generic, credentialing, standardisation and monitoring, with data abstracted by a multi-national, multi-speciality review body. RESULTS: QA in RCT involving AVG in all four domains is highly variable, often sub-optimally described and has not improved over the past three decades. Few RCT established or defined a pre-RCT level of experience, none documented a pre-trial education programme, or had minimal standards of peri-operative management, no study had a defined pre-trial monitoring programme, and none assessed technical performance. CONCLUSION: QA in RCT is a relatively new area that is expanding to ensure evidence is reliable and reproducible. This review demonstrates that QA has not previously been detailed, but can be measured in surgical RCT of vascular access, and that a four-domain approach can easily be implemented into future RCT.

What are the observed procedural costs of vascular access surgery? Protocol for a systematic review.

INTRODUCTION: A central component in the introduction of a novel surgical procedure or technique is an evaluation of its cost efficiency when compared with a benchmark standard of care. Accurate assessment of costs is thus essential in ensuring appropriate allocation of resources within a healthcare system. The treatment of kidney failure requires a significant volume of resources, and vascular access provision is the main modifiable cost. The costs of providing this service are obscured by generic NHS reference costs, which lack adequate granularity to allow meaningful comparisons between treatments. The aim of this systematic review will be to assess the reporting of procedural costs in all published economic analyses of vascular access surgery and perform a comparison of the reported procedural costs involved in arteriovenous fistula (AVF) and arteriovenous graft (AVG) creation. This will provide an estimate as to the accuracy of the NHS reference costs in this field. METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be followed. A systematic search will be performed of the MEDLINE, Embase and Cochrane databases to identify full-text economic analyses of vascular access for haemodialysis in which the procedural cost of AVF or AVG creation is reported. Publications in English from 1 January 2000 to 30 August 2023, will be eligible for inclusion. Studies will be selected by title and abstract review, followed by a full-text review using inclusion and exclusion criteria. Studies not reporting the procedural costs of surgery will be excluded. Data collected will pertain to procedural costs of AVF and AVG creation. Costs will be adjusted to a common currency using a gross domestic product (GDP) deflator index and conversion rates based on purchasing power parities for GDP. Comparison with NHS reference costs will indicate their reliability for use in future economic analyses in this field. ETHICS AND DISSEMINATION: Ethical approval is not required for this systematic review. Findings will be disseminated through peer-reviewed publications and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42023458779.

Early-cannulation arteriovenous grafts: Multidisciplinary learning is essential to optimize outcomes.

BACKGROUND: It is likely that there will be an increasing role for early-cannulation arteriovenous grafts (ecAVG) with a wider recognition of the need to tailor vascular access to avoid futile procedures and unnecessary TCVC. However, experience of these products is not common and limited to early surgical adopters, with little information on the systemic changes and multi-disciplinary care needed to optimize outcomes. The aim of this study was to report the impact of a multi-disciplinary approach on quantifiable outcomes. METHODS: A retrospective analysis of a prospectively maintained database of 295 ecAVG implanted over an 8-year time-period was performed. Indicative outcomes were chosen to reflect nephrology (patient selection), nursing care (cannulation complications of infection and pseudoaneurysm) and radiology (thrombosis) on cumulative impact (functional patency) over three distinct time periods. RESULTS: The incidence of ecAVG increased 10-fold over the three time periods. The use of ecAVG changed significantly from salvage tertiary access to TCVC avoidance and salvage of existing AVF. Nursing complications reduced markedly with significantly fewer over-cannulation episodes and pseudo-aneurysms. With an improved pro-active surveillance programme, the time to first thrombosis doubled and the risk of thrombosis halved. Ultimately this resulted in significantly improved functional patency with a risk of ecAVG loss less than one-third by the last time-period. CONCLUSIONS: All aspects of ecAVG use require scrutiny and critical appraisal. Failure or success is not simply achieved by performing good technical surgery with an efficacious product, but by the care taken across a wide range of elements spanning case selection, implantation, use and maintenance.

