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Cancer Reports (Hoboken, N.J.) Aug 2023Hepatocellular carcinoma (HCC) has a high recurrence rate even after radical hepatectomy. More optimal biomarkers may help improve recurrence and prognosis.
BACKGROUND AND OBJECTIVES
Hepatocellular carcinoma (HCC) has a high recurrence rate even after radical hepatectomy. More optimal biomarkers may help improve recurrence and prognosis.
METHODS
We investigated whether the oncological properties of N-glycolylneuraminic acid (NeuGc) can participate in the prognosis of HCC. We evaluated the NeuGc antigen (Ag) expression in the HCC tissues and measured the preoperative anti-NeuGc IgG antibodies (Abs) in the sera of the patients with HCC. We compared the clinical characteristics and survival rate in the hepatectomized patients (initial; n = 66, recurrent; n = 34) with and without the NeuGc Ag or Abs.
RESULTS
Multivariate analyses showed positive expression of NeuGc Ag in HCC tissues (Odds ratio; initial = 6.3, recurrent = 14.0) and higher titers of preoperative anti-NeuGc Ab (Odds ratio; initial = 4.9; recurrent = 3.8), which could be the predictive factors related to early recurrence. Both the NeuGc Ag-positive and Ab-positive groups in the initial hepatectomized patients exhibited significantly shorter recurrent free survival compared to those in the negative groups.
CONCLUSIONS
Our findings suggested that anti-NeuGc Ab titers and NeuGc Ag expression in the HCC tissues can be used as the predictive factors for the postoperative recurrence and prognosis of HCC.
Topics: Humans; Carcinoma, Hepatocellular; Antigens, Heterophile; Liver Neoplasms; Neuraminic Acids; Biomarkers, Tumor
PubMed: 37265054
DOI: 10.1002/cnr2.1831 -
Clinical Chemistry and Laboratory... Jul 2023The International Federation of Clinical Chemistry Committee on Clinical Applications of Cardiac Biomarkers (IFCC C-CB) provides educational documents to facilitate the...
The International Federation of Clinical Chemistry Committee on Clinical Applications of Cardiac Biomarkers (IFCC C-CB) provides educational documents to facilitate the interpretation and use of cardiac biomarkers in clinical laboratories and practice. Our aim is to improve the understanding of certain key analytical and clinical aspects of cardiac biomarkers and how these may interplay. Measurements of cardiac troponin (cTn) have a prominent place in the clinical work-up of patients with suspected acute coronary syndrome. It is therefore important that clinical laboratories know how to recognize and assess analytical issues. Two emerging analytical issues resulting in falsely high cTn concentrations, often several fold higher than the upper reference limit (URL), are antibody-mediated assay interference due to long-lived cTn-antibody complexes, called macrotroponin, and crosslinking antibodies that are frequently referred to as heterophilic antibodies. We provide an overview of antibody-mediated cTn assay interference and provide recommendations on how to confirm the interference and interpret the results.
Topics: Humans; Myocardial Infarction; Biomarkers; Chemistry, Clinical; Antibodies; Troponin
PubMed: 36952681
DOI: 10.1515/cclm-2023-0028 -
Journal of Mass Spectrometry and... Apr 2023Therapeutic drug monitoring (TDM) of immunosuppressants is essential for optimal care of transplant patients. Immunoassays and liquid chromatography-mass spectrometry...
INTRODUCTION
Therapeutic drug monitoring (TDM) of immunosuppressants is essential for optimal care of transplant patients. Immunoassays and liquid chromatography-mass spectrometry (LC-MS) are the most commonly used methods for TDM. However, immunoassays can suffer from interference from heterophile antibodies and structurally similar drugs and metabolites. Additionally, nominal-mass LC-MS assays can be difficult to optimize and are limited in the number of detectable compounds.
OBJECTIVES
The aim of this study was to implement a mass spectrometry-based test for immunosuppressant TDM using online solid-phase extraction (SPE) and accurate-mass full scan-single ion monitoring (FS-SIM) data acquisition mode.
METHODS
LC-MS analysis was performed on a TLX-2 multi-channel HPLC with a Q-Exactive Plus mass spectrometer. TurboFlow online SPE was used for sample clean up. The accurate-mass MS was set to positive electrospray ionization mode with FS-SIM for quantitation of tacrolimus, sirolimus, everolimus, and cyclosporine A. MS fragmentation pattern was used for compound confirmation.
RESULTS
The method was validated in terms of precision, analytical bias, limit of quantitation, linearity, carryover, sample stability, and interference. Quantitation of tacrolimus, sirolimus, everolimus, and cyclosporine A correlated well with results from an independent reference laboratory (r = 0.926-0.984).
CONCLUSIONS
Accurate-mass FS-SIM can be successfully utilized for immunosuppressant TDM with good correlation with results generated by standard methods. TurboFlow online SPE allows for a simple "protein crash and shoot" sample preparation protocol. Compared to traditional MRM, analyte quantitation by FS-SIM facilitates a streamlined assay optimization process.
