scholarly journals Temporal change in Syndecan-1 as a therapeutic target and a biomarker for the severity classification of COVID-19

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Fumihiro Ogawa ◽  
Yasufumi Oi ◽  
Kento Nakajima ◽  
Reo Matsumura ◽  
Tomoki Nakagawa ◽  
...  

Abstract Background Coronavirus disease 2019 (COVID-19) pneumonitis associated with severe respiratory failure is associated with high mortality. The pathogenesis of COVID-19 is associated with microembolism or microvascular endothelial injuries. Here, we report that syndecan-1 (SDC-1), a component of the endothelial glycocalyx, may be a biomarker of severity classification for COVID-19 related to endothelial injury. Methods and analysis We analyzed the data of COVID-19 patients for 1 year from February 2020 at Yokohama City University Hospital and Yokohama City University Medical Center Hospital. We selected COVID-19 patients who required admission care, including intensive care, and analyzed the classification of severe and critical COVID-19 retrospectively, using various clinical data and laboratory data with SDC-1 by ELISA. Results We analyzed clinical and laboratory data with SDC-1 in five severe COVID-19 and ten critical COVID-19 patients. In the two groups, their backgrounds were almost the same. In laboratory data, the LDH, CHE, and CRP levels showed significant differences in each group (P = 0.032, P < 0.0001, and P = 0.007, respectively) with no significant differences in coagulation-related factors (platelet, PT-INR, d-dimer, ISTH score; P = 0.200, 0.277, 0.655, and 0.36, respectively). For the clinical data, the SOFA score was significantly different from admission day to day 14 of admission (p < 0.0001). The SDC-1 levels of critical COVID-19 patients were significantly higher on admission day and all-time course compared with the levels of severe COVID-19 patients (P = 0.009 and P < 0.0001, respectively). Conclusions Temporal change of SDC-1 levels closely reflect the severity of COVID-19, therefore, SDC-1 may be a therapeutic target and a biomarker for the severity classification of Covid-19.

2021 ◽  
Author(s):  
Fumihiro Ogawa ◽  
Yasufumi Oi ◽  
Kento Nakajima ◽  
Reo Matsumura ◽  
Tomoki Nakagawa ◽  
...  

Abstract Background: Coronavirus disease 2019 (COVID-19) pneumonitis associated with severe respiratory failure is associated with high mortality. The pathogenesis of COVID-19 is associated with microemboli or microvascular endothelial injuries. Here, we report that serum syndecan-1 (SDC-1), a component of the endothelial glycocalyx, may be a biomarker of severity classification for COVID-19 related to endothelial injury.Methods and analysis: We analyzed the data of COVID-19 patients for one year from February 2020 at Yokohama City University Hospital and Yokohama City University Medical Center Hospital. We selected COVID-19 patients who required admission care, including intensive care, and analyzed the classification of severe and critical COVID-19 retrospectively, using various clinical data and laboratory data with serum SDC-1 by ELISA. Results: We analyzed clinical and laboratory data with SDC-1 in five severe COVID-19 and ten critical COVID-19 patients. In the two groups, their backgrounds were almost the same. In laboratory data, the LDH, CHE, and CRP levels showed significant differences in each group (P=0.032, P <0.0001, and P = 0.007, respectively) with no significant differences in coagulation-related factors (platelet, PT-INR, D-dimer, ISTH score; P=0.200, 0.277, 0.655, and 0.36, respectively). For the clinical data, the SOFA score was significantly different from admission day to day 14 of admission (p<0.0001). The SDC-1 levels of critical COVID-19 patients were significantly higher on admission day and all-time course compared with the levels of severe COVID-19 patients (P=0.009 and P <0.0001, respectively).Conclusions: Annual changes in serum SDC-1 levels closely reflect the severity of COVID-19, therefore, serum SDC-1 may be a therapeutic target and a biomarker for the severity classification of Covid-19.


2019 ◽  
Vol 8 (9) ◽  
pp. 1320
Author(s):  
Kazumasa Oda ◽  
Hideshi Okada ◽  
Akio Suzuki ◽  
Hiroyuki Tomita ◽  
Ryo Kobayashi ◽  
...  

