Antemortem Clinical Diagnoses Research Articles

Clinicopathological discrepancies in the diagnoses of childhood causes of death in the CHAMPS network: An analysis of antemortem diagnostic inaccuracies

IntroductionDetermining aetiology of severe illness can be difficult, especially in settings with limited diagnostic resources, yet critical for providing life-saving care. Our objective was to describe the accuracy of antemortem...

The discrepancy of antemortem clinical diagnosis and postmortem autopsy diagnosis of lung pathologies in under-five deaths and the reasons for discrepancies: a case series analysis

BackgroundDiagnostic autopsy is the most reliable approach to definitively ascertain the cause of death and evaluate the accuracy of antemortem clinical diagnoses. Identifying diagnostic discrepancies is vital to understanding common gaps in antemortem clinical diagnoses and modifying antemortem diagnostic approaches to increase the accuracy of clinical diagnosis. The objective of this study was to determine the frequency of diagnostic discrepancies between antemortem clinical diagnoses and postmortem autopsies on lung pathologies and to understand the reasons for diagnostic discrepancies among cases included in Child Health and Mortality Prevention Surveillance (CHAMPS) in Ethiopia.MethodsA clinical case series study of deaths among children under-five in the CHAMPS study at three sites in Ethiopia between October 2019 and April 2022 was conducted. The antemortem clinical diagnoses and postmortem pathological diagnoses of the lung were compared for each case. Two senior physicians assessed the findings for both agreement and disagreement. McNemar’s test was used to assess for statistically significant differences between antemortem and postmortem diagnoses.ResultsSeventy-five cases were included (73.3% male). Over half (54.7%) died between the 1st and 7th day of life. Sepsis (66.7%), pneumonia (6.7%), and meconium aspiration syndrome (5.0%) were the most common immediate causes of death. Half (52%) of cases were correctly diagnosed antemortem. The magnitude of diagnostic discrepancy was 35% (95% CI: 20-47%). The most common contributing factors to diagnostic discrepancy were gaps in knowledge (22/75, 35.5%) and problems in consultation and teamwork (22/75, 35.5%).ConclusionsMisdiagnoses were common among young children who died with positive lung pathology findings. In-service education initiatives and multidisciplinary collaboration are needed to mitigate high rates of diagnostic discrepancies among young children to potentially prevent future deaths.

Creutzfeldt-Jakob Disease Misdiagnosed as Multiple System Atrophy.

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by various combinations of autonomic failure, parkinsonism, and cerebellar syndromes. Although consensus criteria have been widely used to diagnose MSA, accurate clinical diagnosis remains challenging. Other neurodegenerative disorders, such as Lewy body disease, can mimic MSA. We described clinical and neuropathologic findings of two patients with Creutzfeldt-Jakob disease (CJD) who had antemortem clinical diagnoses of MSA. The brain bank for neurodegenerative disorders was queried for cases with a clinical diagnosis of MSA, but neuropathologic findings of CJD. Case 1 was a 55-year-old man with a 6-month history of orthostatic hypotension, parkinsonism, cerebellar ataxia, bradyphrenia, and memory impairment. Case 2 was a 65-year-old man who had a 5-year history of cerebellar ataxia, parkinsonism, and cognitive impairment, as well as a 7-year history of dream enactment behavior. Neither case had characteristic α-synuclein immunoreactive neuronal or glial inclusions typical of MSA. Instead, they had spongiform encephalopathy with neuronal loss and gliosis with prion protein-immunoreactive kuru-like plaques. Genetic analyses in case 1 had wild-type PRNP, whereas case 2 revealed a 4-octapeptide repeat insertion in PRNP. Even when clinical features suggest MSA, CJD should also be considered if the progression is rapid or the disease course is atypical, such as the absence of autonomic dysfunction for an extended period.

The Face of God Revealed

Many years have passed since I visited Donny in the hospital, where he was admitted with a newly diagnosed and terminal lung cancer. Despite years of separation, his wife Rose took him back into her home and cared for Donny at the end of his life. In the months after his death, I learned more about their relationship; Donny's drinking and infidelities, the emotional and verbal abuse that Rose put up with. At the end of one office visit, I was incredulous in silent amazement and asked her, "Why did you do it?" Rose looked at me and simply said, "Because he was one of us; because he was family." As she repeated this, I saw the face of God gazing at me. Well before caring for Donny and Rose, a spiritual director encouraged me to work on describing my image of God. It was an arid time and place on my interior journey and the activity felt forced and inauthentic. Although Rose died more than 5 years ago, I still think of her and reflect on my life as a physician practicing in the shadow of the COVID-19 pandemic. As she looks at me, my uncertainties scatter and her image draws down and stirs divine wellsprings in me.