PubMed: 36937810
DOI: 10.1016/j.jmsacl.2023.03.002 -
BMJ Open Feb 2023Infectious mononucleosis (IM) is a clinical syndrome that is characterised by lymphadenopathy, fever and sore throat. Although generally not considered a serious...
OBJECTIVES
Infectious mononucleosis (IM) is a clinical syndrome that is characterised by lymphadenopathy, fever and sore throat. Although generally not considered a serious illness, IM can lead to significant loss of time from school or work due to profound fatigue, or the development of chronic illness. This study aimed to derive and externally validate clinical prediction rules (CPRs) for IM caused by Epstein-Barr virus (EBV).
DESIGN
Prospective cohort study.
SETTING AND PARTICIPANTS
328 participants were recruited prospectively for the derivation cohort, from seven university-affiliated student health centres in Ireland. Participants were young adults (17-39 years old, mean age 20.6 years) with sore throat and one other additional symptom suggestive of IM. The validation cohort was a retrospective cohort of 1498 participants from a student health centre at the University of Georgia, USA.
MAIN OUTCOME MEASURES
Regression analyses were used to develop four CPR models, internally validated in the derivation cohort. External validation was carried out in the geographically separate validation cohort.
RESULTS
In the derivation cohort, there were 328 participants, of whom 42 (12.8%) had a positive EBV serology test result. Of 1498 participants in the validation cohort, 243 (16.2%) had positive heterophile antibody tests for IM. Four alternative CPR models were developed and compared. There was moderate discrimination and good calibration for all models. The sparsest CPR included presence of enlarged/tender posterior cervical lymph nodes and presence of exudate on the pharynx. This model had moderate discrimination (area under the receiver operating characteristic curve (AUC): 0.70; 95% CI: 0.62-0.79) and good calibration. On external validation, this model demonstrated reasonable discrimination (AUC: 0.69; 95% CI: 0.67-0.72) and good calibration.
CONCLUSIONS
The alternative CPRs proposed can provide quantitative probability estimates of IM. Used in conjunction with serological testing for atypical lymphocytosis and immunoglobulin testing for viral capsid antigen, CPRs can enhance diagnostic decision-making for IM in community settings.
Topics: Young Adult; Humans; Adult; Adolescent; Infectious Mononucleosis; Herpesvirus 4, Human; Clinical Decision Rules; Epstein-Barr Virus Infections; Prospective Studies; Retrospective Studies; Antigens, Viral; Pain; Pharyngitis
PubMed: 36849213
DOI: 10.1136/bmjopen-2022-068877 -
Applied and Environmental Microbiology Mar 2023Bacterial outer membrane vesicles (OMVs) are considered a promising vaccine platform for their high built-in adjuvanticity and ability to efficiently induce immune...
Bacterial outer membrane vesicles (OMVs) are considered a promising vaccine platform for their high built-in adjuvanticity and ability to efficiently induce immune responses. OMVs can be engineered with heterologous antigens based on genetic engineering strategies. However, several critical issues should still be validated, including optimal exposure to the OMV surface, increased production of foreign antigens, nontoxicity, and induction of powerful immune protection. In this study, engineered OMVs with the lipoprotein transport machinery (Lpp) were designed to present SaoA antigen as a vaccine platform against Streptococcus suis. The results suggest that Lpp-SaoA fusions can be delivered on the OMV surface and do not have significant toxicity. Moreover, they can be engineered as lipoprotein and significantly accumulated in OMVs at high levels, thus accounting for nearly 10% of total OMV proteins. Immunization with OMVs containing Lpp-SaoA fusion antigen induced strong specific antibody responses and high levels of cytokines, as well as a balanced Th1/Th2 immune response. Furthermore, the decorated OMV vaccination significantly enhanced microbial clearance in a mouse infection model. It was found that antiserum against lipidated OMVs significantly promoted the opsonophagocytic uptake of S. suis in RAW246.7 macrophages. Lastly, OMVs engineered with Lpp-SaoA induced 100% protection against a challenge with 8× the 50% lethal dose (LD) of S. suis serotype 2 and 80% protection against a challenge with 16× the LD in mice. Altogether, the results of this study provide a promising versatile strategy for the engineering of OMVs and suggest that Lpp-based OMVs may be a universal adjuvant-free vaccine platform for important pathogens. Bacterial outer membrane vesicles (OMVs) have become a promising vaccine platform due to their excellent built-in adjuvanticity properties. However, the location and amount of the expression of the heterologous antigen in the OMVs delivered by the genetic engineering strategies should be optimized. In this study, we exploited the lipoprotein transport pathway to engineer OMVs with heterologous antigen. Not only did lapidated heterologous antigen accumulate in the engineered OMV compartment at high levels, but also it was engineered to be delivered on the OMV surface, thus leading to the optimal activation of antigen-specific B cells and T cells. Immunization with engineered OMVs induced a strong antigen-specific antibodies in mice and conferred 100% protection against S. suis challenge. In general, the data of this study provide a versatile strategy for the engineering of OMVs and suggest that OMVs engineered with lipidated heterologous antigens may be a vaccine platform for significant pathogens.