Bayesian Disease Mapping to Identify High-Risk Population for Oral Cancer: A Retrospective Spatiotemporal Analysis.

Objectives: Bayesian mapping is an effective spatiotemporal approach to identify high-risk geographic areas for diseases and has not been used to identify oral cancer hotspots in Australia previously. This retrospective disease mapping study was undertaken to identify the oral cancer trends and patterns within the Queensland state in Australia. Methods: This study included data obtained from Queensland state Cancer Registry from 1982 to 2018. Domains mapped included the oral cancer incidence and mortality in Queensland (QLD). Local government areas (LGAs) and suburbs were utilized as geographical units for the estimation using Bayesian mapping approach. Results: Of the 78 LGAs, 21 showed high-oral cancer incidence as measured using higher median smoothed incidence risk (SIR), above the state average. Specifically, nine LGAs within predominantly rural areas had SIR above 100% of the state average. Of these, only one LGA (Mount Isa City) had a median smoothed SIR and 95% CI of 2.61 (2.14-3.15) which was constantly above 100% of the state average. Furthermore, mortality risk estimated using smoothed mortality risk (SMR), were significantly higher than the state average in 31 LGAs. Seventeen LGAs had a median SMR above 100% of the state average while three LGAs had the highest overall, 3- and 5-year mortality risks. Considering the 95% credible interval which is indicative of the uncertainty around the estimates, three LGAs had the highest overall mortality risks-Yarrabah Aboriginal Shire (3.80 (2.16-6.39)), Cook Shire (3.37 (2.21-5.06)), and Mount Isa City (3.04 (2.40-3.80)). Conclusion: Bayesian disease mapping approach identified multiple incidence and mortality hotspots within regional areas of the Queensland. Findings from our study can aid in designing targeted public health screening and interventions for primary prevention of oral cancer in regional and remote communities.

Quality assurance in surgical trials of arteriovenous grafts for haemodialysis: protocol for a systematic review.

INTRODUCTION: Decisions regarding the optimal vascular access for haemodialysis patients are becoming increasingly complex, and the provision of vascular access is open to variations in systems of care as well as surgical experience and practice. Two main surgical options are recognised: arteriovenous fistula and arteriovenous graft (AVG). All recommendations regarding AVG are based on a limited number of randomised controlled trials (RCTs). It is essential that when considering an RCT of a surgical procedure, an appropriate definition of quality assurance (QA) is made for both the new approach and the comparator, otherwise replication of results or implementation into clinical practice may differ from published results. The aim of this systematic review will be to assess the methodological quality of RCT involving AVG, and the QA measures implemented in delivering interventions in these trials. METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be followed. A systematic search will be performed of the MEDLINE, Embase and Cochrane databases to identify relevant literature. Studies will be selected by title and abstract review, followed by a full-text review using inclusion and exclusion criteria. Data collected will pertain to generic measures of QA, credentialing of investigators, procedural standardisation and performance monitoring. Trial methodology will be compared against a standardised template developed by a multinational, multispecialty review body with experience in vascular access. A narrative approach will be taken to synthesise and report data. ETHICS AND DISSEMINATION: Ethical approval is not required as it is a protocol for a systematic review. Findings will be disseminated through peer-reviewed publications and conference presentations, with the ultimate aim of providing recommendations for future RCT of AVG design.

Oral cavity and oropharyngeal carcinoma disparities in age and survival in Indigenous and non-Indigenous populations of Queensland.

