Background
The diagnosis of systemic autoimmune rheumatic diseases (SARD) is based on the detection of serum antinuclear antibodies (ANA) for which indirect immunofluorescence (IIF) is the golden ...standard. New solid‐phase immunoassays have been developed to be used alone or in combination with the detection of extractable antinuclear antibodies (ENA) to improve SARD diagnosis. The purpose of this study was to compare the clinical performances of different ANA screening methods alone or in combination with ENA screening methods for SARD diagnosis.
Methods
A total of 323 patients were screened for ANA by IIF, EliA™ CTD Screen, and ELISA methods. Agreements were calculated between the methods. Then, EliA™ CTD Screen positive samples were screened for ENA by line immunoassay (LIA) and fluorescence enzyme immunoassay (FEIA).
Results
The diagnostic accuracy of EliA™ CTD Screen (79% sensitivity and 91% specificity) was better than that of ELISA or IIF. The combination of EliA™ CTD plus IIF had the highest sensitivity (93%). ENA determination revealed that Ro52 and Ro60 were the most prevalent specificities. The use of IIF alone was not able of detecting up to 36% of samples positive for Ro52, and 41% for Ro60.
Conclusions
EliA™ CTD Screen has a better diagnostic performance when compared to IIF and ELISA. The combined use of EliA™ CTD Screen and IIF clearly improves the rate and accuracy of SARD diagnosis. The use of EliA™ CTD Screen as first‐line screening technique allows the detection of antibodies, which could not be detected by IIF alone.
There is still room for improvement in ANA screening testing. Currently there are different methods available for systemic autoimmune rheumathic disease sift, but the optimization of screening protocols does not only rely on the selection of the best method–there is no perfect test‐ but in the detection of the optimal combination for the specific laboratory routine. In our study we compared the performance of two protocols in our routine samples: solid phase test+IIF and ELISA+IIF. IIF together with EliA CTD Screen (solid phase test) resulted in the highest sensitivity, while EliA CTD Screen showed the best sensitivity/specificity balance.
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a disease (coronavirus disease 2019, COVID-19) that may develop into a systemic disease with immunosuppression and ...death in its severe form. Myeloid-derived suppressive cells (MDSCs) are inhibitory cells that contribute to immunosuppression in patients with cancer and infection. Increased levels of MDSCs have been found in COVID-19 patients, although their role in the pathogenesis of severe COVID-19 has not been clarified. For this reason, we raised the question whether MDSCs could be useful in the follow-up of patients with severe COVID-19 in the intensive care unit (ICU). Thus, we monitored the immunological cells, including MDSCs, in 80 patients admitted into the ICU. After 1, 2, and 3 weeks, we examined for a possible association with mortality (40 patients). Although the basal levels of circulating MDSCs did not discriminate between the two groups of patients, the last measurement before the endpoint (death or ICU discharge) showed that patients discharged alive from the ICU had lower levels of granulocytic MDSCs (G-MDSCs), higher levels of activated lymphocytes, and lower levels of exhausted lymphocytes compared with patients who had a bad evolution (death). In conclusion, a steady increase of G-MDSCs during the follow-up of patients with severe COVID-19 was found in those who eventually died.
Context:
Cushing's syndrome (CS) is challenging to diagnose. Increased prevalence of CS in specific patient populations has been reported, but routine screening for CS remains questionable. To ...decrease the diagnostic delay and improve disease outcomes, simple new screening methods for CS in at-risk populations are needed.
Objective:
To develop and validate a simple scoring system to predict CS based on clinical signs and an easy-to-use biochemical test.
Design:
Observational, prospective, multicenter.
Setting:
Referral hospital.
Patients:
A cohort of 353 patients attending endocrinology units for outpatient visits.
Interventions:
All patients were evaluated with late-night salivary cortisol (LNSC) and a low-dose dexamethasone suppression test for CS.
Main Outcome Measures:
Diagnosis or exclusion of CS.
