Normal morphometry of the biliary tree in pediatric and adult populations: A systematic review and meta-analysis.

PURPOSE: This study aimed to characterise the normal morphometry of the biliary tree in pediatric and adult populations, through a systematic review and meta-analysis. METHODS: This study, conducted using the PRISMA guidelines and registered with PROSPERO, searched MEDLINE, EMBASE, SCOPUS and Web of Science databases up to October 2022, and updated to August 2023. Studies that reported extractable data on diameter and length of the right, left and common hepatic ducts (LHD, RHD and CHD), and common bile duct (CBD) were included. Quality of the included studies were assessed using the Anatomical Quality Assessment (AQUA) tool. Statistical analysis included subgroup analyses according to sex, age, geographical location, and imaging modality. RESULTS: In total, 60 studies were included, of which 44 studies reported adequate data for meta-analysis on 23,796 subjects. Overall, the pooled mean diameter of the CBD was 4.69 mm (95 % CI: 4.28-5.11). Significant differences were found between pediatric (1.32 mm, 95 % CI: 1.03-1.61) and adult (4.97 mm, 95 % CI: 4.67-5.27) subjects, as well as US (3.82 mm, 95 % CI: 3.15-4.49) and other imaging modalities, including MRI (6.21 mm, 95 % CI: 4.85-7.57) and ERCP (7.24 mm, 95 % CI: 6.08-8.40). The CBD diameter measured significantly larger distally (5.20 mm, 95 % CI: 4.60-5.80) than proximally (4.01 mm, 95 % CI: 3.51-4.51). CONCLUSIONS: The results obtained from this evidence-based study may guide the establishment of standardised reference values and ranges of the normal biliary tree in pediatric and adult populations and aid clinical understanding.

Perfusion magnetic resonance imaging in Asherman syndrome.

BACKGROUND: Microvascular scarring compromises the functionality of the endometrium, and vascular flow at the junctional zone (JZ) may be the key to understanding poor reproductive outcomes in women with Asherman syndrome (AS). AIMS: To investigate whether vascular perfusion of the uterus, measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is impaired in women with intrauterine adhesions (IUA) and AS. MATERIALS AND METHODS: A prospective observational cohort pilot study of 23 women with IUA treated with hysteroscopic synecholysis and a control group of two patients with cervix cancer were subject to DCE-MRI with gadolinium to assess uterine vascularity. Twelve regions of interest (ROIs) were allocated on the DCE-MRI image incorporating the JZ, with control ROI placed at the psoas muscle. Individual ROIs were compared to the mean total perfusion (TP) in the same uterus. Pre- and post-operative perfusion analyses were performed on five women. Receiver operator curves (ROC) were used to analyse MRI as a predictor of IUA. RESULTS: There was no significant difference in perfusion; a trend toward reduced perfusion was observed in women with IUA compared to the controls. The ROC was predictive of higher-grade and inoperable IUA. CONCLUSIONS: Reduced perfusion on DCE-MRI as assessed by ROC predicted higher-stage AS. The results of this study support further investigation of DCE-MRI as a prognostic tool for AS prior to surgical intervention to assist in providing prognostic guidance for women suffering from AS.

Epilepsy in Africa: a multifaceted perspective on diagnosis, treatment, and community support.

Epilepsy is the most widespread neurological disorder in Africa, affecting an estimated 25 million people. The disorder is characterized by recurrent seizures, which can be caused by a variety of factors, including past trauma, central nervous system infections, and genetic disorders. Diagnosis and treatment of epilepsy are challenging in African patients due to several factors, including the low socioeconomic status of the residents and limited access to appropriate medication. Phenobarbital remains the only drug widely available to patients, but it is not always effective and can have significant side effects. In addition to the medical challenges, individuals with epilepsy also face a lot of social stigmas in Africa. Widespread superstitions and false beliefs lead to prejudices against these people, making it difficult for them to live fulfilling social lives. With the development of new treatment modalities, such as gene therapy, stem cell therapy, and P-glycoprotein inhibitors, it is more important now than ever to increase the research output for the African region to create the best possible treatment and maximize patient outcomes.

