Comprehensive Evaluation Of Patient Characteristics And Clinical Parameters As A Diagnostic Aid In Tuberculosis

10.5580/2bd7 ◽  
2012 ◽  
Vol 5 (1) ◽  
2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 206.1-207
Author(s):  
C. Grönwall ◽  
L. Liljefors ◽  
H. Bang ◽  
A. Hensvold ◽  
M. Hansson ◽  
...  

Background:Seropositive rheumatoid arthritis (RA) is characterized by the presence of rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPA) with different fine-specificities. Yet, other serum anti-modified protein autoantibodies (AMPA), e.g. anti-carbamylated (Carb), anti-acetylated (KAc), and anti-malondialdehyde acetaldehyde (MAA) modified protein antibodies, have been described. By using RA patient single-cell derived monoclonal antibodies we have previously shown that individual ACPA clones recognize small distinct citrulline-containing epitopes giving them extensive multireactivity when these epitopes are found in many peptides and proteins. Moreover, certain CCP2+ multireactive ACPA clones bind also to cabamylated and acetylated autoantigens [1].Objectives:To provide a comprehensive evaluation of serum IgG and IgA autoreactivity to different post-translational modifications in RA.Methods:We analyzed 30 different IgG and IgA AMPA reactivities to modified antigens by ELISA and autoantigen arrays, in N=1985 newly diagnosed RA patients and population controls. The study utilized both previously established (i.e IgG and IgA CCP2; IgG ACPA fine-specificities; IgG anti-Carb fibrinogen and Carb FCS; IgG and IgA Cit/Carb/KAc/Orn(Ac)-vimentin), and novel assays (e.g. IgG anti-MAA and IgG anti-acetylated histones). Association with patient characteristics such as smoking and disease activity were explored. The newly developed assays were also evaluated in SLE disease controls and CCP2+ RA-risk individuals without arthritis.Results:Carb and KAc reactivities by different assays were primarily seen in patients also positive for citrulline-reactivity. Modified vimentin (mod-Vim) peptides were used for direct comparison of different AMPA reactivities, revealing that IgA AMPA recognizing mod-Vim was mainly detected in subsets of patients with high IgG anti-Cit-Vim levels and a history of smoking. IgG acetylation reactivity was mainly detected in a subset of patients with Cit and Carb reactivity. Anti-acetylated histone 2B reactivity was RA-specific and associated with high anti-CCP2 IgG levels, multiple ACPA fine-specificities, and smoking. This reactivity was also found to be present in CCP2+ RA-risk individuals without arthritis. Our data further demonstrate that IgG autoreactivity to MAA was increased in RA compared to controls with highest levels in CCP2+ RA, but was not RA-specific, and showed low correlation with other AMPA. Anti-MAA was instead associated with disease activity and was not significantly increased in CCP2+ individuals at risk of RA. Notably, RA patients could be subdivided into four different subsets based on their AMPA IgG and IgA reactivity profiles.Conclusion:We conclude that autoantibodies exhibiting different patterns of ACPA fine-specificities as well as Carb and KAc reactivity are present in RA and may be derived from multireactive B-cell clones. Anti-Carb and anti-KAc could be considered reactivities within the “Cit-umbrella” similar to ACPA fine-specificities, while MAA is distinctly different.References:[1]Sahlström P, Hansson M, Steen J, Amara K, Titcombe PJ, Forsström B, Stålesen R, Israelsson L, Piccoli L, Lundberg K, Klareskog L, Mueller DL, Catrina AI, Skriner K, Malmström V, Grönwall C. Different Hierarchies of Anti-Modified Protein Autoantibody Reactivities in Rheumatoid Arthritis. Arthritis Rheumatol. 2020 Oct;72(10):1643-1657. PMID: 32501655Caroline Grönwall: None declared, Lisa Liljefors: None declared, Holger Bang Employee of: Employee at ORGENTEC Diagnostika GmbH, Aase Hensvold: None declared, Monika Hansson: None declared, Linda Mathsson-Alm Employee of: Employee at Thermo Fisher Scientific, Lena Israelsson: None declared, Anna Svärd: None declared, Cyril CLAVEL: None declared, Elisabet Svenungsson: None declared, Iva Gunnarsson: None declared, Guy Serre: None declared, Saedis Saevarsdottir: None declared, Alf Kastbom: None declared, Lars Alfredsson: None declared, Vivianne Malmström: None declared, Johan Rönnelid: None declared, Anca Catrina: None declared, Karin Lundberg: None declared, Lars Klareskog: None declared


