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Proximal tubule (PT) cells maintain a high-capacity apical endocytic pathway to recover essentially all proteins that escape the glomerular filtration barrier. The multi ligand receptors megalin and cubilin play pivotal roles in the endocytic uptake of normally filtered proteins in PT cells but also contribute to the uptake of nephrotoxic drugs, including aminoglycosides. We previously demonstrated that opossum kidney (OK) cells cultured under continuous fluid shear stress (FSS) are superior to cells cultured under static conditions in recapitulating essential functional properties of PT cells in vivo . To identify drivers of the high-capacity, efficient endocytic pathway in the PT, we compared FSS-cultured OK cells with less endocytically active static-cultured OK cells. Megalin and cubilin expression are increased, and endocytic uptake of albumin in FSS-cultured cells is > 5-fold higher compared with cells cultured under static conditions. To understand how differences in receptor expression, distribution, and trafficking rates contribute to increased uptake, we used biochemical, morphological, and mathematical modeling approaches to compare megalin traffic in FSS- versus static-cultured OK cells. Our model predicts that culturing cells under FSS increases the rates of all steps in megalin trafficking. Importantly, the model explains why, despite seemingly counterintuitive observations (a reduced fraction of megalin at the cell surface, higher colocalization with lysosomes, and a shorter half-life of surface-tagged megalin in FSS-cultured cells), uptake of albumin is dramatically increased compared with static-grown cells. We also show that FSS-cultured OK cells more accurately exhibit the mechanisms that mediate uptake of nephrotoxic drugs in vivo compared with static-grown cells. This culture model thus provides a useful platform to understand drug uptake mechanisms, with implications for developing interventions in nephrotoxic injury prevention., Competing Interests: OW serves as a consultant to Aktis Oncology and Judo Bio. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lackner, Cowan, Long, Weisz and Shipman.)

Introduction: Radiologist reporting times are a key component of radiology department workload assessment, but reliable measurement remains challenging. Currently, there are three contenders for this task: median reporting times (MRTs), extracted directly from a department's radiology information system (RIS); study-ascribed times (SATs), using published tables of individual descriptors derived from a combination of measurement and consensus; and radiology reporting figures (RRFs), using published tables of measured times based on modality and numbers of anatomical areas., Methods: We review these techniques, their possible uses and some potential pitfalls. We discuss the level of precision that can realistically be attained in measuring reporting times, and list the strengths and weaknesses of each technique, comparing them in relation to each of eight potential applications., Results: We believe that SATs are challenging for practical use due to their static nature, absent common descriptors and large number. RRFs are more user-friendly but are also static and require ongoing updates; currently, they do not include ultrasound. MRTs cannot currently be extracted from every RIS, but where available they are easy to use and their dynamic nature provides the most objective data. They underestimate the unmeasurable components of a radiologist's work and therefore the total time spent in a reporting session., Conclusion: MRTs are superior to the other methods in flexibility, precision and ease of use. All institutions should have access to this data and we call on vendors of Radiology Information Systems which are currently not capable of providing it to make the necessary modifications., (© 2023 Royal Australian and New Zealand College of Radiologists.)

Significance Statement: Loss of function of the 2Cl - /H + antiporter ClC-5 in Dent disease causes an unknown impairment in endocytic traffic, leading to tubular proteinuria. The authors integrated data from biochemical and quantitative imaging studies in proximal tubule cells into a mathematical model to determine that loss of ClC-5 impairs endosome acidification and delays early endosome maturation in proximal tubule cells, resulting in reduced megalin recycling, surface expression, and half-life. Studies in a Dent mouse model also revealed subsegment-specific differences in the effects of ClC-5 knockout on proximal tubule subsegments. The approach provides a template to dissect the effects of mutations or perturbations that alter tubular recovery of filtered proteins from the level of individual cells to the entire proximal tubule axis., Background: Loss of function of the 2Cl - /H + antiporter ClC-5 in Dent disease impairs the uptake of filtered proteins by the kidney proximal tubule, resulting in tubular proteinuria. Reduced posttranslational stability of megalin and cubilin, the receptors that bind to and recover filtered proteins, is believed to underlie the tubular defect. How loss of ClC-5 leads to reduced receptor expression remains unknown., Methods: We used biochemical and quantitative imaging data to adapt a mathematical model of megalin traffic in ClC-5 knockout and control cells. Studies in ClC-5 knockout mice were performed to describe the effect of ClC-5 knockout on megalin traffic in the S1 segment and along the proximal tubule axis., Results: The model predicts that ClC-5 knockout cells have reduced rates of exit from early endosomes, resulting in decreased megalin recycling, surface expression, and half-life. Early endosomes had lower [Cl - ] and higher pH. We observed more profound effects in ClC-5 knockout cells expressing the pathogenic ClC-5 E211G mutant. Alterations in the cellular distribution of megalin in ClC-5 knockout mice were consistent with delayed endosome maturation and reduced recycling. Greater reductions in megalin expression were observed in the proximal tubule S2 cells compared with S1, with consequences to the profile of protein retrieval along the proximal tubule axis., Conclusions: Delayed early endosome maturation due to impaired acidification and reduced [Cl - ] accumulation is the primary mediator of reduced proximal tubule receptor expression and tubular proteinuria in Dent disease. Rapid endosome maturation in proximal tubule cells is critical for the efficient recovery of filtered proteins., (Copyright © 2023 by the American Society of Nephrology.)

