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OBJECTIVE: To evaluate the importance of lesion density (lesion volume/prostate volume) on prostate cancer (PCa) and clinically significant prostate cancer (csPCa) detection rates in cognitive targeted biopsy (cTB). MATERIALS AND METHODS: 300 consecutive patients who underwent combined transrectal cTB and systematic transrectal prostate biopsy were included retrospectively. Lesion density was calculated as the largest lesion volume divided by prostate volume. According to ROC analysis and Youden’s index, patients were grouped into low lesion density (Low-LD) and high lesion density (High-LD) groups. Detection rates of PCa and csPCa were compared. Subgroup analyses were performed for high PI-RADS lesions ( 4–5) and anatomical zones. RESULTS: Mean lesion diameter and prostate volume were 14.1 ± 7.2 mm and 83.9 ± 42.8 mm³, respectively. High lesion density was independently associated with csPCa in univariate and multivariate analysis (p < 0.05). PCa and csPCa detection rates were significantly higher in the High-LD group (53.6% vs. 32.0%, p < 0.001; and 37.1% vs. 16.7%, p < 0.001, respectively). Similar results were observed when only MRI-targeted cores were analysed. Subgroup analysis of PI-RADS 4–5 lesions confirmed that csPCa detection rates were also higher in High-LD group (39.0% vs. 21.5%, p = 0.005). csPCa detection was lowest in anterior lesions, especially in Low-LD patients (6%). CONCLUSIONS: Lesion density significantly affects the diagnostic accuracy of cTB. Patients with low lesion density have lower csPCa detection rates and may benefit from software-assisted fusion targeting over cognitive targeting.
Foreign body ingestions are a common presentation in the emergency department. Many of these involve sharp or pointed objects, which may be challenging to detect when made of radiolucent material such as wood. While computed tomography (CT) increases sensitivity, perforation and mucosal injury are often diagnosed late because of false-negative scans. We report the rare case of duodenal toothpick perforation with negative radiographic imaging. A 25-year-old male presented to urgent care after suspected accidental ingestion of a toothpick. The patient had no symptoms and no recollection of toothpick ingestion. After a normal X-ray, he was referred to the emergency department, where CT imaging of the neck, chest, and abdomen did not reveal any foreign body or secondary inflammatory changes. Gastroenterology was consulted and performed an endoscopy, identifying a 4-5 cm wooden toothpick embedded in and perforating the second portion of the duodenum. The foreign body was removed without complications. This case highlights the importance of high clinical suspicion when encountering asymptomatic patients with potential foreign body ingestion of sharp radiolucent objects, even in the absence of radiographic or laboratory evidence of perforation. Endoscopic evaluation in these patients may be warranted to prevent delayed presentation and complications.
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Naturally occurring elongated mineral particles (EMPs) are microscopic particles derived from rocks and soils and are defined by their high aspect ratios. They include both asbestiform minerals, some of which are recognised carcinogens, and non-asbestiform minerals. While occupational exposure to commercially used EMPs such as asbestos has been extensively studied, population-scale exposure to naturally occurring EMPs in environmental settings remains poorly understood. Direct measurements of ambient EMP concentrations are rare due to their low abundance and the analytical difficulty of isolating fibres from complex ambient particulate matter. To address these challenges, a cost-effective, filter-based air-sampling network was established in Riverhead, Auckland, New Zealand, where erionite and other elongated mineral particles have been reported in local geology. A multi-tiered analytical workflow was applied, combining automated scanning electron microscopy with energy dispersive spectroscopy (SEM-EDS) for high-throughput screening with transmission electron microscopy and selected-area electron diffraction (TEM-SAED) for mineralogical confirmation. Automated SEM-EDS screening identified 449 EMPs across the sampled locations, of which 29 exhibited Si:Al ratios within the range characteristic of erionite. However, subsequent TEM-SAED analysis confirmed that none of these particles were erionite. These results indicate that airborne erionite was not detected in the analysed filters within the spatial and temporal scope and analytical detection limits of the monitoring campaign. The study demonstrates the utility of combining dense monitoring networks with automated SEM-based screening as a scalable framework for environmental EMP surveillance in regions where fibrous minerals occur in local geology.
