Complementary Markers Research Articles

Thrombotic and Atherogenetic Predisposition in Polyglobulic Donors.

This work analyses the results of research regarding the predisposition of genetic hematological risks associated with secondary polyglobulia. The subjects of the study were selected based on shared laboratory markers and basic clinical symptoms. JAK2 (Janus Kinase 2) mutation negativity represented the common genetic marker of the subjects in the sample of interest. A negative JAK2 mutation hypothetically excluded the presence of an autonomous myeloproliferative disease at the time of detection. The parameters studied in this work focused mainly on thrombotic, immunological, metabolic, and cardiovascular risks. The final goal of the work was to discover the most significant key markers for the diagnosis of high-risk patients and to exclude the less important or only complementary markers, which often represent a superfluous economic burden for healthcare institutions. These research results are applicable as a clinical guideline for the effective diagnosis of selected parameters that demonstrated high sensitivity and specificity. According to the results obtained in the present research, groups with a high incidence of mutations were evaluated as being at higher risk for polycythemia vera disease. It was not possible to clearly determine which of the patients examined had a higher risk of developing the disease as different combinations of mutations could manifest different symptoms of the disease. In general, the entire study group was at risk for manifestations of polycythemia vera disease without a clear diagnosis. The group with less than 20% incidence appeared to be clinically insignificant for polycythemia vera testing and thus there is a potential for saving money in mutation testing. On the other hand, the JAK V617F (somatic mutation of JAK2) parameter from this group should be investigated as it is a clear exclusion or confirmation of polycythemia vera as the primary disease.

Post-Reperfusion Pulmonary Artery Pressure is a Clinical Marker of Primary Graft Dysfunction Risk Following Lung Transplant

<h3>Purpose</h3> Primary graft dysfunction is a known risk factor of early mortality after lung transplant (LT). PGD represents ischemia-reperfusion injury in the allograft, which subsequently causes capillary leaks. Clinical models which identify patients at high risk for PGD are limited. We hypothesize high systolic pulmonary artery pressure (sPA pressure) after reperfusion in LT is a clinical marker for those at risk of developing PGD. <h3>Methods</h3> This is a retrospective review of a single site institutional lung transplant database. We included consecutive lung transplant patients from March 2020 through September 2021. Only double lung transplant patients were included, and patients with pre-transplant ECMO use were excluded as ECMO flow could impact sPA pressures. PGD was defined according to modified ISHLT criteria. Receiver operating characteristic (ROC) curve was used to find the cut off value for PGD. <h3>Results</h3> 51 patients were included in this study. PGD occurred in 43.1% (n = 22). One-year survival was reduced in recipients with PGD (p=0.005). The ROC curve of post-reperfusion sPA pressures showed 41 mmHg was the cut off for PGD (sensitivity 0.89, specificity 0.72, area under curve (AUC) 0.84), which is significantly superior to the ROC curve of pre-LT sPA pressures (sensitivity 0.44, specificity 0.68, AUC 0.54, p<0.01). The ROC curve of the difference between patient pre- and post-reperfusion sPA pressures has a sensitivity 0.86, specificity 0.68, AUC 0.71. <h3>Conclusion</h3> Patients with elevated sPA pressure after reperfusion are at increased risk of PGD after LT. Post-reperfusion sPA pressure is more indicative of PGD risk than pre-LT sPA pressure. Using post-reperfusion sPA pressure as a complementary clinical marker of PGD would allow earlier intervention in PGD, which could subsequently improve survival in these LT patients.

The albumin to globulin ratio is associated with clinical outcome in Japanese patients with ulcerative colitis.

The albumin to globulin ratio (AGR) is a recognized chronic inflammation marker. No evidence regarding the relationship between AGR level and ulcerative colitis (UC) exists. The aim of this study was to evaluate the association between AGR and clinical outcomes among Japanese subjects with UC. The study subjects consisted of 273 Japanese individuals with UC. AGR was divided into 4 categories (low, moderate, high, and very high). The definition of complete mucosal healing (MH) was based on the Mayo endoscopic subscore of 0. Clinical remission (CR) was defined as no rectal bleeding and no abnormally high stool frequency (<3 times per day). The percentage of MH was 26.4%. High AGR and very high AGR were significantly positively correlated with CR (adjusted odds ratio [OR], 5.85; 95% confidence interval [CI], 2.52-14.18 and adjusted OR, 4.97; 95% CI, 2.14-12.04) and complete MH (adjusted OR, 4.03; 95% CI, 1.56-11.51 and adjusted OR, 5.22; 95% CI, 1.97-14.89), respectively after adjustment for confounding factors (P for trend=0.001). Only in the low C-reactive protein (CRP) group (≤0.1 mg/dL), very high AGR was significantly positively correlated with complete MH but not CR (adjusted OR, 4.38; 95% CI, 1.06-21.77; P for trend=0.017). In the high CRP group, no correlation between AGR and complete MH was found. Among Japanese patients with UC, AGR may be independently positively correlated with complete MH. In particular, among UC patients with low CRP, AGR might be a useful complementary marker for complete MH.

