CD, or not CD, that is the question: a digital interobserver agreement study in coeliac disease.

OBJECTIVE: Coeliac disease (CD) diagnosis generally depends on histological examination of duodenal biopsies. We present the first study analysing the concordance in examination of duodenal biopsies using digitised whole-slide images (WSIs). We further investigate whether the inclusion of immunoglobulin A tissue transglutaminase (IgA tTG) and haemoglobin (Hb) data improves the interobserver agreement of diagnosis. DESIGN: We undertook a large study of the concordance in histological examination of duodenal biopsies using digitised WSIs in an entirely virtual reporting setting. Our study was organised in two phases: in phase 1, 13 pathologists independently classified 100 duodenal biopsies (40 normal; 40 CD; 20 indeterminate enteropathy) in the absence of any clinical or laboratory data. In phase 2, the same pathologists examined the (re-anonymised) WSIs with the inclusion of IgA tTG and Hb data. RESULTS: We found the mean probability of two observers agreeing in the absence of additional data to be 0.73 (±0.08) with a corresponding Cohen's kappa of 0.59 (±0.11). We further showed that the inclusion of additional data increased the concordance to 0.80 (±0.06) with a Cohen's kappa coefficient of 0.67 (±0.09). CONCLUSION: We showed that the addition of serological data significantly improves the quality of CD diagnosis. However, the limited interobserver agreement in CD diagnosis using digitised WSIs, even after the inclusion of IgA tTG and Hb data, indicates the importance of interpreting duodenal biopsy in the appropriate clinical context. It further highlights the unmet need for an objective means of reproducible duodenal biopsy diagnosis, such as the automated analysis of WSIs using artificial intelligence.

Histopathology at autopsy: why bother?

AIMS: The frequency of histopathological sampling at autopsy varies, even though inadequate sampling may limit the value of autopsy reports. This study aims to investigate the contribution of histopathology at autopsy in a major teaching hospital. METHODS AND RESULTS: A total of 532 coronial autopsy reports from Manchester Royal Infirmary were analysed retrospectively. Gross and microscopic diagnoses were compared and classified as concordant, discordant, histology needed (i.e. indeterminate or unremarkable gross findings) or autolysed. Revisions made to the cause of death following histopathology were categorised as: altered direct cause of death, altered indirect cause of death, concordant with supportive information, irrelevant or inconclusive. The study was limited to brain, heart, kidney, liver, lung and spleen. Histopathology had been requested in 141 cases (27%), which were further analysed. The greatest discordance between gross and microscopic findings was observed in the lung (11.6%). The organs most frequently requiring histopathology to provide a diagnosis were the kidney and lung, at 52.8 and 28.2%, respectively. Alterations were made to the direct cause of death in 45% of cases where histopathology was taken; it provided additional or supportive information in a further 38%. Diagnoses of primary malignancy had a sensitivity of 74% [confidence interval (CI) = 0.59-0.86] and bronchopneumonia had a sensitivity of 45% (CI = 0.29-0.62). CONCLUSION: Histopathology has a major impact on the interpretation of organ pathology and determining a cause of death at autopsy.

Very Short Answer Questions: A Novel Approach To Summative Assessments In Pathology.

BACKGROUND: A solid understanding of the science underpinning treatment is essential for all doctors. Pathology teaching and assessment are fundamental components of the undergraduate medicine curriculum. Assessment drives learning and the choice of assessments influences students' learning behaviours. The use of multiple-choice questions is common but is associated with significant cueing and may promote "rote learning". Essay-type questions and Objective Structured Clinical Examinations (OSCEs) are resource-intensive in terms of delivery and marking and do not allow adequate sampling of the curriculum. To address these limitations, we used a novel online tool to administer Very Short Answer questions (VSAQs) and evaluated the utility of the VSAQs in an undergraduate summative pathology assessment. METHODS: A group of 285 medical students took the summative assessment, comprising 50 VSAQs, 50 single best answer questions (SBAQs), and 75 extended matching questions (EMQs). The VSAQs were machine-marked against pre-approved responses and subsequently reviewed by a panel of pathologists, with the software remembering all new marking judgements. RESULTS: The total time taken to mark all 50 VSAQs for all 285 students was 5 hours, compared to 70 hours required to manually mark an equivalent number of questions in a paper-based pathology exam. The median percentage score for the VSAQs test (72%) was significantly lower than that of the SBAQs (80%) and EMQs (84%), p <0.0001. VSAQs had a higher Cronbach alpha (0.86) than SBAQs (0.76), and EMQs (0.77). VSAQs, SBAQs and EMQs had a mean point-biserial of 0.35, 0.30 and 0.28, respectively. CONCLUSION: VSAQs are an acceptable, reliable and discriminatory method for assessing pathology, and may enhance students' understanding of how pathology supports clinical decision-making and clinical care by changing learning behaviour.

Post-mortem imaging as an alternative to autopsy in the diagnosis of adult deaths: a validation study.

