Increased Kynurenine Indicates a Fatal Course of COVID-19

(1) Background: An inefficient immune response accompanied by an overwhelming inflammatory reaction is involved in severe courses of COVID-19. Kynurenine (KYN) has important immune-modulatory functions and may contribute to a failure in controlling SARS-CoV-2. The present study aims to explore biomarkers that hint at a fatal outcome of COVID-19 early on. (2) Methods: We established a cohort of 148 hospitalized COVID-19 patients for this study. Thirty-one patients died due to a severe COVID-19 course, and 117 recovered within 90 days. We built a biobank by collecting left-over material from these patients whenever blood arrived at the central laboratory of our University hospital for analysis of routine markers. The scientific laboratory analysis comprised KYN, Tryptophan (TRP), KYN/TRP ratio, ferritin, interleukin-6 (IL-6), C-reactive protein (CRP), creatinine, N-terminal pro-natriuretic peptide (NTproBNP), troponin T (TnT), fibrinogen, D-Dimer, prothrombin time (PT), activated partial thromboplastin time (aPTT), antithrombin (AT), protein C, protein S, factor XIII, lupus aPTT, angiotensin-2, vitamin D metabolites, and telomeres in all COVID-19 patients. Basic clinical characteristics and anteceding diseases including cardiovascular, oncologic, renal, hypertension, pulmonary, metabolic (diabetes, obesity) were recorded in a database together with the laboratory data. (3) Results: At the time of diagnosis of SARS-CoV-2 infection those patients who deceased within 90 days afterwards due to COVID-19, had a significantly higher age, higher KYN, KYN/TRP ratio, ferritin, creatinine, and NTproBNP values than SARS-CoV-2 patients who survived COVID-19 along the same time span. In a Kaplan-Meier analysis the variables age, KYN, ferritin, D-Dimer, TnT, NTproBNP, and creatinine showed a significant influence on survival time. Gender, however, showed no influence. In a combined Cox regression analysis KYN had the highest hazard ratio (1.188, 95% CI: 1.071–1.319) followed by age (1.041, 95% CI: 1.011–1.073). In a ROC analysis, KYN values above the cut off limit of 4.82 nmol/l (as specified by Youden index) had a sensitivity of 82% (95% CI: 66–95%) and a specificity of 72% (95% CI: 65–82%) to predict COVID-19 related death within 90 days observation time. (4) Conclusions: Kynurenine is a promising blood biomarker to predict an increased risk of mortality in SARS-CoV-2 infected people already at the time of the first positive SARS-CoV-2 verification detected in these persons.

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Atrial high-rate episodes predict major adverse cardio/cerebrovascular events in patients with cardiac implantable electrical devices

Scientific Reports ◽

10.1038/s41598-021-98258-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ju-Yi Chen ◽

Tse-Wei Chen ◽

Wei-Da Lu

Keyword(s):

Cox Regression ◽

High Rate ◽

Youden Index ◽

Cox Regression Analysis ◽

Cerebrovascular Events ◽

Increased Risk ◽

Electrical Devices ◽

Time Dependent Covariates ◽

Cutoff Threshold

AbstractPatients with atrial high-rate episodes (AHRE) have a high risk of neurologic events, although the causal role and optimal cutoff threshold of AHRE for major adverse cardio/cerebrovascular events (MACCE) are unknown. This study aimed to identify independent factors for AHRE and subsequent atrial fibrillation (AF) after documented AHRE. We enrolled 470 consecutive patients undergoing cardiac implantable electrical device (CIED) implantations. The primary endpoint was subsequent MACCE after AHRE ≥ 6 min, 6 h, and 24 h. AHRE was defined as > 175 beats per minute (bpm) (Medtronic®) or > 200 bpm (Biotronik®) lasting ≥ 30 s. Multivariate Cox regression analysis with time-dependent covariates was used to determine variables associated with independent risk of MACCE. The patients’ median age was 76 year, and 126 patients (26.8%) developed AHRE ≥ 6 min, 63 (13.4%) ≥ 6 h, and 39 (8.3%) ≥ 24 h. During follow-up (median: 29 months), 142 MACCE occurred in 123 patients. Optimal AHRE cutoff value was 6 min, with highest Youden index for MACCE. AHRE ≥ 6 min ~ 24 h was independently associated with MACCE and predicted subsequent AF. Male gender, lower body mass index, or BMI, and left atrial diameter were independently associated with AHRE ≥ 6 min ~ 24 h. Patients with CIEDs who develop AHRE ≥ 6 min have an independently increased risk of MACCE. Comprehensive assessment of patients with CIEDs is warranted.