The importance of the autopsy in ascertaining the cause of death and as an audit tool at the university college hospital, Ibadan.

Different reasons for autopsies include medico-legal causes, medical education and deducing the cause of death. An additional benefit is auditing with regards to patient care in the diagnosis and treatment of diseases. The main objective of this study was to determine the concordance between ante-mortem clinical diagnoses and post-mortem causes of death. From January 2009 to December 2015, Autopsy records at the Department of Pathology, University College Hospital, Ibadan were reviewed. Discrepancies between the clinical diagnoses and postmortem findings were categorised using Goldman criteria into major and minor classes. Goldman's criteria can be sub-categorised into five classes: Class I, Class II, Class III, Class IV and Class V. Classification of the cause of death categories was by the International Classification of Diseases, Version 10. The study was carried out with respect to the world medical association's Declaration of Helsinki (2013). Data analysis was carried out with the use of the Statistical Package for the Social Sciences (SPSS version 22). Five hundred and thirty-three cases were involved with a male-female ratio of 1.6. The most common postmortem causes of death were traumatic Injuries (20.6%), Circulatory system-related deaths (19.7%), infections (16.9%) and malignant neoplasms (9.4%). Only 298 (55.9%) of the cases showed a concordance between the post-mortem causes of death and the clinical diagnosis. The post-mortem autopsy is useful in the audit of current medical practice in our environment.

Diagnostic discrepancies between antemortem clinical diagnosis and autopsy findings in pediatric cancer patients.

Prevalence of discrepancies between antemortem clinical diagnoses and postmortem autopsy findings is uncertain in pediatric oncology given improving diagnostic capabilities over time. Primary objective was to describe discrepancies between antemortem and postmortem diagnosis of pediatric cancer deaths. Secondary objective was to compare clinical characteristics of deaths with and without major diagnostic discrepancies. This was a retrospective study that included pediatric cancer patients diagnosed and treated in Ontario and who died from 2003 to 2012. Antemortem clinical diagnoses associated with mortality were determined by reviewing the patient's health records 2weeks prior to death while the postmortem diagnoses were determined by the autopsy report. Discrepancies among these diagnoses were classified using the Goldman criteria where major discrepancies were directly related to the cause of death in contrast to minor discrepancies. Among the 821 patients who died, 118 (14%) had an autopsy and were included. Of these autopsies, 12 (10%) had a major diagnostic discrepancy between antemortem and postmortem diagnoses. Major discrepancies consisted of opportunistic infections (n = 5), missed cancer diagnosis (n = 3), and organ complications (n = 4). Death in a high acuity setting (12/12, 100% vs. 60/106, 57%; P = 0.003) and treatment-related mortality (12/12, 100% vs. 60/106, 57%; P = 0.003) were significantly associated with major discrepancy. Major diagnostic discrepancy was found in 10% of pediatric oncology autopsies. Missed infections and organ complications were predominant etiologies. Death in a high acuity setting and treatment-related mortality were associated with major diagnostic discrepancies. Autopsies continue to be important for improving diagnostic insight and may improve future clinical care.

Confirmation of 123I-FP-CIT SPECT Quantification Methods in Dementia with Lewy Bodies and Other Neurodegenerative Disorders.

