8 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
Clinically Silent Small Vessel Disease of the Brain in Patients with Obstructive Sleep Apnea Hypopnea Syndrome
Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with increased risk of cerebrovascular disease. The aim of the present study was to investigate the association between the presence of the small vessel disease (SVD) of the brain in patients with OSAHS. The study included 24 patients with moderate to severe OSAHS and 34 healthy volunteers. All the subjects underwent magnetic resonance imaging (MRI) of the brain, in order to sought periventricular white matter (PVWM), deep white matter (DWM) and brainstem SVD. Among patients with OSAHS, 79.1% had SVD (grade 1–3, Fazekas score) in DWM and 91.7% in PVWM while 22.4% had brainstem—white matter hyperintensities (B-WMH). Patients with OSAHS had a much higher degree of SVD in the DWM and PVWM compared to the control group (p < 0.001). The multivariate analysis showed an independent significant association of OSAHS with SVD (DWM and PVWM) (p = 0.033, OR 95% CI: 8.66 (1.19–63.08) and: p = 0.002, OR 95% CI: 104.98 (5.15–2141)). The same analysis showed a moderate association of OSAHS with B-WMH (p = 0.050, OR 15.07 (0.97–234.65)). Our study demonstrated an independent significant association of OSAHS with SVD and a moderate association of OSAHS with B-WMH
Accuracy of the sleep clinical record for the diagnosis of pediatric moderate-to-severe obstructive sleep apnea syndrome
Purpose The sleep clinical record (SCR) has been used to diagnose
obstructive sleep apnea syndrome (OSAS) in children when access to
polysomnography (PSG) is limited. Our aim was to determine the best SCR
score that could facilitate diagnosis of moderate-to-severe OSAS in
children with snoring. Methods Healthy children with history of snoring,
who were referred for PSG, were prospectively recruited. The SCR score
was calculated. Receiver operating characteristic curves (ROCs) were
plotted to determine the area under curve (AUC), and the optimum SCR
cutoff value was determined using the Youden index (J). Results Two
hundred and seventy-three children were recruited (mean age 6.3 +/- 2.5
years; median obstructive apnea-hypopnea index 1.5 episodes/h; range
0-61.1). The mean SCR score was 6.9 +/- 3.6. Forty-six children had
moderate-to-severe OSAS. Subjects with moderate-to-severe OSAS had a
significantly higher mean SCR score (10.2 +/- 2.9) than those with mild
OSAS (6.2 +/- 3.3; P < 0.001). Based on the plotted ROC, the AUC was
0.811 (95% confidence interval: 0.747-0.876; P < 0.001). Calculation of
J, based on its ROC coordinates, indicated that the optimum cutoff SCR
score to predict moderate-to-severe OSAS was 8.25, corresponding to a
sensitivity of 83% and a specificity of 70%. Conclusion Among children
with history of snoring, an SCR score above 8.25 can identify those with
moderate-to-severe OSAS
Vascular function and ocular involvement in sarcoidosis
Ocular involvement occurs in sarcoidosis (Sar) patients mainly in the
form of uveitis. This study was designed to determine if uveitis in Sar
patients is associated with vascular impairment. We enrolled 82 Sar
patients and 77, age and sex matched, control subjects (Cl). Sar
patients were divided into those with ocular sarcoidosis (OS) and those
without ocular sarcoidosis (WOS). Endothelial function was evaluated by
flow-mediated dilation (FMD). Pulse wave velocity (PWV) was measured as
an index of aortic stiffness and augmentation index (AIx) as a measure
of arterial wave reflections. Although there was no significant
difference in sex, age and mean arterial pressure, patients with OS
compared to WOS patients and Cl subjects had impaired FMD (p < 0.001),
increased AIx (p = 0.02) and increased PWV (p = 0.001). Interestingly,
impaired FMD in Sar patients was independently, from possible covariates
(age, sex, smoking habits, arterial hypertension, dyslipidemia),
associated with increased odds of ocular involvement (odds ratio = 1.69,
p = 0.001). More precisely ROC curve analysis revealed that FMD had a
significant diagnostic ability for the detection of OS (AUC = 0.77, p <
0.001) with a sensitivity of 79% and a specificity of 68% for an FMD
value below 6.00%. To conclude in the present study we have shown that
ocular involvement in Sar patients is associated with impaired
endothelial function and increased arterial stiffness. These results
strengthen the vascular theory which considers uveitis a consequence of
vascular dysfunction in Sar patients and reveals a possible clinical
importance of the use of endothelial function tests. (C) 2015 Elsevier
Inc. All rights reserved
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
Efficacy and safety of early soluble urokinase plasminogen receptor plasma-guided anakinra treatment of COVID-19 pneumonia: a subgroup analysis of the SAVE-MORE randomised trialResearch in context
Summary: Background: The SAVE-MORE trial demonstrated that anakinra treatment in COVID-19 pneumonia with plasma soluble urokinase plasminogen activator (suPAR) levels of 6 ng/mL or more was associated with 0.36 odds for a worse outcome compared to placebo when expressed by the WHO-Clinical Progression Scale (CPS) at day 28. Herein, we report the results of subgroup analyses and long-term outcomes. Methods: This prospective, double-blind, randomised clinical trial, recruited patients with a confirmed SARS-CoV-2 infection, in need of hospitalisation, lower respiratory tract infection and plasma suPAR ≥6 ng/mL from 37 academic and community hospitals in Greece and Italy. Patients were 1:2 randomised to subcutaneous treatment with placebo or anakinra (100 mg) once daily for 10 days. Pre-defined subgroups of Charlson's comorbidity index (CCI), sex, age, level of suPAR, and time from symptom onset were analysed for the primary endpoint (overall comparison of distribution of frequencies of the scores from the WHO-CPS between treatments on day 28), by multivariable ordinal regression analysis in the intention to treat (ITT) population. This trial is registered with the EU Clinical Trials Register (2020-005828-11) and ClinicalTrials.gov (NCT04680949). Findings: Patients were enrolled between 23 December 2020 and 31 March 2021; 189 patients in the placebo arm and 405 patients in the anakinra arm were the ITT population. Multivariable analysis showed that anakinra treatment was accompanied by significantly lower odds for worse outcome compared to placebo at day 28 for all studied subgroups (CCI ≥ 2, OR: 0.34, 95% confidence intervals [CI] 0.22–0.50; CCI 9 ng/mL, OR: 0.35, 95% CI 0.19–0.66; suPAR 6–9 ng/mL, OR: 0.35, 95% CI 0.24–0.52; patients ≥65 years, OR: 0.41, 95% CI 0.25–0.66; and patients <65 years, OR: 0.29, 95% CI 0.19–0.45). The benefit was uniform, irrespective of the time from start of symptoms until the start of the study drug. At days 60 and 90, anakinra treatment had odds of 0.40 (95% CI 0.28–0.57) and 0.46 (95% CI 0.32–0.67) respectively, for a worse outcome compared to placebo. The costs of general ward stay, ICU stay, and drugs were lower with anakinra treatment. Interpretation: Anakinra represents an important therapeutic tool in the management of COVID-19 that may be administered in all subgroups of patients; benefits are maintained until day 90. Funding: Hellenic Institute for the Study of Sepsis; Swedish Orphan Biovitrum AB