Quantitative MRI in the Local Staging of Prostate Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Local staging of prostate cancer (PCa) is important for treatment planning. Radiologist interpretation using qualitative criteria is variable with high specificity but low sensitivity. Quantitative methods may be useful in the diagnosis of extracapsular extension (ECE). PURPOSE: To assess the performance of quantitative MRI markers for detecting ECE. STUDY TYPE: Systematic review and meta-analysis. SUBJECTS: 4800 patients from 28 studies with histopathologically confirmed PCa on radical prostatectomy were pooled for meta-analysis. Patients from 46 studies were included for systematic review. FIELD STRENGTH/SEQUENCE: Diffusion-weighted, T2-weighted, and dynamic contrast-enhanced MRI at 1.5 T or 3 T. ASSESSMENT: PubMed, Embase, Web of Science, Scopus, and Cochrane databases were searched to identify studies on diagnostic test accuracy or association of any quantitative MRI markers with ECE. Results extracted by two independent reviewers for tumor contact length (TCL) and mean apparent diffusion coefficient (ADC-mean) were pooled for meta-analysis, but not for other quantitative markers including radiomics due to low number of studies available. STATISTICAL TESTS: Hierarchical summary receiver operating characteristic (HSROC) curves were computed for both TCL and ADC-mean, but summary operating points were computed for TCL only. Heterogeneity was investigated by meta-regression. Results were significant if P ≤ 0.05. RESULTS: At the 10 mm threshold for TCL, summary sensitivity and specificity were 0.76 [95% confidence interval (CI) 0.71-0.81] and 0.68 [95% CI 0.63-0.73], respectively. At the 15 mm threshold, summary sensitivity and specificity were 0.70 [95% CI 0.53-0.83] and 0.74 [95% CI 0.60-0.84] respectively. The area under the HSROC curves for TCL and ADC-mean were 0.79 and 0.78, respectively. Significant sources of heterogeneity for TCL included timing of MRI relative to biopsy. DATA CONCLUSION: Both 10 mm and 15 mm thresholds for TCL may be reasonable for clinical use. From comparison of the HSROC curves, ADC-mean may be superior to TCL at higher sensitivities. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

A systematic review and meta-analysis of portal vein morphometry in pediatric and adult populations: Drawing the line between normal and abnormal findings.

PURPOSE: The morphometry of the hepatic portal vein is of clinical importance, particularly in pre-operative assessments, surgical management, and diagnoses of liver conditions. This systematic review and meta-analysis aimed to characterize the morphometry of the normal portal vein in both pediatric and adult patients. METHODS: The study, conducted using the PRISMA guidelines and registered with PROSPERO, utilized the MEDLINE, EMBASE, SCOPUS and Web of Science databases up to May 2020, and updated to May 2023. All studies reporting extractable data on diameter, length, and cross-sectional area (CSA) of the main, left, and right portal veins (PV, LPV, RPV, respectively) were included. The AQUA Tool was used to assess the quality of the included studies. Data analysis included subgroup analyses based on geographical location, sex, age, and imaging modality. RESULTS: A total of 122 studies with 11,637 subjects were eligible for inclusion. Overall, the pooled mean diameter of the PV (PVD) was 10.09 mm (95% CI: 9.56-10.62). Significant differences in diameter were found between pediatric (6.60 mm; 95% CI: 5.38-7.82) and adult (10.72 mm; 95% CI: 10.25-11.19) subjects. Additionally, there was a significantly larger PVD measurement from computed tomography (CT) than other imaging modalities: CT, 13.28 mm (95% CI: 11.71-14.84); magnetic resonance imaging (MRI), 10.50 mm (95% CI: 9.35-11.66) and ultrasound (US), 9.81 mm (95% CI: 9.47-10.16). The mean diameters of the LPV and RPV were 8.27 mm (95% CI: 6.78-9.77) and 8.33 mm (95% CI: 6.70-9.95), respectively. Mean PV length in adults is 48.63 mm (95% CI: 35.63-61.64). Mean CSA of the PV was 1.09 cm2. CONCLUSIONS: The study obtained aim to improve the understanding of portal vein anatomy, especially with relevance to surgical interventions of the liver in both pediatric and adult patients. Measurements from ultrasound imaging closely approximates the generated pooled PVD mean for pediatric and adult patients. CT imaging, however, significantly exceeded the established 13 mm threshold for adults. For pediatric patients, a threshold of 8 mm is proposed as a diagnostic upper limit for a normal PVD. Although not significant, the PVD decreased from the portal confluence towards its bifurcation.

