Minimizing mistakes in clinical diagnosis.

It would be quite reasonable for us to expect the progress made in diagnostic technology to be accompanied by a parallel improvement in diagnostic accuracy. In reality, however, the frequency of misdiagnoses remains the same, despite the fast progress which has been made by medical technology in the last 30 years. Autopsy is the best source of information on diagnostic accuracy. According to one hypothesis, an increase in the number of autopsies performed and the follow-up on them could reduce the number of diagnostic mistakes. In recent times, however, the number of autopsies in comparison with the registered number of deaths has been declining steeply. We studied the autopsy reports for 1997, kept at the archive of the Institute for Forensic Medicine. We only took into account the deaths which occurred within 24 h of admittance to the emergency wards of the Ljubljana University Hospital, including those patients who died subsequently as a consequence of accident or injury. We also included cases of sudden deaths which occurred during operating or within 24 h after it. Following selection, we analyzed 444 out of the total of 921 autopsy reports, for each of which we carried out a comparison between the postmortem diagnosis and the clinical diagnosis, contained in the medical report on the death and the causes of death, which is modeled on WHO recommendations, i.e., the International Classification of Diseases (ICD), and in the medical documents, if any were submitted. Data are entered in these by using the ABC system where: A) direct cause of death, B) are circumstances that influenced the occurrence of death, and C) is original cause of death. The findings were then organized into five groups, depending on the degree to which the clinical diagnosis agreed with the postmortem diagnosis. The first group is comprised of the cases where the clinical and postmortem diagnoses agree completely; the second group is comprised of the cases of partial disagreement on the direct cause of death; the third group is comprised of the cases of disagreement on the original disease; the fourth group, of complete disagreement between the clinical and postmortem diagnoses. The fifth group is comprised of those cases where, under the ABC standards on the classification of diseases, injuries and causes of deaths as specified by the WHO, the documentation was incomplete. A complete agreement between the diagnoses was established in 48.87% of cases; partial disagreement in 22.74%; and total disagreement in 13.5%. 9.68% of cases were classified as falling into group 5. For the three diseases that are among the most common causes of death, we established the percentage of agreement, the percentage of overdiagnosis and the percentage of underdiagnosis. The most frequently underdiagnosed disease (in 61% of cases) was pulmonary thromboembolia; in 15% a thromboembolia was confirmed in autopsy. In 24%, a myocardial infarction was not diagnosed clinically and in 60% the clinical diagnosis of a myocardial infarction was confirmed in autopsy. In 33% a heart failure was not diagnosed during the clinical stages but only in autopsy, in 66% the clinical diagnosis of a heart failure was confirmed in autopsy.     

Pharmacogenetics in medico-legal context

Medico-legal autopsy is the primary method in determining the cause and manner of death when the death is suspected to be unnatural. In some of these autopsies, the death remains ambiguous, even after a complete autopsy including histological investigation and toxicological screenings. In cases where there are no morphological abnormalities, medico-legal genetics may offer additional means to provide knowledge of possible genetic mutations, which may have initiated the process or predisposed the individual to stress risk conditions leading to death. One class of ambiguous deaths consists of drug-related deaths where the interpretation of the toxicological results are not clear. In such situations post mortem genotyping and the analysis of metabolite rations may provide an insight to the findings. A few cases demonstrating the potential strength of pharmacogenetics in medico-legal context has been published. However, there is a paramount need for serious scientific studies before the field of post mortem pharmacogenetics can be utilized in routine medico-legal analyses casework and brought routinely into courtroom.     