OBJECTIVES: To investigate the risk and prognosis of oral squamous cell carcinoma (SCC) between Indigenous and non-Indigenous populations of Queensland. MATERIALS AND METHODS: Retrospective analysis of data from the Queensland Cancer Registry (QCR) between the years 1982-2018. Main outcome measures were age at diagnosis and cumulative survival to compare the risk and prognosis of oral SCC between the populations. RESULTS: 9424 patients with self-declared ethnicity were identified with oral SCC from the QCR, with a male to female ratio of 2.56:1. Of these patients, 9132 were non-Indigenous (96.9%) and 292 Indigenous (3.1%). Indigenous people were significantly younger at diagnosis (mean (SD) age 54.3 (10.1) years), compared to 62.0 (12.1) years in non-Indigenous people. Mean survival in the full cohort was 4.3 years (SD: 5.6), with Indigenous people presenting a significant shorter mean survival of 2.0 years (SD: 3.5) when compared with 4.4 years (SD: 5.7) in non-Indigenous people (p < 0.001). CONCLUSIONS: Indigenous Australians are diagnosed at a significantly younger age and present with worse survival and poorer prognosis. Due to missing variables in the Queensland Cancer Registry, it is not possible in the current study to ascertain the scientific or social reasons behind these disparities. CLINICAL RELEVANCE: Results from this study can inform public policy and raise awareness in Queensland regarding disparity in oral cancer prognosis.

Predicting oral cancer survival-Development and validation of an Asia-Pacific nomogram.

BACKGROUND: Nomograms are graphical calculating devices that predict response to treatment during cancer management. Oral squamous cell carcinoma (OSCC) is a lethal and deforming disease of rising incidence and global significance. The aim of this study was to develop a nomogram to predict individualized OSCC survival using a population-based dataset obtained from Queensland, Australia and externally validated using a cohort of OSCC patients treated in Hong Kong. METHODS: Clinico-pathological data for newly diagnosed OSCC patients, including age, sex, tumour site and grading, were accessed retrospectively from the Queensland Cancer Registry (QCR) in Australia and the Clinical Data Analysis and Reporting System (CDARS) in Hong Kong. Multivariate Cox proportional hazard regression was used to construct overall survival (OS) and cancer-specific survival (CSS) prediction models. Nomograms were internally validated using 10-fold cross validation, and externally validated against the Hong Kong dataset. RESULTS: Data from 9885 OSCC patients in Queensland and 465 patients from Hong Kong were analysed. All clinico-pathological variables significantly influenced survival outcomes. Nomogram calibration curves demonstrated excellent agreement between predicted and actual probability for Queensland patients. External validation in the Hong Kong population demonstrated slightly poorer nomogram performance, but predictive power remained strong. CONCLUSION: Based upon readily available data documenting patient demographic and clinico-pathological variables, predictive nomograms offer pragmatic aid to clinicians in individualized treatment planning and prognosis assessment in contemporary OSCC management.

Influence of time between surgery and adjuvant radiotherapy on prognosis for patients with head and neck squamous cell carcinoma: A systematic review.

The timing of postoperative radiotherapy following surgical intervention in patients with head and neck cancer remains a controversial issue. This review aims to summarize findings from available studies to investigate the influence of time delays between surgery and postoperative radiotherapy on clinical outcomes. Articles between 1 January 1995 and 1 February 2022 were sourced from PubMed, Web of Science, and ScienceDirect. Twenty-three articles met the study criteria and were included; ten studies showed that delaying postoperative radiotherapy might negatively impact patients and lead to a poorer prognosis. Delaying the start time of radiotherapy, 4 weeks after surgery did not result in poorer prognoses for patients with head and neck cancer, although delays beyond 6 weeks might worsen patients' overall survival, recurrence-free survival, and locoregional control. Prioritization of treatment plans to optimize the timing of postoperative radiotherapy regimes is recommended.

Recruitment into randomised trials of arteriovenous grafts: A systematic review.

Although randomised controlled trials (RCT) are considered the optimal form of evidence, there are relatively few in surgery. Surgical RCT are particularly likely to be discontinued with poor recruitment cited as a leading reason. Surgical RCT present challenges over and above those seen in drug trials as the treatment under study may vary between procedures, between surgeons in one unit, and between units in multi-centred RCT. The most contentious and debated area of vascular access remains the role of arteriovenous grafts, and thus the quality of the data that is used to support opinions, guidelines and recommendations is critical. The aim of this review was to determine the extent of variation in the planning and recruitment in all RCT involving AVG. The findings of this are stark: there have been only 31 RCT performed in 31 years, the vast majority of which exhibited major limitations severe enough to undermine the results. This underlines the need for better quality RCT and data, and further inform the design of future studies. Perhaps most fundamental is the planning for a RCT that accounts for the intended population, the uptake of a RCT and the attrition for the significant co-morbidity in this population.