The cells that comprise the proximal tubule (PT) are specialized for high-capacity apical endocytosis necessary to maintain a protein-free urine. Filtered proteins are reclaimed via receptor-mediated endocytosis facilitated by the multiligand receptors megalin and cubilin. Despite the importance of this pathway, we lack a detailed understanding of megalin trafficking kinetics and how they are regulated. Here, we utilized biochemical and quantitative imaging methods in a highly differentiated model of opossum kidney (OK) cells and in mouse kidney in vivo to develop mathematical models of megalin traffic. A preliminary model based on biochemically quantified kinetic parameters was refined by colocalization of megalin with individual apical endocytic compartment markers. Our model predicts that megalin is rapidly internalized, resulting in primarily intracellular distribution of the receptor at steady state. Moreover, our data show that early endosomes mature rapidly in PT cells and suggest that Rab11 is the primary mediator of apical recycling of megalin from maturing endocytic compartments. Apical recycling represents the rate-limiting component of endocytic traffic, suggesting that this step has the largest impact in determining the endocytic capacity of PT cells. Adaptation of our model to the S1 segment of mouse PT using colocalization data obtained in kidney sections confirms basic aspects of our model and suggests that our OK cell model largely recapitulates in vivo membrane trafficking kinetics. We provide a downloadable application that can be used to adapt our working parameters to further study how endocytic capacity of PT cells may be altered under normal and disease conditions., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Physiological Society.)

Introduction: Pectus excavatum (PX) denotes a concavity of the sternum and is the most common chest wall deformity. Many characteristic signs have been described on frontal chest radiographs including increased density of the inferomedial right lung, blurring of the right heart border, steeply angled anterior ribs, horizontal posterior ribs, straight or convex left heart border and loss of silhouette of the descending thoracic aorta. These signs are often subtle and rarely all present in any individual. We describe a further sign in women with PX, the medial breast margin sign. This sign consists of more sharply defined and more vertically oriented medial breast borders on frontal chest radiographs than in those of women with normal chest wall morphology. This study aims to document the sensitivity, specificity and inter-observer reliability of the new sign, and compare with that of the previously described signs in patients with varying degrees of PX., Methods: The frontal chest radiographs of 185 women with PX and 50 women with normal chest wall morphology were assessed by two reviewers for the presence of the new sign and previously described signs. All the signs had their sensitivity, specificity and inter-observer reliability calculated., Results: The new sign had a sensitivity of 0.48, a specificity of 0.96 and inter-observer reliability of κ = 0.79, ranking third, second and first among all other signs, respectively., Conclusion: The medial breast margin sign is useful in diagnosing PX and is comparable to the previously described classic signs., (© 2019 The Royal Australian and New Zealand College of Radiologists.)

Introduction: The need to measure reporting workload in teaching departments remains a current pertinent need. In Australia, the Pitman-Jones reporting RVUs have been in the public domain since 2003 (revised in 2009). These are expressed in arbitrary units. In New Zealand, single-site Christchurch Hospital reporting times have been validated and placed in the public domain. Concurrently, the RANZCR has been developing a formulaic descriptor lexicon for imaging studies (the Body System Framework). There is a need to bring these three strands of work together into a common public resource. In 2015, under the auspices of the Chief Accreditation Officer, RANZCR convened the Radiologist Workload Working Group. The goal of the group was to develop a robust method of measuring radiologist workload in teaching departments in Australia and New Zealand for the RANZCR accreditation processes of teaching departments as training sites. This paper concerns itself with one aspect of the group's work, namely reaching a consensus on radiologist study ascribable times for common imaging studies., Method: The BSF examination descriptors were reduced to a smaller, generic dataset of descriptors at the expense of loss of specificity. BSF study ascribable times had been previously obtained by stopwatch observation. The dataset was harmonized with the Christchurch descriptors to ensure commonality of case mix. The two lead authors reached an approximate consensus study ascribable time for each descriptor in agreement with the BSF and Christchurch data. Specifically, the Christchurch reporting times were relied on extensively to validate the new dataset's study ascribable times. The first draft of descriptors and times was tabled at the meetings of the RANZCR Radiologist Workload Working Group, and was progressively refined by iterative consensus., Results: The output of the Radiologist Workload Working Group comprises a simplified modality-based table of robust descriptors and 'best estimate' corresponding study ascribable times. These can be used with the extant Pitman-Jones methodology in order to estimate the reporting workload of a medical imaging teaching department in units of time. As a first for Australia and New Zealand, nuclear medicine and PET study ascribable times have been incorporated and balanced against radiology study ascribable times., Conclusion: The RANZCR 2016 study ascribable times are ready for use by the Australian and New Zealand radiologist and nuclear medicine specialist community. We hope these times will also stimulate further data collection in our two countries towards a robust, bi-national study ascribable times database., (© 2018 The Royal Australian and New Zealand College of Radiologists.)