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4641-4641
Author(s):  
Lan Zhang ◽  
Xingnong Ye ◽  
Shengjie Wang ◽  
Keyi Jin ◽  
Shuna Luo ◽  
...  

Abstract Myeloproliferative neoplasms (MPNs) include three classical subtypes: polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Since prefibrotic primary myelofibrosis (pre-PMF) was recognized as a separate entity in the 2016 revised classification of MPN, it has been a subject of debate among experts due to its indefinite diagnosis. However, pre-PMF usually has a distinct outcome compared with either ET or overt PMF. We conducted a retrospective study of MPN patients from October 2014 to June 2020 in the Fourth Affiliated Hospital of Zhejiang University. Patients who were diagnosed with ET, pre-PMF or overt-MF according to the 2016 WHO Classification were included. We reviewed the clinical parameters, haematologic information, and genetic mutations of patients using next-generation sequencing (NGS). Mutation screening was performed in 44 patients by next-generation sequencing techniques, 84 genes and 258 mutations were detected. JAK2 was the most frequently mutated gene (25/44, 56.82%), followed by TET2 (14/44, 31.82%), KMT2C (13/44, 29.55%), and ASXL1 (10/44, 23.73%) in MPN (Figure 1-A). The VAFs of all studied genes with mutation frequencies >10% are shown in Figure 1-B. Of the 20 patients with ET, 9 (45%) were positive for the JAK2 mutation, 5 (25%) carried FAT1, 5 (25%) carried KMT2C, and 4 (20%) carried CALR. Of the 5 patients with pre-PMF, 4 (80%) carried JAK2, 3 (60%) carried EP300, and 2 (40%) carried TET2. Of the 19 patients with overt PMF, 12 (63%) carried JAK2, 10 (53%) carried TET2, 7 (37%) carried ASXL1, and 6 (32%) carried KMT2C, as reported in Figure 2. The median follow-up was 36 months for ET, 42 months for pre-PMF, and 53 months for overt PMF. Overall survival between pre-PMF, overt PMF, and ET was significantly different (P<0.001), as shown in Figure 3. During the follow-up time, only one death of ET was registered, so we analysed the impact of clinical parameters and mutational status at diagnosis on outcome in PMF, including pre-PMF and overt PMF. We performed Kaplan-Meier curves to examine the relationships between the clinical parameters and patient survival. We found that male sex (P=0.0107), MPN10 symptoms (P=0.0354), anaemia (haemoglobin<120g/L, P=0.0239), and thrombocytopenia (platelet count <100 ×10 9/L, P=0.0002) were significantly related to inferior OS (Figure 4). Pre-PMF patients exhibited higher leukocyte counts, higher LDH values, a higher frequency of splenomegaly, and a higher incidence of hypertension than ET patients. On the other hand, pre-PMF patients had higher platelet counts and haemoglobin levels than overt PMF patients. Molecular analysis revealed that the frequency of EP300 mutations was significantly increased in pre-PMF patients compared with ET and overt PMF patients. In terms of outcome, male sex, along with symptoms including MPN10, anaemia, thrombocytopenia, and KMT2A and CUX1 mutations, indicated a poor prognosis for PMF patients. In conclusion, we identified differences in the clinical, haematologic, and molecular presentations of ET, pre-PMF, and overt PMF patients, indicating that comprehensive evaluation of not only BM features but also clinical, haematologic, and molecular profiles is needed for accurate diagnosis and treatment of these three disease entities. The molecular analysis revealed that pre-PMF might be relevant to EP300 mutation, demonstrating the value of molecular examination. The results of this study indicated that comprehensive evaluation of BM features, clinical phenotypes, haematologic parameters, and molecular profiles is needed for the accurate diagnosis and treatment of ET, pre-PMF, and overt PMF patients. Acknowledgment:The research was supported by the Public Technology Application Research Program of Zhejiang, China (LGF21H080003), the Key Project of Jinhua Science and Technology Plan, China (2020XG-29 and 2020-3-011), the Academician Workstation of the Fourth Affiliated Hospital of the Zhejiang University School of Medicine (2019-2024), the Key Medical Discipline of Yiwu, China (Hematology, 2018-2020) and the Key Medical Discipline of Jinhua, China (Hematology, 2019-2021). Correspondence to: Dr Jian Huang, Department of Hematology, The Fourth Affiliated Hospital of Zhejiang University School of Medicine. N1 Shangcheng Road. Yiwu, Zhejiang, Peoples R China. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.