Oral cancer in Australia: Rising incidence and worsening mortality.

BACKGROUND: Oral cancer, predominantly squamous cell carcinoma (SCC), is a lethal and deforming disease of rising incidence. Although largely preventable by eliminating harmful tobacco and alcohol risk factor behaviour, 5-year survival rates remain around 50%, primarily due to late presentation of advanced stage disease. Whilst low socio-economic status, regional and remote location and indigenous status are associated with head and neck cancer in general, detailed incidence and demographic data for oral SCC in Australia are limited. This study aimed to characterise the Queensland population at risk of oral SCC development. METHODS: Following ethical approval, the Queensland Cancer Register (QCR) dataset was analysed to determine patterns of incidence, anonymised patient demographics, clinical presentation and outcome data for oral SCC cases diagnosed between 1982 and 2018. RESULTS: Data from 9887 patients were obtained. Mean age at diagnosis was 64.55 years, with a male-to-female ratio of 2.51:1; males were diagnosed at a younger age (p < 0.001). At study census date, 59% of patients had died, with females demonstrating longer mean survival (p < 0.001). Clinicopathological data confirmed that SCC most commonly arose from tongue sites (49%) and, whilst tumours were predominantly moderately differentiated in nature (63%), patients with poorly differentiated carcinomas exhibited shortest survival times (p < 0.05). Over the 36-year study period, the number of diagnoses increased 4.49-fold, whilst the number of deaths increased 19.14-fold. CONCLUSION: Oral SCC poses a significant and growing healthcare problem in Queensland. In the absence of national screening, characterising the high-risk oral SCC population facilitates pragmatic opportunities to raise disease awareness, to deliver targeted screening and effective primary prevention strategies, and to provide early interventional treatment intervention to reduce disease mortality and morbidity.

The Impact of Surgery on Circulating Malignant Tumour Cells in Oral Squamous Cell Carcinoma.

IMPORTANCE: The extent to which surgical management of oral squamous cell carcinoma (OSCC) disseminates cancer is currently unknown. OBJECTIVE: To determine changes in numbers of malignant cells released into systemic circulation immediately following tumour removal and over the first seven post-operative days. DESIGN: An observational study from March 2019 to February 2021. SETTING: This study was undertaken at Queen Mary University Hospital, Hong Kong. PARTICIPANTS: Patients with biopsy-proven oral SCC were considered for eligibility. Patients under 18 years of age, pregnant or lactating women and those unable to understand the study details or unable to sign the consent form were excluded. Twenty-two patients were enrolled (12 male and 10 female) with mean age of 65.5 years. INTERVENTION: Primary tumour management was performed in accord with multi-disciplinary team agreement. Anaesthesia and post-operative care were unaltered and provided in accord with accepted clinical practice. MAIN OUTCOMES AND MEASURES: Three types of malignant cells detected in peripheral blood samples were enumerated and sub-typed based on the presence of chromosomal aneuploidy and immunohistochemical characteristics. To test the hypothesis that malignant cells are released by surgery, the numbers of single circulating tumour cells (CTCs), circulating tumour microemboli (CTM) and circulating endothelial cells (CTECs) were recorded pre-operatively, upon tumour removal and the second and seventh post-operative days. RESULTS: Of a potential 88 data collection points, specimens were not obtainable in 12 instances. Tumour removal resulted in a statistically significant increase in CTCs and a non-statistically significant rise in CTMs. CTCs, CTMs and CTECs were detected in the majority of patients up to the seventh post-operative day. Individual patients demonstrated striking increases in post-operative CTCs and CTECs numbers. CONCLUSIONS/RELEVANCE: Surgical management of OSCC has a significant impact on the systemic distribution of cancer cells. Malignant cells persisted post-operatively in a manner independent of recognised staging methods suggesting differences in tumour biology between individuals. Further investigation is warranted to determine whether circulating malignant cell enumeration can be used to refine risk stratification for patients with OSCC.