Liquid biopsy is a non-invasive molecular test that uses biofluid to detect cancer. This is a rapidly growing field that encompasses a diverse class of assays that rely on circulating nucleic acids, proteins, and cells to identify cancer. Recently, there is particular interest in using circulating tumor DNA (ctDNA) to screen for cancer, to monitor treatment response, and to help guide therapeutic decisions. Here, we will review the procedural aspects of ctDNA assays, as well as the various applications of ctDNA assays in cancer care. The utility of various biofluids to conduct ctDNA assays, the technical considerations for performing the assays, and several possible available assay formats that can be used for ctDNA analysis are reviewed. Several protocols that can be used for ctDNA isolation, detection, and quantification are presented, including targeted ctDNA qPCR.
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Bone tumors, especially in advanced stages, pose serious diagnostic and therapeutic challenges due to their aggressive nature and the invasiveness of traditional biopsy techniques. Liquid biopsy offers a promising, minimally invasive alternative by analyzing tumor-derived components from bodily fluids, such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and extracellular vesicles (EVs). These biomarkers enable dynamic and precise disease monitoring. This review aimed to investigate the role of liquid biopsy in the diagnosis, prognosis, and treatment guidance of bone tumors, highlighting recent molecular advances and clinical findings. A structured narrative review was conducted using PubMed, covering studies published up to July 2024. Studies involving osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma were included, focusing on the clinical implications of CTCs, ctDNA, and EVs from plasma, serum, and other fluids. Liquid biopsy technologies demonstrated high diagnostic accuracy in bone tumors. In osteosarcoma, CTC detection using qRT-PCR and FISH methods showed sensitivities up to 98.6% and was strongly associated with metastatic disease and recurrence risk. ctDNA profiling identified tumor-specific mutations, hypomethylation markers (e.g., IRX1), and early relapse indicators with up to 97.4% specificity. EV-associated biomarkers, particularly miRNAs, such as miR-25-3p and a 3-miRNA signature, distinguished tumor subtypes and predicted metastasis-free survival. Advanced techniques, like SERS and MALDI-TOF MS profiling of exosomes, achieved diagnostic accuracies near 100%. EV RNA sequencing revealed differential gene expression and fusion events linked to metastatic progression and long-term outcomes. Liquid biopsy holds strong potential for transforming bone tumor care. Its clinical adoption depends on further validation through standardized methods and large-scale studies.
Intraoperative loss of surgical needles represents a rare but significant challenge in operative settings, particularly in microsurgical procedures involving free tissue transfer where fine sutures (8-0 to 10-0) are employed. Current hospital protocols typically use intraoperative portable radiography to localize misplaced needles. However, the diagnostic utility of X-ray imaging in detecting small-caliber needles remains poorly defined. Following ethical approval, a cadaveric study was conducted using a range of monofilament Ethilon™ needles (3-0 to 10-0 caliber), which were inserted at four anatomically relevant surgical sites. Anteroposterior radiographs were obtained using a standard intraoperative C-arm. A total of 53 participants - including consultant surgeons, radiology trainees, nursing staff, and surgical registrars-were asked to identify needle number and location using blinded image review. Radiographic identification of needles was accurate for calibers 3-0, 4-0, 5-0, and 6-0, with identification rates approaching or exceeding 99%. Smaller needle calibers showed a dramatic decline in detection accuracy. The 8-0 needles were correctly localized in 3.77% of attempts, just one 9-0 needle was successfully identified. None of the 10-0 needles were detected across all anatomical sites. While portable radiography remains a reliable modality for locating surgical needles of caliber 3-0 to 6-0, it proves ineffective for the detection of finer microsurgical needles (≥8-0). These results have important implications for operative protocols and clinical decision-making. The routine X-ray imaging in cases of microsurgical needle loss warrants reconsideration to favor evidence-informed strategies that minimize intraoperative delays, prolonged anesthesia and unnecessary radiation exposure.
The world is constantly changing, yet a risk assessment is based on the knowledge available at one point in time. There will therefore be a gap between the range of possibilities known or conceivable to the assessor at that time and all the possibilities that could occur over infinite time. This will leave the door open to surprises. Anticipating surprises, therefore, requires the narrowing of this knowledge gap. We outline an approach to narrowing it that transforms risk assessors' small-world representations into a large-world representation by configuring them into a small-world network. Small-world representations are individuals' partial and subjective perspectives on an aspect of reality. What we call a large-world representation integrates these small-world representations. This transformation narrows the knowledge gap by integrating dispersed knowledge about, and intersecting alternative framings of, a focal risk, thereby dynamically updating the knowledge landscape underpinning its assessment. We use the 9/11 attack as an example. That surprise resulted from a failure to intersect the frames "suicide attack" and "hijacking," meaning that the possibility of a "suicide hijacking" went unconsidered. Configuring risk assessors into a small-world network would have increased the chance that these two frames would intersect in a risk assessment, thereby anticipating this surprise outcome. In sum, the approach we outline operationalizes the recently extended (C, U) risk-assessment framework. It increases the chance that surprises are anticipated by enabling risk assessors to see as an integral whole what they could otherwise see only fragmentarily.
