scholarly journals A serum protein network predicts the need for systemic immunomodulatory therapy in autoimmune uveitis

2021 ◽  
Author(s):  
Jonas J.W. Kuiper ◽  
Fleurieke H. Verhagen ◽  
Sanne Hiddingh ◽  
Roos A.W. Wennink ◽  
Anna M. Hansen ◽  
...  
Keyword(s):  
Serum Protein ◽  
Clinical Decision Making ◽  
Severe Disease ◽  
Protein Network ◽  
Immunomodulatory Therapy ◽  
Anatomical Location ◽  
Disease Course ◽  
Autoimmune Uveitis ◽  
Increased Risk

Objective biomarkers that can predict a severe disease course of autoimmune uveitis are lacking, and warranted for early identification of high-risk patients to improve visual outcome. The need for non-steroid immunomodulatory therapy (IMT) to control autoimmune uveitis is indicative of a more severe disease course. We used aptamer-based proteomics and a bioinformatic pipeline to uncover the serum protein network of 52 treatment-free patients and 26 healthy controls, and validation cohorts of 114 and 67 patients. Network-based analyses identified a highly co-expressed serum signature (n=85 proteins) whose concentration was consistently low in controls, but varied between cases. Patients that were positive for the signature at baseline showed a significantly increased risk for IMT during follow-up, independent of anatomical location of disease. In an independent cohort (n=114), we established robust risk categories and confirmed that patients with high levels of the signature at diagnosis had a significantly increased risk to start IMT during follow-up. Finally, we further validated the predictive association of the signature in a third cohort of 67 treatment-naive North-American patients. A serum protein signature was highly predictive for IMT in human autoimmune uveitis and may serve as an objective blood biomarker to aid in clinical-decision making.

scholarly journals SARS-CoV-2 infections in people with PCD: neither frequent, nor particularly severe

2020 ◽  
Author(s):  
Eva SL Pedersen ◽  
Myrofora Goutaki ◽  
Amanda L Harris ◽  
Lucy Dixon ◽  
Michele Manion ◽  
...  
Keyword(s):  
Incidence Rate ◽  
Severe Symptom ◽  
Demographic Data ◽  
Severe Disease ◽  
Median Number ◽  
Disease Course ◽  
Increased Risk ◽  
Using Data ◽  
Ciliary Dyskinesia

AbstractPeople with pre-existing chronic health conditions are reportedly at high risk of getting the coronavirus disease (COVID-19) and of having a severe disease course but little data exist on rare diseases such as Primary Ciliary Dyskinesia (PCD). We studied risk and severity of SARS-CoV-2 infections among people with PCD using data from the COVID-PCD, a participatory study that collects data in real-time directly from people with PCD. Data was collected using online questionnaires. A baseline questionnaire collected information on demographic data, information about the PCD diagnosis and severity. A short weekly questionnaire collected information about current symptoms and incident SARS-CoV-2 infections. 578 people participated in the COVID-PCD by December 7, 2020, with a median number of follow-up weeks of 9 (interquartile range: 4-19 weeks). 256 (45%) of the participants had been tested for SARS-CoV-2 and 12 tested positive prior to study entry or during study follow up (2.1% of the total included population, 95% confidence interval (CI) 1.1-3.6%). 4 people tested positive during the study follow-up, corresponding to an incidence rate of 2.5 per 100 person-years (95% CI: 0.9-6.5). Overall, reported severity was mild with two reporting no symptoms, eight reporting mild symptoms, one reporting severe symptom without hospitalisation, and one reporting hospitalisation for 9 days. The study suggests that with careful personal protection, people with PCD do not seem to have an increased risk of infection with SARS-COV-2, nor an especially severe disease course.Take home messageIn this longitudinal study of people with PCD followed weekly via online questionnaires, the incidence rate of COVID-19 and the proportion of participants infected were low, and the observed severity mostly mild.

scholarly journals Choice of faecal immunochemical test matters: comparison of OC-Sensor and HM-JACKarc, in the assessment of patients at high risk of colorectal cancer

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Caroline J. Chapman ◽  
Ayan Banerjea ◽  
David J Humes ◽  
Jaren Allen ◽  
Simon Oliver ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Decision Making ◽  
Full Range ◽  
Clinical Decision ◽  
Detection Rates ◽  
Faecal Immunochemical Test ◽  
Specimen Collection ◽  
Increased Risk ◽  
Immunochemical Test