Red Meat Derived Glycan, N-acetylneuraminic Acid (Neu5Ac) Is a Major Sialic Acid in Different Skeletal Muscles and Organs of Nine Animal Species-A Guideline for Human Consumers.

Sialic acids (Sias) are acidic monosaccharides and red meat is a notable dietary source of Sia for humans. Among the Sias, N-acetylneuraminic acid (Neu5Ac) and 2-keto-3-deoxy-D-glycero-D-galacto-2-nonulosonic acid (KDN) play multiple roles in immunity and brain cognition. On the other hand, N-glycolylneuraminic acid (Neu5Gc) is a non-human Sia capable of potentiating cancer and inflammation in the human body. However, their expression within the animal kingdom remains unknown. We determined Neu5Ac and KDN in skeletal muscle and organs across a range (n = 9) of species using UHPLC and found that (1) caprine skeletal muscle expressed the highest Neu5Ac (661.82 ± 187.96 µg/g protein) following by sheep, pig, dog, deer, cat, horse, kangaroo and cattle; (2) Among organs, kidney contained the most Neu5Ac (1992−3050 µg/g protein) across species; (3) ~75−98% of total Neu5Ac was conjugated, except for in dog and cat muscle (54−58%); (4) <1% of total Sia was KDN, in which ~60−100% was unconjugated, with the exception of sheep liver and goat muscle (~12−25%); (5) Neu5Ac was the major Sia in almost all tested organs. This study guides consumers to the safest red meat relating to Neu5Ac and Neu5Gc content, though the dog and cat meat are not conventional red meat globally.

Explainable ensemble learning model improves identification of candidates for oral cancer screening.

OBJECTIVES: Artificial intelligence could enhance the use of disparate risk factors (crude method) for better stratification of patients to be screened for oral cancer. This study aims to construct a meta-classifier that considers diverse risk factors to identify patients at risk of oral cancer and other suspicious oral diseases for targeted screening. MATERIALS AND METHODS: A retrospective dataset from a community oral cancer screening program was used to construct and train the novel voting meta-classifier. Comprehensive risk factor information from this dataset was used as input features for eleven supervised learning algorithms which served as base learners and provided predicted probabilities that are weighted and aggregated by the meta-classifier. Training dataset was augmented using SMOTE-ENN. Additionally, Shapley additive explanations (SHAP) values were generated to implement the explainability of the model and display the important risk factors. RESULTS: Our meta-classifier had an internal validation recall, specificity, and AUROC of 0.83, 0.86, and 0.85 for identifying the risk of oral cancer and 0.92, 0.60, and 0.76 for identifying suspicious oral mucosal disease respectively. Upon external validation, the meta-classifier had a significantly higher AUROC than the crude/current method used for identifying the risk of oral cancer (0.78 vs 0.46; p = 0.001) Also, the meta-classifier had better recall than the crude method for predicting the risk of suspicious oral mucosal diseases (0.78 vs 0.47). CONCLUSION: Overall, these findings showcase that our approach optimizes the use of risk factors in identifying patients for oral screening which suggests potential clinical application.

Saliva-based cell-free DNA and cell-free mitochondrial DNA in head and neck cancers have promising screening and early detection role.