Our rationale was to conduct a retrospective study comparing 3 123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (123I-FP-CIT) SPECT quantitative methods in patients with neurodegenerative syndromes as referenced to neuropathologic findings. Methods:123I-FP-CIT-SPECT and neuropathologic findings among patients with neurodegenerative syndromes from the Mayo Alzheimer Disease Research Center and Mayo Clinic Study of Aging were examined. Three 123I-FP-CIT SPECT quantitative assessment methods-MIMneuro, DaTQUANT, and manual region-of-interest creation on a workstation-were compared with neuropathologic findings describing the presence or absence of Lewy body disease (LBD). Striatum-to-background ratios (SBRs) generated by DaTQUANT were compared with the calculated SBRs of the manual method and MIMneuro. The left and right SBRs for caudate, putamen, and striatum were evaluated with the manual method. For DaTQUANT and MIMneuro, the left, right, total, and average SBRs and z scores for whole striatum, caudate, putamen, anterior putamen, and posterior putamen were calculated. Results: The cohort included 24 patients (20 [83%] male, mean age for all patients at death, 75.4 ± 10.0 y). The antemortem clinical diagnoses were Alzheimer disease dementia (n = 6), probable dementia with Lewy bodies (n = 12), mixed Alzheimer disease dementia and probable dementia with Lewy bodies (n = 1), Parkinson disease with mild cognitive impairment (n = 2), corticobasal syndrome (n = 1), idiopathic rapid-eye-movement sleep behavior disorder (n = 1), and behavioral-variant frontotemporal dementia (n = 1). Seventeen (71%) had LBD. All 3 123I-FP-CIT SPECT quantitative methods had an area under the receiver-operating-characteristics curve ranging from more than 0.93 to up to 1.000 (P < 0.001) and showed excellent discrimination between LBD and non-LBD patients in each region assessed (P < 0.001). There was no significant difference between the accuracy of the regions in discriminating the 2 groups, with good discrimination for both caudate and putamen. Conclusion: All 3 123I-FP-CIT SPECT quantitative methods showed excellent discrimination between LBD and non-LBD patients in each region assessed, using both SBRs and z scores.

Diagnosis Across the Spectrum of Progressive Supranuclear Palsy and Corticobasal Syndrome

Atypical parkinsonian syndromes (APS), including progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA), may be difficult to distinguish in early stages and are often misdiagnosed as Parkinson disease (PD). The diagnostic criteria for PSP have been updated to encompass a range of clinical subtypes but have not been prospectively studied. To define the distinguishing features of PSP and CBS subtypes and to assess their usefulness in facilitating early diagnosis and separation from PD. This cohort study recruited patients with APS and PD from movement disorder clinics across the United Kingdom from September 1, 2015, through December 1, 2018. Patients with APS were stratified into the following groups: those with Richardson syndrome (PSP-RS), PSP-subcortical (including PSP-parkinsonism and progressive gait freezing subtypes), PSP-cortical (including PSP-frontal and PSP-CBS overlap subtypes), MSA-parkinsonism, MSA-cerebellar, CBS-Alzheimer disease (CBS-AD), and CBS-non-AD. Data were analyzed from February 1, through May 1, 2019. Baseline group comparisons used (1) clinical trajectory; (2) cognitive screening scales; (3) serum neurofilament light chain (NF-L) levels; (4) TRIM11, ApoE, and MAPT genotypes; and (5) volumetric magnetic resonance imaging measures. A total of 222 patients with APS (101 with PSP, 55 with MSA, 40 with CBS, and 26 indeterminate) were recruited (129 [58.1%] male; mean [SD] age at recruitment, 68.3 [8.7] years). Age-matched control participants (n = 76) and patients with PD (n = 1967) were included for comparison. Concordance between the antemortem clinical and pathologic diagnoses was achieved in 12 of 13 patients with PSP and CBS (92.3%) undergoing postmortem evaluation. Applying the Movement Disorder Society PSP diagnostic criteria almost doubled the number of patients diagnosed with PSP from 58 to 101. Forty-nine of 101 patients with reclassified PSP (48.5%) did not have the classic PSP-RS subtype. Patients in the PSP-subcortical group had a longer diagnostic latency and a more benign clinical trajectory than those in PSP-RS and PSP-cortical groups. The PSP-subcortical group was distinguished from PSP-cortical and PSP-RS groups by cortical volumetric magnetic resonance imaging measures (area under the curve [AUC], 0.84-0.89), cognitive profile (AUC, 0.80-0.83), serum NF-L level (AUC, 0.75-0.83), and TRIM11 rs564309 genotype. Midbrain atrophy was a common feature of all PSP groups. Eight of 17 patients with CBS (47.1%) undergoing cerebrospinal fluid analysis were identified as having the CBS-AD subtype. Patients in the CBS-AD group had a longer diagnostic latency, relatively benign clinical trajectory, greater cognitive impairment, and higher APOE-ε4 allele frequency than those in the CBS-non-AD group (AUC, 0.80-0.87; P < .05). Serum NF-L levels distinguished PD from all PSP and CBS cases combined (AUC, 0.80; P < .05). These findings suggest that studies focusing on the PSP-RS subtype are likely to miss a large number of patients with underlying PSP tau pathology. Analysis of cerebrospinal fluid defined a distinct CBS-AD subtype. The PSP and CBS subtypes have distinct characteristics that may enhance their early diagnosis.