The value of the hospital autopsy. A study of causes and modes of death estimated before and after autopsy

Among 312 consecutive deaths in a Danish Central Hospital autopsy was performed in the pathology department on 266 cases, i.e. 85%. Retrospectively, the underlying causes of death were estimated from the clinical information alone by an experienced clinician and subsequently compared with the autopsy report. The definite cause of death was determined jointly by the clinician and the pathologist. The clinician's diagnosis was thereby confirmed as incorrect in 18% of the cases if small differences in site and type of malignant tumours were not considered. This is less than in many other investigations, but it is stressed that this could partly be because formal errors in completing the death certificate were avoided. The main causes of death were ischaemic heart disease and neoplasia. Clinical diagnosis of malignant diseases was never found to be erroneous. There was a slight tendency to clinically overestimate ischaemic heart disease, but in general the different errors outweighed each other, so that the total number of different causes of death before and after autopsy was nearly the same. The original death certificate was investigated in 12 accidental cases. Hereby it was found that the mode of death was originally stated erroneously as natural in 7 cases, i.e. 4.5%. It is concluded that hospital autopsy is still needed for the control and correction of causes of death, and it is stressed that clinicians as well as pathologists should be more aware of cases with a trauma in the history to avoid errors in the mode of death. Such errors can imply legal as well as insurance problems.     

Usefulness of Systematic Histological Examination in Routine Forensic Autopsy*

Abstract: The forensic community does not agree on the need to perform histological examination at forensic autopsy. The aim of our study was to determine the usefulness of systematic standard histology in forensic autopsies. A prospective study was carried out on 428 autopsy cases for which standard histological examination was systematic. Mechanism of death not shown by gross anatomic findings was discovered by histology in about 40% of the cases. Cause of death was established by only histology in 8.4% of the cases. Microscopic findings affected the manner of death in 13% of the cases. Histology provided complementary information about prior medical condition of the deceased in about 49% of the cases. Traumatic lesions were better documented by histology in about 22% of the cases. According to the results of our study, systematic standard histology for the main organs should be used in routine forensic autopsies.     

The tissue survival problem in using current methods of morphological study]

Time course of ultrastructural changes and RNA production in human brain and myocardial cells during the period between clinical and biological death is studied. Changes in the cytoplasm of brain neurons develop 4 hours after death, and 8 h post mortem the destructive changes in the cytoplasm and nuclei progress. During the period of 4-13 h post mortem the endotheliocyte nuclei are capable of producing RNA. Active production of RNA is on-going in the myocyte nuclei 4 h after death; the synthetic activity decreases by 8 h and by 13 h the synthetic activity in autopsy material is over.     

Cadaver mix-up--an avoidable problem?

Depending on local conditions it may happen from time to time that no officer involved in the previous investigation is present during the forensic autopsy. In this case, the post mortem examiner often has to rely solely on written documentation concerning the identity of the deceased. The authors report a case where the body had already been mixed up with another body by the undertaker prior to the inspection by the police. In spite of clear distinguishing characteristics in the written documentation, this led to the wrong body being autopsied. For the post mortem examiner, the only safe way to identify a body seems to be the presence of persons who had known the deceased or of police officers as acknowledging witnesses. If these conditions are not given, other means of safe information on the identity are called for, for example a "police body card" similar to an evidence card.     

Digital autopsy archive using the personal computer

The development of a dissection register for Legal medicine well differentiated and considering special requirement of the subject was not achieved in history because of complexity of post mortem findings in many cases. Realizing that an all satisfying concept failed we looked for the possibility of using electronic data processing for rapid and flourish collection of autopsy results not requiring much time for the coroner. Based on personal computer software "dBase" a database program was developed easy to handle using different forms asking for characteristic circumstances of the case and essential post mortem findings. Short codes for locations and ascertainments were chosen to enable rapid selection of interesting statements as far as handling for statistical evaluations later on. Less then 10 minutes are needed for recording post mortem results in this way short time after autopsy.     

