scholarly journals 313. Host Protein Biomarkers Predicting Severity of Lung Damage due to COVID-19

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S262-S262
Author(s):  
Isabell Kerschbaumer ◽  
Melissa Fazzari ◽  
Shana R Burstein ◽  
Aisha Furey ◽  
Amy S Fox ◽  
...  

Abstract Background Biomarkers to predict the severity of lung damage due to COVID-19 are urgently needed to inform management and treatment decisions. Our objective was to investigate the predictive value of host proteins for worsening respiratory failure in one of the by COVID-19 most affected and diverse patient populations in the US. Methods We performed a prospective single-center cross-sectional study of 34 adult patients admitted to Montefiore Medical Center in the Bronx, New York, for respiratory symptoms due to PCR-confirmed COVID-19. Exclusion criteria were age < 21, history of prior SARS-CoV-2 infection, and/or underlying severe chronic lung diseases requiring home O2 and/or high dose steroids. We stratified and compared patients by whether they developed worsening respiratory failure, necessitating transfer to the intensive care unit (ICU) during their hospital stay. Using a custom Luminex Assay, we measured hospital admission serum concentrations of 8 host proteins, representing respiratory-associated epithelial (RAGE, SP-D, CC16), endothelial (Ang-2, vWF), and immune pathways (S100A12, ICAM-1, VCAM-1). Results Except for race and WHO COVID-19 scores, demographics, co-morbidities, symptoms, and symptom duration were not statistically significantly different between patients requiring transfer to the ICU (n=15) and non-ICU patients (n=19). Higher log-transformed levels for 5/8 proteins (S100A12, ICAM-1, Ang-2, RAGE, SP-D) showed significant or marginally significant increased cause-specific hazard for ICU transfer (n=15). Estimated cumulative incidence functions further showed a significantly or near significantly increased risk for ICU transfer for patients with above the median values of S100A12 or ICAM-1 (p=0.013), Ang-2 (p=0.056) or RAGE (p=0.077), respectively (Figure 1). Host proteins predicting need for ICU transfer did not correlate strongly with other clinical laboratory markers for COVID-19 severity (CRP, LDH, D-Dimer, Fibrinogen, Ferritin). Figure 1. Patients with above median levels of host protein markers S100A12, ICAM-1, Ang-2, and RAGE have a significantly or near significantly increased risk for severe respiratory failure requiring transfer to the ICU. Comparison of estimated cumulative incidence at 7 days post admission for host protein markers above and below median levels for (A) S10012 (median 96,675 pg/ml); (B) ICAM-1 (median (1,192,277 pg/ml); (C) Ang-2 (median 3463 pg/ml); (D) RAGE (median 6356 pg/ml); and (E) SP-D (median 11,832 pg/ml). Conclusion These results suggest that host proteins have additional predictive value for the severity of COVID-19-associated lung damage at time of presentation to the hospital. Disclosures Inessa Gendlina, Nothing to disclose

2018 ◽  
Vol 69 (2) ◽  
pp. 346-349 ◽  
Author(s):  
Marina Ruxandra Otelea ◽  
Oana Cristina Arghir ◽  
Corina Zugravu ◽  
Eugenia Naghi ◽  
Sabina Antoniu ◽  
...  

Regarding the widely distribution of respiratory exposure hazards in occupational settings, workers have an increased risk for chronic lung diseases. For assessing the quality of life and lung function in workers exposed to chemicals and dust, St George�s Respiratory Questionnaire (SGRQ) and spirometry were performed among 40 patients, admitted in Occupational Clinic Department of Colentina Hospital, Bucharest, Romania, during February, 2017. SGRQ showed different predictors for patients according to their occupational exposure and total symptoms score correlated better with decreased spirometric parameters in defining lung function deterioration. Quality of life is earlier affected than lung function deterioration and emphasises the need of more sensitive methods for an earlier identification and better evaluation of respiratory hazards in different workplaces.