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While both considered rare in contemporary Australian anaesthetic practice, the symptoms of epidural complication can mimic those of spinal tuberculosis, as we outline here in this unusual case. A 33-year-old woman presented to hospital with new neurological deficits days after receiving a lumbar epidural for labour analgesia. A complication of epidural was initially suspected; however, spinal tuberculosis was found be the cause. This case demonstrates many of the challenges and unique requirements involved in providing neuraxial anaesthesia to the obstetric cohort, namely: consenting linguistically diverse patients, providing advice on discharge, and the role of anaesthetics in expediting time-critical investigations.
It is often debated whether group selection can explain altruistic behaviors that lower the fitness of individual organisms for the benefit of their group. Several models of group selection are simulated here with more details and fewer simplifying assumptions than previous quantitative studies. The simulated models include island models with selective extinction, selective dispersal, selective migration, outsider exclusion, conformity, altruistic punishment, haystack model, and a new model with floating group territories. The simulations are repeated with different parameter sets in order to map the parameter areas that lead to either fixation of altruism, fixation of egoism, or stable polymorphism. This can help decide whether a particular behavior can be explained by genetic group selection. The conditions for group selection to override counteracting individual selection are found to be very restrictive. These conditions are met for eusocial insects, some parasites, and a few other species. The necessary conditions are unlikely to have been met in the evolutionary history of humans and most other group-living animals. Altruistic behaviors in humans could not have evolved without involving cultural mechanisms, including norms, rewards and punishments, reputation, and leadership. A comprehensive open-source simulation program is provided to facilitate further research.
In eating disorders, service models provide a structure for the delivery of assessment and treatment to people across a range of settings. High-quality service models can improve a person's satisfaction with the care provided, sustain them in treatment and promote better outcomes. To capture and explore the perspectives of former service users, carers and eating disorder clinicians on their experiences of eating disorder service models. This phenomenological study used semi-structured interviews to explore perspectives of former Australian service users (n = 5), carers (n = 15) and eating disorder clinicians (n = 29) on eating disorder service models. Thematic analysis identified four themes: (1) Navigating the service system, (2) Weight as a measure of progress, (3) Competent clinicians: a needle in a haystack and (4) Who is steering the ship? The first three themes were shared across all participant groups, while the fourth was specific to clinicians. Service models were described by participants as overstretched, contributing to shorter treatment duration, with skilled clinician shortages further constraining care. Participants reported over-reliance on weight to determine service model access (and thus, access to treatment) and as a trigger for discharge, despite consensus that recovery cannot be measured by weight alone. To enhance eating disorder service models, participants proposed strengthening the workforce, facilitating timely access, using more holistic outcome measures, and tailoring care to individual needs within coordinated, stepped service pathways. These findings highlight opportunities for system-level reform and the need for clearer leadership to guide consistent standards and accountability. When people seek help for an eating disorder, typically their care is provided through a service model. Eating disorder service models can be located in a hospital, or the community, and provide a structure for how assessment and treatment is delivered to help a person recover.Service models for eating disorders can be very different. This means that people who access service models have varied experiences. In this study, clinicians who work in Australian eating disorder service models, people who have received assessment and/or treatment for an eating disorder in Australia and carers of people who have an eating disorder were all interviewed. There were some common themes identified from the information provided in the interviews. Many people reported that they found locating and accessing eating disorder service models complicated. In addition, there were not enough clinicians who understand eating disorders to provide adequate support. Lastly, eating disorders needed clear leadership, so eating disorder service models can improve how they provide care and be more consistent in how they support people.