The epidemiological study on registered cases of sudden infant death syndrome (SIDS) in Tokyo: examination of the effect of autopsy on diagnosis of SIDS and the mortality statistics in Japan

In the United States and most of European countries, a diagnosis of sudden infant death syndrome (SIDS) may be given only after an autopsy has been performed. Under the new definition of SIDS in Japan, an autopsy is now mandatory for the diagnosis of SIDS. However, according to the official records on autopsies, the proportion of autopsy for sudden infant death in Japan is still low (less than 30%). If a physician suspects SIDS from a review of the patient's medical history and medical findings, he can write 'suspected SIDS' as the cause of death on the death certificate without performing an autopsy. Such a clinical diagnosis is entered in the Vital Statistics section by the Japanese Ministry of Health and Welfare. In this report, a comparative epidemiological survey of registered cases of SIDS--after autopsy and with no autopsy--was carried out by examining the data from the death certificates registered by the Japanese Ministry of Health and Welfare (vital statistics in Tokyo from January 1979 to December 1996). There were 369 cases of SIDS registered in Tokyo. We found 247 diagnosed after autopsy (66.9%) and 122 with no autopsy (33.1%). The following epidemiological variables were used: address of the deceased (a specific area in Tokyo), sex, year of death, time of death, month of death, age at death, occupation of householders, and place of death. There were epidemiological differences at the 0.05 significance level between registered cases diagnosed after autopsy and those diagnosed without autopsies, as follows: year (P=0.016) and place of death (P=0.037). In addition, there were slight epidemiological differences at the 0.10 significance level between registered cases diagnosed after autopsy and with no autopsy, as follows: month of death (P=0.076) and age at death (P=0.082). This suggests that the quality of diagnosis of SIDS is not completely guaranteed. With respect to the area of residence, the incidence of SIDS is high in those areas where autopsy is performed frequently. In Tokyo, the medical examiner system is enforced only in the urban area and there is a possibility that SIDS is being underdiagnosed in the rural area of the Metropolitan Tokyo. It is likely that the diagnosis of SIDS without autopsy will influence the quality of SIDS diagnoses. The administrative inadequacy in the autopsy system in Japan should be corrected to improve the accuracy of SIDS diagnosis.     

Death certificates in Germany, England, The Netherlands, Belgium and the USA

Every country has its own legal system regarding post mortem examinations and death certificates. The authorities want to know the cause and the manner of death of their citizens and especially whether someone is responsible for the death of someone else. In this article a comparison is made between the legal regulations in the Netherlands, Belgium, Germany, England and the USA. Specific attention is given to the following aspects: which official performs the post mortem exam, what is the role of the attending physician by issuing the death certificate and how is the privacy of the deceased protected.     

An analysis of the usefulness of specific stages in the pathologic investigation of sudden infant death

Retrospective analysis of autopsy findings in 60 infants who had been found unexpectedly dead in their cribs or beds in South Australia from 1994 to 1998 was undertaken to determine the diagnostic usefulness of individual stages in the postmortem investigation. Positive findings occurred in 2 of 43 scene examinations (3%), 2 of 60 external examinations (3%), 2 of 11 radiologic examinations (18%), 8 of 60 internal examinations (13%), 7 of 60 histologic examinations (12%), and 3 of 58 microbiologic examinations (5%). No positive findings were detected on toxicologic screening. Not every case underwent each diagnostic step. This gave alternative diagnoses to sudden infant death syndrome (SIDS) in 15 cases (25%). This study demonstrates an increase in the percentage of cases of unexpected infant death due to causes other than SIDS; it also shows the diagnostic yield of individual stages in the postmortem evaluation of such cases. Negative findings were important in giving validity to the diagnosis in the 45 cases that were ultimately designated as SIDS.     

Validation of diagnoses on death certificates for male alcoholics in Stockholm

The mortality and the causes of death have been studied in a cohort consisting of 1548 male alcoholics in Stockholm. During the period 1969-1981 there were 542 cases of death in this population. The mortality rates were triple those for males in Stockholm generally. Using the official causes of death there was a highly significant excess mortality in the following diagnostic groups: Cancer in the upper digestive region, primary hepatic cancer, cirrhosis in the liver, pancreatitis, pneumonia, alcoholism and alcoholic poisoning, suicides and other causes of violent death as well as ischemic heart disease. The underlying and contributing causes of death on the death certificates were reclassified according to ICD-rules using clinical records and autopsy protocols. It was found that the underlying cause of death was incorrect in 21.8% of the cases. Important information was withheld in further 19.8%. After validation there was no longer any excess mortality in ischemic heart disease. The number of alcohol-related diagnoses, i.e. alcoholic cardiomyopathy, cirrhosis and fatty liver with alcoholism and alcoholic intoxication, was much greater. It is concluded that there is a underreporting of alcohol-related diseases and injuries which has a great influence on the reliability of death statistics.     