Topics: Animals; Mice; Streptococcus suis; Antigens, Heterophile; Bacterial Outer Membrane Proteins; Bacterial Outer Membrane; Vaccines; Lipoproteins; Antibodies, Bacterial; Bacterial Vaccines
PubMed: 36809058
DOI: 10.1128/aem.02047-22 -
TouchREVIEWS in Endocrinology Nov 2022For over 50 years, immunoassays have been extensively used to quantitate hormones in blood, other fluids and tissues. Each assay has its own sensitivity, specificity and... (Review)
Review
For over 50 years, immunoassays have been extensively used to quantitate hormones in blood, other fluids and tissues. Each assay has its own sensitivity, specificity and other analytical components. Despite the differences between commercial products, these assays provide important clinical information about hormone levels in patients. However, inaccurate results can occur because of technical issues, as well as patient-specific factors that can interfere with immunoassay hormone measurements. The latter include excessive normal blood or serum components, the presence of cross-reacting substances, extremely high levels of hormones leading to the high-dose hook effect, and interference from a variety of endogenous factors such as human antibodies that interact with the assay components or high levels of biotin in the serum from exogenous ingestion. This article briefly reviews the sources and recognition of endogenous interference, and describes methods to determine the correct serum hormone concentration.
PubMed: 36694886
DOI: 10.17925/EE.2022.18.2.141 -
Journal of Virology Feb 2023The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is becoming a dominant circulator and has several mutations in the spike glycoprotein,...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is becoming a dominant circulator and has several mutations in the spike glycoprotein, which may cause shifts of immunogenicity, so as to result in immune escape and breakthrough infection among the already infected or vaccinated populations. It is unclear whether infection with Omicron could generate adequate cross-variant protection. To investigate this possibility, we used Syrian hamsters as an animal model for infection of SARS-CoV-2. The serum from Omicron BA.1 variant-infected hamsters showed a significantly lower neutralization effect against infection of the same or different SARS-CoV-2 variants than the serum from Beta variant-infected hamsters. Furthermore, the serum from Omicron BA.1 variant-infected hamsters were insufficient to protect against rechallenge of SARS-CoV-2 Prototype, Beta and Delta variants and itself. Importantly, we found that rechallenge with different SARS-CoV-2 lineages elevated cross-variant serum neutralization titers. Overall, our findings indicate a weakened immunogenicity feature of Omicron BA.1 variant that can be overcome by rechallenge of a different SARS-CoV-2 lineages. Our results may lead to a new guideline in generation and use of the vaccinations to combat the pandemic of SARS-CoV-2 Omicron variant and possible new variants. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant causes breakthrough infections among convalescent patients and vaccinated populations. However, Omicron does not generate robust cross-protective responses. Here, we investigate whether heterologous SARS-CoV-2 challenge is able to enhance antibody response in a sensitive animal model, namely, Syrian hamster. Of note, a heterologous challenge of Beta and Omicron BA.1 variant significantly broadens the breadth of SARS-CoV-2 neutralizing responses against the prototype, Beta, Delta, and Omicron BA.1 variants. Our findings confirm that vaccination strategy with heterologous antigens might be a good option to protect against the evolving SARS-CoV-2.
Topics: Animals; Cricetinae; Antibodies, Neutralizing; Antibodies, Viral; Antigens, Heterophile; Breakthrough Infections; COVID-19; Mesocricetus; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Immunogenicity, Vaccine
PubMed: 36651747
DOI: 10.1128/jvi.01684-22 -
EJIFCC Dec 2022Isolated increase in thyrotropin stimulating hormone (TSH) in a clinically euthyroid patient may be caused by the formation of a macromolecule between TSH and...
Isolated increase in thyrotropin stimulating hormone (TSH) in a clinically euthyroid patient may be caused by the formation of a macromolecule between TSH and autoantibodies causing discordant thyroid function test results. Despite the effort to eliminate interferences in immunoassays, these assays are still vulnerable to different interferences. Immunoassay interferences may cause erroneous results and lead to misdiagnosis which may subject a patient to unnecessary investigations and treatment. Immunoassays are affected by multiple substances; these may be endogenous or exogenous such as heterophile antibodies, autoantibodies, macromolecules, and human anti-mouse antibodies. This case reports a 47-year-old African woman who presented with a persistent elevated TSH with thyroid hormones within normal reference limits. She was found to have a macro-TSH which was associated with IgA paraprotein.
PubMed: 36605299
DOI: No ID Found