BACKGROUND: Cell-free DNA (cfDNA) and cell-free mitochondrial DNA (cf-mtDNA) have been postulated as potential diagnostic and prognostic biomarkers for different human malignancies. Early detection of head and neck malignancies is fundamental for optimal patient management. This study, therefore, aimed to assess the utility of saliva-based liquid biopsy as a noninvasive source of cfDNA and cf-mtDNA for detecting head and neck cancer (HNSCC). METHODS: One hundred thirty-three patients diagnosed with either oral leukoplakia (OLK) or HNSCC were compared with 137 healthy volunteers. An unstimulated whole saliva sample was collected from each participant. The absolute copy numbers of salivary cf-mtDNA and cfDNA were quantified using Multiplex Quantitative PCR. Two diagnostic indices based on the investigated molecules were assessed for their ability to differentiate between different diagnostic categories. RESULTS: The median scores of cfDNA and cf-mtDNA were statistically significantly higher among HNSCC patients (p < 0.05), revealing area under the curve values of 0.758 and 0.826, respectively. The associated accuracy for this test in discriminating HNSCC from other diagnostic categories was 77.37% for the cfDNA-based index and 80.5% for the cf-mtDNA-based index. The median score of cfDNA was statistically significantly higher for patients with severe epithelial dysplasia (OED) compared to those with epithelial keratosis with no OED and mild OED. However, there was no significant difference between controls and OLK individuals. CONCLUSION: cfDNA and cf-mtDNA showed potential for use as precision medicine tools to detect HNSCC. Further multi-centre prospective studies are warranted to assess the prognostic utility of these molecules.

Construction of machine learning-based models for cancer outcomes in low and lower-middle income countries: A scoping review.

Background: The impact and utility of machine learning (ML)-based prediction tools for cancer outcomes including assistive diagnosis, risk stratification, and adjunctive decision-making have been largely described and realized in the high income and upper-middle-income countries. However, statistical projections have estimated higher cancer incidence and mortality risks in low and lower-middle-income countries (LLMICs). Therefore, this review aimed to evaluate the utilization, model construction methods, and degree of implementation of ML-based models for cancer outcomes in LLMICs. Methods: PubMed/Medline, Scopus, and Web of Science databases were searched and articles describing the use of ML-based models for cancer among local populations in LLMICs between 2002 and 2022 were included. A total of 140 articles from 22,516 citations that met the eligibility criteria were included in this study. Results: ML-based models from LLMICs were often based on traditional ML algorithms than deep or deep hybrid learning. We found that the construction of ML-based models was skewed to particular LLMICs such as India, Iran, Pakistan, and Egypt with a paucity of applications in sub-Saharan Africa. Moreover, models for breast, head and neck, and brain cancer outcomes were frequently explored. Many models were deemed suboptimal according to the Prediction model Risk of Bias Assessment tool (PROBAST) due to sample size constraints and technical flaws in ML modeling even though their performance accuracy ranged from 0.65 to 1.00. While the development and internal validation were described for all models included (n=137), only 4.4% (6/137) have been validated in independent cohorts and 0.7% (1/137) have been assessed for clinical impact and efficacy. Conclusion: Overall, the application of ML for modeling cancer outcomes in LLMICs is increasing. However, model development is largely unsatisfactory. We recommend model retraining using larger sample sizes, intensified external validation practices, and increased impact assessment studies using randomized controlled trial designs. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=308345, identifier CRD42022308345.

Predicting Overall Survival Using Machine Learning Algorithms in Oral Cavity Squamous Cell Carcinoma.

BACKGROUND/AIM: Machine learning (ML) models are often modelled to predict cancer prognosis but rarely consider spatial factors in a region. Hence this study explored machine learning algorithms utilising Local Government Areas (LGAs) in Queensland, Australia to spatially predict 3- and 5-year prognosis of oral cancer patients and provide clinical interpretability of the predicted outcome made by the ML model. PATIENTS AND METHODS: Data from a total of 3,841 oral cancer patients were retrieved from the Queensland Cancer Registry (QCR). Synthesizing minority oversampling technique together with edited nearest neighbours (SMOTE-ENN) was used to pre-process unbalanced datasets. Five ML models: logistic regression, random forest classifier, XGBoost, Gaussian Naïve Bayes and Voting Classifier were trained. Predictive features were age, sex, LGAs, tumour site and differentiation. Outcomes were 3- and 5-year overall survival of patients. Model performances on test set were evaluated using area under the curve and F1 scores. SHapley Additive exPlanations (SHAP) method was applied to the best performing model for model interpretation of the predicted outcome. RESULTS: The Voting Classifier was the best performing model with F1 score of 0.58 and 0.64 for 3- and 5-year overall survival, respectively. Age was the most important feature in the Voting Classifier in 3- and 5-year prognosis prediction. LGAs at diagnosis was the top 3 predictive feature for both 3- and 5-year models. CONCLUSION: The Voting Classifier demonstrated the best overall performance in classifying both 3- and 5-year overall survival of oral cancer patients in Queensland. SHAP method provided clinical understanding of the predictive features of the Voting Classifier.