The importance of medico-legal autopsies. An analysis of the complex problems regarding damages

One hundred forty-four medico-legal autopsies were performed at the University Institute of Forensic Medicine in Copenhagen during the period 1973-77, all requested by the National Office of Social Security in order to estimate whether the cause of death could be related to the work of the deceased. The total number of medico-legal autopsies in the same period was 4050. The material included only four women. One hundred seventeen men died during work, 26 cases were accepted. Clear cases of accidents were always accepted and damages were paid. In cases where the deceased died on his way to or from work damages were rejected. Nineteen men (13%) had died after returning to their homes. Two cases among these were accepted (fall from scaffolding during working hours, arsenic poisoning where death occurred later in hospital). The mean age of the group was about 50 years, which is less than in an average medico-legal population. In all cases but two the autopsy revealed the cause of death, i.e. that unknown causes of death totalled 1.4%. The manner of death was elucidated in all cases. The most frequent cause of death in men turned out to be coronary sclerosis and coronary thrombosis. All such cases were rejected as being due to working conditions, because in no case was extraordinary working stress found to be evident. The two cases of death which occurred at home showed the importance of being aware of injuries due to working conditions, even if death could not be directly related to an industrial accident.     

Analysis of Forensic Autopsy in 120 Cases of Medical Disputes Among Different Levels of Institutional Settings

Despite advances in medical science, the causes of death can sometimes only be determined by pathologists after a complete autopsy. Few studies have investigated the importance of forensic autopsy in medically disputed cases among different levels of institutional settings. Our study aimed to analyze forensic autopsy in 120 cases of medical disputes among five levels of institutional settings between 2001 and 2012 in Wenzhou, China. The results showed an overall concordance rate of 55%. Of the 39% of clinically missed diagnosis, cardiovascular pathology comprises 55.32%, while respiratory pathology accounts for the remaining 44. 68%. Factors that increase the likelihood of missed diagnoses were private clinics, community settings, and county hospitals. These results support that autopsy remains an important tool in establishing causes of death in medically disputed case, which may directly determine or exclude the fault of medical care and therefore in helping in resolving these cases.     

Site-dependent production of gamma-hydroxybutyric acid in the early postmortem period

This study compared endogenous gamma-hydroxybutyric acid (GHB) concentrations in various postmortem fluid samples of 25 autopsy cases. All bodies were stored between 10-20 degrees C until autopsy, and the intervals between death and autopsy were less than 2 days (6-48 h). GHB concentrations were measured by headspace gas chromatography after GHB was converted to gamma-butyrolactone. Endogenous GHB concentrations were significantly higher in femoral venous blood (4.6+/-3.4 microg/ml, n=23) than in cerebrospinal fluid (1.8+/-1.5 microg/ml, n=9), vitreous humor (0.9+/-1.7 microg/ml, n=8), bile (1.0+/-1.1 microg/ml, n=9) and urine (0.6+/-1.2 microg/ml, n=12). GHB concentrations were similar in blood samples taken from different sites. Cut-off limits of 30 and 10 microg/ml are proposed for blood and urine, respectively, to discriminate between exogenous and endogenous GHB in decedents showing no or little putrefaction (postmortem intervals usually 48 h or less). The criterion established for endogenous GHB in postmortem urine may also be applicable to analytical results in cerebrospinal fluid, vitreous humor and bile from deceased persons.     