2021 ◽  
pp. 239719832110340
Author(s):  
Yasser A Radwan ◽  
Reto D Kurmann ◽  
Avneek S Sandhu ◽  
Edward A El-Am ◽  
Cynthia S Crowson ◽  
...  

Objectives: To study the incidence, risk factors, and outcomes of conduction and rhythm disorders in a population-based cohort of patients with systemic sclerosis versus nonsystemic sclerosis comparators. Methods: An incident cohort of patients with systemic sclerosis (1980–2016) from Olmsted County, MN, was compared to age- and sex-matched nonsystemic sclerosis subjects (1:2). Electrocardiograms, Holter electrocardiograms, and a need for cardiac interventions were reviewed to determine the occurrence of any conduction or rhythm abnormalities. Results: Seventy-eight incident systemic sclerosis cases and 156 comparators were identified (mean age 56 years, 91% female). The prevalence of any conduction disorder before systemic sclerosis diagnosis compared to nonsystemic sclerosis subjects was 15% versus 7% ( p = 0.06), and any rhythm disorder was 18% versus 13% ( p = 0.33). During a median follow-up of 10.5 years in patients with systemic sclerosis and 13.0 years in nonsystemic sclerosis comparators, conduction disorders developed in 25 patients with systemic sclerosis with cumulative incidence of 20.5% (95% confidence interval: 12.4%–34.1%) versus 28 nonsystemic sclerosis patients with cumulative incidence of 10.4% (95% confidence interval: 6.2%–17.4%) (hazard ratio: 2.57; 95% confidence interval: 1.48–4.45), while rhythm disorders developed in 27 patients with systemic sclerosis with cumulative incidence of 27.3% (95% confidence interval: 17.9%–41.6%) versus 43 nonsystemic sclerosis patients with cumulative incidence of 18.0% (95% confidence interval: 12.3%–26.4%) (hazard ratio: 1.62; 95% confidence interval: 1.00–2.64). Age, pulmonary hypertension, and smoking were identified as risk factors. Conclusion: Patients with systemic sclerosis have an increased risk of conduction and rhythm disorders both at disease onset and over time, compared to nonsystemic sclerosis patients. These findings warrant increased vigilance and screening for electrocardiogram abnormalities in systemic sclerosis patients with pulmonary hypertension.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Robert Terziev ◽  
Dimitri Psimaras ◽  
Yannick Marie ◽  
Loic Feuvret ◽  
Giulia Berzero ◽  
...  

AbstractThe incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival > 30 months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms. We investigated a panel of candidate single nucleotide polymorphisms (SNPs) to assess genetic risk. Eighty-one HGG patients (18 grade IV and 63 grade III, 50M/31F) were included in the study. The median age at the time of radiotherapy was 48 years old (range 18–69). The median follow-up after the completion of radiotherapy was 79 months. A total of 44 patients (44/81, 54.3%) developed RIL during follow-up. Twenty-nine of the 44 patients developed consistent symptoms such as subcortical dementia (n = 28), gait disturbances (n = 12), and urinary incontinence (n = 9). The cumulative incidence of RIL was 21% at 12 months, 42% at 36 months, and 48% at 60 months. Age > 60 years, smoking, and the germline SNP rs2120825 (PPARg locus) were associated with an increased risk of RIL. Our study identified potential risk factors for the development of RIL (age, smoking, and the germline SNP rs2120825) and established the rationale for testing PPARg agonists in the prevention and management of late-delayed radiation-induced neurotoxicity.