Thoracic skeletal muscle index is effective for CT-defined sarcopenia evaluation in patients with head and neck cancer.

PURPOSE: Computed tomography (CT)-defined sarcopenia, as a measurement of low skeletal muscle (SM), is a poor prognostic indicator in patients with head and neck cancer (HNC), independent of weight or nutritional status. We used SM measures at the second thoracic vertebra (T2) to determine T2-SM index (SMI) thresholds for sarcopenia, and investigate the impact of low T2-SMI on overall survival (OS), and weight loss during radiotherapy (RT). METHODS: Adult patients with newly diagnosed HNC with a diagnostic PET-CT or RT planning CT scan were included. SM was analysed at T2 and a model applied to predict SM at L3. T2-SMI thresholds for sarcopenia were established with predicted measures, stratified by BMI and sex. Impact of sarcopenia and low T2-SMI on OS and weight loss during RT was investigated. RESULTS: A total of 361 scans were analysed (84% males, 54% oropharynx tumours). Sarcopenia was found in 49%, demonstrating worse OS (p = 0.037). T2-SMI cutoff values were: females-74 cm2/m2 [area under the curve (AUC): 0.89 (95%CI 0.80-0.98)], males (BMI < 25)-63 cm2/m2 [AUC 0.93 (95%CI 0.89-0.96)], males (BMI ≥ 25)-88cm2/m2 [AUC 0.86 (95%CI 0.78-0.93)]. No difference in OS with T2-SMI categories. Lowest T2-SMI quartile of < 63 cm2/m2 demonstrated worse OS (p = 0.017). Weight loss during RT was higher in patients; who were not sarcopenic (6.2% vs 4.9%, p = 0.023); with higher T2-SMI (6.3% vs 4.9%, p = 0.014) and; in the highest quartiles (3.6% vs 5.7% vs 7.2%, p < 0.001). CONCLUSIONS: These T2-SMI thresholds are effective in assessing CT-defined sarcopenia in HNC. Further assessment of clinical application is warranted.

Changes in serial multiparametric MRI and FDG-PET/CT functional imaging during radiation therapy can predict treatment response in patients with head and neck cancer.