Results:
Twenty-six cases of CS were diagnosed in the cohort. A risk scoring system was developed by logistic regression analysis, and cutoff values were derived from a receiver operating characteristic curve. This risk score included clinical signs and symptoms (muscular atrophy, osteoporosis, and dorsocervical fat pad) and LNSC levels. The estimated area under the receiver operating characteristic curve was 0.93, with a sensitivity of 96.2% and specificity of 82.9%.
Conclusions:
We developed a risk score to predict CS in an at-risk population. This score may help to identify at-risk patients in non-endocrinological settings such as primary care, but external validation is warranted.
A prediction model for Cushing's syndrome diagnosis in at-risk populations was developed based on clinical variables and late night salivary cortisol levels.
Zinc transporter 8 autoantibodies (ZNt8A) are 1 of the 4 main autoantibodies used for the diagnosis of type 1 diabetes (T1D), with glutamic acid decarboxylase autoantibodies (GADA), islet antigen-2 ...autoantibodies (IA-2A), and insulin autoantibodies (IAA). The objective of this study is to evaluate the diagnostic efficiency of these autoantibodies for the diagnosis of T1D in pediatric patients.
A retrospective analysis of patients under 16 years of age with suspected T1D was made between June 2020 and January 2021. A total of 80 patients were included in the study, with 1 sample per patient. Subjects were classified according to diagnosis.
Of the subjects included in the study, 50 developed T1D. The diagnostic efficacy was IA-2A (cutoff ≥ 28 U/L) sensitivity 0.26 (95% CI: 0.14-0.38) and specificity 0.97 (95% CI: 0.79-1.0); GADA (cutoff ≥ 17 U/mL) sensitivity 0.40 (95% CI: 0.26-0.54) and specificity 0.87 (95% CI: 0.75-0.99); ZnT8A (cut off ≥ 15 U/L) sensitivity 0.62 (95% CI: 0.49-0.75) and specificity 0.97 (95% CI: 0.90-1.0). ZnT8A obtained the most significantly global diagnostic accuracy (0.75), and GADA with ZnT8A showed the highest correlation.
The results obtained indicate a higher efficiency of anti-ZnT8 autoantibodies for the diagnosis of T1D in pediatric patients. Clinical efficiency of diabetic autoantibodies is method and assay dependent and influences combined diagnostic strategies.
The definition of Insulin autoimmune syndrome includes the presence of high levels of blood insulin and insulin autoantibodies. We encountered a 45-years-old white man with a high insulin serum value ...that do not fit with the C-peptide result. To discard or to confirm an analytical interference and diagnose a possible Insulin Autoimmune Syndrome we performed the following investigations: dilution linearity test, heterophilic antibody blocking, polyethylene glycol precipitation, measurements with alternative assays, and gel filtration chromatography by size exclusion. The latter technique confirmed that most of the insulin was complexed with a 150-kDa protein, corresponding to immunoglobulin G, identified as insulin autoantibodies. These antibodies were responsible for hypoglycemia attacks in the patient, who had a previous autoimmune disease. This case highlights the importance of carefully analyzing the results and ruling out possible interferences, as well as considering all kinds of pathologies, even if they are infrequent.
S100B is a calcium-binding protein released into the blood from astroglial cells due to brain injury. Some authors have described a correlation between S100B serum concentration and severity of brain ...damage. There is not much information about the accuracy of urinary S100B for predicting outcome after severe traumatic brain injury (TBI). 55 patients with severe TBI were included in the study. Blood and urine samples were drawn to determine S100B levels on admission and on the subsequent 24, 48, 72 and 96h. S100B concentrations (serum and urine) were significantly higher in patients who were dead a month after the accident compared to survivors. ROC-analysis showed that S100B at 24h post-severe TBI is a useful tool for predicting mortality (serum: AUC 0.958, urine: AUC 0.778). The best cut-offs for S100B were 0.461μg/L and 0.025μg/L (serum and urine respectively), with a sensitivity of 90% for both measurements and a specificity of 88.4% (serum) and 62.8% (urine). We can state that the determination of S100B levels both in urine and serum acts as a sensitive and an effective biomarker for the early prediction of mortality after severe TBI.