Endothelial disorders are related to various diseases. An initial endothelial injury is characterized by endothelial glycocalyx injury. We aimed to evaluate endothelial glycocalyx injury by measuring serum syndecan-1 concentrations in patients during comprehensive medical examinations. A single-center, prospective, observational study was conducted at Asahi University Hospital. The participants enrolled in this study were 1313 patients who underwent comprehensive medical examinations at Asahi University Hospital from January 2018 to June 2018. One patient undergoing hemodialysis was excluded from the study. At enrollment, blood samples were obtained, and study personnel collected demographic and clinical data. No treatments or exposures were conducted except for standard medical examinations and blood sample collection. Laboratory data were obtained by the collection of blood samples at the time of study enrolment. According to nonlinear regression, the concentrations of serum syndecan-1 were significantly related to age (p = 0.016), aspartic aminotransferase concentration (AST, p = 0.020), blood urea nitrogen concentration (BUN, p = 0.013), triglyceride concentration (p < 0.001), and hematocrit (p = 0.006). These relationships were independent associations. Endothelial glycocalyx injury, which is reflected by serum syndecan-1 concentrations, is related to age, hematocrit, AST concentration, BUN concentration, and triglyceride concentration.


2007 ◽  
Vol 28 (9) ◽  
pp. 1030-1035 ◽  
Author(s):  
Cristina Bellini ◽  
Christiane Petignat ◽  
Patrick Francioli ◽  
Aline Wenger ◽  
Jacques Bille ◽  
...  

Objective.Surveillance of nosocomial bloodstream infection (BSI) is recommended, but time-consuming. We explored strategies for automated surveillance.Methods.Cohort study. We prospectively processed microbiological and administrative patient data with computerized algorithms to identify contaminated blood cultures, community-acquired BSI, and hospital-acquired BSI and used algorithms to classify the latter on the basis of whether it was a catheter-associated infection. We compared the automatic classification with an assessment (71% prospective) of clinical data.Setting.An 850-bed university hospital.Participants.All adult patients admitted to general surgery, internal medicine, a medical intensive care unit, or a surgical intensive care unit over 3 years.Results.The results of the automated surveillance were 95% concordant with those of classical surveillance based on the assessment of clinical data in distinguishing contamination, community-acquired BSI, and hospital-acquired BSI in a random sample of 100 cases of bacteremia. The two methods were 74% concordant in classifying 351 consecutive episodes of nosocomial BSI with respect to whether the BSI was catheter-associated. Prolonged episodes of BSI, mostly fungemia, that were counted multiple times and incorrect classification of BSI clinically imputable to catheter infection accounted for 81% of the misclassifications in automated surveillance. By counting episodes of fungemia only once per hospital stay and by considering all cases of coagulase-negative staphylococcal BSI to be catheter-related, we improved concordance with clinical assessment to 82%. With these adjustments, automated surveillance for detection of catheter-related BSI had a sensitivity of 78% and a specificity of 93%; for detection of other types of nosocomial BSI, the sensitivity was 98% and the specificity was 69%.Conclusion.Automated strategies are convenient alternatives to manual surveillance of nosocomial BSI.


2020 ◽  
Vol 34 (5) ◽  
pp. 98-103
Author(s):  
Tai-Hwan Uhm ◽  
Jee Hee Kim ◽  
Sang-Kyu Park ◽  
Eun-Jwoo Kwag ◽  
Mi-Sook Kim ◽  
...  

This study examined several trauma scoring systems that serve as the basis for applying the Secondary Assessment of Victim Endpoint (SAVE) severity classification to propose a method that can be applied during triage. By using an exploratory method, data collected from different trauma scoring systems was qualitatively evaluated. First, it was confirmed that the survival risk ratio (SRR) of the International Classification of Disease-based Injury Severity Score (ICISS) can be used for SAVE severity classification. Second, the Korean Trauma Data Bank (KTDB) of the Central Emergency Medical Center does not indicate the SRR of each injury according to the Korean standard classification of disease and cause of death (KCD). Third, the SRR of injuries, from data acquired from the United States can be used for classification of SAVE severity classification. Fourth, the addition of SRR from the KCD to the KTDB can be used for SAVE severity classification.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 38-39
Author(s):  
Katharina Versmold ◽  
Carina Raiser ◽  
Imi Faghmous ◽  
Pablo Katz ◽  
Aijing Shang ◽  
...  

