The clinical value of minimal invasive autopsy in COVID-19 patients

Background Minimally invasive autopsy (MIA) is a validated and safe method to establish the cause of death (COD), mainly in low-resource settings. However, the additional clinical value of MIA in Coronavirus disease (COVID-19) patients in a high-resource setting is unknown. The objective was to assess if and how MIA changed clinical COD and contributing diagnoses in deceased COVID-19 patients. Methods and findings A prospective observational cohort from April to May 2020 in a 981-bed teaching hospital in the epicenter of the COVID-19 pandemic in Belgium was established. Patients who died with either PCR-confirmed or radiologically confirmed COVID-19 infection were consecutively included. MIA consisted of whole-body CT and CT-guided Tru-Cut (R) biopsies. Diagnostic modalities were clinical chart review, radiology, microbiology, and histopathology which were assessed by two independent experts per modality. MIA COD and contributing diagnoses were established during a multi-disciplinary meeting. Clinical COD (CCOD) and contributing diagnosis were abstracted from the discharge letter. The main outcomes were alterations in CCOD and contributing diagnoses after MIA, and the contribution of each diagnostic modality. We included 18 patients, of which 7 after intensive care unit hospitalization. MIA led to an alteration in 15/18 (83%) patients. The CCOD was altered in 5/18 (28%) patients. MIA found a new COD (1/5), a more specific COD (1/5), a less certain COD (1/5), or a contributing diagnosis to be the COD (2/5). Contributing diagnoses were altered in 14/18 (78%) patients: 9 new diagnoses, 5 diagnoses dismissed, 3 made more specific, and 2 made less certain. Overall, histopathology contributed in 14/15 (93%) patients with alterations, radiology and microbiology each in 6/15 (40%), and clinical review in 3/15 (20%). Histopathology was deemed the most important modality in 10 patients, radiology in two patients, and microbiology in one patient. Conclusion MIA, especially histological examination, can add valuable new clinical information regarding the cause of death in COVID-19 patients, even in a high-resource setting with wide access to premortem diagnostic modalities. MIA may provide important clinical insights and should be applied in the current ongoing pandemic

Dissecting Digital Card Games to Yield Digital Biomarkers for the Assessment of Mild Cognitive Impairment: Methodological Approach and Exploratory Study

BackgroundMild cognitive impairment (MCI), the intermediate cognitive status between normal cognitive decline and pathological decline, is an important clinical construct for signaling possible prodromes of dementia. However, this condition is underdiagnosed. To assist monitoring and screening, digital biomarkers derived from commercial off-the-shelf video games may be of interest. These games maintain player engagement over a longer period of time and support longitudinal measurements of cognitive performance. ObjectiveThis paper aims to explore how the player actions of Klondike Solitaire relate to cognitive functions and to what extent the digital biomarkers derived from these player actions are indicative of MCI. MethodsFirst, 11 experts in the domain of cognitive impairments were asked to correlate 21 player actions to 11 cognitive functions. Expert agreement was verified through intraclass correlation, based on a 2-way, fully crossed design with type consistency. On the basis of these player actions, 23 potential digital biomarkers of performance for Klondike Solitaire were defined. Next, 23 healthy participants and 23 participants living with MCI were asked to play 3 rounds of Klondike Solitaire, which took 17 minutes on average to complete. A generalized linear mixed model analysis was conducted to explore the differences in digital biomarkers between the healthy participants and those living with MCI, while controlling for age, tablet experience, and Klondike Solitaire experience. ResultsAll intraclass correlations for player actions and cognitive functions scored higher than 0.75, indicating good to excellent reliability. Furthermore, all player actions had, according to the experts, at least one cognitive function that was on average moderately to strongly correlated to a cognitive function. Of the 23 potential digital biomarkers, 12 (52%) were revealed by the generalized linear mixed model analysis to have sizeable effects and significance levels. The analysis indicates sensitivity of the derived digital biomarkers to MCI. ConclusionsCommercial off-the-shelf games such as digital card games show potential as a complementary tool for screening and monitoring cognition. Trial RegistrationClinicalTrials.gov NCT02971124; https://clinicaltrials.gov/ct2/show/NCT0297112

The clinical value of minimal invasive autopsy in COVID-19 patients

Background Minimally invasive autopsy (MIA) is a validated and safe method to establish the cause of death (COD), mainly in low-resource settings. However, the additional clinical value of MIA in Coronavirus disease (COVID-19) patients in a high-resource setting is unknown. The objective was to assess if and how MIA changed clinical COD and contributing diagnoses in deceased COVID-19 patients. Methods and findings A prospective observational cohort from April to May 2020 in a 981-bed teaching hospital in the epicenter of the COVID-19 pandemic in Belgium was established. Patients who died with either PCR-confirmed or radiologically confirmed COVID-19 infection were consecutively included. MIA consisted of whole-body CT and CT-guided Tru-Cut (R) biopsies. Diagnostic modalities were clinical chart review, radiology, microbiology, and histopathology which were assessed by two independent experts per modality. MIA COD and contributing diagnoses were established during a multi-disciplinary meeting. Clinical COD (CCOD) and contributing diagnosis were abstracted from the discharge letter. The main outcomes were alterations in CCOD and contributing diagnoses after MIA, and the contribution of each diagnostic modality. We included 18 patients, of which 7 after intensive care unit hospitalization. MIA led to an alteration in 15/18 (83%) patients. The CCOD was altered in 5/18 (28%) patients. MIA found a new COD (1/5), a more specific COD (1/5), a less certain COD (1/5), or a contributing diagnosis to be the COD (2/5). Contributing diagnoses were altered in 14/18 (78%) patients: 9 new diagnoses, 5 diagnoses dismissed, 3 made more specific, and 2 made less certain. Overall, histopathology contributed in 14/15 (93%) patients with alterations, radiology and microbiology each in 6/15 (40%), and clinical review in 3/15 (20%). Histopathology was deemed the most important modality in 10 patients, radiology in two patients, and microbiology in one patient. Conclusion MIA, especially histological examination, can add valuable new clinical information regarding the cause of death in COVID-19 patients, even in a high-resource setting with wide access to premortem diagnostic modalities. MIA may provide important clinical insights and should be applied in the current ongoing pandemic