OBJECTIVES: To test if tumour changes measured using combination of diffusion-weighted imaging (DWI) MRI and FDG-PET/CT performed serially during radiotherapy (RT) in mucosal head and neck carcinoma can predict treatment response. METHODS: Fifty-five patients from two prospective imaging biomarker studies were analysed. FDG-PET/CT was performed at baseline, during RT (week 3), and post RT (3 months). DWI was performed at baseline, during RT (weeks 2, 3, 5, 6), and post RT (1 and 3 months). The ADCmean from DWI and FDG-PET parameters SUVmax, SUVmean, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were measured. Absolute and relative change (%∆) in DWI and PET parameters were correlated to 1-year local recurrence. Patients were categorised into favourable, mixed, and unfavourable imaging response using optimal cut-off (OC) values of DWI and FDG-PET parameters and correlated to local control. RESULTS: The 1-year local, regional, and distant recurrence rates were 18.2% (10/55), 7.3% (4/55), and 12.7% (7/55), respectively. ∆Week 3 ADCmean (AUC 0.825, p = 0.003; OC ∆ > 24.4%) and ∆MTV (AUC 0.833, p = 0.001; OC ∆ > 50.4%) were the best predictors of local recurrence. Week 3 was the optimal time point for assessing DWI imaging response. Using a combination of ∆ADCmean and ∆MTV improved the strength of correlation to local recurrence (p ≤ 0.001). In patients who underwent both week 3 MRI and FDG-PET/CT, significant differences in local recurrence rates were seen between patients with favourable (0%), mixed (17%), and unfavourable (78%) combined imaging response. CONCLUSIONS: Changes in mid-treatment DWI and FDG-PET/CT imaging can predict treatment response and could be utilised in the design of future adaptive clinical trials. CLINICAL RELEVANCE STATEMENT: Our study shows the complementary information provided by two functional imaging modalities for mid-treatment response prediction in patients with head and neck cancer. KEY POINTS: •FDG-PET/CT and DWI MRI changes in tumour during radiotherapy in head and neck cancer can predict treatment response. •Combination of FDG-PET/CT and DWI parameters improved correlation to clinical outcome. •Week 3 was the optimal time point for DWI MRI imaging response assessment.

Mid-treatment 18F-FDG PET imaging changes in parotid gland correlates to radiation-induced xerostomia.

BACKGROUND: The aim of this study was to measure functional changes in parotid glands using mid-treatment FDG-PET/CT and correlate early imaging changes to subsequent xerostomia in mucosal head and neck squamous cell carcinoma patients undergoing radiotherapy. MATERIALS AND METHODS: 56 patients from two prospective imaging biomarker studies underwent FDG-PET/CT at baseline and during radiotherapy (week 3). Both parotid glands were volumetrically delineated at each time point. PET parameter SUVmedian were calculated for ipsilateral and contralateral parotid glands. Absolute and relative change (Δ) in SUVmedian were correlated to moderate-severe xerostomia (CTCAE grade ≥ 2) at 6 months. Four predictive models were subsequently created using multivariate logistic regression using clinical and radiotherapy planning parameters. Model performance was calculated using ROC analysis and compared using Akaike information criterion (AIC) RESULTS: 29 patients (51.8%) developed grade ≥ 2 xerostomia. Compared to baseline, there was an increase in SUVmedian at week 3 in ipsilateral (8.4%) and contralateral (5.5%) parotid glands. Increase in ipsilateral parotid Δ SUVmedian (p = 0.04) and contralateral mean parotid dose (p = 0.04) were correlated to xerostomia. The reference 'clinical' model correlated to xerostomia (AUC 0.667, AIC 70.9). Addition of ipsilateral parotid Δ SUVmedian to the clinical model resulted in the highest correlation to xerostomia (AUC 0.777, AIC 65.4). CONCLUSION: Our study shows functional changes occurring in the parotid gland early during radiotherapy. We demonstrate that integration of baseline and mid-treatment FDG-PET/CT changes in the parotid gland with clinical factors has the potential to improve xerostomia risk prediction which could be utilised for personalised head and neck radiotherapy.

Impact of tumour region of interest delineation method for mid-treatment FDG-PET response prediction in head and neck squamous cell carcinoma undergoing radiotherapy.

