Post-mortem MRI as an alternative to non-forensic autopsy in foetuses and children: from research into clinical practice

Although post-mortem MRI (PMMR) was proposed as an alternative to conventional autopsy more than a decade ago, the lack of systematic validation has limited its clinical uptake. Minimally invasive autopsy (MIA) using PMMR together with ancillary investigations has now been shown to be as accurate as conventional autopsy in foetuses, newborns and infants and is particularly useful for cerebral, cardiac and genitourinary imaging. Unlike conventional autopsy, PMMR provides a permanent three-dimensional auditable record, with accurate estimation of internal organ volumes. MIA is becoming highly acceptable to parents and professionals, and there is widespread political support and public interest in its clinical implementation in the UK. In the short to medium term, it is desirable that a supraregional network of specialist centres should be established to provide this service within the current National Health Service framework.The value of paediatric and perinatal autopsy in confirming or refuting ante-mortem diagnosis, advancing medical science and providing accurate epidemiological data about disease prevalence is undisputed. A number of studies have shown that clinically important information is obtained from autopsy in the majority of hospital deaths, and such information may have prevented death in around 10% of cases, if it had been available.^1–3 However, these proportions have been largely unchanged over several decades, and there remains widespread variation in clinical practice, with judgements made regarding which cases do and do not need a full autopsy often depending on an individual pathologist''s or coroner''s preference.Advances in early antenatal diagnosis and screening programmes have resulted in an increase in the number of terminations of pregnancies in the past decade, and improvements in antenatal ultrasound imaging mean that there is now complete agreement between prenatal ultrasound and autopsy findings in >80% of cases.⁴ However, in up to one-quarter of cases, additional information which changes the underlying diagnosis or the information given to parents during counselling may be acquired from a formal autopsy.^5–9 This figure may be higher in paediatric rather than perinatal cases.¹ Several studies have also shown a significant discrepancy rate between what clinicians think is the cause of death and full traditional autopsy findings,^3,10 and error rates can be as high as 50% on medical certificates in stillbirths.¹¹The clinical information gained from performing a full post-mortem examination forms the basis of National Health Service autopsy service provision following foetal and childhood deaths in the UK, and despite its inherent limitations is the key part in developing appropriate preventative measures.¹²

Declining autopsy rates

Autopsy rates in the UK and across mainland Europe¹³ have been declining for the past decade. The UK national data show that only 44% of stillbirths, 38% of perinatal deaths and 25% of neonatal deaths result in an autopsy being performed.¹² This is well below the UK Royal Colleges'' recommendations of 75% and means that a large amount of information that could be used to counsel parents about future pregnancies and contribute to epidemiological studies regarding infantile deaths is currently missing. Consented (non-forensic) paediatric autopsies are virtually non-existent.¹⁴This decline cannot be attributed to clinicians failing to offer autopsies to parents, as the number of clinicians offering autopsies has increased in recent years from 89% to 97% in stillbirths and from 77% to 87% in neonatal deaths.¹² Therefore, the current low autopsy rate is primarily due to parental refusal (Figure 1).Open in a separate windowFigure 1.Changes in the neonatal autopsy rate (line with diamonds) and proportion of cases in which autopsy was offered to parents (line with squares) between 2000 and 2007 in the UK (adapted from the CEMACH data¹²).This reluctance to consent for a conventional invasive autopsy is multifactorial, including religious reasons, fear of disfigurement (especially towards opening the head), the time an autopsy takes, which may delay burial or funeral plans, and not wanting to put a baby or child through any more tests when it may not provide additional information.¹⁵     

Legal and ethical obligations to conduct a clinical drug trial in Australia as an investigator initiated and sponsored study for an overseas pharmaceutical company

Most multi-centre trials are both financed and sponsored by the pharmaceutical company involved. What follows will map the path adopted for an investigator initiated and sponsored study for a new indication of an established medication. The chief investigators of a company-sponsored, investigator-initiated, multi-centre, placebo-controlled study of an established medication, Pharmaceutical Benefit Scheme (PBS) listed for treatment of one condition but trialled in the management of another condition (trial of off-label use), were approached to submit a protocol to repeat the type of study with a different compound. The new study would test a different agent, also PBS listed, for the same condition as in the initial study and with the same off-licence application. The company would finance the study, provide the medication and matched placebo but only review the investigator-initiated protocol which would be sponsored by the principal investigator. This required the investigator to implement the trial, as would normally be done by the pharmaceutical company, yet also act as its principal investigator. The principal investigator, with colleagues and a Clinical Research Organisation (CRO), developed a protocol, adapted for the new agent, and submitted it for approval. Upon acceptance a contract was negotiated with the pharmaceutical company which had to overcome jurisdictional conflicts between common law and civil law legal systems. A CRO was contracted to undertake administrative functions which dictated special contractual agreements to overcome possible conflicts of interest for a sponsor/investigator to protect patient interests. There was need to find indemnification insurance with jurisdictional problems, co-investigators, ethics committee approvals and finance management as just some of the difficulties encountered. The paper will outline how these obstacles were overcome and how ethical and legal issues were respected through compromise. The ethical and legal obligations were addressed in a fashion which allowed the conduct of a trial adopting a proven methodology but novel infrastructure such that it was a totally independent study with regards conduct and reporting of final data, irrespective of the results being either positive or negative. This may represent a more acceptable way to ensure that future clinical trials are devoid of undue influence from the pharmaceutical industry which may still fund the study.     