2020 ◽  
Author(s):  
Sean Legler ◽  
Matthew Diehl ◽  
Biran Hilliard ◽  
Andrew Olson ◽  
Rebecca Markowitz ◽  
...  

BACKGROUND Increasing incidence of coronavirus 2019 (COVID-19) infection has challenged healthcare systems to increase capacity while needing to conserve personal protective equipment (PPE) supplies and minimize nosocomial spread. Telemedicine shows promise to address these challenges but lacks comprehensive evaluation in the inpatient environment. OBJECTIVE To evaluate an intra-hospital telemedicine program (virtual care), along with its impact on exposure risk and communication. METHODS We conducted a natural experiment of virtual care on patients admitted for COVID-19. The primary exposure variable was documented use of virtual care. Patient characteristics, PPE use rates and their association with virtual care use were assessed. In parallel, we conducted surveys with patients and clinicians to capture satisfaction with virtual care along the domains of communication, medical treatment, and exposure risk. RESULTS Of 137 total patients in our primary analysis, 43 patients used virtual care. In total, there were 82 inpatient days of use and 401 inpatient days without use. Hospital utilization and illness severity was similar in patients who opted-in vs opted-out. Virtual care was associated with a significant reduction in PPE use and physical exam rate. Surveys of 41 patients and clinicians showed high rates of recommendation for further use, and subjective improvements in communication. However, providers and patients expressed limitations in usability, medical assessment and empathetic communication. CONCLUSIONS In this pilot natural experiment, only a subset of patients used inpatient virtual care. When used, virtual care was associated with reductions in PPE use, reductions in exposure risk, and patient and provider satisfaction.


Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 508
Author(s):  
Michele Ghidini ◽  
Alice Indini ◽  
Erika Rijavec ◽  
Claudia Bareggi ◽  
Monica Cattaneo ◽  
...  

Over the last months, as oncology specialists, we have frequently been contacted for estimating prognosis for cancer patients affected by COVID-19 infection. Until now, there have been no clear markers to guide decision making regarding the appropriateness of invasive ventilation in cancer patients affected by COVID-19 infection. We developed a practical tool encompassing a prognostic score, “The Milano Policlinico ONCOVID-ICU score.” The score is composed of three groups of variables: patient’s characteristics such as sex, age, BMI, and comorbidities; oncological variables (treatment intent, life expectancy, on or off-treatment status); and clinical parameters in association with laboratory values (the Sequential Organ Failure Assessment (SOFA) score and D-dimer). The SOFA score includes six different clinical parameters and during the first few days of ICU admissions has an important prognostic role. The oncological history should never represent, per se, a contraindication to intensive care and must be considered together with other variables, such as laboratory values, clinical parameters, and patient characteristics, in order to make the hardest but best possible choice. To our knowledge, “The Milano Policlinico ONCOVID-ICU score” is the first prognostic score proposed in this setting of patients and requires further validation. This tool may be useful to assess the prognosis of cancer patients in critical conditions.


Author(s):  
Michele Ghidini ◽  
Alice Indini ◽  
Erika Rijavec ◽  
Claudia Bareggi ◽  
Monica Cattaneo ◽  
...  