Autopsy interrogation of emergency medicine dispute cases: how often are clinical diagnoses incorrect?

AimsEmergency medicine is a ‘high risk’ specialty. Some diseases develop suddenly and progress rapidly, and sudden unexpected deaths in the emergency department (ED) may cause medical disputes. We aimed to...

Are respiratory complications common causes of death in inflammatory myopathies? An autopsy study

Polymyositis (PM) and dermatomyositis (DM) are idiopathic inflammatory myopathies that are associated with a variety of clinical manifestations including pulmonary complications. The objective of the present study was to determine the causes of deaths in this complex patient population. A computer-assisted search of medical and autopsy records identified a total of 39 patients with either PM or DM who underwent an autopsy at the Mayo Clinic (Rochester, MN, USA) over a 29-year period from 1 January 1981 to 31 December 2009. The immediate causes of death along with contributing causes were determined by reviewing all available clinical data and autopsy findings. We also analysed the discordance between ante-mortem clinical diagnoses provided by clinicians and the final diagnosis by the post-mortem analysis. Respiratory (33%), infectious (28%) and cardiovascular diseases (26%) accounted for the majority of immediate causes of death. Acute exacerbation of chronic interstitial lung disease (15%) and bronchopneumonia (15%) were the most common specific causes. Immediate cause of death was not suspected in nearly one third of cases and included bronchopneumonia, sepsis, acute myocardial infarction, aspiration pneumonia, pulmonary embolism, aortic stenosis, mycotic aneurysm rupture and acute haemoperitoneum. We conclude that pulmonary injury is the immediate cause of death in one third of patients with PM/DM; acute exacerbation of chronic interstitial lung disease and bronchopneumonia were the most common specific causes. Immediate cause of death was not established ante-mortem in nearly one third of cases, and some of these causes were treatable.

Virtual Autopsy as an Alternative to Traditional Medical Autopsy in the Intensive Care Unit

Autopsy is an important educational and quality-control tool in the intensive care unit (ICU), but rates of traditional medical autopsies have declined worldwide. "Virtual" autopsy involving only advanced radiographic techniques might provide an alternative approach to postmortem examinations. To assess the value of postmortem multidetector computed tomography as an alternative to medical autopsy. Prospective cohort study. (ClinicalTrials.gov registration number: NCT01040520) 9 ICUs in a single academic medical center. Consent for both medical and virtual autopsies was sought from the families of all consecutive patients who died in the ICU between 1 January and 30 June 2010. Clinical records were reviewed to determine whether unsuspected autopsy findings would have altered care if known (major diagnosis) or would not have altered care (minor diagnosis). Of 285 patients, 47 underwent both virtual and medical autopsy. Of 196 clinical diagnoses made before death, 173 (88%) were identified by virtual autopsy and 183 (93%) by medical autopsy. Fourteen new major and 88 new minor diagnoses were detected by any autopsy method. The main diagnoses missed by virtual autopsy were cardiovascular events (9 of 72) and cancer (12 of 30). In contrast, medical autopsy missed 13 traumatic fractures and 2 pneumothoraces. Among 115 additional patients in whom only virtual autopsy was performed, 11 new major diagnoses were made. Virtual autopsy was performed in only 57% of patients (n = 162); among this group, consent for traditional medical autopsy was obtained for only one third. Virtual autopsy may be useful for identifying diagnoses that traditionally have been identified by medical autopsy. This may also hold true, at least in part, for the educational aspect of medical autopsy (confirming antemortem clinical diagnoses). Further studies are required to confirm these preliminary results. University Medical Center Hamburg-Eppendorf, Germany.

Clinical setting and extent of premortem evaluation do not predict autopsy discrepancy rates

Autopsy rates have been affected by a number of factors, including technological advances and clinician beliefs of the diminished value of the autopsy. Such factors have resulted in a cultural shift in medicine away from the autopsy. Despite this shift, a number of studies have shown significant differences between antemortem clinical diagnoses and postmortem findings. Surveys of clinician beliefs about the autopsy have pointed toward antemortem diagnostic advancements as an important factor in declining rates. No study to date has addressed the hypothesis that such perceptions in diagnostic certainty have been matched by an actual decay in the yield of valuable or new information obtained by the autopsy. To address this hypothesis, we retrospectively compared the class I and class II discrepancies identified in 284 patients who died in three clinical settings with differing intensities of antemortem diagnostic workup. Despite a significantly different intensity of antemortem workup for patients in each clinical setting, including patients on a medical intensive care unit, patients on a surgical service and patients in an affiliated nursing home, discrepancy rates were found to be similar. Overall discrepancy rates for the medical intensive care unit, surgery service and nursing home patients were 27.8, 32.7 and 31.3%, respectively (P=0.84). In addition, we found no statistical difference in the complexity of workup in discrepant and nondiscrepant cases in each clinical setting. Our study data refute the hypothesis that the intensity of antemortem diagnostic evaluation correlates with an actual decrease in the rate of major diagnostic discrepancies identified at autopsy.