Background: The aim of this study was to evaluate the impact of tumour region of interest (ROI) delineation method on mid-treatment 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) response prediction in mucosal head and neck squamous cell carcinoma during radiotherapy. Methods: A total of 52 patients undergoing definitive radiotherapy with or without systemic therapy from two prospective imaging biomarker studies were analysed. FDG-PET was performed at baseline and during radiotherapy (week 3). Primary tumour was delineated using a fixed SUV 2.5 threshold (MTV2.5), relative threshold (MTV40%) and a gradient based segmentation method (PET Edge). PET parameters SUVmax, SUVmean, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were calculated using different ROI methods. Absolute and relative change (∆) in PET parameters were correlated to 2-year locoregional recurrence. Strength of correlation was tested using receiver operator characteristic analysis using area under the curve (AUC). Response was categorized using optimal cut-off (OC) values. Correlation and agreement between different ROI methods was determined using Bland-Altman analysis. Results: A significant difference in SUVmean, MTV and TLG values were noted between ROI delineation methods. When measuring relative change at week 3, a greater agreement was seen between PET Edge and MTV2.5 methods with average difference in ∆SUVmax, ∆SUVmean, ∆MTV and ∆TLG of 0.0%, 3.6%, 10.3% and 13.6% respectively. A total of 12 patients (22.2%) experienced locoregional recurrence. ∆MTV using PET Edge was the best predictor of locoregional recurrence (AUC =0.761, 95% CI: 0.573-0.948, P=0.001; OC ∆>50%). The corresponding 2-year locoregional recurrence rate was 7% vs. 35%, P=0.001. Conclusions: Our findings suggest that it is preferable to use gradient based method to assess volumetric tumour response during radiotherapy and offers advantage in predicting treatment outcomes compared with threshold-based methods. This finding requires further validation and can assist in future response-adaptive clinical trials.

The first Australian uterus transplantation procedure: A result of a long-term Australian-Swedish research collaboration.

AIMS: The aim is to report the results of Australia's first uterus transplantation (UTx). METHODS: Following long-standing collaboration between the Swedish and Australian teams, Human Research Ethics approval was obtained to perform six UTx procedures in a collaborative multi-site research study (Western Sydney Local District Health 2019/ETH13038), including Royal Hospital for Women, Prince of Wales Hospital, and Westmead Hospital in New Souh Wales. Surgeries were approved in both the live donor (LD) and deceased donor models in collaboration with the inaugural Swedish UTx team. RESULTS: This is the first UTx procedure to occur in Australia, involving a mother donating her uterus to her daughter. The total operative time for the donor was 9 h 54 min. Concurrently, recipient surgery was synchronised to minimise graft ischaemic time, and the total operative time for the recipient was 6 h 12 min. Surgery was by laparotomy in the LD and recipient. The total warm ischaemic time of the graft was 1 h 53 min, and the cold ischaemic time was 2 h 17 min (total ischaemic time 4 h 10 min). The patient's first menstruation occurred 33 days after the UTx procedure. CONCLUSION: Twenty-five years of Swedish and Australian collaboration has led to Australia's first successfully performed UTx surgery at The Royal Hospital for Women, Sydney, Australia.

The use of the second thoracic vertebral landmark for skeletal muscle assessment and computed tomography-defined sarcopenia evaluation in patients with head and neck cancer.

BACKGROUND: The cross-sectional area (CSA) of skeletal muscle (SM) at the third lumbar vertebra (L3) is used to determine computed tomography (CT)-defined sarcopenia. We investigated the feasibility of SM assessment at the second thoracic vertebra (T2) in patients with head and neck cancer (HNC). METHODS: Diagnostic PET-CT scans were used to develop a prediction model for L3-CSA using T2-CSA. Effectiveness of the model and cancer-specific survival (CSS) were investigated. RESULTS: Scans of 111 patients (85% male) were evaluated. The predictive formula: L3-CSA (cm2 ) = 174.15 + [0.212 × T2-CSA (cm2 )] - [40.032 × sex] - [0.928 × age (years)] + [0.285 × weight (kg)] had good correlation r = 0.796, ICC = 0.882 (p < 0.001). SM index (SMI) mean difference (bias) was -3.6% (SD 10.2, 95% CI -8.7% to 1.3%). Sensitivity (82.8%), specificity (78.2%), with moderate agreement (ƙ = 0.540, p < 0.001). Worse 5-year CSS with lower quartile T2-SMI (51%, p = 0.003). CONCLUSIONS: SM at T2 can be effectively used for CT-defined sarcopenia evaluation in HNC.

The discovery and characterization of two novel structural motifs on the carboxy-terminal domain of kinetoplastid RNA editing ligases.

