3 research outputs found
Genetic prediction of ICU hospitalization and mortality in COVID-19 patients using artificial neural networks
There is an unmet need of models for early prediction of morbidity and mortality of Coronavirus disease-19 (COVID-19). We aimed to a) identify complement-related genetic variants associated with the clinical outcomes of ICU hospitalization and death, b) develop an artificial neural network (ANN) predicting these outcomes and c) validate whether complement-related variants are associated with an impaired complement phenotype. We prospectively recruited consecutive adult patients of Caucasian origin, hospitalized due to COVID-19. Through targeted next-generation sequencing, we identified variants in complement factor H/CFH, CFB, CFH-related, CFD, CD55, C3, C5, CFI, CD46, thrombomodulin/THBD, and A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS13). Among 381 variants in 133 patients, we identified 5 critical variants associated with severe COVID-19: rs2547438 (C3), rs2250656 (C3), rs1042580 (THBD), rs800292 (CFH) and rs414628 (CFHR1). Using age, gender and presence or absence of each variant, we developed an ANN predicting morbidity and mortality in 89.47% of the examined population. Furthermore, THBD and C3a levels were significantly increased in severe COVID-19 patients and those harbouring relevant variants. Thus, we reveal for the first time an ANN accurately predicting ICU hospitalization and death in COVID-19 patients, based on genetic variants in complement genes, age and gender. Importantly, we confirm that genetic dysregulation is associated with impaired complement phenotype.- Pfizer Pharmaceuticals(undefined
Comparison of Ticagrelor Versus Clopidogrel on Cerebrovascular Microembolic Events and Platelet Inhibition during Transcatheter Aortic Valve Implantation
The impact of the antiplatelet regimen and the extent of associated
platelet inhibition on cerebrovascular microembolic events during
transcatheter aortic valve implantation (TAVI) are unknown. Our aim was
to evaluate the effects of ticagrelor versus clopidogrel and of platelet
inhibition on the number of cerebrovascular microembolic events in
patients undergoing TAVI. Patients scheduled for TAVI were randomized
previous to the procedure to either aspirin and ticagrelor or to aspirin
and clopidogrel. Platelet inhibition was expressed in P2Y12 reaction
units (PRU) and percentage of inhibition. High intensity transient
signals (HITS) were assessed with transcranial Doppler (TCD). Safety
outcomes were recorded according to the VARC-2 definitions. Among 90
patients randomized, 6 had an inadequate TCD signal. The total number of
procedural HITS was lower in the ticagrelor group (416.5 [324.8,
484.2]) (42 patients) than in the clopidogrel group (723.5 [471.5,
875.0]) (42 patients), p <0.001. After adjusting for the duration of the
procedure, diabetes, extra-cardiac arteriopathy, BMI, hypertension,
aortic valve calcium content, procedural ACT, and pre-implantation
balloon valvuloplasty, patients on ticagrelor had on average 256.8 (95%
CI: [-335.7, -176.5]) fewer total procedural HITS than patients on
clopidogrel. Platelet inhibition was greater with ticagrelor 26 [10,
74.5] PRU than with clopidogrel 207.5 (120 to 236.2) PRU, p <0.001, and
correlated significantly with procedural HITS (r = 0.5, p <0.05). In
conclusion, ticagrelor resulted in fewer procedural HITS, compared with
clopidogrel, in patients undergoing TAVI, while achieving greater
platelet inhibition. (c) 2021 Published by Elsevier Inc
Genetic prediction of ICU hospitalization and mortality in COVID-19 patients using artificial neural networks
There is an unmet need of models for early prediction of morbidity and
mortality of Coronavirus disease-19 (COVID-19). We aimed to a) identify
complement-related genetic variants associated with the clinical
outcomes of ICU hospitalization and death, b) develop an artificial
neural network (ANN) predicting these outcomes and c) validate whether
complement-related variants are associated with an impaired complement
phenotype. We prospectively recruited consecutive adult patients of
Caucasian origin, hospitalized due to COVID-19. Through targeted
next-generation sequencing, we identified variants in complement factor
H/CFH, CFB, CFH-related, CFD, CD55, C3, C5, CFI, CD46,
thrombomodulin/THBD, and A Disintegrin and Metalloproteinase with
Thrombospondin motifs (ADAMTS13). Among 381 variants in 133 patients, we
identified 5 critical variants associated with severe COVID-19:
rs2547438 (C3), rs2250656 (C3), rs1042580 (THBD), rs800292 (CFH) and
rs414628 (CFHR1). Using age, gender and presence or absence of each
variant, we developed an ANN predicting morbidity and mortality in
89.47% of the examined population. Furthermore, THBD and C3a levels
were significantly increased in severe COVID-19 patients and those
harbouring relevant variants. Thus, we reveal for the first time an ANN
accurately predicting ICU hospitalization and death in COVID-19
patients, based on genetic variants in complement genes, age and gender.
Importantly, we confirm that genetic dysregulation is associated with
impaired complement phenotype