The Role of Autopsy in Quality Assurance: Pilot Study of a Method for Prospective Reporting of Diagnostic Errors Discovered at Autopsy.

ABSTRACT: Hospital autopsies frequently reveal errors in diagnosis that could have affected the patient's clinical outcome. The aims of this study were (1) to investigate the ability of autopsy at our institution to elucidate unrecognized antemortem diagnoses and (2) to pilot a method for tabulating diagnostic discrepancies on a prospective basis. The study sample consisted of 296 cases from our hybrid hospital/forensic autopsy service during the period 2016 to 2018. Discrepancies in autopsy and clinical diagnosis were reported by pathologists at the time of autopsy report generation using a standard form. The rates of major discrepancies between autopsy and clinical diagnoses were 37.5% for in-hospital cases and 25% for patients who died outside our hospital (P < 0.05). The most common discrepant category was infection. The overall rates of discrepant causes of death were 14% (in hospital) and 8% (out of hospital) (ns). Overall percentages of cases with major diagnostic discrepancies were higher in our study than have been previously reported. It is possible that the nature of our patient population plays a role in this result. This study describes an important prospective reporting tool that will allow us to track rates of medical errors and improve diagnosis and treatment of the critically ill.

Quantitative susceptibility mapping of carotid arterial tissue ex vivo: Assessing sensitivity to vessel microstructural composition.

PURPOSE: To characterize microstructural contributions to the magnetic susceptibility of carotid arteries. METHOD: Arterial vessels were scanned using high-resolution quantitative susceptibility mapping (QSM) at 7 Tesla. Models of vessel degradation were generated using ex vivo porcine carotid arteries that were subjected to several different enzymatic digestion treatments that selectively removed microstructural components (smooth muscle cells, collagen, and elastin). Magnetic susceptibilities measured in these tissue models were compared to those in untreated (native) porcine arteries. Magnetic susceptibility measured in native porcine carotid arteries was further compared to the susceptibility of cadaveric human carotid arteries to investigate their similarity. RESULTS: The magnetic susceptibility of native porcine vessels was diamagnetic (χnative = -0.1820 ppm), with higher susceptibilities in all models of vessel degradation (χelastin-degraded = -0.0163 ppm; χcollagen-degraded = -0.1158 ppm; χdecellularized = -0.1379 ppm; χfixed native = -0.2199 ppm). Magnetic susceptibility was significantly higher in collagen-degraded compared to native porcine vessels (Tukey-Kramer, P < .01) and between elastin-degraded and all other models (including native, Tukey-Kramer, P < .001). The susceptibility of fixed healthy human arterial tissue was diamagnetic, and no significant difference was found between fixed human and fixed porcine arterial tissue susceptibilities (analysis of variance, P > .05). CONCLUSIONS: Magnetic susceptibility measured using QSM is sensitive to the microstructural composition of arterial vessels-most notably to collagen. The similarity of human and porcine arterial tissue susceptibility values provides a solid basis for translational studies. Because vessel microstructure becomes disrupted during the onset and progression of carotid atherosclerosis, QSM has the potential to provide a sensitive and specific marker of vessel disease.

An arch worth revisiting: a study on the feline humeral supracondylar foramen and its evolutionary significance.

The supracondylar foramen with a (seemingly) osseous peripheral arch noticed on the medio-distal feline humeri had remained disputed among anatomists. Some scholars have argued in favor of homology between this foramen and the supracondyloid foramen formed in presence of the ligament of Struthers in humans. Other theories include its presence as a retinaculum holding the median nerve and brachial artery to their anatomical position in a flexed elbow. Unfortunately, these theories lack investigative rigor. The emergence of non-invasive imaging modalities, such as micro-computed tomography, has enabled researchers to inspect the internal anatomy of bones without dismantling them. Thus, a micro-computed tomographic investigation was conducted on three feline (Felis catus) humeri specimens while the internal anatomy of the supracondylar foramina was examined. Unlike the humerus, the thin peripheral arch of the feline supracondylar foramen failed to elicit any osseous trabeculae or foci of calcification. While adhering to the humeral periosteum at its origin, the non-osseous arch, typical of a muscular tendon, attaches into the bony saddle related to the medial humeral epicondyle suggestive of a tendon or aponeurotic extension of a (vestigial) brachial muscle, with the coracobrachialis longus emerging to be the most likely candidate.

Experimental testing combined with inverse-FE for mechanical characterisation of penile tissues.