Parasitic protozoans of the Trypanosoma and Leishmania species have a uniquely organized mitochondrial genome, the kinetoplast. Most kinetoplast-transcribed mRNAs are cryptic and encode multiple subunits for the electron transport chain following maturation through a uridine insertion/deletion process called RNA editing. This process is achieved through an enzyme cascade by an RNA editing catalytic complex (RECC), where the final ligation step is catalyzed by the kinetoplastid RNA editing ligases, KREL1 and KREL2. While the amino-terminal domain (NTD) of these proteins is highly conserved with other DNA ligases and mRNA capping enzymes, with five recognizable motifs, the functional role of their diverged carboxy-terminal domain (CTD) has remained elusive. In this manuscript, we assayed recombinant KREL1 in vitro to unveil critical residues from its CTD to be involved in protein-protein interaction and dsRNA ligation activity. Our data show that the α-helix (H)3 of KREL1 CTD interacts with the αH1 of its editosome protein partner KREPA2. Intriguingly, the OB-fold domain and the zinc fingers on KREPA2 do not appear to influence the RNA ligation activity of KREL1. Moreover, a specific KWKE motif on the αH4 of KREL1 CTD is found to be implicated in ligase auto-adenylylation analogous to motif VI in DNA ligases. In summary, we present in the KREL1 CTD a motif VI for auto-adenylylation and a KREPA2 binding motif for RECC integration.

Value of central review of RECIST v1.1 outcomes in the AGITG INTEGRATE randomised phase 2 international trial for advanced oesophago-gastric cancer.

PURPOSE: Activity estimates should be accurately evaluated in phase 2 clinical trials to ensure appropriate decisions about proceeding to phase 3 trials. RECIST v1.1. progression-free survival (PFS) is a common endpoint in oncology; however, it can be influenced by assessment criteria and trial design. We assessed the value of central adjudication of investigator-assessed PFS times of participants in a double-blind, randomised phase 2 trial evaluating regorafenib versus placebo in advanced gastro-oesophageal cancer (AGITG INTEGRATE) to inform plans for central review in future trials. METHODS: We calculated the proportion of participants with a disagreement between the site investigator assessment and blinded independent central review and in whom central review resulted in a change, then evaluated the effect of central review on study conclusions by comparing hazard ratios (HRs) for PFS based on site review versus central review. Post-progression unblinding was assessed with similar methods. Simulation studies explored the effect of differential and non-differential measurement error on treatment effect estimation and study power. RESULTS: Disagreements between site assessments versus central review occurred in 8/147 (5.4%) participants, 5 resulting in amended date of progression (3.4%). PFS HRs (sites vs central review progression dates) were similar (0.39 vs 0.40). RECIST progression occurred in 82/86 (95%) of cases where post-progression unblinding was requested by the site investigator. CONCLUSIONS: Blinded independent central review was feasible and supported the reliability of site assessments, trial results, and conclusions. Modelling showed that when treatment effects were large and outcome assessments blinded, central review was unlikely to affect conclusions.

Comparison of Skeletal Muscle Changes at Three Vertebral Levels Following Radiotherapy in Patients With Oropharyngeal Carcinoma.

Evaluation of skeletal muscle (SM) depletion, or sarcopenia, utilizes the cross-sectional area (CSA) of computed tomography (CT) scans at the lumbar level L3. However, alternate vertebral landmarks are used in patients with head and neck cancer due to scan unavailability. Muscle changes following radiotherapy at cervical (C3) and thoracic (T2) levels were compared to L3 in patients with oropharyngeal carcinoma. Muscle density data were derived retrospectively from diagnostic PET-CT scans at C3, T2 and L3 pretreatment, and up to six months post. CSA changes were compared to L3 in scans of 33 patients (88% male, mean age 61 (SD 8.5) years). On matched pair analysis; mean L3-CSA change -12.1 cm2 (SD 9.7, 95%CI -15.5 to -8.6, and p < 0.001), T2-CSA -30.5 cm2 (SD 34.8, 95%CI -42.8 to -18.1, and p < 0.001) and C3-CSA +2.1 cm2 (SD 4.1, 95%CI 0.63 to 3.5, and p < 0.00). No difference was found in the percentage change of T2-CSA with L3-CSA (mean -2.2%, SD 10.6, 95%CI -6.0 to 1.6, and p = 0.240), however, was significantly different to C3-CSA (mean 13.2%, SD 11.6, 95%CI 9.1 to 17.3, and p < 0.001). Results suggest SM at C3 does not change proportionately and may not be a reliable representation of whole-body SM change over time.