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Predictors of retention in care in HIV-infected patients in a large hospital cohort in Italy

Epidemiology and Infection ◽

10.1017/s0950268817003107 ◽

2018 ◽

Vol 146 (5) ◽

pp. 606-611 ◽

Cited By ~ 1

Author(s):

Roberta Prinapori ◽

Barbara Giannini ◽

Niccolò Riccardi ◽

Francesca Bovis ◽

Mauro Giacomini ◽

...

Keyword(s):

Hiv Infection ◽

Cox Regression ◽

Univariate Analysis ◽

Laboratory Data ◽

Retention In Care ◽

Large Hospital ◽

Loss To Follow Up ◽

Cox Regression Analysis ◽

Increased Risk

AbstractRetention in care is a key feature of the cascade of continuum of care, playing an important role in achieving therapeutic success and being crucial for reduction of HIV transmission. The aim of this study was to evaluate the rate of retention in care in a large referral centre in the North of Italy and to identify predictors associated with failed retention. All new HIV-infected subjects were consecutive enrolled from 1 January 2008 to 31 December 2014. Demographics, immune-virological status, hepatitis co-infection and timing of initiation of combined antiretroviral therapy (cART) data were collected at baseline and at the time of last observation. Failed retention in care was defined as lack of laboratory data, clinical visits and drug dispensation for more than 6 months from the last visit. Cox regression analysis was used. Multivariate analysis of variables with P<0.05 in univariate analysis was performed. We enrolled 269 patients (mean age 46.1 years). Males were 197 (73%), Italian 219 (81%) with mean length of disease of 5.1 years. cART was prescribed for 257 patients (95%). The rate of retention in care was 78.4% and the rate of virological suppression was 75%. Predictors of being loss to follow-up were foreign origin (P = 0.048), CD4+ count <200/mmc (P = 0.001) and not being treated for HIV infection (P = 0.0004). Predictors of cART efficacy were shorter duration of HIV infection and baseline HIV-RNA <100 000 copies/ml. These findings underline the necessity to improve retention in care by identifying groups at increased risk of being loss to follow-up. Retention in care of vulnerable population is crucial to reach 90-90-90 UNAIDS endpoint.

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Albumin–Globulin Ratio Is an Independent Determinant of 28-Day Mortality in Patients with Critical Illness

Disease Markers ◽

10.1155/2021/9965124 ◽

2021 ◽

Vol 2021 ◽

pp. 1-5

Author(s):

Bin Liu ◽

Kun Xiao ◽

Peng Yan ◽

Tianyu Sun ◽

Jiang Wang ◽

...

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Critical Illness ◽

Critically Ill ◽

Critically Ill Patients ◽

Cox Regression ◽

Independent Predictor ◽

Laboratory Data ◽

Cox Regression Analysis ◽

Increased Risk

Background. Critical illness in the intensive care unit (ICU) has been a global health priority. Systemic nutritional status has turned out to be related to the prognosis of critically ill patients. The albumin-globulin ratio (AGR) has been reported to be a novel prognostic factor of many diseases. This study is aimed at investigating whether the AGR could predict the mortality risk in critically ill patients. Methods. We enrolled 582 adult patients admitted to the respiratory intensive care unit (RICU). We collected the clinical and laboratory data. X-tile software was used to determine the optimal cut-off values for the AGR. Patients were divided into three groups according to the AGR (low AGR group with AGR < 0.8 , medium AGR group with AGR ranging from 0.8 to 1.1, and high AGR group with AGR > 1.1 ). Kaplan-Meier analysis was used for survival analysis. A Cox proportional hazard model was applied to the univariate and multivariate analyses for the potential predictors associated with survival. Results. Our present study showed that the AGR was related to the 28-day survival of critically ill patients in the RICU. The rate of pneumonia in the low AGR group was significantly higher than that in the other groups. Patients with a lower AGR present an increased risk of 28-day mortality compared to patients with a higher AGR. Cox regression analysis showed that the AGR might be an independent predictor of prognosis to 28-day survival in critically ill patients in the RICU. Medium and high AGR values remained independently associated with better 28-day survival than low AGR values (HR: 0.484 (0.263-0.892) ( p = 0.02 ); HR: 0.332 (0.166-0.665) ( p = 0.002 )). Conclusion. The AGR might be an independent predictor of prognosis in critically ill patients.