Background Paroxysmal nocturnal hemoglobinuria (PNH) is a life-threatening disease of dysregulated complement activation. It is a rare disease with an estimated incidence of 1 to 1.5 cases per million people globally. Eculizumab is a humanized monoclonal anti-complement component 5 antibody that was approved for the treatment of patients with PNH in the United States and European Union in 2007, yet unmet medical needs remain. Up to half of patients continue to require blood transfusions despite treatment with eculizumab, and hemolytic activity remains detectable in many patients (Brodsky et al. Blood. 2008). Eculizumab is not available in many countries. In places where treatment is approved, there are further impediments to access, such as cost of treatment, reimbursement issues, infrastructure limitations, and patient restrictions (Risitano et al. Am J Hematol. 2018; Risitano et al. Front Immunol. 2019). Data published on real-world outcomes of eculizumab are limited. Here we describe a study that will retroactively analyze data from patients with PNH treated with eculizumab at the Essen University Hospital in Germany. Study Design and Methods This retrospective, secondary data use, cohort study will include all patients at the Essen University Hospital who were diagnosed with PNH and treated with eculizumab prior to April 2018. Clinical data from medical records were entered into an electronic case report form (eCRF). Source data verification has been performed for all clinical data. Laboratory data were extracted directly from the hospital computer system. The Essen University hospital also checked and verified missing laboratory data. Patient-level data in the eCRF and laboratory data were fully anonymized. The primary objective of the study is to understand the remaining unmet medical need by describing the eculizumab dose and frequency of dose adjustment and describing the proportions of patients who experience intravascular and extravascular hemolysis while on treatment. The secondary objectives include explorations of the association between lactate dehydrogenase (LDH) and hemoglobin stabilization with clinical outcomes (eg, breakthrough hemolysis and the need for red blood cell transfusion), the association between PNH clone size and clinical outcomes and the risk of thrombosis, the changes in LDH and hemoglobin levels over time, the need for red blood cell transfusion during eculizumab treatment, and the proportion of eculizumab-treated patients with positive monospecific Coombs test results. In addition, opportunities to apply machine-learning methodologies to predict patients who may not respond to eculizumab will be explored. Many of the analyses will be descriptive. The associations between LDH and hemoglobin with clinical outcomes will be evaluated using rank correlation coefficients or logistic regression. Multivariable regression will be used to explore the prognostic value of clone size on clinical outcomes and thrombosis events. This retrospective study includes 85 patients with PNH with complete clinical and laboratory data (Table). The median age of the cohort was 38 years old, and the cohort was split evenly between men and women. Many patients received a diagnosis of PNH prior to the availability of eculizumab, as the year of diagnosis was 2010 or earlier for 53 patients (62%). The median years of follow-up from initiation of eculizumab was 4.7 years. Overall, 34% had aplastic anemia at diagnosis, and symptoms of fatigue, abdominal pain, and kidney failure were reported in 60%, 34%, and 15%, respectively. At data cutoff, 92% of patients were still alive. Summary The patient demographics in this study are comparable to other studies in PNH, suggesting a representative population. With median follow-up time of nearly 5 years, this study will allow for a long-term assessment of the patient experience with eculizumab. High-quality study data is ensured via full source data verification of clinical data and verification of missing laboratory data. These study results will help to address many research questions in PNH, identify the remaining unmet medical need, and also inform new drug development. Disclosures Versmold: F. Hoffmann-La Roche Ltd: Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Raiser:F. Hoffmann-La Roche Ltd: Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Faghmous:F. Hoffmann-La Roche Ltd: Ended employment in the past 24 months, Other: All authors received medical writing support for this abstract, furnished by Scott Battle, funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. ; Kite Pharma: Current Employment. Katz:F. Hoffmann-La Roche Ltd: Current Employment, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Shang:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Xu:F. Hoffmann-La Roche Ltd: Current Employment, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Röth:Novartis: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Biocryst: Consultancy, Honoraria; Apellis: Consultancy, Honoraria; Alexion Pharmaceuticals Inc.: Consultancy, Honoraria, Research Funding.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5084-5084
Author(s):  
Hee Won Moon ◽  
Tae Young Kim ◽  
Seong- Ho Kang ◽  
Hyun-Sook Chi ◽  
Eul Zu Seo ◽  
...  

Abstract Recent studies proposed the classification of multiple myeloma (MM) by the pathways involved in the early pathogenesis; nonhyperdiploid variants with a high incidence of IgH translocations and hyperdiploid variants associated with no IgH translocation. Most studies applied cytogenetic study or flow cytometry to define the ploidy. In this study, we combined the cytogenetic results and fluorescent in situ hybridization results to define the ploidy and investigated IgH tranlocation and 13q deletion in relation to the ploidy level on Korean patients with MM. A total of 135 cases diagnosed as MM between 1997 and 2003 from Seoul National University Hospital and the Asan Medical center were enrolled in this study. Conventional cytogenetic studies and FISH studies with different probes specific for the regions containing the genes or chromosomes (RB1, D13S319, D13S25, IgH/FGFR3, IgH/BCL2, IGH dual color, break apart rearrangement probe, IgH/CCND1, 1q, p53, p16, MLL, CEP 7, 11, 12) were performed. Of 135 patients with MM, 62 (45.9%) patients had hyperdiploid karyotype by cytogenetics and FISH. IgH translocations were observed in 37.4% of Korean patients with MM and were more frequent (54.7%) in hyperdiploid variants than in nonhyperdiploid variants (17.4%). Incidence of deletion 13q was 34.7% and also more frequent in hyperdiploid variants (54.2%) than in nonhyperdiploid variants (16.1%). In conclusion, IgH translocations and 13q deletions were not associated with nonhyperdiploid MM and appeared more frequently in hyperdiploid variant in Korean patients with MM.