Hammerhead ribozyme-based U-insertion and deletion RNA editing assays for multiplexing in HTS applications.

Untranslatable mitochondrial transcripts in kinetoplastids are decrypted post-transcriptionally through an RNA editing process that entails uridine insertion/deletion. This unique stepwise process is mediated by the editosome, a multiprotein complex that is a validated drug target of considerable interest in addressing the unmet medical needs for kinetoplastid diseases. With that objective, several in vitro RNA editing assays have been developed, albeit with limited success in discovering potent inhibitors. This manuscript describes the development of three hammerhead ribozyme (HHR) FRET reporter-based RNA editing assays for precleaved deletion, insertion, and ligation assays that bypass the rate-limiting endonucleolytic cleavage step, providing information on U-deletion, U-insertion, and ligation activities. These assays exhibit higher editing efficiencies in shorter incubation times while requiring significantly less purified editosome and 10,000-fold less ATP than the previously published full round of in vitro RNA editing assay. Moreover, modifications in the reporter ribozyme sequence enable the feasibility of multiplexing a ribozyme-based insertion/deletion editing (RIDE) assay that simultaneously surveils U-insertion and deletion editing suitable for HTS. These assays can be used to find novel chemical compounds with chemotherapeutic applications or as probes for studying the editosome machinery.

A prediction model for skeletal muscle evaluation and computed tomography-defined sarcopenia diagnosis in a predominantly overweight cohort of patients with head and neck cancer.

PURPOSE: This study investigates the feasibility of computed tomography (CT)-defined sarcopenia assessment using a prediction model for estimating the cross-sectional area (CSA) of skeletal muscle (SM) in CT scans at the third lumbar vertebra (L3), using measures at the third cervical level (C3) in a predominantly overweight population with head and neck cancer (HNC). METHODS: Analysis was conducted on adult patients with newly diagnosed HNC who had a diagnostic positron emission tomography-CT scan. CSA of SM in CT images was measured at L3 and C3 in each patient, and a predictive formula developed using fivefold cross-validation and linear regression modelling. Correlation and agreement between measured CSA at L3 and predicted values were evaluated using intraclass correlation coefficients (ICC) and Bland-Altman plot. The model's ability to identify sarcopenia was investigated using Cohen's Kappa (k). RESULTS: A total of 109 patient scans were analysed, with 64% of the cohort being overweight or obese. The prediction model demonstrated high level of correlation between measured and predicted CSA measures (ICC 0.954, r = 0.916, p < 0.001), and skeletal muscle index (SMI) (ICC 0.939, r = 0.883, p < 0.001). Bland-Altman plot showed good agreement in SMI, with mean difference (bias) = 0.22% (SD 8.65, 95% CI - 3.35 to 3.79%), limits of agreement (- 16.74 to 17.17%). The model had a sensitivity of 80.0% and specificity of 85.0%, with moderate agreement on sarcopenia diagnosis (k = 0.565, p = 0.004). CONCLUSION: This model is effective in predicting lumbar SM CSA using measures at C3, and in identifying low SM in a predominately overweight group of patients with HNC.

Final Analysis of the Magnetic Resonance Imaging in Active Surveillance Trial.