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Sex differences in transaortic flow rate and association with all-cause mortality in patients with severe aortic stenosis

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeab045 ◽

2021 ◽

Author(s):

Sahrai Saeed ◽

Anastasia Vamvakidou ◽

Spyridon Zidros ◽

George Papasozomenos ◽

Vegard Lysne ◽

...

Keyword(s):

Sex Differences ◽

Aortic Stenosis ◽

Flow Rate ◽

Cox Regression ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

Cox Regression Analysis ◽

Increased Risk ◽

All Cause Mortality

Abstract Aims It is not known whether transaortic flow rate (FR) in aortic stenosis (AS) differs between men and women, and whether the commonly used cut-off of 200 mL/s is prognostic in females. We aimed to explore sex differences in the determinants of FR, and determine the best sex-specific cut-offs for prediction of all-cause mortality. Methods and results Between 2010 and 2017, a total of 1564 symptomatic patients (mean age 76 ± 13 years, 51% men) with severe AS were prospectively included. Mean follow-up was 35 ± 22 months. The prevalence of cardiovascular disease was significantly higher in men than women (63% vs. 42%, P < 0.001). Men had higher left ventricular mass and lower left ventricular ejection fraction compared to women (both P < 0.001). Men were more likely to undergo an aortic valve intervention (AVI) (54% vs. 45%, P = 0.001), while the death rates were similar (42.0% in men and 40.6% in women, P = 0.580). A total of 779 (49.8%) patients underwent an AVI in which 145 (18.6%) died. In a multivariate Cox regression analysis, each 10 mL/s decrease in FR was associated with a 7% increase in hazard ratio (HR) for all-cause mortality (HR 1.07; 95% CI 1.03–1.11, P < 0.001). The best cut-off value of FR for prediction of all-cause mortality was 179 mL/s in women and 209 mL/s in men. Conclusion Transaortic FR was lower in women than men. In the group undergoing AVI, lower FR was associated with increased risk of all-cause mortality, and the optimal cut-off for prediction of all-cause mortality was lower in women than men.

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Fast-Track Programs in Total Hip and Knee Replacement at Swedish Hospitals—Influence on 2-Year Risk of Revision and Mortality

Journal of Clinical Medicine ◽

10.3390/jcm10081680 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1680

Author(s):

Urban Berg ◽

Annette W-Dahl ◽

Anna Nilsdotter ◽

Emma Nauclér ◽

Martin Sundberg ◽

...

Keyword(s):

Fast Track ◽

Cox Regression ◽

Cox Regression Analysis ◽

Total Hip ◽

Total Knee Replacements ◽

Risk Of Death ◽

Kaplan Meier ◽

Increased Risk ◽

Hip And Knee Arthroplasty ◽

Total Knee

Purpose: We aimed to study the influence of fast-track care programs in total hip and total knee replacements (THR and TKR) at Swedish hospitals on the risk of revision and mortality within 2 years after the operation. Methods: Data were collected from the Swedish Hip and Knee Arthroplasty Registers (SHAR and SKAR), including 67,913 THR and 59,268 TKR operations from 2011 to 2015 on patients with osteoarthritis. Operations from 2011 to 2015 Revision and mortality in the fast-track group were compared with non-fast-track using Kaplan–Meier survival analysis and Cox regression analysis with adjustments. Results: The hazard ratio (HR) for revision within 2 years after THR with fast-track was 1.19 (CI: 1.03–1.39), indicating increased risk, whereas no increased risk was found in TKR (HR 0.91; CI: 0.79–1.06). The risk of death within 2 years was estimated with a HR of 0.85 (CI: 0.74–0.97) for TKR and 0.96 (CI: 0.85–1.09) for THR in fast-track hospitals compared to non-fast-track. Conclusions: Fast-track programs at Swedish hospitals were associated with an increased risk of revision in THR but not in TKR, while we found the mortality to be lower (TKR) or similar (THR) as compared to non-fast track.

