Studying the clinical, radiological, histological, microbiological, and immunological evolution during the different COVID-19 disease stages using minimal invasive autopsy.

The WHO defines different COVID-19 disease stages in which the pathophysiological mechanisms differ. We evaluated the characteristics of these COVID-19 disease stages. Forty-four PCR-confirmed COVID-19 patients were included in a prospective minimal invasive autopsy cohort. Patients were classified into mild-moderate (n = 4), severe-critical (n = 32) and post-acute disease (n = 8) and clinical, radiological, histological, microbiological and immunological data were compared. Classified according to Thoracic Society of America, patients with mild-moderate disease had no typical COVID-19 images on CT-Thorax versus 71.9% with typical images in severe-critical disease and 87.5% in post-acute disease (P < 0.001). Diffuse alveolar damage was absent in mild-moderate disease but present in 93.8% and 87.5% of patients with severe-critical and post-acute COVID-19 respectively (P = 0.002). Other organs with COVID-19 related histopathological changes were liver and heart. Interferon-γ levels were significantly higher in patients with severe-critical COVID-19 (P = 0.046). Anti-SARS CoV-2 IgG was positive in 66%, 40.6% and 87.5% of patients with mild-moderate, severe-critical and post-acute COVID-19 respectively (n.s.). Significant differences in histopathological and immunological characteristics between patients with mild-moderate disease compared to patients with severe-critical disease were found, whereas differences between patients with severe-critical disease and post-acute disease were limited. This emphasizes the need for tailored treatment of COVID-19 patients.

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

BACKGROUND: Mild 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. OBJECTIVE: This 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. METHODS: First, 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. RESULTS: All 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. CONCLUSIONS: Commercial off-the-shelf games such as digital card games show potential as a complementary tool for screening and monitoring cognition. TRIAL REGISTRATION: ClinicalTrials.gov NCT02971124; https://clinicaltrials.gov/ct2/show/NCT02971124.

[Delay in accurate diagnostics during the Covid-19 pandemic: a case of fatal MSSA disseminated infection in an elder patient]. / Uitstel van accurate diagnose tijdens de COVID-19 pandemie.

Periprosthetic joint infections at an advanced age can lead to significant diagnostic and therapeutic challenges, mostly related to an atypical form of presentation in this population. We describe in this case the delayed diagnostic process of a disseminated invasive Staphylococcus aureus infection in a frail patient with a total hip prosthesis. The detection of Staphylococcus aureus in a urine sample was a supplementary hint towards the possible existence of a Staphylococcus aureus bacteraemia. The course of this case shows that teleconsultation and ambulatory based diagnostics are not appropriate for frail older patients with (sub)acute bone and joint infections, even in times of pandemic and constrainedly deferred care.

Detecting Mild Cognitive Impairment via Digital Biomarkers of Cognitive Performance Found in Klondike Solitaire: A Machine-Learning Study.

BACKGROUND: Mild cognitive impairment (MCI) is a condition that entails a slight yet noticeable decline in cognition that exceeds normal age-related changes. Older adults living with MCI have a higher chance of progressing to dementia, which warrants regular cognitive follow-up at memory clinics. However, due to time and resource constraints, this follow-up is conducted at separate moments in time with large intervals in between. Casual games, embedded into the daily life of older adults, may prove to be a less resource-intensive medium that yields continuous and rich data on a patient's cognition. OBJECTIVE: To explore whether digital biomarkers of cognitive performance, found in the casual card game Klondike Solitaire, can be used to train machine-learning models to discern games played by older adults living with MCI from their healthy counterparts. METHODS: Digital biomarkers of cognitive performance were captured from 23 healthy older adults and 23 older adults living with MCI, each playing 3 games of Solitaire with 3 different deck shuffles. These 3 deck shuffles were identical for each participant. Using a supervised stratified, 5-fold, cross-validated, machine-learning procedure, 19 different models were trained and optimized for F1 score. RESULTS: The 3 best performing models, an Extra Trees model, a Gradient Boosting model, and a Nu-Support Vector Model, had a cross-validated F1 training score on the validation set of ≥0.792. The F1 score and AUC of the test set were, respectively, >0.811 and >0.877 for each of these models. These results indicate psychometric properties comparative to common cognitive screening tests. CONCLUSION: The results suggest that commercial card games, not developed to address specific mental processes, may be used for measuring cognition. The digital biomarkers derived from Klondike Solitaire show promise and may prove useful to fill the current blind spot between consultations.

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® 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. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04366882.

Systemic BCG infection in a patient with pancytopaenia and fever 9†years after intravesical BCG administration for bladder cancer.

BCG is an attenuated live strain of Mycobacterium bovis that is used as an intravesical immunotherapy for superficial bladder cancer. Although generally well tolerated, BCG instillation can lead to systemic diseases. We present a case of a 75-year-old man who was treated for recurrent localised transitional cell carcinoma (TCC) of the bladder with intravesical instillation of BCG in 2006. His medical history included Parkinson's disease. The patient reported worsening of Parkinson symptoms in the preceding month. In addition, he had progressive pancytopaenia and a bone marrow biopsy showed a granulomatous inflammatory infiltrate. Cultures from bone marrow aspiration grew M. bovis He was successfully treated with tuberculostatic drugs and made a full recovery. In addition, there was partial amelioration of the Parkinson symptoms. This case shows that physicians should be aware that BCG instillation for TCC can cause systemic disease even years after treatment.