PURPOSE: This study aimed to assess the medium-term oncologic outcomes of an active surveillance protocol, replacing confirmatory biopsy with serial multiparametric magnetic resonance imaging. MATERIALS AND METHODS: A total of 172 men were enrolled in this single-arm prospective trial. Men with prostate cancer (Gleason 3+3=6 or Gleason 3+4=7 with ≤10% Gleason pattern 4 overall and <2 cores Gleason pattern 4) eligible for surveillance were included in the study. Men underwent baseline multiparametric magnetic resonance imaging and template ± targeted biopsy, then multiparametric magnetic resonance imaging at years 1 and 2 with a 3-year end-of-protocol biopsy. Biopsies during the 3-year protocol period were triggered by abnormalities on multiparametric magnetic resonance imaging and/or increases in prostate specific antigen density (>0.2 ng/ml/cc). RESULTS: The sensitivity, specificity, positive predictive value, and negative predictive value of multiparametric magnetic resonance imaging to detect progression to clinically significant prostate cancer were 57% (95% CI 39%-74%), 82% (95% CI 74%-89%), 50% (95% CI 38%-62%), and 86% (95% CI 81%-90%), respectively. Both multiparametric magnetic resonance imaging and prostate specific antigen density were significant predictors for progression (multiparametric magnetic resonance imaging OR 6.20, 95% CI 2.72-14.16, P < .001; prostate specific antigen density OR 6.19, 95% CI 2.14-17.92, P = .001). Only 2.3% (4/172) of patients had false-negative multiparametric magnetic resonance imaging and high-risk pathological features (pT3 or high-volume International Society of Urological Pathology >2). After a median 69 months (Q1-Q3 56-79) follow-up of all patients in the cohort, freedom from biochemical recurrence, metastasis, and prostate cancer-related death were 99.3%, 100%, and 100%, respectively. CONCLUSIONS: Final analysis of the Magnetic Resonance Imaging in Active Surveillance trial indicates that there is minimal risk to omitting 1-year confirmatory biopsy during active surveillance if baseline magnetic resonance-targeted + saturation template biopsy was performed; however, standardized 3-year systematic biopsy should be performed due to occasional magnetic resonance imaging-invisible tumors.

A new and automated risk prediction of coronary artery disease using clinical endpoints and medical imaging-derived patient-specific insights: protocol for the retrospective GeoCAD cohort study.

INTRODUCTION: Coronary artery disease (CAD) is the leading cause of death worldwide. More than a quarter of cardiovascular events are unexplained by current absolute cardiovascular disease risk calculators, and individuals without clinical risk factors have been shown to have worse outcomes. The 'anatomy of risk' hypothesis recognises that adverse anatomical features of coronary arteries enhance atherogenic haemodynamics, which in turn mediate the localisation and progression of plaques. We propose a new risk prediction method predicated on CT coronary angiography (CTCA) data and state-of-the-art machine learning methods based on a better understanding of anatomical risk for CAD. This may open new pathways in the early implementation of personalised preventive therapies in susceptible individuals as a potential key in addressing the growing burden of CAD. METHODS AND ANALYSIS: GeoCAD is a retrospective cohort study in 1000 adult patients who have undergone CTCA for investigation of suspected CAD. It is a proof-of-concept study to test the hypothesis that advanced image-derived patient-specific data can accurately predict long-term cardiovascular events. The objectives are to (1) profile CTCA images with respect to variations in anatomical shape and associated haemodynamic risk expressing, at least in part, an individual's CAD risk, (2) develop a machine-learning algorithm for the rapid assessment of anatomical risk directly from unprocessed CTCA images and (3) to build a novel CAD risk model combining traditional risk factors with these novel anatomical biomarkers to provide a higher accuracy CAD risk prediction tool. ETHICS AND DISSEMINATION: The study protocol has been approved by the St Vincent's Hospital Human Research Ethics Committee, Sydney-2020/ETH02127 and the NSW Population and Health Service Research Ethics Committee-2021/ETH00990. The project outcomes will be published in peer-reviewed and biomedical journals, scientific conferences and as a higher degree research thesis.