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High rate of second ACL injury following ACL reconstruction in male professional footballers: an updated longitudinal analysis from 118 players in the UEFA Elite Club Injury Study

British Journal of Sports Medicine ◽

10.1136/bjsports-2020-103555 ◽

2021 ◽

pp. bjsports-2020-103555

Author(s):

Francesco Della Villa ◽

Martin Hägglund ◽

Stefano Della Villa ◽

Jan Ekstrand ◽

Markus Waldén

Keyword(s):

Acl Reconstruction ◽

Cox Regression ◽

Injury Rate ◽

Acl Injury ◽

High Rate ◽

Football Players ◽

Professional Football ◽

Cox Regression Analysis ◽

Career Length ◽

Increased Risk

BackgroundStudies on subsequent anterior cruciate ligament (ACL) ruptures and career length in male professional football players after ACL reconstruction (ACLR) are scarce.AimTo investigate the second ACL injury rate, potential predictors of second ACL injury and the career length after ACLR.Study designProspective cohort study.SettingMen’s professional football.Methods118 players with index ACL injury were tracked longitudinally for subsequent ACL injury and career length over 16.9 years. Multivariable Cox regression analysis with HR was carried out to study potential predictors for subsequent ACL injury.ResultsMedian follow-up was 4.3 (IQR 4.6) years after ACLR. The second ACL injury rate after return to training (RTT) was 17.8% (n=21), with 9.3% (n=11) to the ipsilateral and 8.5% (n=10) to the contralateral knee. Significant predictors for second ACL injury were a non-contact index ACL injury (HR 7.16, 95% CI 1.63 to 31.22) and an isolated index ACL injury (HR 2.73, 95% CI 1.06 to 7.07). In total, 11 of 26 players (42%) with a non-contact isolated index ACL injury suffered a second ACL injury. RTT time was not an independent predictor of second ACL injury, even though there was a tendency for a risk reduction with longer time to RTT. Median career length after ACLR was 4.1 (IQR 4.0) years and 60% of players were still playing at preinjury level 5 years after ACLR.ConclusionsAlmost one out of five top-level professional male football players sustained a second ACL injury following ACLR and return to football, with a considerably increased risk for players with a non-contact or isolated index injury.

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684 Cardiac troponins and adverse outcomes in European patients with atrial fibrillation: a report from the ESC-EHRA EORP atrial fibrillation general long-term registry

European Heart Journal Supplements ◽

10.1093/eurheartj/suab127.052 ◽

2021 ◽

Vol 23 (Supplement_G) ◽

Author(s):

Marrco Vitolo ◽

Vincenzo Livio Malavasi ◽

Marco Proietti ◽

Igor Diemberger ◽

Laurent Fauchier ◽

...

Keyword(s):