Author(s):  
Kazumasa Oda ◽  
Hideshi Okada ◽  
Akio Suzuki ◽  
Hiroyuki Tomita ◽  
Ryo Kabayashi ◽  
...  

Endothelial disorders are related to various diseases. An initial endothelial injury is characterized by endothelial glycocalyx injury. We aimed to evaluate endothelial glycocalyx injury by measuring serum syndecan-1 concentrations in patients during comprehensive medical examinations. A single-center, prospective, observational study was conducted at Asahi University Hospital. The participants enrolled in this study were 1313 patients who underwent comprehensive medical examinations at Asahi University Hospital from January 2018, to June 2018. One patient undergoing hemodialysis was excluded from the study. At enrollment, blood samples were obtained, and study personnel collected demographic and clinical data. No treatments or exposures were conducted except for standard medical examinations and blood sample collection. Laboratory data were obtained by collection of blood samples at the time of study enrolment. According to nonlinear regression, the concentrations of serum syndecan-1 were significantly related to age (p = 0.016), aspartic aminotransferase concentration (AST, p = 0.020), blood urea nitrogen concentration (BUN, p = 0.013), triglyceride concentration (p &lt; 0.001), and hematocrit (p = 0.006). These relationships were independent associations. Endothelial glycocalyx injury, which is reflected by serum syndecan-1 concentrations, is related to age, hematocrit, AST concentration, BUN concentration, and triglyceride concentration.


1993 ◽  
Vol 32 (05) ◽  
pp. 365-372 ◽  
Author(s):  
T. Timmeis ◽  
J. H. van Bemmel ◽  
E. M. van Mulligen

AbstractResults are presented of the user evaluation of an integrated medical workstation for support of clinical research. Twenty-seven users were recruited from medical and scientific staff of the University Hospital Dijkzigt, the Faculty of Medicine of the Erasmus University Rotterdam, and from other Dutch medical institutions; and all were given a written, self-contained tutorial. Subsequently, an experiment was done in which six clinical data analysis problems had to be solved and an evaluation form was filled out. The aim of this user evaluation was to obtain insight in the benefits of integration for support of clinical data analysis for clinicians and biomedical researchers. The problems were divided into two sets, with gradually more complex problems. In the first set users were guided in a stepwise fashion to solve the problems. In the second set each stepwise problem had an open counterpart. During the evaluation, the workstation continuously recorded the user’s actions. From these results significant differences became apparent between clinicians and non-clinicians for the correctness (means 54% and 81%, respectively, p = 0.04), completeness (means 64% and 88%, respectively, p = 0.01), and number of problems solved (means 67% and 90%, respectively, p = 0.02). These differences were absent for the stepwise problems. Physicians tend to skip more problems than biomedical researchers. No statistically significant differences were found between users with and without clinical data analysis experience, for correctness (means 74% and 72%, respectively, p = 0.95), and completeness (means 82% and 79%, respectively, p = 0.40). It appeared that various clinical research problems can be solved easily with support of the workstation; the results of this experiment can be used as guidance for the development of the successor of this prototype workstation and serve as a reference for the assessment of next versions.


1995 ◽  
Vol 34 (01/02) ◽  
pp. 75-78 ◽  
Author(s):  
R. D. Appel ◽  
O. Golaz ◽  
Ch. Pasquali ◽  
J.-C. Sanchez ◽  
A. Bairoch ◽  
...  

Abstract:The sharing of knowledge worldwide using hypermedia facilities and fast communication protocols (i.e., Mosaic and World Wide Web) provides a growth capacity with tremendous versatility and efficacy. The example of ExPASy, a molecular biology server developed at the University Hospital of Geneva, is striking. ExPASy provides hypermedia facilities to browse through several up-to-date biological and medical databases around the world and to link information from protein maps to genome information and diseases. Its extensive access is open through World Wide Web. Its concept could be extended to patient data including texts, laboratory data, relevant literature findings, sounds, images and movies. A new hypermedia culture is spreading very rapidly where the international fast transmission of documents is the central element. It is part of the emerging new “information society”.


Sign in / Sign up

Export Citation Format

Share Document