Erectile dysfunction (ED) predominantly affects men in their 40-70s and can lead to poor quality of life. One option for ED treatment is surgical implantation of an inflatable penile prosthesis (IPP). However, they can be associated with negative outcomes including infection, migration or fibrosis. To improve outcomes, the interaction between the IPP device and surrounding tissues needs further investigation and this could be achieved using pre-clinical testbeds, but they need to be informed by extensive tissue testing. In this study, an experimental approach is adopted to characterise the mechanics of horse penile tissue and establish a testing protocol for penile tissue. The whole penis segments were tested in plate compression tests to obtain whole penis behaviour which is necessary for validation of a pre-clinical testbed, whilst tensile and compression tests were performed on individual penile tissues, namely corpus cavernosa and tunica albuginea. The second part of the paper deals with the development of a computational model employing an inverse finite element approach to estimate the material parameters of each tissue layer. These material parameters are in good agreement with the experimental results obtained from the individual tissue layers and whole organ tissue tests. This paper presents the first study proposing realistic nonlinear elastic material parameters for penile tissues and offers a validated testbed for IPPs. STATEMENT OF SIGNIFICANCE: Erectile Dysfunction (ED) affects over half the male population aged 40-70 potentially leading to poor quality of life. Patients not responding to conventional treatments of ED, are advised to use penile prostheses which can create an erection using implanted inflatable cylinders. A significant drawback of such prostheses, however, is the substantial tissue damage they can induce during their usage. Preclinical testbeds, including computational and bench-top models, could offer an efficient means of improving device designs to mitigate this damage but such testbeds require extensive knowledge of penile tissue properties. In this study, the authors determine penile tissue mechanics and apply an inverse FE approach to characterise the penile material properties required to validate preclinical models of the penis.

Inverse material parameter estimation of patient-specific finite element models at the carotid bifurcation: The impact of excluding the zero-pressure configuration and residual stress.

The carotid bifurcation experiences a complex loading environment due to its anatomical structure. Previous in-vivo material parameter estimation methods often use simplified model geometries, isotropic hyperelastic constitutive equations or neglect key aspects of the vessel, such as the zero-pressure configuration or residual stress, all of which have independently been shown to alter the stress environment of the vessel wall. Characterizing the location of high stress in the vessel wall has often been proposed as a potential indicator of structural weakness. However, excluding the afore-mentioned zero-pressure configuration, residual stress and patient-specific material parameters can lead to an incorrect estimation of the true stress values observed, meaning that stress alone as a risk indicator of rupture is insufficient. In this study, we investigate how the estimated material parameters and overall stress distributions in geometries of carotid bifurcations, extracted from in-vivo MR images, alter with the inclusion of the zero-pressure configuration and residual stress. This approach consists of the following steps: (1) geometry segmentation and hexahedral meshing from in-vivo magnetic resonance images (MRI) at two known phases; (2) computation of the zero-pressure configuration and the associated residual stresses; (3) minimization of an objective function built on the difference between the stress states of an "almost true" stress field at two known phases and a "deformed" stress field by altering the input material parameters to determine patient-specific material properties; and (4) comparison of the stress distributions throughout these carotid bifurcations for all cases with estimated material parameters. This numerical approach provides insights into the need for estimation of both the zero-pressure configuration and residual stress for accurate material property estimation and stress analysis for the carotid bifurcation, establishing the reliability of stress as a rupture risk metric.

Is 5q deletion in de novo Acute Myelogenous Leukemia (AML) with excess blasts a surrogate marker for the cryptic t(7;21)(p22;q22)? A case report and review of literature.

Although the 5q- syndrome is common in both de novo and treatment related myelodysplastic syndrome (MDS) and the World Health Organization defined 5q- syndrome as a specific type of MDS, it is less common in acute myelogenous leukemia (AML). Recently, it was suggested that AML with diploidy/tetraploidy and/or 5q alterations may be associated with the cryptic translocation, t(7;21)(p22;q22) resulting in RUNX1-USP42 gene fusion and this association may have been underestimated. Here, we report another case of de novo AML with cryptic t(7;21)(p22;q22) associated with a 5q deletion.

Development of a Collagen Fibre Remodelling Rupture Risk Metric for Potentially Vulnerable Carotid Artery Atherosclerotic Plaques.