Atrial Fibrillation ◽

Regression Analysis ◽

Cox Regression ◽

Adverse Outcomes ◽

Cox Regression Analysis ◽

Coronary Syndrome ◽

Increased Risk ◽

History Of ◽

Cardiac Troponins

Abstract Aims Cardiac troponins (cTn) have been reported to be predictors for adverse outcomes in atrial fibrillation (AF), patients, but their actual use is still unclear. To assess the factors associated with cTn testing in routine clinical practice and to evaluate the association of elevated levels of cTn with adverse outcomes in a large contemporary cohort of European AF patients. Methods and results Patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry were stratified into three groups according to cTn levels as (i) cTn not tested, (ii) cTn in range (≤99th percentile), and (iii) cTn elevated (>99th percentile). The composite outcome of any thromboembolism/any acute coronary syndrome (ACS)/cardiovascular (CV) death, defined as major adverse cardiovascular events (MACE) and all-cause death were the main endpoints. 10 445 (94.1%) AF patients were included in this analysis [median age 71 years, interquartile range (IQR): 63–77; males 59.7%]. cTn were tested in 2834 (27.1%). Overall, cTn was elevated in 904 (8.7%) and in-range in 1930 (18.5%) patients. Patients in whom cTn was tested tended to be younger (P < 0.001) and more frequently presenting with first detected AF and atypical AF-related symptoms (i.e. chest pain, dyspnoea, or syncope) (P < 0.001). On multivariable logistic regression analysis, female sex, in-hospital enrollment, first-detected AF, CV risk factors, history of coronary artery disease (CAD), and atypical AF symptoms were independently associated with cTn testing. After a median follow-up of 730 days (IQR: 692–749), 957 (9.7%) composite endpoints occurred while all-cause death was 9.5%. Kaplan–Meier analysis showed a higher cumulative risk for both outcomes in patients with elevated cTn levels (Figure) (Log Rank tests, P < 0.001). On adjusted Cox regression analysis, elevated levels of cTn were independently associated with a higher risk for MACE [hazard ratio (HR): 1.74, 95% confidence interval (CI): 1.40–2.16] and all-cause death (HR 1.45, 95% CI: 1.21–1.74). Elevated levels of cTn were independently associated with a higher occurrence of MACE, all-cause death, any ACS, CV death and hospital readmission even after the exclusion of patients with history of CAD, diagnosis of ACS at discharge, those who underwent coronary revascularization during the admission and/or who were treated with oral anticoagulants plus antiplatelet therapy. Conclusions Elevated cTn levels were independently associated with an increased risk of all-cause mortality and adverse CV events, even after exclusion of CAD patients. Clinical factors that might enhance the need to rule out CAD were associated with cTn testing.

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Varicella zoster virus infections increase the risk of disease flares in patients with SLE: a matched cohort study

Lupus Science & Medicine ◽

10.1136/lupus-2019-000339 ◽

2019 ◽

Vol 6 (1) ◽

pp. e000339 ◽

Cited By ~ 3

Author(s):

Fangfang Sun ◽

Yi Chen ◽

Wanlong Wu ◽

Li Guo ◽

Wenwen Xu ◽

...

Keyword(s):

Propensity Score ◽

Varicella Zoster Virus ◽

Cox Regression ◽

Control Period ◽

Cox Regression Analysis ◽

Varicella Zoster ◽

Propensity Score Weighting ◽

Kaplan Meier ◽

Increased Risk ◽

Risk Of Disease

ObjectiveTo explore whether varicella zoster virus (VZV) infection could increase the risk of disease flares in patients with SLE.MethodsPatients who had VZV reactivations between January 2013 and April 2018 were included from the SLE database (n=1901) of Shanghai Ren Ji Hospital, South Campus. Matched patients with SLE were selected as background controls with a 3:1 ratio. Patients with SLE with symptomatic bacterial infections of the lower urinary tract (UTI) were identified as infection controls. Baseline period and index period were defined as 3 months before and after infection event, respectively. Control period was the following 3 months after the index period. Flare was defined by SELENA SLEDAI Flare Index. Kaplan-Meier analysis, Cox regression model and propensity score weighting were applied.ResultsPatients with VZV infections (n=47), UTI controls (n=28) and matched SLE background controls (n=141) were included. 16 flares (34%) in the VZV group within the index period were observed, as opposed to only 7.1% in UTI controls and 9.9% in background controls. Kaplan-Meier curve revealed that patients with a VZV infection had a much lower flare-free survival within the index period compared with the controls (p=0.0003). Furthermore, after adjusting for relevant confounders including baseline disease activity and intensity of immunosuppressive therapy, Cox regression analysis and propensity score weighting confirmed that VZV infection within 3 months was an independent risk factor for SLE flares (HR 3.70 and HR 4.16, respectively).ConclusionsIn patients with SLE, recent VZV infection within 3 months was associated with increased risk of disease flares.