BJS Open ◽  
2021 ◽  
Vol 5 (Supplement_1) ◽  
Author(s):  
Jacob Rapier ◽  
Steven Hornby ◽  
Jacob Rapier

Abstract Introduction The NUn score was created to try and predict the risk of anastomotic leak or major complications (using the Clavien- Dindo classification) from upper GI resections with an oesophageal anastomosis. A score of > 10 was used to predict an increased risk. In this study we attempt validation. Methods A database of 101 patients was studied, who underwent an Oesophagectomy for cancer between March 2017 and 2020. 72 patients had complete Post-operative day 4 bloods, needed to calculate the score. These patients were then studied for post-operative complications. Results A total of 12 patients had a NUn score of > 10 (16.67%). There was 1 death (1.37%) and 11 anastomotic leaks (15.28%). Of these the NUn score did not predict the death and predicted 8 of the 11 anastomotic leaks. From our data Conclusion From our analysis the NUNs score cannot be shown to be sensitive, specific or have useful positive predictive value. The average Nun score was not reliable, with confidence intervals crossing 10. There may be some merit in using the test for its negative predictive value, but further analysis into this is needed. The results of this audit are consistent with previous efforts at external validation.


HNO ◽  
2021 ◽  
Author(s):  
Patrick J. Schuler ◽  
Jens Greve ◽  
Thomas K. Hoffmann ◽  
Janina Hahn ◽  
Felix Boehm ◽  
...  

Abstract Background One of the main symptoms of severe infection with the new coronavirus‑2 (SARS-CoV-2) is hypoxemic respiratory failure because of viral pneumonia with the need for mechanical ventilation. Prolonged mechanical ventilation may require a tracheostomy, but the increased risk for contamination is a matter of considerable debate. Objective Evaluation of safety and effects of surgical tracheostomy on ventilation parameters and outcome in patients with COVID-19. Study design Retrospective observational study between March 27 and May 18, 2020, in a single-center coronavirus disease-designated ICU at a tertiary care German hospital. Patients Patients with COVID-19 were treated with open surgical tracheostomy due to severe hypoxemic respiratory failure requiring mechanical ventilation. Measurements Clinical and ventilation data were obtained from medical records in a retrospective manner. Results A total of 18 patients with confirmed SARS-CoV‑2 infection and surgical tracheostomy were analyzed. The age range was 42–87 years. All patients received open tracheostomy between 2–16 days after admission. Ventilation after tracheostomy was less invasive (reduction in PEAK and positive end-expiratory pressure [PEEP]) and lung compliance increased over time after tracheostomy. Also, sedative drugs could be reduced, and patients had a reduced need of norepinephrine to maintain hemodynamic stability. Six of 18 patients died. All surgical staff were equipped with N99-masks and facial shields or with powered air-purifying respirators (PAPR). Conclusion Our data suggest that open surgical tracheostomy can be performed without severe complications in patients with COVID-19. Tracheostomy may reduce invasiveness of mechanical ventilation and the need for sedative drugs and norepinehprine. Recommendations for personal protective equipment (PPE) for surgical staff should be followed when PPE is available to avoid contamination of the personnel.


2021 ◽  
Vol 7 (3) ◽  
pp. 233
Author(s):  
Philipp Foessleitner ◽  
Herbert Kiss ◽  
Julia Deinsberger ◽  
Julia Ott ◽  
Lorenz Zierhut ◽  
...  

Pregnant women have an increased risk of vulvovaginal candidosis. Recurrent candidosis is under debate as a contributor to preterm birth, and vertical transmission may cause diaper dermatitis and oral thrush in the newborn. Apart from cultural methods, the gold standard for diagnosing candidosis is Gram staining, which is time-consuming and requires laboratory facilities. The objective of this prospective study was to validate a point-of-care vaginal yeast detection assay (SavvyCheckÔ Vaginal Yeast Test) and to evaluate it in asymptomatic pregnant women. We enrolled 200 participants, 100 of whom had vulvovaginal candidosis according to Gram stain (study group) and 100 were healthy pregnant controls (control group). Of these, 22 participants (11%) had invalid test results. The point-of-care test of the remaining 85 and 93 study participants in the study and control groups, respectively, showed a sensitivity of 94.1%, specificity of 98.9%, positive predictive value of 90.3%, and negative predictive value of 99.4% when compared with Gram stain. In conclusion, we found a high correlation between the SavvyCheckÔ Vaginal Yeast Test and Gram-stained smears during pregnancy. This suggests a potential role of this point-of-care test as a screening tool for asymptomatic pregnant women in early gestation.