Machine Learning-Based Genome-Wide Salivary DNA Methylation Analysis for Identification of Noninvasive Biomarkers in Oral Cancer Diagnosis.

This study aims to examine the feasibility of ML-assisted salivary-liquid-biopsy platforms using genome-wide methylation analysis at the base-pair and regional resolution for delineating oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs). A nested cohort of patients with OSCC and OPMDs was randomly selected from among patients with oral mucosal diseases. Saliva samples were collected, and DNA extracted from cell pellets was processed for reduced-representation bisulfite sequencing. Reads with a minimum of 10× coverage were used to identify differentially methylated CpG sites (DMCs) and 100 bp regions (DMRs). The performance of eight ML models and three feature-selection methods (ANOVA, MRMR, and LASSO) were then compared to determine the optimal biomarker models based on DMCs and DMRs. A total of 1745 DMCs and 105 DMRs were identified for detecting OSCC. The proportion of hypomethylated and hypermethylated DMCs was similar (51% vs. 49%), while most DMRs were hypermethylated (62.9%). Furthermore, more DMRs than DMCs were annotated to promoter regions (36% vs. 16%) and more DMCs than DMRs were annotated to intergenic regions (50% vs. 36%). Of all the ML models compared, the linear SVM model based on 11 optimal DMRs selected by LASSO had a perfect AUC, recall, specificity, and calibration (1.00) for OSCC detection. Overall, genome-wide DNA methylation techniques can be applied directly to saliva samples for biomarker discovery and ML-based platforms may be useful in stratifying OSCC during disease screening and monitoring.

An Analysis of Vascular Access Thrombosis Events From the Proactive IV irOn Therapy in hemodiALysis Patients Trial.

Introduction: Treatment of anemia in dialysis patients has been associated with increased risk of vascular access thrombosis (VAT). Proactive IV irOn Therapy in hemodiALysis Patients (PIVOTAL) was a clinical trial of proactive compared with reactive i.v. iron therapy in patients requiring hemodialysis. We analyzed the trial data to determine whether randomized treatment arm, alongside other clinical and laboratory variables, independently associated with VAT. Methods: In PIVOTAL, 2141 adult patients were randomized. The type of vascular access (arteriovenous fistula [AVF], arteriovenous graft [AVG], or central venous catheter [CVC]) was recorded at baseline and every month after randomization. The associations between clinical and laboratory data and first VAT were evaluated in a multivariate analysis. Results: A total of 480 (22.4%) participants experienced VAT in a median of 2.1 years of follow-up. In multivariable analyses, treatment arm (proactive vs. reactive) was not an independent predictor of VAT (hazard ratio [HR] 1.13, P = 0.18). Diabetic kidney disease (HR 1.45, P < 0.001), AVG use (HR 2.29, P < 0.001), digoxin use (HR 2.48, P < 0.001), diuretic use (HR 1.25, P = 0.02), female sex (HR 1.33, P = 0.002), and previous/current smoker (HR 1.47, P = 0.004) were independently associated with a higher risk of VAT. Angiotensin receptor blocker (ARB) use (HR 0.66, P = 0.01) was independently associated with a lower risk of VAT. Conclusion: In PIVOTAL, VAT occurred in nearly 1 quarter of participants in a median of just >2 years. In this post hoc analysis, randomization to proactive i.v. iron treatment arms did not increase the risk of VAT.