Autopsies in children continue to reveal unanticipated discrepancies between autopsy findings and antemortem clinical diagnoses

Autopsies played a major role in advancing medical knowledge and education during the 19th and 20th centuries, but autopsy rates have fallen, particularly since the 1950s.1 2 Goldman developed a...

Antemortem diagnosis of frontotemporal lobar degeneration

The objective of this article is to study the accuracy of antemortem clinical diagnoses of frontotemporal lobar degenerations (FTLDs). From brain autopsies performed on subjects enrolled in the Mayo Alzheimer Center between 1991 and 2003, cases with neuropathological diagnoses of FTLD were identified. Neuropathological diagnoses of FTLDs were based on consensus criteria for FTLD. The initial clinical histories, neuropsychological test results, brain imaging studies, and initial clinical diagnoses were reviewed. There were 34 pathological FTLD cases among 433 subjects who underwent autopsy; 29 of these 34 cases were diagnosed as FTLD antemortem based on the sum of clinical, neuropsychological, and imaging features (sensitivity, 85%). The specificity was 99%. Among the 34 cases with pathological FTLD, 27 (79%) had clinical histories diagnostic of an FTLD syndrome, 20 (62%) had neuropsychological profiles consistent with FTLD, 17 (50%) had magnetic resonance scans consistent with FTLD, and 7 of 8 who had functional imaging studies had ones consistent with FTLD. In those with incorrect antemortem diagnoses, three were thought to have Alzheimer's disease, one was considered hard to classify, and one was diagnosed with vascular dementia. The antemortem consensus diagnosis of FTLD was moderately sensitive and very specific. With experienced clinicians and awareness of the unique manifestations of FTLD, accurate antemortem diagnosis was feasible.

Agreement between ante-mortem diagnoses, death certificates and post-mortem causes of death in critically ill patients

Objectives: The aims of the study were: i) to determine the agreement between the ante-mortem clinical diagnoses, death certificates and post-mortem causes of death; ii) to determine the incidence of unexpected findings; and iii) to compare the post-mortem rates on the intensive care unit with national recommendations. Design: Retrospective observational study. Setting: Adult general intensive care unit. Subjects: Critically ill patients. Interventions: Post-mortem examination. Measurements and main results: The post-mortem rate was calculated by checking the post-mortem register. The disease or condition leading directly to death (Ia on the death certificate and post-mortem report) in patients who died on the intensive care unit in our hospital was compared with the ante-mortem clinical diagnosis. The level of agreement between the ante-mortem cause of death, death certificate and post-mortem report was assessed. Unexpected post-mortem findings were noted and their probable impact on the patient's outcom...

VALUE OF NECROPSY IN ACQUIRED IMMUNODEFICIENCY SYNDROME

Necropsy findings in 101 adult patients with the acquired immunodeficiency syndrome (AIDS) from two metropolitan hospitals were compared retrospectively with the antemortem clinical diagnoses. 94% of the patients were male and 68% were homosexual or bisexual. 75 (74%) patients had AIDS-related diseases at necropsy that were not suspected clinically. The commonest of the unsuspected AIDS-related diseases were cytomegalovirus infection (49% of all cases), systemic fungal infection (20%), systemic Kaposi's sarcoma (14%), Mycobacterium avium intracellulareinfection (11%), and systemic herpes infection (9%). Cryptococcal infection and cytomegalovirus retinitis were always diagnosed antemortem; and Pneumocystis cariniipneumonia went undiagnosed in only 5 of 58 (9%) patients who had proven infection either clinically or at necropsy. 8 patients who died with fungal pneumonia had undergone bronchoscopy; however, in only 1 patient was it diagnosed antemortem. Tuberculosis was undiagnosed in 4 patients. 4 cases of central nervous system lymphoma diagnosed only at necropsy had been treated empirically for toxoplasmosis. Bacterial pneumonias contributed considerably to mortality in 30% of the patients.