Atherosclerotic plaque rupture in carotid arteries can lead to stroke which is one of the leading causes of death or disability worldwide. The accumulation of atherosclerotic plaque in an artery changes the mechanical properties of the vessel. Whilst healthy arteries can continuously adapt to mechanical loads by remodelling their internal structure, particularly the load-bearing collagen fibres, diseased vessels may have limited remodelling capabilities. In this study, a local stress modulated remodelling algorithm is proposed to explore the mechanical response of arterial tissue to the remodelling of collagen fibres. This stress driven remodelling algorithm is used to predict the optimum distribution of fibres in healthy and diseased human carotid bifurcations obtained using Magnetic Resonance Imaging (MRI). In the models, healthy geometries were segmented into two layers: media and adventitia and diseased into four components: adventitia, media, plaque atheroma and lipid pool (when present in the MRI images). A novel meshing technique for hexahedral meshing of these geometries is also demonstrated. Using the remodelling algorithm, the optimum fibre patterns in various patient specific plaques are identified and the role that deviations from these fibre configurations in plaque vulnerability is shown. This study provides critical insights into the collagen fibre patterns required in carotid artery and plaque tissue to maintain plaque stability.

An investigation into the critical role of fibre orientation in the ultimate tensile strength and stiffness of human carotid plaque caps.

The development and subsequent rupture of atherosclerotic plaques in human carotid arteries is a major cause of ischaemic stroke. Mechanical characterization of atherosclerotic plaques can aid our understanding of this rupture risk. Despite this however, experimental studies on human atherosclerotic carotid plaques, and fibrous plaque caps in particular, are very limited. This study aims to provide further insights into atherosclerotic plaque rupture by mechanically testing human fibrous plaque caps, the region of the atherosclerotic lesion most often attributed the highest risk of rupture. The results obtained highlight the variability in the ultimate tensile stress, strain and stiffness experienced in atherosclerotic plaque caps. By pre-screening all samples using small angle light scattering (SALS) to determine the dominant fibre direction in the tissue, along with supporting histological analysis, this work suggests that the collagen fibre alignment in the circumferential direction plays the most dominant role for determining plaque structural stability. The work presented in this study could provide the basis for new diagnostic approaches to be developed, which non-invasively identify carotid plaques at greatest risk of rupture. STATEMENT OF SIGNIFICANCE: Mechanical characterisation of the atherosclerotic plaque cap is of utmost importance for understanding the mechanisms that govern the rupture strength of this tissue in-vivo. Studies has shown that plaque tissue is heterogenous and comprises of many structural components, each of which exhibits a varying mechanical response. However, rupture generally is located to the plaque cap, whereby the stress exerted on this location exceeds its mechanical strength causing failure. This work shows, for the first time, that the underlying collagen fibre architecture of carotid plaque caps governs their strength and stiffness. This study shows that plaque caps with collagen fibres aligned in the predominately circumferential direction experience higher stresses and lower strains before failure while those with predominately axial fibres display the opposite trend. Furthermore, total collagen content was found not to play a dominant role in determining the mechanical response of the tissue. The present study provides critical insights into human atherosclerotic plaque tissue mechanics and offers clinically relevant insights for mechanically sensitive imaging techniques, such as strain-based ultrasound or MRI.

Exploring arterial tissue microstructural organization using non-Gaussian diffusion magnetic resonance schemes.

The purpose of this study was to characterize the alterations in microstructural organization of arterial tissue using higher-order diffusion magnetic resonance schemes. Three porcine carotid artery models namely; native, collagenase treated and decellularized, were used to estimate the contribution of collagen and smooth muscle cells (SMC) on diffusion signal attenuation using gaussian and non-gaussian schemes. The samples were imaged in a 7 T preclinical scanner. High spatial and angular resolution diffusion weighted images (DWIs) were acquired using two multi-shell (max b-value = 3000 s/mm2) acquisition protocols. The processed DWIs were fitted using monoexponential, stretched-exponential, kurtosis and bi-exponential schemes. Directionally variant and invariant microstructural parametric maps of the three artery models were obtained from the diffusion schemes. The parametric maps were used to assess the sensitivity of each diffusion scheme to collagen and SMC composition in arterial microstructural environment. The inter-model comparison showed significant differences across the considered models. The bi-exponential scheme based slow diffusion compartment (Ds) was highest in the absence of collagen, compared to native and decellularized microenvironments. In intra-model comparison, kurtosis along the radial direction was the highest. Overall, the results of this study demonstrate the efficacy of higher order dMRI schemes in mapping constituent specific alterations in arterial microstructure.