Lipohemarthrosis of the knee: MRI as an alternative to the puncture of the knee joint

Joint effusions are common after sports injuries. In a specific form they can be very accurate for the diagnosis of intraarticular fractures; however, assessment can be tricky. Several imaging means are compared which outline the advantages and disadvantages of each technique. Electronic Publication     

Ultrasound-guided biopsy of greater omentum: an effective method to trace the origin of unclear ascites

Objectives

Thickened greater omentum is encountered with high frequency in patients with ascites. The purpose of our study was to assess the utility of greater omentum biopsy under the guidance of ultrasound (US) in tracing the origin of unclear ascites and differentiating benign and malignant ascites.

Materials and methods

We retrospectively reviewed our institutional database for all records of greater omentum biopsy cases. One hundred and ninety-four patients with unclear ascites and thickened greater omentum were included in the study. The sonograms of greater omentum were evaluated before undergoing the ultrasound-guided biopsy and a biopsy was considered successful if a specific benign or malignant diagnosis was rendered by the pathologist.

Results

Successful biopsy was rendered for 182 biopsy procedures (93.8%, 182/194) including tuberculosis (n = 114), chronic inflammation (n = 3), metastases (n = 58), malignant mesothelioma (n = 6) and pseudomyxoma peritonei (n = 1). Twelve biopsies were non-diagnostic. According to the results of biopsy and follow-up, the sensitivity and specificity of biopsy in distinguishing malignant ascites from benign ascities were respectively 95.6% (65/68) and 92.9% (117/126). The greater omentum of 84 cases of tuberculous peritonitis showed “cerebral fissure” sign and was well seen as an omental cake infiltrated with irregular nodules when involved by carcinomatosis. No “cerebral fissure” sign was observed in peritoneal carcinomatosis. The sensitivity and specificity of this sign in indicating the existence of tuberculous peritonitis were 73.5% (89/121) and 100% (73/73). Moreover, if the specific “cerebral fissure” sign was combined with the biopsy results, the specificity of biopsy in distinguishing malignant ascites from benign ascits increased to 96.8% (122/126).

Conclusion

Ultrasound-guided biopsy of greater omentum is an important and effective method to diagnose the unclear ascites for patients with thickened omentum if certain techniques could be paid attention to. “Cerebral fissure” sign of greater omentum was a specific sign in indicating the tuberculous peritonitis and could increase the specificity of biopsy in distinguishing malignant ascites from benign ascits if combined with the biopsy results.     

An alternative radiometric method for calculating the sedimentation rates: Application to an intertidal region (SW of Spain)

A new method using the inventory determined for the activity of the radionuclide ¹³⁷Cs, coming from global radioactive fallout has been utilised to calculate the sedimentation rates.The method has been applied in a wide intertidal region in the Bay of Cádiz Natural Park (SW Spain).The sedimentation rates estimated by the ¹³⁷Cs inventory method ranged from 0.26 cm/year to 1.72 cm/year. The average value of the sedimentation rate obtained is 0.59 cm/year, and this rate has been compared with those resulting from the application of the ²¹⁰Pb dating technique. A good agreement between the two procedures has been found.From the study carried out, it has been possible for the first time, to draw a map of sedimentation rates for this zone where numerous physico-chemical, oceanographic and ecological studies converge, since it is situated in a region of great environmental interest. This area, which is representative of common environmental coastal scenarios, is particularly sensitive to perturbations related to climate change, and the results of the study will allow to make short and medium term evaluations of this change.     

Vitreous humor as an alternative sample to blood for the supercritical fluid extraction of morphine and 6-monoacetylmorphine

The use of vitreous humor as an alternative sample to blood was investigated for the detection of heroin abuse by quantifying levels of morphine and 6-monoacetylmorphine (6-MAM) in post-mortem samples. The levels achieved in each of the two toxicological specimens were compared on a case-to-case basis to determine if a correlation existed. A total of 20 positive morphine cases were examined. In general, the levels of morphine in blood were higher than in the corresponding vitreous humor samples, with some correlation existing. 6-MAM was found in 15 blood samples and 17 vitreous humor samples. Although no correlation was found between the levels of 6-MAM in blood and vitreous humor, the latter may still be used for verification of heroin abuse.     

CT-Guided transgluteal drainage of deep pelvic abscesses in children: selective use as an alternative to transrectal drainage

OBJECTIVE: The transgluteal approach to abscess drainage through the greater sciatic foramen has been described in adults, but this route has not been as extensively studied in children. We performed CT-guided transgluteal percutaneous abscess drainage in seven children and assessed the results of drainage and catheter tolerance. CONCLUSION: Transgluteal catheters are well tolerated by children, and the transgluteal route is an effective approach to selected pelvic abscesses in children.     