Over the last two months, as oncology specialists, we have frequently been contacted for estimating prognosis for cancer patients affected by COVID-19 infection. Until now, there have been no clear markers to guide decision making regarding the appropriateness of invasive ventilation in cancer patients affected by COVID-19 infection. Therefore, we developed a practical tool encompassing a prognostic score. We aimed at identifying a subgroup of patients likely to have a better outcome and therefore may be potential candidates for invasive ventilation, "The Milano Policlinico ONCOVID-ICU score". The score is composed by three groups of variables: patient’s characteristics such as sex, age, BMI and comorbidities; oncological variables (treatment intent, life expectancy, on or off-treatment status) and clinical parameters in association with laboratory values (SOFA score and D-dimer). The SOFA score includes six different clinical parameters and during the first few days of ICU admissions has an important prognostic role. The oncological history should never represent, per se, a contraindication to intensive care and must be considered together with other variables, such as laboratory values, clinical parameters and patient characteristics, in order to make the hardest but best possible choice. The Milano Policlinico ONCOVID-ICU score, to our knowledge, is the first prognostic score proposed in this setting of patients and may be a useful tool to assess the prognosis of cancer patients being in this critical condition.


2021 ◽  
Vol 12 ◽  
Author(s):  
Caroline Grönwall ◽  
Lisa Liljefors ◽  
Holger Bang ◽  
Aase H. Hensvold ◽  
Monika Hansson ◽  
...  

Seropositive rheumatoid arthritis (RA) is characterized by the presence of rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPA) with different fine-specificities. Yet, other serum anti-modified protein autoantibodies (AMPA), e.g. anti-carbamylated (Carb), -acetylated (KAc), and malondialdehyde acetaldehyde (MAA) modified protein antibodies, have been described. In this comprehensive study, we analyze 30 different IgG and IgA AMPA reactivities to Cit, Carb, KAc, and MAA antigens detected by ELISA and autoantigen arrays in N=1985 newly diagnosed RA patients. Association with patient characteristics such as smoking and disease activity were explored. Carb and KAc reactivities by different assays were primarily seen in patients also positive for anti-citrulline reactivity. Modified vimentin (mod-Vim) peptides were used for direct comparison of different AMPA reactivities, revealing that IgA AMPA recognizing mod-Vim was mainly detected in subsets of patients with high IgG anti-Cit-Vim levels and a history of smoking. IgG reactivity to acetylation was mainly detected in a subset of patients with Cit and Carb reactivity. Anti-acetylated histone reactivity was RA-specific and associated with high anti-CCP2 IgG levels, multiple ACPA fine-specificities, and smoking status. This reactivity was also found to be present in CCP2+ RA-risk individuals without arthritis. Our data further demonstrate that IgG autoreactivity to MAA was increased in RA compared to controls with highest levels in CCP2+ RA, but was not RA-specific, and showed low correlation with other AMPA. Anti-MAA was instead associated with disease activity and was not significantly increased in CCP2+ individuals at risk of RA. Notably, RA patients could be subdivided into four different subsets based on their AMPA IgG and IgA reactivity profiles. Our serology results were complemented by screening of monoclonal antibodies derived from single B cells from RA patients for the same antigens as the RA cohort. Certain CCP2+ clones had Carb or Carb+KAc+ multireactivity, while such reactivities were not found in CCP2- clones. We conclude that autoantibodies exhibiting different patterns of ACPA fine-specificities as well as Carb and KAc reactivity are present in RA and may be derived from multireactive B-cell clones. Carb and KAc could be considered reactivities within the “Cit-umbrella” similar to ACPA fine-specificities, while MAA reactivity is distinctly different.


1983 ◽  
Vol 14 (1) ◽  
pp. 7-21 ◽  
Author(s):  
Robert E. Owens ◽  
Martha J. Haney ◽  
Virginia E. Giesow ◽  
Lisa F. Dooley ◽  
Richard J. Kelly

This paper examines the test item content of several language assessment tools. A comparison of test breadth and depth is presented. The resultant information provides a diagnostic aid for school speech-language pathologists.


1971 ◽  
Author(s):  
Gary J. Echternach ◽  
Robert F. Boldt ◽  
Wayne S. Sellman

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