2009 ◽  
Vol 83 (19) ◽  
pp. 10314-10318 ◽  
Author(s):  
Cromwell T. Cornillez-Ty ◽  
Lujian Liao ◽  
John R. Yates ◽  
Peter Kuhn ◽  
Michael J. Buchmeier

ABSTRACT The severe acute respiratory syndrome coronavirus (SARS-CoV) generates 16 nonstructural proteins (nsp's) through proteolytic cleavage of a large precursor protein. Although several nsp's exhibit catalytic activities that are important for viral replication and transcription, other nsp's have less clearly defined roles during an infection. In order to gain a better understanding of their functions, we attempted to identify host proteins that interact with nsp's during SARS-CoV infections. For nsp2, we identified an interaction with two host proteins, prohibitin 1 (PHB1) and PHB2. Our results suggest that nsp2 may be involved in the disruption of intracellular host signaling during SARS-CoV infections.


CHEST Journal ◽  
2021 ◽  
Author(s):  
Nandita R. Nadig ◽  
Katherine R. Sterba ◽  
Annie N. Simpson ◽  
Kenneth J. Ruggiero ◽  
Catherine T. Hough ◽  
...  

2021 ◽  
Vol 15 ◽  
pp. 175346662110160
Author(s):  
Timothy N. Perkins ◽  
Tim D. Oury

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease in which most patients die within 3 years of diagnosis. With an unknown etiology, IPF results in progressive fibrosis of the lung parenchyma, diminishing normal lung function, which results in respiratory failure, and eventually, death. While few therapies are available to reduce disease progression, patients continue to advance toward respiratory failure, leaving lung transplantation the only viable option for survival. As incidence and mortality rates steadily increase, the need for novel therapeutics is imperative. The receptor for advanced glycation endproducts (RAGE) is most highly expressed in the lungs and plays a significant role in a number of chronic lung diseases. RAGE has long been linked to IPF; however, confounding data from both human and experimental studies have left an incomplete and perplexing story. This review examines the present understanding of the role of RAGE in human and experimental models of IPF, drawing parallels to recent advances in RAGE biology. Moreover, this review discusses the role of RAGE in lung injury response, type 2 immunity, and cellular senescence, and how such mechanisms may relate to RAGE as both a biomarker of disease progression and potential therapeutic target in IPF. The reviews of this paper are available via the supplemental material section.


2021 ◽  
Author(s):  
Luka Vranić ◽  
Tin Nadarević ◽  
Davor Štimac

Background: Barrett’s esophagus (BE) requires surveillance to identify potential neoplasia at early stage. Standard surveillance regimen includes random four-quadrant biopsies by Seattle protocol. Main limitations of random biopsies are high risk of sampling error, difficulties in histology interpretation, common inadequate classification of pathohistological changes, increased risk of bleeding and time necessary to acquire the final diagnosis. Probe-based confocal laser endomicroscopy (pCLE) has emerged as a potential tool with an aim to overcome these obvious limitations. Summary: pCLE represents real-time microscopic imaging method that offers evaluation of epithelial and subepithelial structures with 1000-fold magnification. In theory, pCLE has potential to eliminate the need for biopsy in BE patient. The main advantages would be real-time diagnosis and decision making, greater diagnostic accuracy and to evaluate larger area compared to random biopsies. Clinical pCLE studies in esophagus show high diagnostic accuracy and its high negative predictive value offers high reliability and confidence to exclude dysplastic and neoplastic lesions. However, it still cannot replace histopathology due to lower positive predictive value and sensitivity. Key messages: Despite promising results, its role in routine use in patients with Barrett’s esophagus remains questionable primarily due to lack of well-organized double-blind randomized trials.


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