► Blood and urine samples were drawn on admission and every 24h up to 4days. ► Serum and urine S100B levels were higher in patients dead within a month of trauma. ► S100B in serum and urine at 24h post-severe TBI is useful for predicting mortality. ► S100B acts as a sensitive biomarker for the prediction of mortality after severe TBI.
Despite improvements in the process of organ donation and transplants, the number of organ donors is progressively declining in developed countries. Therefore, the early detection of patients at risk ...for brain death (BD) is a priority for transplant teams seeking more efficient identification of potential donors. In the extensive literature on S100B as a biomarker for traumatic brain injury (TBI), no evidence appears to exist on its prognostic capacity as a predictor of BD after severe TBI. The objective of this study is to assess the value of including acute S100B levels in standard clinical data as an early screening tool for BD after severe TBI. This prospective study included patients with severe TBI (Glasgow Coma Scale score GCS ≤ 8) admitted to our Neurocritical Care Unit over a 30 month period. We collected the following clinical variables: age, gender, GCS score, pupillary alterations at admission, hypotension and pre-hospital desaturation, CT scan results, isolated TBI or other related injuries, Injury Severity Score (ISS), serum S100B levels at admission and 24 h post-admission, and a final diagnosis regarding BD. Of the 140 patients studied, 11.4% developed BD and showed significantly higher S100B concentrations (p<0.001). Multivariate analysis showed that bilateral unresponsive mydriasis at admission and serum S100B at 24 h post-admission had odds ratios (ORs) of 21.35 (p=0.005) and 4.9 (p=0.010), respectively. The same analysis on patients with photomotor reflex in one pupil at admission left only the 24 h S100B sample in the model (OR=15.5; p=0.009). Receiver operating characteristics (ROC) curve analysis on this group showed the highest area under the curve (AUC) (0.86; p=0.001) for 24 h S100B determinations. The cut off was set at 0.372 μg/L (85.7% sensitivity, 79.3% specificity, positive predictive value PPV=18.7% and negative predictive value NPV=98.9%). This study shows that pupillary responsiveness at admission, as well as 24 h serum S100B levels, could serve as screening tools for the early detection of patients at risk for BD after severe TBI.
Cardiovascular diseases continue to lead the ranking of mortality in Spain. The implementation of geostatistical analysis techniques in the clinical laboratory are innovative tools that allow the ...design of new strategies in primary prevention of cardiovascular disease. The aim of this study was to study the prevalence and geolocation of severe dyslipidemia in the health areas under study in order to implement prevention strategies in primary care. A retrospective cohort study of low-density protein-bound cholesterol, triglyceride and lipoprotein (a) levels in the years 2019 and 2020 were carried out. In addition, a geostatistical analysis was performed including representation in choropleth maps and the detection of clustering clusters, using geographic information in zip code format included in the demographic data of each analytic.
The analytical data included in the study were triglycerides (n=365,384), low density protein-bound cholesterol (n=289,594) and lipoprotein to lipoprotein (a) (n=502). Areas with the highest and lowest percentage of cases were identified for the established cut-off points of LDL-C>190mg/dL and TG>150mg/dL. Two clustering clusters with statistical significance were detected for cLDL>190mg/dL and a total of 6 clusters for TG values>150mg/dL.
The detection of clusters, as well as the representation of choropleth maps, can be of great help in detecting geographic areas that require greater attention to intervene and improve cardiovascular risk.
Noonan syndrome (NS) is a genetic disorder characterized by a wide range of distinctive features and health problems. It caused in 50% of cases by missense mutations in PTPN11 gene. It has been ...postulated that it is possible to predict the disease course based into the impact of mutations on the protein.
We report two cases of severe NS phenotype including hydrops fetalis. PTPN11 gene was studied in germinal cells of both patients by sequencing.
Two different mutations (p.Gly503Arg and p.Met504Val) was detected in PTPN11 gene.
These mutations have been reported previously, and when they were germinal variants, patients presented classic NS, NS with other malignancies and recently, p.Gly503Arg has been also observed in a patient with severe NS and hydrops fetalis, as our cases. Therefore, these observations shade light on that it is not always possibly to determine the genotype-phenotype relation based into the impact of mutations on the protein in NS patients with PTPN11 mutations.
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