The potential use of mitochondrial ribosomal genes (12S and 16S) in DNA barcoding and phylogenetic analysis of trematodes

BackgroundGenetic markers like the nuclear ribosomal RNA (rRNA) genes, internal transcribed spacer regions, mitochondrial protein-coding genes, and genomes have been utilized for molecular identification of parasitic trematodes. However, challenges such as the design of broadly applicable primers for the vast number of species within Digenea and the genetic markers’ ability to provide sufficient species-level resolution limited their utility. This study presented novel and broadly applicable primers using the mitochondrial 12S and 16S rRNA genes for Digenea and aimed to show their suitability as alternative genetic markers for molecular identification of orders Plagiorchiida, Echinostomida, and Strigeida.ResultsOur results revealed that the mitochondrial 12S and 16S rRNA genes are suitable for trematode molecular identification, with sufficient resolution to discriminate closely related species and achieve accurate species identification through phylogenetic placements. Moreover, the robustness of our newly designed primers to amplify medically important parasitic trematodes encompassing three orders was demonstrated through successful amplification. The convenience and applicability of the newly designed primers and adequate genetic variation of the mitochondrial rRNA genes can be useful as complementary markers for trematode molecular-based studies.ConclusionsWe demonstrated that the mitochondrial rRNA genes could be alternative genetic markers robust for trematode molecular identification and potentially helpful for DNA barcoding where our primers can be widely applied across the major Digenea orders. Furthermore, the potential of the mitochondrial rRNA genes for molecular systematics can be explored, enhancing their appeal for trematode molecular-based studies. The novelty of utilizing the mitochondrial rRNA genes and the designed primers in this study can potentially open avenues for species identification, discovery, and systematics in the future.

The Role of Neutrophil Lymphocyte Ratio , Vitamin D, and NGAL as Cardiovascular Disease Marker in Chronic Kidney Disease

Chronic kidney disease (CKD) patients have higher risk to develop cardiovascular disease (CVD) than non-CKD patients. Neutrophil lymphocyte ratio (NLR) in CKD patients reflects inflammation status and role as complementary prognostic marker to evaluate cardiovascular risk in stage 3 to 5 CKD. High prevalence of vitamin D deficiency commonly found in CKD patients, leads to endothelial dysfunction and increase inflammation. NGAL is used as renal injury biomarker but nowadays NGAL has been known plays important role in CVD pathophysiology. CVD identification in CKD patients is necessary to obtain CVD risk and to stratify mortality earlier in CKD patients. This study aimed to obtain the differences and continued to obtain cut off of NLR, vitamin D and NGAL in CKD patients undergoing hemodialysis (HD) with and without CVD if the differences was significantly. A cross-sectional study was conducted in dr. Cipto Mangunkusumo National Hospital Jakarta, in December- February 2020. Total subjects were 83, consists of two groups with and without the CVD. There were no significant differences of NLR and vitamin D in CKD patients undergoing hemodialysis (HD) with and without CVD. The significant difference was found only in NGAL with cut off 5.64 ng/ml. NLR was lower, meanwhile vitamin D and NGAL were higher in CKD patients undergoing HD with and without CVD.

SOX11 is a sensitive and specific marker for pulmonary high-grade neuroendocrine tumors

BackgroundSynaptophysin (SYN), chromogranin A (CGA), CD56 and insulinoma-associated protein 1 (INSM1) are proposed neuroendocrine (NE) markers used for diagnosis of pulmonary NE tumors. These NE markers have been identified in subsets of non-NE tumors requiring differential diagnosis, thus we sought to explore new NE markers.MethodsWe evaluated the immunohistochemical expression of SOX11, a transcription factor involved in neurogenesis, in pulmonary NE tumors and large cell carcinomas (LCCs).ResultsWe found that SOX11 showed a sensitivity similar to INSM1 and CGA, and less than SYN and CD56 in small cell lung carcinomas (SCLCs) and large cell neuroendocrine carcinomas (LCNECs). While SOX11 is more specific than the other four markers for diagnosis of high-grade neuroendocrine carcinomas (HG-NECs) because 1) None of LCCs (0/63), the most challenging non-NE tumor type for differential diagnosis due to overlapped morphology with LCNECs displayed SOX11 positivity. While expression of at least one of SYN, CGA, CD56 or INSM1 was identified in approximately 60% (18/30) of LCCs. 2) SOX11 was only expressed in 1 of 37 carcinoid tumors in contrast to diffuse expression of SYN, CGA, CD56 and INSM1. In HG-NECs, we noticed that SOX11 was a good complementary marker for SCLC diagnosis as it was positive in 7 of 18 SYN−/CGA−/CD56− SCLCs and 3 of 8 SYN−/CGA−/CD56−/INSM1− SCLCs, and SOX11 positivity in 4 of 6 SYN−/CGA−/CD56− cases previously diagnosed as LCCs with NE morphology provides additional evidence of NE differentiation for reclassification into LCNECs, which was further confirmed by electromicroscopical identification of neurosecretory granules. We also found SOX11 expression cannot predict the prognosis in patients with HG-NECs.ConclusionsTherefore, SOX11 is a useful complementary transcriptional NE marker for diagnosis and differential diagnosis of SCLC and LCNEC.