Glioblastoma is the most common and lethal adult primary brain cancer, and its incidence is predicted to increase among older patients. Elderly age has been associated with worse outcomes compared to younger patients with glioblastoma. It is unknown if very elderly patients are at even further increased risk of worse outcomes compared to elderly patients. Patients ≥ 65 years old with primary glioblastoma treated surgically at a single institution (6/1/2008-12/31/2020) were identified through chart review. Patient demographics, disease characteristics, management data, and clinical outcomes were collected. Kaplan-Meier curves were generated to study overall survival. Chi square, independent t, and Wilcoxon-Mann-Whitney tests were used to identify associations between variables, and factors that affected clinical outcomes were identified using a multivariate logarithmic regression model. P-values < 0.05 were considered significant. A total of 165 elderly (65-74 years) and 79 very elderly (≥ 75 years) patients were included. Compared to elderly patients, very elderly patients were more likely to have a higher mFI-5 score (elderly 0.8 ± 0.9; very elderly 1.2 ± 0.9; p = 0.0018) and lower KPS score (elderly 73.6 ± 16.3; very elderly 69.1 ± 16.3; p = 0.0439) pre-operatively. Very elderly patients were less likely to receive post-operative adjuvant radiotherapy (elderly 70.4 %; very elderly 56.6 %; p = 0.0359) or adjuvant temozolomide chemotherapy (elderly 37.2 %; very elderly 21.3 %; p = 0.0165). In multivariate analysis, age ≥ 75 years was an independent predictor of extended ICU (OR 4.71, p = 0.0045) and overall length of stay (OR 2.03, p = 0.0374) compared to elderly patients. Adjuvant chemoradiation was associated with increased median overall survival in both the elderly (p < 0.0001) and very elderly (p < 0.0001). Very elderly patients with glioblastoma may be less likely to receive adjuvant chemoradiation than elderly counterparts, but use of these modalities is associated with increased overall survival in both cohorts.
Immune checkpoint inhibitors (ICIs) have limited activity in mismatch repair proficient or microsatellite stable (MMRp/MSS) colorectal cancer (CRC). KRAS mutations, present in approximately 40% of these cancers, can generate neoantigens that are targets for therapeutic vaccines. In this single-arm, phase I study (NCT04117087), we evaluated mKRAS-VAX, a pooled mutant KRAS (mKRAS) peptide vaccine targeting six KRAS mutations with nivolumab and ipilimumab in 13 patients with pretreated metastatic MMRp/MSS CRC. Both primary endpoints of safety and immunogenicity (within 17 weeks post-vaccination) were met. Secondary endpoints included treatment efficacy defined by RECIST v1.1 criteria. All adverse events attributed to mKRAS-VAX were grade 1 or 2, and the addition of mKRAS-VAX did not increase the frequency of severe immune-related adverse events beyond the expected profile of dual ICIs alone. mKRAS-VAX elicited an increase in tumor-specific mKRAS-reactive T-cells in 8/12 biomarker-evaluable patients (75%) by direct ex vivo IFNγ ELISpot and in 12 patients (100%) following in vitro expansion. Our findings support further development of mKRAS vaccines with ICIs for advanced MMRp/MSS CRC.
Circulating tumor DNA (ctDNA) is a promising biomarker in melanoma, with higher sensitivity for tumor burden detection than conventional diagnostics. While well established in research, clinical routine implementation remains pending. Key global questions concern optimal clinical applications and barriers to adoption. A web-based survey of 116 members of the Melanoma World Society Study Group assessed international expert opinions on ctDNA utility across predefined clinical scenarios. The questionnaire included 18 general questions on ctDNA use and 5 clinical vignettes with de-identified patient data and retrospectively obtained ctDNA results. ctDNA was rated most valuable for detecting minimal residual disease (mean score 3.63), surveillance of recurrent disease (3.85), and stage IV melanoma (3.82), with limited utility in early stages. Experts considered ctDNA superior to S100 and LDH for early relapse detection and identifying progressive disease. Most participants (80%) agreed that ctDNA correlates with radiographic response, and 82% favored its integration into routine follow-ups. In urgent high-tumor-burden settings, 82.8% would initiate BRAFi/MEKi therapy based on ctDNA if tissue analysis was pending, and 93.9% if unavailable. For central nervous system lesions, 62% did not support blood ctDNA, while 66% considered cerebrospinal fluid valuable. Pragmatic approaches with small to mid-size targeted panels and short turnaround times were preferred. Major barriers included the need for prospective trials (85%), standardized guidelines (83%), and reimbursement policies (82%). Key opinion leaders regarded ctDNA as a valuable adjunct selected melanoma scenarios. Validation through prospective studies, guideline development, and reimbursement frameworks are essential for broader clinical implementation.