BACKGROUND: Public objection to autopsy has led to a search for minimally invasive alternatives. Imaging has potential, but its accuracy is unknown. We aimed to identify the accuracy of post-mortem CT and MRI compared with full autopsy in a large series of adult deaths. METHODS: This study was undertaken at two UK centres in Manchester and Oxford between April, 2006, and November, 2008. We used whole-body CT and MRI followed by full autopsy to investigate a series of adult deaths that were reported to the coroner. CT and MRI scans were reported independently, each by two radiologists who were masked to the autopsy findings. All four radiologists then produced a consensus report based on both techniques, recorded their confidence in cause of death, and identified whether autopsy was needed. FINDINGS: We assessed 182 unselected cases. The major discrepancy rate between cause of death identified by radiology and autopsy was 32% (95% CI 26-40) for CT, 43% (36-50) for MRI, and 30% (24-37) for the consensus radiology report; 10% (3-17) lower for CT than for MRI. Radiologists indicated that autopsy was not needed in 62 (34%; 95% CI 28-41) of 182 cases for CT reports, 76 (42%; 35-49) of 182 cases for MRI reports, and 88 (48%; 41-56) of 182 cases for consensus reports. Of these cases, the major discrepancy rate compared with autopsy was 16% (95% CI 9-27), 21% (13-32), and 16% (10-25), respectively, which is significantly lower (p<0·0001) than for cases with no definite cause of death. The most common imaging errors in identification of cause of death were ischaemic heart disease (n=27), pulmonary embolism (11), pneumonia (13), and intra-abdominal lesions (16). INTERPRETATION: We found that, compared with traditional autopsy, CT was a more accurate imaging technique than MRI for providing a cause of death. The error rate when radiologists provided a confident cause of death was similar to that for clinical death certificates, and could therefore be acceptable for medicolegal purposes. However, common causes of sudden death are frequently missed on CT and MRI, and, unless these weaknesses are addressed, systematic errors in mortality statistics would result if imaging were to replace conventional autopsy. FUNDING: Policy Research Programme, Department of Health, UK.

Mortality from pulmonary embolism is decreasing in hospital patients.

OBJECTIVES: Pulmonary embolism is believed to be a common cause of death of hospital inpatients. The aims of this study were to estimate the number of deaths caused by pulmonary embolism and the potential to reduce this by the use of caval filters according to accepted indications. DESIGN: Review of autopsy reports and death notification records from 2007 and 2008. When pulmonary embolism was given as cause of death (in the autopsy report or in section 1 a-c or part 2 of the Medical Certificate of the Cause of Death), hospital records were reviewed for evidence of pre-mortem diagnosis of pulmonary embolism or deep vein thrombosis (DVT) and for evidence of accepted indications for caval filter placement. SETTING: Large UK teaching hospital. PARTICIPANTS: Hospital inpatients whose deaths were attributed to pulmonary embolism. MAIN OUTCOME MEASURES: Proportion of deaths adjudged at autopsy to be due to pulmonary embolism; evidence of pre-mortem diagnosis of DVT or pulmonary embolism; total number of hospital admission and deaths. RESULTS: From a total of 186,517 adult inpatient admissions there were 2583 (1.4%) adult inpatient deaths of which 696 (27%) underwent autopsy. Of those undergoing autopsy, 14 (2.0%, 95% CI 1.2-3.3%) deaths were caused by pulmonary embolism. Pulmonary embolism was recorded as a cause of death in a further 12 (0.7%) of 1773 patients who did not undergo autopsy. Of these, five had a pre-mortem diagnosis of DVT or pulmonary embolism. CONCLUSIONS: The proportion of deaths caused by pulmonary embolism appears to be considerably lower than the widely published rate, and of this small number, few have a pre-mortem diagnosis of DVT or pulmonary embolism. There is little scope for further reduction of pulmonary embolism mortality through use of caval filters according to guidelines. Current policy on pulmonary embolism risk prevention appears to be based on an over-estimate of the level of risk.

Viral detection in hydrops fetalis, spontaneous abortion, and unexplained fetal death in utero.

This study was undertaken to investigate the occurrence of viral infection in fetal death by examining tissues for the presence of DNA of several viral agents. Tissue specimens including heart, kidney, liver, lung, and placenta of 73 cases of fetal death were examined with 27 cases of elective termination of pregnancy as a control group. DNA extracted from these samples was tested for the presence of HSV, CMV, EBV, VZV, HHV-6, HHV-7, and PVB19. Viral DNA was found in one or more tissue samples from 25/73 cases (34%): CMV in 20, HSV in 5, parvovirus B19 in 5, HHV-7 in 3, and HHV-6 in 2. The presence of HHV-6 in fetal tissue has been reported rarely. No study so far has reported the detection of HHV-7 in fetal tissues with normal or adverse outcomes. Viral DNA was not found in any of the termination of pregnancy samples. Among the positive cases, eight had dual infection. One further case was positive for three viruses: HSV, CMV, and HHV-7. HHV-6 was the sole infectious agent in two cases, HHV-7 in one case, PVB19 in three, and CMV in ten cases. The finding of multiple viral DNA in 12% of the cases suggests the involvement of complex risk factors in cases of fetal loss. Although the cause of fetal death often includes other factors (e.g., chromosomal abnormalities) these data suggest the incidence of viral infective etiology may be higher than considered previously. However, larger studies are required to establish this link.

Cystic adventitial disease of the femoral vein presenting as deep vein thrombosis: a case report and review of the literature.

Cystic adventitial disease of veins is a rare condition. We report the case of a 28-year-old man who presented with a swollen leg secondary to obstruction of the common femoral vein as a result of this disease. He underwent excision of the cyst and made a full recovery. The presentation, investigation, treatment and pathology of this condition is discussed.