AbstractObjectivesCurrently, NICE recommends the use of faecal immunochemical test (FIT) at faecal haemoglobin concentrations (f-Hb) of 10 μg Hb/g faeces to stratify for colorectal cancer (CRC) risk in symptomatic populations. This f-Hb cut-off is advised across all analysers, despite the fact that a direct comparison of analyser performance, in a clinical setting, has not been performed.MethodsTwo specimen collection devices (OC-Sensor, OC-S; HM-JACKarc, HM-J) were sent to 914 consecutive individuals referred for follow up due to their increased risk of CRC. Agreement of f-Hb around cut-offs of 4, 10 and 150 µg Hb/g faeces and CRC detection rates were assessed. Two OC-S devices were sent to a further 114 individuals, for within test comparisons.ResultsA total of 732 (80.1%) individuals correctly completed and returned two different FIT devices, with 38 (5.2%) CRCs detected. Median f-Hb for individuals diagnosed with and without CRC were 258.5 and 1.8 µg Hb/g faeces for OC-S and 318.1 and 1.0 µg Hb/g faeces for HM-J respectively. Correlation of f-Hb results between OC-S/HM-J over the full range was rho=0.74, p<0.001. Using a f-Hb of 4 µg Hb/g faeces for both tests found an agreement of 88.1%, at 10 µg Hb/g faeces 91.7% and at 150 µg Hb/g faeces 96.3%. A total of 114 individuals completed and returned two OC-S devices; correlation across the full range was rho=0.98, p<0.001.ConclusionsWe found large variations in f-Hb when different FIT devices were used, but a smaller variation when the same FIT device was used. Our data suggest that analyser-specific f-Hb cut-offs are applied with regard to clinical decision making, especially at lower f-Hb.

scholarly journals Genotype–phenotype associations of polymorphisms within the gene locus of NOD-like receptor pyrin domain containing 3 in Swiss inflammatory bowel disease patients

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Priyatharsan Yoganathan ◽  
Jean-Benoit Rossel ◽  
Sebastian Bruno Ulrich Jordi ◽  
Yannick Franc ◽  
Luc Biedermann ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Severe Disease ◽  
Regulatory Region ◽  
Disease Course ◽  
Pyrin Domain ◽  
Homozygous Genotype ◽  
Increased Risk ◽  
Major Allele ◽  
The Impact

Abstract Background Genetic variations within the regulatory region of the gene encoding NOD-like receptor pyrin domain containing 3 (NLRP3) have been associated with Crohn’s Disease (CD). NLRP3 is part of the NLRP3-inflammasome that mediates the maturation of IL-1β and IL-18. Carrying the major allele of the single nucleotide polymorphisms (SNPs) rs10733113, rs4353135 and rs55646866 is associated with an increased risk for CD. We here studied the impact of these polymorphisms on clinical characteristics in patients of the Swiss IBD Cohort Study (SIBDCS). Methods We included 981 Crohn’s disease (CD) patients and 690 ulcerative colitis (UC) patients of the SIBDCS. We analyzed whether three CD-associated NLRP3 polymorphisms have an impact on the clinical disease course in these patients. Results In CD patients presence of the major allele (G) of rs10733113 was associated with less surgeries and lower maximal CDAI and a similar trend was observed for rs55646866 and rs4353135. Presence of the major allele of all three SNPs was negatively correlated to maximal CDAI. In UC patients homozygous genotype for the major allele (CC) for rs55646866 was associated with a higher age at diagnosis and a higher MTWAI index. Homozygous genotype for the major allele of all three polymorphisms was associated with a higher number of ambulatory visits and longer hospital stays. Conclusions In CD patients presence of the major allele of all three polymorphisms was associated with markers of a less severe disease course, while in UC the homozygous genotype for all major alleles suggested a more severe disease activity.