The Importance of Complementary Immunological Markers in the Diagnosis of Minimal Residual Disease in Multiple Myeloma

Background. The population of non-tumor plasma cells in healthy subjects’ bone marrow is known to be fairly heterogeneous. Among them, there may be a small number of CD19-, CD56+, CD45- plasma cells which differ from the main bulk of the normal plasmacytic cells by the lack of CD19 and CD45 expression and the presence of CD56 expression. It is the fact which makes the monitoring of minimal residual disease (MRD) especially challenging in multiple myeloma (MM) since normal and aberrant plasma cells should be compared. For this reason, a study of such complementary diagnostic markers as CD27, CD28, CD117, and CD81 is extremely important. Aim. To analyze the role of complementary diagnostic markers (CD27, CD28, CD117, and CD81) of MRD in MM patients at different disease stages. Materials &amp; Methods. The present study enrolled 62 MM patients aged 31-76 years (median 58 years); 25 women and 37 men. The analysis focused on morphological and immunophenotypic properties of bone marrow plasma cells. MRD was detected by 8-color flow cytometry with the use of FACSCanto II Flow Cytometer (USA) based on EuroFlow standards. Results. At the stage of primary diagnosis of MM, the imunophenotype of plasma cells was analyzed in all 62 patients using two 8-color panels recommended by the EuroFlow Consortium (2012). In accordance with primary immunophenotyping data, MRD was evaluated on the basis of not only the main diagnostic markers of plasma cells (CD38, CD138, CD45, CD56, and CD19), but also the complementary ones, such as CD27, CD28, CD117, and CD81. The study was basically conducted after induction therapy and upon remission. With cut-off &gt; 0.01 % of aberrant plasma cells, the MRD incidence was the following: 91.0 % with CD27, 90.6 % with CD28, 87.0 % with CD117, and 96.7 % with CD81 markers. Respectively, no MRD was detected in 9.0 % with CD27, 9.4 % with CD28, 13.0 % with CD117, and 3.3 % with CD81 markers.

Correlated MR spectroscopic imaging of breast cancer to investigate metabolites and lipids: acceleration and compressed sensing reconstruction.

The main objective of this work was to detect novel biomarkers in breast cancer by spreading the MR spectra over two dimensions in multiple spatial locations using an accelerated 5D EP-COSI technology. The 5D EP-COSI data were non-uniformly undersampled with an acceleration factor of 8 and reconstructed using group sparsity-based compressed sensing reconstruction. Different metabolite and lipid ratios were then quantified and statistically analyzed for significance. Linear discriminant models based on the quantified metabolite and lipid ratios were generated. Spectroscopic images of the quantified metabolite and lipid ratios were also reconstructed. The 2D COSY spectra generated using the 5D EP-COSI technique showed differences among healthy, benign, and malignant tissues in terms of their mean values of metabolite and lipid ratios, especially the ratios of potential novel biomarkers based on unsaturated fatty acids, myo-inositol, and glycine. It is further shown the potential of choline and unsaturated lipid ratio maps, generated from the quantified COSY signals across multiple locations in the breast, to serve as complementary markers of malignancy that can be added to the multiparametric MR protocol. Discriminant models using metabolite and lipid ratios were found to be statistically significant for classifying benign and malignant tumor from healthy tissues. Accelerated 5D EP-COSI technique demonstrates the potential to detect novel biomarkers such as glycine, myo-inositol, and unsaturated fatty acids in addition to commonly reported choline in breast cancer, and facilitates metabolite and lipid ratio maps which have the potential to play a significant role in breast cancer detection. This study presents the first evaluation of a multidimensional MR spectroscopic imaging technique for the detection of potentially novel biomarkers based on glycine, myo-inositol, and unsaturated fatty acids, in addition to commonly reported choline. Spatial mapping of choline and unsaturated fatty acid ratios with respect to water in malignant and benign breast masses are also shown. These metabolic characteristics may serve as additional biomarkers for improving the diagnostic and therapeutic evaluation of breast cancer.