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Do Children With Constipation Have Increased Risk of Asthma? Real-World Data From a Nationwide Population-Based Cohort Study

Frontiers in Pediatrics ◽

10.3389/fped.2021.714406 ◽

2021 ◽

Vol 9 ◽

Author(s):

Yen-Chu Huang ◽

Meng-Che Wu ◽

Yu-Hsun Wang ◽

James Cheng-Chung Wei

Keyword(s):

Cohort Study ◽

Cox Regression ◽

Population Based ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Research Database ◽

Real World Data ◽

Childhood Disorders ◽

Cox Regression Analysis ◽

Increased Risk

Background: Asthma is one of the most burdensome childhood disorders. Growing evidence disclose intestinal dysbiosis may contribute to asthma via the gut-lung axis. Constipation can lead to alteration of the gut microbiota. The clinical impact of constipation on asthma has not been researched. Therefore, we aim to assess whether pediatric constipation influence the risk of developing asthma by a nationwide population-based cohort study.Methods: We analyzed 10,363 constipated patients and 10,363 individuals without constipation between 1999 and 2013 from Taiwan's National Health Insurance Research Database. Analysis of propensity score was utilized to match age, sex, comorbidities, and medications at a ratio of 1:1. In addition, multiple Cox regression analysis was performed to evaluate the adjusted hazard ratio of asthma. Furthermore, sensitivity tests and a stratified analysis were performed.Results: After adjustment for age, sex, comorbidities, and medications, constipated patients had a 2.36-fold greater risk of asthma compared to those without constipation [adjusted hazard ratio (aHR): 2.36, 95% C.I. 2.04–2.73, p < 0.001]. Furthermore, the severity of constipation is associated with an increased risk of asthma; the adjusted hazard ratio was 2.25, 2.85, and 3.44 within < 3, 3–12, and ≥12 times of laxatives prescription within 1 year, respectively (p < 0.001).Conclusion: Constipation was correlated with a significantly increased risk of asthma. Pediatricians should be aware of the possibility of asthma in constipated patients. Further research is warranted to investigate the possible pathological mechanisms of this association.

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Cesarean section and offspring’s risk of multiple sclerosis: a Danish nationwide cohort study

Multiple Sclerosis Journal ◽

10.1177/1352458513480010 ◽

2013 ◽

Vol 19 (11) ◽

pp. 1473-1477 ◽

Cited By ~ 11

Author(s):

Nete M Nielsen ◽

Peter Bager ◽

Egon Stenager ◽

Bo V Pedersen ◽

Nils Koch-Henriksen ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cesarean Section ◽

Cox Regression ◽

Mode Of Delivery ◽

Study Cohort ◽

Cox Regression Analysis ◽

Medical Birth Register ◽

Increased Risk ◽

Rate Ratios ◽

Log Linear

Background: Apart from a recent study reporting a 2- to 3-fold increased risk of multiple sclerosis (MS) among women and men who were delivered by Cesarean section (C-section), little attention has been given to the possible association between mode of delivery and the risk of MS. Objectives: We studied the association between C-section and risk of MS, in a cohort of 1.7 million Danes born from 1973 to 2005. Methods: Information on C-section and MS was obtained from the Danish Medical Birth Register and the Danish MS Register, respectively. The association between C-section and MS was evaluated by means of MS incidence rate ratios (RR) with 95% confidence intervals (CI) obtained in log-linear Poisson regression analyses. Results: There were 930 cases of MS in the study cohort, of whom 80 (9%) were delivered by C-section. Overall, we found there was no significant association between C-section and risk of MS (RR = 1.17; 0.92–1.46). Analyses stratified by sex revealed no unusual risk of MS for women (RR = 1.08: 0.80–1.42) nor men (RR = 1.37: 0.91–1.98). A supplementary sibling-matched Cox regression analysis likewise suggested there was no excess risk of MS in persons delivered by C-section (HR = 1.03; 0.63–1.69). Conclusions: Mode of delivery appears to be unimportant in relation to MS development in the offspring.

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