Psoriasis and Psoriatic Arthritis in the Context of the COVID-19 Pandemic: A Plenary Session From the GRAPPA 2020 Annual Meeting

2021 ◽  
pp. jrheum.201671
Author(s):  
Philip J. Mease ◽  
Leonard H. Calabrese ◽  
Kristina Callis Duffin ◽  
Rebecca H. Haberman ◽  
Rodrigo Firmino ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Annual Meeting ◽  
Severe Disease ◽  
Vaccine Safety ◽  
Global Scale ◽  
Disease Course ◽  
Risk Of Infection ◽  
Psoriatic Disease ◽  
Increased Risk ◽  
Infectious Disease Specialists

The coronavirus disease 2019 (COVID-19; caused by SARS-CoV-2) pandemic has affected the healthcare system on a global scale, and we utilized the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2020 annual meeting to examine how COVID-19 might affect patients with psoriatic disease (PsD) and the clinicians who care for them. Pressing issues and concerns identified included whether having psoriasis increased the risk of acquiring COVID-19, vaccine safety, and the acceptability of telehealth. The general message from rheumatologists, dermatologists, infectious disease specialists, and patient research partners was that data did not suggest that having PsD or its treatment significantly increased risk of infection or more severe disease course, and that the telehealth experience was a success overall.

scholarly journals Early Description of Coronavirus 2019 Disease in Kidney Transplant Recipients in New York

2020 ◽  
Vol 31 (6) ◽  
pp. 1150-1156 ◽  
Author(s):  
Keyword(s):  
New York ◽  
Kidney Transplant ◽  
Severe Disease ◽  
Treatment Protocol ◽  
Current Treatment ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Radiographic Findings ◽  
Increased Risk

BackgroundThe novel SARS-CoV-2 virus has caused a global pandemic of coronavirus disease 2019 (COVID-19). Although immunosuppressed individuals are thought to be at an increased risk of severe disease, little is known about their clinical presentation, disease course, or outcomes.MethodsWe report 15 kidney transplant recipients from the Columbia University kidney transplant program who required hospitalization for confirmed COVID-19, and describe their management, clinical course, and outcomes.ResultsPatients presented most often with a fever (87%) and/or cough (67%). Initial chest x-ray most commonly showed bilateral infiltrates, but 33% had no acute radiographic findings. Patients were managed with immunosuppression reduction and the addition of hydroxychloroquine and azithromycin. Although 27% of our patients needed mechanical ventilation, over half were discharged home by the end of follow-up.ConclusionsKidney transplant recipients with COVID-19 have presentations that are similar to that of the general population. Our current treatment protocol appears to be associated with favorable outcomes, but longer follow-up of a larger cohort of patients is needed.

scholarly journals An Epidemiological Cohort Study of SARS-CoV-2 and COVID-19 in German Healthcare Workers – Interim Analysis after Six Months of Follow-up

2021 ◽  
Author(s):  
Stephan Gehring ◽  
Omar Okasha ◽  
Frank Kowalzik ◽  
Tobias Engelmann ◽  
Daniel Schreiner ◽  
...  
Keyword(s):  
Healthcare Workers ◽  
Natural Infection ◽  
Severe Disease ◽  
Smartphone Application ◽  
Case Definitions ◽  
Humoral Immune ◽  
Increased Risk ◽  
Transmission Period ◽  
Incident Cases

Abstract BackgroundHealthcare workers (HCWs) are at increased risk of SARS-CoV-2 infection. We assessed incidence of SARS-CoV-2 infection and COVID-19 before the roll out of COVID-19 vaccines in a cohort of HCWs in Mainz, Germany.MethodsUsing prospective observational cohort design, antibody status was assessed at baseline and every 6 weeks (±2 weeks). Daily self-reported COVID-19 symptoms were collected using a smartphone application. Symptomatic HCWs were tested using RT-PCR. We estimated symptomatic and asymptomatic SARS-CoV-2 infection rates based on two case definitions of varying sensitivity and specificity.Results3664 HCWs were enrolled with a median follow-up of 101 days. The seroprevalence of anti-SARS-CoV-2 antibodies increased from 2.7% at baseline to 3.8%, with the number of seroconversions (65) outweighing seroreversions (26) by end of follow-up. Among HCWs who seroconverted, 12 (~19%) did not report any symptoms. The estimated incidence rate was 4.5 per 1000 person-months, but none the incident cases developed severe disease. Anti-SARS-CoV-2 antibodies fell below diagnostic cut-off value in a third of those positive at baseline and in one incident case.ConclusionsWe observed increasing COVID-19 rates among HCWs during an accelerated community transmission period, with relatively lower rate of asymptomatic infections. Our findings indicate a relatively long-lasting humoral immune response following natural infection.