Introduction: Historically, there has been no objective method of measuring the time required for radiologists to produce reports during normal work. We have created a technique for semi-automated measurement of radiologist reporting time, and through it produced a robust set of absolute time requirements and relative value units for consultant reporting of diagnostic examinations in our hospital., Methods: A large sample of reporting times, recorded automatically by the Radiology Information System (COMRAD, Software Innovations, Christchurch, New Zealand) along with the description of each examination being reported, was placed in a database. Analysis was confined to diagnostic reporting by consultant radiologists. A spreadsheet was produced, listing the total number and the frequency of reporting times of each distinct examination. Outliers with exceptionally long report times (more than 10 min for plain radiography, 30 min for ultrasound, or 60 min for CT or MRI with some exceptions) were culled; this removed 9.5% of the total. Complex CTs requiring separate workstation time were assigned times by consensus. The median time for the remainder of each sample was the assigned absolute reporting time in minutes and seconds. Relative value units were calculated using the reporting time for a single view department chest X-ray of 1 min 38 s including verifying a report made using speech recognition software., Results: A schedule of absolute and relative values, based on over 179 000 reports, forms Table 2 of this paper., Conclusions: The technique provides a schedule of reporting times with reduced subjective input, which is more robust than existing systems for measuring reporting time., (© 2013 The Authors. Journal of Medical Imaging and Radiation Oncology © 2013 The Royal Australian and New Zealand College of Radiologists.)

Introduction: We describe how techniques traditionally used in the manufacturing industry (lean management, the theory of constraints and production planning) can be applied to planning radiology services to reduce the impact of constraints such as limited radiologist hours, and to subsequently reduce delays in accessing imaging and in report turnaround., Methods: Targets for imaging and reporting were set aligned with clinical needs. Capacity was quantified for each modality and for radiologists and recorded in activity lists. Demand was quantified and forecasting commenced based on historical referral rates. To try and mitigate the impact of radiologists as a constraint, lean management processes were applied to radiologist workflows. A production planning process was implemented., Results: Outpatient waiting times to access imaging steadily decreased. Report turnaround times improved with the percentage of overnight/on-call reports completed by a 1030 target time increased from approximately 30% to 80 to 90%. The percentage of emergency and inpatient reports completed within one hour increased from approximately 15% to approximately 50% with 80 to 90% available within 4 hours. The number of unreported cases on the radiologist work-list at the end of the working day reduced. The average weekly accuracy for demand forecasts for emergency and inpatient CT, MRI and plain film imaging was 91%, 83% and 92% respectively. For outpatient CT, MRI and plain film imaging the accuracy was 60%, 55% and 77% respectively. Reliable routine weekly and medium to longer term service planning is now possible., Conclusions: Tools from industry can be successfully applied to diagnostic imaging services to improve performance. They allow an accurate understanding of the demands on a service, capacity, and can reliably predict the impact of changes in demand or capacity on service delivery., (© 2013 The Royal Australian and New Zealand College of Radiologists.)

Introduction: Accurate and transparent measurement and monitoring of radiologist workload is highly desirable for management of daily workflow in a radiology department, and for informing decisions on department staffing needs. It offers the potential for benchmarking between departments and assessing future national workforce and training requirements. We describe a technique for quantifying, with minimum subjectivity, all the work carried out by radiologists in a tertiary department., Methods: Six broad categories of clinical activities contributing to radiologist workload were identified: reporting, procedures, trainee supervision, clinical conferences and teaching, informal case discussions, and administration related to referral forms. Time required for reporting was measured using data from the radiology information system. Other activities were measured by observation and timing by observers, and based on these results and extensive consultation, the time requirements and frequency of each activity was agreed on. An activity list was created to record this information and to calculate the total clinical hours required to meet the demand for radiologist services., Results: Diagnostic reporting accounted for approximately 35% of radiologist clinical time; procedures, 23%; trainee supervision, 15%; conferences and tutorials, 14%; informal case discussions, 10%; and referral-related administration, 3%. The derived data have been proven reliable for workload planning over the past 3 years., Conclusions: A transparent and robust method of measuring radiologists' workload has been developed, with subjective assessments kept to a minimum. The technique has value for daily workload and longer term planning. It could be adapted for widespread use., (© 2013 The Authors. Journal of Medical Imaging and Radiation Oncology © 2013 The Royal Australian and New Zealand College of Radiologists.)