574例高坠死亡案件分析

目的通过对大量高坠死亡案件的现场分析、尸体的损伤形态学观察并结合案情调查资料,构建高坠案件法医病理学案例库,为研究疑难坠落死亡案件奠定基础。方法收集并回顾分析5省市574例高坠死亡案件资料,包括死者个人信息、现场勘查资料、尸检结果、精神疾病史和毒物检验结果。结果男性的意外死亡率明显高于女性;在0～10岁年龄组未见自杀案例;在60岁以上年龄组,自杀率明显高于意外死亡;大多数的意外案例都发生在工作地点;坠落高度在10m以下的案例中,落地最先接触部位以头部居多,而在10～25m高度,足或下肢多见。结论大多数高坠案例都有明确的结论,但部分案例成伤机制及死亡方式判断呈现明显分歧,应为今后坠落伤研究的重点方向。     

105例精神病人尸体检验的法医学分析

目的回顾分析精神病人尸体检验案例的死亡原因及死亡方式,为医疗卫生服务和司法鉴定提供参考。方法收集中国刑事警察学院物证鉴定中心2004—2019年受理并结案的精神病人尸体检验案例105例,分为疾病死亡、自杀死亡、意外死亡及他杀死亡4组,统计各组的常见死亡原因,分析各组之间年龄、病程、体重指数(body mass index,BMI)、性别的差异。结果105例中,男性60例、女性45例,精神病病程(12.9±10.4)年,死亡时年龄(51.3±11.4)岁,61.0%为精神分裂症。疾病死亡50例(47.6%),该组死者年龄最大、精神病病程最长、BMI最低,肺动脉血栓栓塞、呼吸系统感染、心脏性疾病是常见死亡原因。意外死亡26例(24.8%),交通事故是最常见死亡原因。他杀死亡15例(14.3%),全部为男性,颅脑损伤是最常见死亡原因。自杀死亡14例(13.3%),该组死者年龄最小,病程最短,高坠是最主要的自杀方式。结论了解精神病人的常见死亡原因有助于制定措施以降低该群体的死亡率。分析死亡方式时需要综合考虑死者的年龄、病程、性别等因素。     

The use of rapid diagnostic test of procalcitonin serum levels for the postmortem diagnosis of sepsis

Because serum Procalcitonin is reported to be a valid postmortem marker of sepsis, this prospective study was carried out to determine whether the semi-quantitative PCT-Q((R))-Test (B.R.A.H.M.S., Germany) is a reliable indicator of postmortem Procalcitonin (PCT) serum levels, thus enabling a quick "tableside" diagnosis of sepsis. Postmortem PCT-levels of 70 forensic and 78 clinical-pathological autopsy cases (n=148) were examined using the B.R.A.H.M.S-PCT-Q-Test during autopsy. 27 cases were categorized as the cases of sepsis according to the ACCP/SCCM Consensus Conference criteria. 121 cases were assigned to the non-sepsis group. Among the 148 cases, 18 samples could not be analyzed by the reason of strong hemolysis. Using a cut-off point of 2 ng/ml, 20 cases of sepsis were identified (true positive) whereas 3 cases of sepsis were not detected (false negative). In the non-sepsis group (107 cases) 6 cases showed a positive testing (false positive). When applied within 48 h postmortem, the PCT-Q-Test showed a sensitivity of 86.96% and a specificity of 94.39% (at cut-off 2 ng/ml). Likelihood ratios and positive predictive values proved to be lower in the forensic autopsy group (PPV: 59.3% in forensic case vs. 85.1% in clinicopathological cases; NPV: 98.73% in forensic cases vs. 95.2% in clinicopathological cases). The PPVs using a cut-off point of 10 ng/ml were 100% in both groups independent of sepsis prevalences. The results show, that a high NPV for prevalences ranging from 3% to 30% can be reached using a 2 ng/ml cut-off point, whereas a cut-off of 10 ng/ml ensures a high PPV for the respective prevalences in the absence of exclusion criteria. The study provides strong evidence that the introduction of rapid diagnostic test (RDTs) of postmortem PCT serum levels may be useful in achieving rapid distinction between sepsis and non-sepsis-related causes of death, especially in conjunction with the medical case history and further autopsy results. In addition, the use of RDTs enables clinicians to conduct an evidence-based validation of clinical diagnosis, thus facilitating future clinical decision-making.     