scholarly journals Development and Validation of a Simplified Risk Score for the Prediction of Critical COVID-19 Illness in Newly Diagnosed Patients

2021 ◽  
Author(s):  
Stanislas Werfel ◽  
Carolin E. M. Jakob ◽  
Stefan Borgmann ◽  
Jochen Schneider ◽  
Christoph Spinner ◽  
...  
Keyword(s):  
Critical Illness ◽  
Clinical Decision Making ◽  
Validation Cohort ◽  
Predictive Accuracy ◽  
Clinical Decision ◽  
Increased Risk ◽  
Risk Of Progression ◽  
Risk Of Disease ◽  
Development And Validation

AbstractScores for identifying patients at high risk of progression of the coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), are discussed as key instruments for clinical decision-making and patient management during the current pandemic.Here we used the patient data from the multicenter Lean European Open Survey on SARS-CoV-2 - Infected Patients (LEOSS) and applied a technique of variable selection in order to develop a simplified score to identify patients at increased risk of critical illness or death.A total of 1,946 patients, who were tested positive for SARS-CoV-2 were included in the initial analysis. They were split into a derivation and a validation cohort (n=1,297 and 649, respectively). A stability selection among a total of 105 baseline predictors for the combined endpoint of progression to critical phase or COVID-19-related death allowed us to develop a simplified score consisting of five predictors: CRP, Age, clinical disease phase (uncomplicated vs. complicated), serum urea and D-dimer (abbreviated as CAPS-D score). This score showed an AUC of 0.81 (CI95%: 0.77-0.85) in the validation cohort for predicting the combined endpoint within 7 days of diagnosis and 0.81 (CI95%: 0.77-0.85) during the full follow-up. Finally, we used an additional prospective cohort of 682 patients, who were diagnosed largely after the “first wave” of the pandemic to validate predictive accuracy of the score, observing similar results (AUC for an event within 7 days: 0.83, CI95%, 0.78-0.87; for full follow-up: 0.82, CI95%, 0.78-0.86).We thus successfully establish and validate an easily applicable score to calculate the risk of disease progression of COVID-19 to critical illness or death.

scholarly journals Transition to severe phenotype in systemic lupus erythematosus initially presenting with non-severe disease: implications for the management of early disease

2020 ◽  
Vol 7 (1) ◽  
pp. e000394 ◽  
Author(s):  
Dionysis S Nikolopoulos ◽  
Myrto Kostopoulou ◽  
Antigoni Pieta ◽  
Sofia Flouda ◽  
Katerina Chavatza ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Disease Duration ◽  
Severe Disease ◽  
Irreversible Damage ◽  
Mild Phenotype ◽  
Double Stranded Dna ◽  
Increased Risk ◽  
Damage Accrual ◽  
Baseline Factors

ObjectiveChanges in the care of patients with SLE dictate a re-evaluation of its natural history and risk factors for disease deterioration and damage accrual. We sought to decipher factors predictive of a deterioration in phenotype (‘transition’) in patients initially presenting with non-severe disease.MethodsPatients from the ‘Attikon’ cohort with disease duration ≥1 year were included. Disease at diagnosis was categorised as mild, moderate or severe, based on the British Isles Lupus Assessment Group manifestations and physician judgement. ‘Transition’ in severity was defined as an increase in category of severity at any time from diagnosis to last follow-up. Multivariable logistic regression was performed to identify baseline factors associated with this transition.Results462 patients were followed for a median (IQR) of 36 (120) months. At diagnosis, more than half (56.5%) had a mild phenotype. During disease course, transition to more severe forms was seen in 44.2%, resulting in comparable distribution among severity patterns at last follow-up (mild 28.4%, moderate 33.1%, severe 38.5%). Neuropsychiatric involvement at onset (OR 6.33, 95% CI 1.22 to 32.67), male sex (OR 4.53, 95% CI 1.23 to 16.60) and longer disease duration (OR 1.09 per 1 year, 95% CI 1.04 to 1.14) were independently associated with transition from mild or moderate to severe disease. Patients with disease duration ≥3 years who progressed to more severe disease had more than 20-fold increased risk to accrue irreversible damage.ConclusionAlmost half of patients with initially non-severe disease progress to more severe forms of SLE, especially men and patients with positive anti-double-stranded DNA or neuropsychiatric involvement at onset. These data may have implications for the management of milder forms of lupus.

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