Intracompartmental pressure testing: results of an international survey of current clinical practice, highlighting the need for standardised protocols

Despite more recent non-invasive modalities generating some credence in the literature, intracompartmental pressure testing is still considered the 'gold standard' for investigating chronic exertional compartment syndrome (CECS). Intracompartmental pressure testing, when used correctly, has been shown to be accurate and reliable. However, it is a user-dependent investigation, and the manner in which the investigation is conducted plays a large role in the outcome of the test. Despite this, a standard, reproducible protocol for intracompartmental pressure testing has not been described. This results in confusion regarding interpretation of results and reduces the tests' reliability. A summary of the current understanding of CECS is presented, along with the results of a survey of specialists in Australia and New Zealand who perform intracompartmental pressure testing, which confirms that a uniform approach is currently not used in clinical practice. This highlights the need for a consensus and standardised approach to intracompartmental pressure testing.     

Evolution of a protocol for ketamine-induced sedation as an alternative to general anesthesia for interventional radiologic procedures in pediatric patients

PURPOSE: To establish a protocol for credentialed pediatric radiology nurses, with radiologist supervision, to administer ketamine to induce sedation and analgesia during interventional radiologic procedures. MATERIALS AND METHODS: This study was conducted in two phases. The goal of the first phase was to develop a sedation protocol to replace that of using general anesthesia for specified pediatric interventional procedures. Ketamine was administered intravenously (with intermittent bolus or continuous infusion) or intramuscularly. Sedation induction times, adverse events, doses, and sedation and recovery durations were recorded. In phase 2, the results of phase 1 were reviewed and a formal ketamine protocol was developed. RESULTS: Neither sedation failures nor substantial adverse events occurred in phase 1. Mean duration of all sedations was 52 minutes, and median recovery room time was 0 minutes. In phase 2, the results of phase 1 were reviewed and a sedation protocol was proposed to a hierarchy of hospital committees before final approval from the medical staff executive committee. Subsequently, standard order forms for radiology nurse administration of ketamine with radiologist supervision were prepared for exclusive use by the pediatric interventional radiology department. CONCLUSION: Ketamine-induced sedation may be a safe and effective alternative to general anesthesia for some interventional radiologic procedures in pediatric patients. Collaboration between anesthesia and radiology departments is important for development of a safe and successful ketamine sedation program. To the authors' knowledge, this is the first report describing the intravenous infusion of ketamine for sedation in pediatric patients and the only report describing the establishment of a protocol for ketamine administration by credentialed radiology nurses with radiologist supervision.     

Applicability of the Calce method for age estimation in an Indian population: A clinical CT-based study

Age estimation is one of the prerequisites of human identification. Age-progressive changes in the pelvis offer useful evidence for forensic age estimation across all age groups. The acetabulum presents as a durable and taphonomic degradation resistant age marker, and, can be employed for analysing age-progressive changes described by Calce. The present study aimed at determining the applicability of the Calce method for age estimation in an Indian population based on a computed tomographic examination of the acetabulum. Additionally, different morphological features defined by Calce were evaluated to identify the feature which contributes most towards the process of age estimation. CT images obtained from clinically undertaken examinations of individuals aged 17 years and above were scrutinized according to the features defined within the Calce method. No statistically significant bilateral or sex differences were observed. An overall accuracy of 76.66% was observed on applying the Calce method to an Indian population, with lower accuracy percentages for individuals aged 40 years and above. The associated overall inaccuracy and bias were found to be 9.45 and 8.88 years, respectively. Within the various features, acetabular groove was found to contribute most towards the overall accuracy, and apex growth the least. Considering this weighted proportion, population specific models should be derived to render greater applicability to the method for age estimation.     

The value of postmortem computed tomography as an alternative for autopsy in trauma victims: a systematic review

The aim of this study was to assess the role of postmortem computed tomography (PMCT) as an alternative for autopsy in determining the cause of death and the identification of specific injuries in trauma victims. A systematic review was performed by searching the EMBASE and MEDLINE databases. Articles were eligible if they reported both PMCT as well as autopsy findings and included more than one trauma victim. Two reviewers independently assessed the eligibility and quality of the articles. The outcomes were described in terms of the percentage agreement on causes of death and amount of injuries detected. The data extraction and analysis were performed together. Fifteen studies were included describing 244 victims. The median sample size was 13 (range 5–52). The percentage agreement on the cause of death between PMCT and autopsy varied between 46 and 100%. The overall amount of injuries detected on CT ranged from 53 to 100% compared with autopsy. Several studies suggested that PMCT was capable of identifying injuries not detected during normal autopsy. This systematic review provides inconsistent evidence as to whether PMCT is a reliable alternative for autopsy in trauma victims. PMCT has promising features in postmortem examination suggesting PMCT is a good alternative for a refused autopsy or a good adjunct to autopsy because it detects extra injuries overseen during autopsies. To examine the value of PMCT in trauma victims there is a need for well-designed and larger prospective studies.