Natural,Unexpected Deaths: Reliability of a Presumptive Diagnosis*

Abstract: We retrospectively analyzed 100 deaths because of suspicions and concerns expressed by the family. We compared the preautopsy cause of death, as determined by a thorough review of the clinical data and circumstances, to the autopsy‐derived cause of death. In the majority (91/100), the preautopsy and postautopsy proximate causes of death were in agreement. In 9%, the autopsy provided information that resulted in a proximate cause of death different than anticipated. In four instances, the manner of death also was incorrect and was determined to be an accident rather than the originally presumed natural. No homicide or suicide would have been misclassified. In another nine instances, where the premortem and postmortem proximate causes of death were in agreement, the autopsy provided a specific mechanism of death. With a quality initial medicolegal death investigation, a subset of sudden deaths in adults may be reliably certified without an autopsy.     

原发性蛛网膜下腔出血的讨论——附7例尸检报告

本文报告7例法医病理解剖材料,其中脑血管动静脉畸形引起的5例,动脉瘤与巨细胞性动脉炎引起的各1例。因死亡都是发生在头部外伤之后,故引起申诉。肉眼检查时,7例中有6例未查明病因,诊断系依靠病理组织学检查。本文结合文献复习,重点讨论了检验鉴定的方法和注意事项。文中4个重新鉴定的案例,原结论均未发现本病的病因,甚至有的误认是损伤性蛛网膜下腔出血,此点应引以为戒。     

Is there progress in the autopsy diagnosis of sudden unexpected death in adults?

Sudden death is now currently described as natural unexpected death occurring within 1h of new symptoms. Most studies on the subject focused on cardiac causes of death because most of the cases are related to cardiovascular disease, especially coronary artery disease. The incidence of sudden death varies largely as a function of coronary heart disease prevalence and is underestimated. Although cardiac causes are the leading cause of sudden death, the exact incidence of the other causes is not well established because in some countries, many sudden deaths are not autopsied. Many risk factors of sudden cardiac death are identified: age, gender, heredity factors such as malignant mutations, left ventricular hypertrophy and left ventricle function impairment. The role of the police surgeon in the investigation of sudden death is very important. This investigation requires the interrogation of witnesses and of the family members of the deceased. The interrogation of physicians of the rescue team who attempted resuscitation is also useful. Recent symptoms before death and past medical history must be searched. Other sudden deaths in the family must be noted. The distinction between sudden death at rest and during effort is very important because some lethal arrhythmia are triggered by catecholamines during stressful activity. The type of drugs taken by the deceased may indicate a particular disease linked with sudden death. Sudden death in the young always requires systematic forensic autopsy performed by at least one forensic pathologist. According to recent autopsy studies, coronary artery disease is still the major cause of death in people aged more than 35 years. Cardiomyopathies are more frequently encountered in people aged less than 35 years. The most frequent cardiomyopathy revealed by sudden death is now arrhythmogenic right ventricular cardiomyopathy also known simply as right ventricular cardiomyopathy (RVC). The postmortem diagnosis of cardiomyopathies is very important because the family of the deceased will need counseling and the first-degree relatives may undergo a possible screening to prevent other sudden deaths. In each case of sudden death, one important duty of the forensic pathologist is to inform the family of all autopsy results within 1 month after the autopsy. Most of the recent progress in autopsy diagnosis of sudden unexpected death in the adults comes from molecular biology, especially in case of sudden death without significant morphological anomalies. Searching mutations linked with functional cardiac pathology such as long-QT syndrome, Brugada syndrome or idiopathic ventricular fibrillation is now the best way in order to explain such sudden death. Moreover, new syndromes have been described by cardiologists, such as short-QT syndrome and revealed in some cases by a sudden death. Molecular biology is now needed when limits of morphological diagnosis have been reached.