Microbiology in minimally invasive autopsy: best techniques to detect infection. ESGFOR (ESCMID study group of forensic and post-mortem microbiology) guidelines.

This manuscript aims to: 1) provide specific guidelines on PMM techniques in the setting of minimally invasive autopsy (MIA), both for pathologists collecting samples and for microbiologists advising pathologists and interpreting the results and 2) introduce standardization in PMM sampling at MIA. Post-mortem microbiology (PMM) is crucial to identify the causative organism in deaths due to infection. MIA including the use of post-mortem (PM) computed tomography (CT) and PM magnetic resonance imaging (MRI), is increasingly carried out as a complement or replacement for the traditional PM. In this setting, mirroring the traditional autopsy, PMM aims to: detect infectious organisms causing sudden unexpected deaths; confirm clinically suspected but unproven infection; evaluate the efficacy of antimicrobial therapy; identify emergent pathogens; and recognize medical diagnostic errors. Meaningful interpretation of PMM results requires careful evaluation in the context of the clinical history, macroscopic and microscopic findings. These guidelines were developed by a multidisciplinary team with experts in various fields of microbiology and pathology on behalf of the ESGFOR (ESCMID - European Society of Clinical Microbiology and Infectious Diseases - Study Group of Forensic and Post-mortem Microbiology, in collaboration with the ESP -European Society of Pathology-) based on a literature search and the author's expertise. Microbiological sampling methods for MIA are presented for various scenarios: adults, children, developed and developing countries. Concordance between MIA and conventional invasive autopsy is substantial for children and adults and moderate for neonates and maternal deaths. Networking and closer collaboration among microbiologists and pathologists is vital to maximize the yield of PMM in MIA.

Postmortem microbiology sampling following death in hospital: an ESGFOR task force consensus statement.

Postmortem microbiology (PMM) is a valuable tool in the identification of the cause of death and of factors contributory to death where death has been caused by infection. The value of PMM is dependent on careful autopsy planning, appropriate sampling, minimisation of postmortem bacterial translocation and avoidance of sample contamination. Interpretation of PMM results requires careful consideration in light of the clinical history, macroscopic findings and the histological appearances of the tissues. This consensus statement aims to highlight the importance of PMM in the hospital setting and to give microbiological and pathological advice on sampling in deaths occurring in hospital.

Use of macrophages to target therapeutic adenovirus to human prostate tumors.

New therapies are required to target hypoxic areas of tumors as these sites are highly resistant to conventional cancer therapies. Monocytes continuously extravasate from the bloodstream into tumors where they differentiate into macrophages and accumulate in hypoxic areas, thereby opening up the possibility of using these cells as vehicles to deliver gene therapy to these otherwise inaccessible sites. We describe a new cell-based method that selectively targets an oncolytic adenovirus to hypoxic areas of prostate tumors. In this approach, macrophages were cotransduced with a hypoxia-regulated E1A/B construct and an E1A-dependent oncolytic adenovirus, whose proliferation is restricted to prostate tumor cells using prostate-specific promoter elements from the TARP, PSA, and PMSA genes. When such cotransduced cells reach an area of extreme hypoxia, the E1A/B proteins are expressed, thereby activating replication of the adenovirus. The virus is subsequently released by the host macrophage and infects neighboring tumor cells. Following systemic injection into mice bearing subcutaneous or orthotopic prostate tumors, cotransduced macrophages migrated into hypoxic tumor areas, upregulated E1A protein, and released multiple copies of adenovirus. The virus then infected neighboring cells but only proliferated and was cytotoxic in prostate tumor cells, resulting in the marked inhibition of tumor growth and reduction of pulmonary metastases. This novel delivery system employs 3 levels of tumor specificity: the natural "homing" of macrophages to hypoxic tumor areas, hypoxia-induced proliferation of the therapeutic adenovirus in host macrophages, and targeted replication of oncolytic virus in prostate tumor cells.

Clinical, educational, and epidemiological value of autopsy.

The autopsy is now often regarded as of marginal use in modern clinical practice. In this Review we contend that the autopsy remains an important procedure with substantial, if largely underused, potential to advance medical knowledge and improve clinical practice. Many doctors lack familiarity with autopsy practices, and are insufficiently aware of the benefits for not only bereaved families but also present and future patients. In this Review, which has an international perspective, we consider the ascent and decline of the autopsy, the legal frameworks that govern its use, the value and potential pitfalls of alternatives to the conventional method, and the autopsy's role in undergraduate medical education. We also draw attention to the continuing ability of autopsies to improve the completeness and reliability of death certification, which is important for public-health strategies and for some bereaved families.

A bite into the history of the autopsy : From ancient roots to modern decay.

The autopsy has had a checkered history, much of which has been surrounded by controversy. The roots of human dissection are found in the ancient world where rumors flourished that the prosectors of the day were engaged in vivisection as well as dissection. Bound up with the prevailing religious and political systems of the day, the autopsy has alternately been prohibited and encouraged, used to explore the nature of disease, and conceal questionable political policy. This review explores the history of the autopsy from its ancient roots in Egypt, Mesopotamia, Alexandria, and the Far East through the dark ages to medieval times and beyond into the renaissance. The development of the autopsy in Europe during the 17th to 19th centuries is discussed before briefly considering the decline of this diagnostic tool in the 20th century.

Artificial intelligence in predicting bladder cancer outcome: a comparison of neuro-fuzzy modeling and artificial neural networks.