Very uncommonly, Eustachian tube dysfunction can lead to symptomatic chronic elevation of middle ear pressure with aeration of bone and adjacent structures in the skull base and upper cervical spine, and an increased risk of fracture. We present a case demonstrating the natural history of this condition over 11 years before treatment and 10 months after treatment., (© 2013 The Authors. Journal of Medical Imaging and Radiation Oncology © 2013 The Royal Australian and New Zealand College of Radiologists.)

Aim: To estimate the sensitivity and specificity of computed tomography used for the detection of extranodal spread of metastatic head and neck squamous cell carcinoma, by experienced head and neck radiologists., Materials and Methods: Participants had undergone a neck dissection for head and neck squamous cell carcinoma, together with computed tomography scanning prior to surgery (accessible for reporting). Computed tomography images were independently examined by two experienced head and neck radiologists. Nodal involvement by squamous cell carcinoma and the presence or absence of extranodal spread were recorded. Results were compared to the histological specimen. The sensitivity, specificity and positive predictive value of using computed tomography for the detection of nodal involvement and presence or absence of extranodal spread were estimated, and 95 per cent confidence intervals were calculated., Results and Analysis: The study analysed 149 neck dissections. When using computed tomography to detect the extranodal spread of head and neck squamous cell carcinoma, radiologists A and B had sensitivities of 66 and 80 per cent, specificities of 91 and 90 per cent, and positive predictive values of 85 and 87 per cent, respectively., Discussion: The sensitivity and specificity of radiological detection of extranodal spread from head and neck squamous cell carcinoma is not well reported in the literature. Accuracy of reporting improves in the hands of experienced head and neck radiologists. This finding has clinical implications for surgical planning and adjuvant therapy requirements.

We present the first reported case of vertebral osteomyelitis due to Staphylococcus lugdunensis. The infection occurred in an 80-year-old woman who had been taking glucocorticosteroids. S. lugdunensis is a coagulase-negative staphylococcus with considerable potential as a human pathogen. Isolation of this organism should be regarded as significant unless evidence suggests otherwise.

The CT scans of 71 patients with primary squamous cell tumours of head and neck sites were reviewed and compared with clinical examination in the assessment of lymph nodes above and below the hyoid. Above the hyoid, CT and clinical examination disagreed on the presence or absence of metastases in 13/42 cases (31%); below the hyoid where palpation is presumably easier, there was disagreement in 1 of 10 cases (10%). Abandoning infra-hyoid scans to save scanner time would save only seven slices on average per case and it is possible that further, clinically silent lesions would be missed. We conclude that staging scans in head and neck cancer should continue to include the infra-hyoid region. The inadequacies of existing knowledge based on clinical staging are discussed.

Computerized tomographic (CT) imaging provides detailed information on the paranasal sinuses and is now well established as an alternative to standard radiographs. The planning and safety of surgery to the paranasal sinuses is greatly improved by CT imaging. We describe a new CT protocol comprising a limited coronal and axial scan series, based on our experience with the previously described 'CT-Mini-series'.

We present the case of a 56-year-old man who complained of numbness in his cheek, and was shown to have a very large partly thrombosed aneurysm of the ipsilateral petrous carotid artery. The radiological findings and differential diagnosis are discussed. Aneurysm of the petrous carotid should be included in the differential diagnosis of any parasellar mass.

The ureteric diameter on IVU was compared with the MCU findings of reflux or lower urinary tract dysfunction in a group of patients followed up after spinal cord injury. A wide ureter was associated with reflux in 20%, but 8 normal sized ureters on IVU also refluxed--5 of them to a significant degree. In the non-refluxing group, wide ureters were noted more often in patients whose bladder pressures were high and wildly fluctuating than in those with normal bladder pressures. Similarly, the incidence of reflux was higher in patients with high bladder pressures and wild fluctuations of bladder pressure than in those with normal pressures. While a wide ureter on IVU should arouse suspicion that reflux or lower urinary tract dysfunction might be present, these conditions are not necessarily excluded by the finding of a ureter of normal size.