PURPOSE: New techniques for the prediction of tumor behavior are needed, because statistical analysis has a poor accuracy and is not applicable to the individual. Artificial intelligence (AI) may provide these suitable methods. Whereas artificial neural networks (ANN), the best-studied form of AI, have been used successfully, its hidden networks remain an obstacle to its acceptance. Neuro-fuzzy modeling (NFM), another AI method, has a transparent functional layer and is without many of the drawbacks of ANN. We have compared the predictive accuracies of NFM, ANN, and traditional statistical methods, for the behavior of bladder cancer. EXPERIMENTAL DESIGN: Experimental molecular biomarkers, including p53 and the mismatch repair proteins, and conventional clinicopathological data were studied in a cohort of 109 patients with bladder cancer. For all three of the methods, models were produced to predict the presence and timing of a tumor relapse. RESULTS: Both methods of AI predicted relapse with an accuracy ranging from 88% to 95%. This was superior to statistical methods (71-77%; P < 0.0006). NFM appeared better than ANN at predicting the timing of relapse (P = 0.073). CONCLUSIONS: The use of AI can accurately predict cancer behavior. NFM has a similar or superior predictive accuracy to ANN. However, unlike the impenetrable "black-box" of a neural network, the rules of NFM are transparent, enabling validation from clinical knowledge and the manipulation of input variables to allow exploratory predictions. This technique could be used widely in a variety of areas of medicine.

Differential expression of hMLH1 and hMSH2 is related to bladder cancer grade, stage and prognosis but not microsatellite instability.

Defects in the DNA mismatch repair proteins result in microsatellite instability and malignancy in hereditary non-polyposis colorectal carcinoma (HNPCC). However, the role of mismatch repair (MMR) proteins and microsatellite instability (MSI) in transitional cell carcinoma of the bladder is less clear. In our study, the expression of 2 MMR proteins and the frequency of MSI in Transitional cell carcinoma of the bladder (TCC) were investigated. One hundred eleven patients with TCC of the bladder were studied, with complete clinicopathological data (median follow up of 5 years, range 5-16 years). Immunohistochemistry was used to detect the expression levels of hMLH1 and hMSH2. Microsatellite analysis for 14 loci (10 loci from the Bethesda consensus panel and the repeats in the TGFbetaR2, BAX, hMSH3 and hMSH6 genes) was performed on 84 tumors. Reduced expression of either MMR protein was seen in 26 of 111 tumors (23%). Reduced expression was seen more commonly in muscle invasive (p<0.03) and high grade TCC (p<0.03) than in superficial, low grade tumors. By 5 years, reduced expression of either MMR protein was associated with fewer recurrences of superficial tumors (p=0.015) and fewer relapses in all tumors (p=0.03), compared to tumors with normal expression. Nine tumors had reduced expression of both MMR proteins, analysis which suggests a synergistic reduction in expression (p=0.001). MMR expression was related to patient age, younger patients being more likely to have reduced MMR expression than older patients (p<0.01). MSI was seen at multiple loci in 1 tumor (1%) and at a single locus in 6 tumors (7%). MSI was not associated with MMR expression. Our findings indicate that reduced expression of the MMR proteins may have an important contribution in the development of a subset of TCCs and suggest a potential role for MMR expression as prognostic indicators.

Kayser-Fleischer like rings in alcoholic liver disease: a case report.

Kayser-Fleischer rings are brown pigmented rings that run along the periphery of the cornea. Situated in Descemet's membrane and being comprised of granules of deposited copper they have traditionally been thought of as pathognomic of Wilson's disease. However, they can also be seen in other forms of liver disease. We document a case of Kayser-Fleischer like rings occurring in alcoholic liver disease--a previously unreported association.

The autopsy in modern undergraduate medical education: a qualitative study of uses and curriculum considerations.

AIM: Medical education has undergone dramatic changes over the past decade. In the UK, the General Medical Council (GMC), the driving force behind curriculum reform, now requires curricula to be founded on a base of educational theory and research. This qualitative study investigated the roles of the autopsy within the context of the modern medical curriculum. METHODS: Using a phenomenological methodology, a non-representative 'theoretical sample' was selected to include medical educators with a wide range of teaching experience and responsibilities and disparate views both for and against the autopsy. Semistructured, tape-recorded interviews were undertaken to investigate the roles of the autopsy within the medical curriculum. Anonymised interview transcripts were subjected to a themed content analysis. RESULTS: Theoretical saturation was reached after 9 interviews. No new themes were added by a further 5 interviews. All the interviews were polythematic. In all, 43 themes were identified. In addition to confirming overt uses of the autopsy reported in previous studies, educators identified issues of curriculum design and development, the impact on the hidden curriculum, and a range of disadvantages and alternatives to the autopsy. CONCLUSIONS: Educators continue to perceive the autopsy as having a multifactorial role in providing the doctors of tomorrow with the appropriate knowledge and attitudes needed for the practice of medicine in the 21st century.

Curriculum or syllabus: which are we reforming?

Although the concept of 'curriculum' is complex, a common understanding of the term by those involved in medical education is essential, given the current climate of medical curriculum development and reform. It has not previously been established that such a common frame of reference exists. We polled a sample of medical educators with a range of teaching experience and responsibility in an attempt to discover what they understood by 'curriculum' (and whether or not the concept could be articulated). A sample of medical students was similarly polled. In total, 85% of staff and 34.9% of the students responded. The responses obtained were subjected to a content analysis. The answers received were polythematic in 87.5% of cases, dominant themes including 'curriculum as a syllabus', 'curriculum as a meta-syllabus', and 'curriculum as a means to an end'. Our data show that the nature of curriculum is complex and does not lend itself to dictionary-style definitions. Moreover, the majority of those polled view 'curriculum' in two-dimensional terms, tending to equate it to 'syllabus'. This may have significant implications for curriculum reform.