Associations of systemic inflammatory markers with the risks of chronic heart failure: A case-control study

ObjectiveAs a greater proportion of patients survived their initial cardiac insult, Chronic Heart Failure (CHF) is becoming a major cause of worldwide morbidity and mortality. However, the mechanism underlying the inflammation in patients with CHF has not yet been elaborated. This study aims to explore the associations between inflammation and CHF patients, and the predictive performance of inflammatory indicators in identifying patients with CHF. MethodsA matched case-control study was conducted by recruiting 385 patients who were diagnosed with CHF from January 2018 to December 2019 in The First Affiliated Hospital of Chongqing Medical University. Each CHF patient was matched against one control subject without CHF on the criteria of age, sex, Body Mass Index (BMI), smoking status, and comorbidities. The clinical data and systemic inflammatory indicators were compared between the two groups, independent risk factors of CHF were identified by multivariate regression analysis, and the predictive values of systemic inflammatory indicators for CHF were analyzed by Receiver Operating Characteristic (ROC) curve analysis. ResultsAfter processed in the univariate and multivariate regression analysis models, three systemic inflammatory indicators (hs-CRP [high sensitivity C Reactive Protein], LMR [lymphocyte-to-monocyte ratio], and Monocyte-to-High-density-lipoprotein Ratio [MHR]) were considered as independent predictors of CHF, among which the hs-CRP exhibited the best predictive performance (AUC = 0.752, 95%CI 0.717‒0.786, p < 0.001), followed by LMR (AUC = 0.711, 95% CI 0.675‒0.747, p < 0.001) and MHR (AUC = 0.673, 95% CI 0.635‒0.710, p < 0.001). The three-indicator combination showed an improved diagnostic performance (AUC = 0.757, 95% CI 0.724‒0.791, p < 0.001). In addition, the results of subgroup comparisons demonstrated that hs-CRP and MHR were associated with the severity of CHF (p < 0.001). ConclusionsThe systemic inflammatory indicators such as hs-CRP, LMR, and MHR were independently correlated with the attack of CHF and might be the complementary markers of the diagnosis of CHF.

Myocardial Composition in Light-Chain Cardiac Amyloidosis More Than 1 Year After Successful Therapy

ObjectivesThe goals of this study were to characterize myocardial composition during the active and remission phases of light-chain (AL) cardiac amyloidosis. BackgroundCardiac dysfunction in AL amyloidosis is characterized by dual insults to the myocardium from infiltration and toxicity from light chains during the active phase and by infiltration alone in the remission phase. MethodsProspectively enrolled subjects with cardiac AL amyloidosis (21 remission AL amyloidosis; age: 63.4 ± 7.3 years; 47.6% male; and 48 active AL amyloidosis; age: 62.5 ± 7.4 years; 60.4% male) underwent contrast-enhanced cardiac magnetic resonance with T1 and T2 mapping and measurement of extracellular volume (ECV). By definition, serum free light-chain levels were normal for at least 1 year following successful AL therapy in the remission group and abnormal in the active group. ResultsMyocardial ECV was similarly expanded in the remission and active AL amyloidosis groups (0.488 ± 0.082 vs 0.519 ± 0.083, respectively; P = 0.15). However, myocardial T2 relaxation times (47.7 ± 3.2 ms vs 45.5 ± 3.0 ms; P = 0.008) as well as native T1 times (1,368 ms [IQR: 1,290-1,422 ms] vs 1,264 ms [IQR: 1,203-1,380 ms]; P = 0.024) were significantly higher in the remission compared to the active AL amyloidosis group. ConclusionsMyocardial ECV is substantially expanded in the active AL and remission AL cardiac amyloidosis groups, but native T1 values were higher, suggesting a different myocardial composition. There is no evidence of myocardial edema in active AL cardiac amyloidosis. Future phenotyping studies of AL cardiac amyloidosis need to consider complementary myocardial markers that define the interstitial milieu in addition to changes in extracellular volume. (Molecular Imaging of Primary Amyloid Cardiomyopathy; NCT02641145)

Association between serum netrin-1, netrin-4 and risk of the acute coronary syndrome in patients with type 2 diabetes mellitus-A pilot study

The present study was done to assess the diagnostic utility of serum netrin-1 and netrin-4 for recognising the acute coronary syndrome (ACS) in type 2 diabetes mellitus (T2DM) patients. Forty-two T2DM patients with ACS (Cases) and forty-two T2DM patients without ACS (Controls) were compared. Cases had lower serum netrin-1 and netrin-4 levels than controls and were negatively associated with creatinine kinase-total, creatinine kinase-MB, troponin-T and H-FABP. ROC analysis showed that netrin-1 and netrin-4 had good sensitivity and specificity for ACS prediction in T2DM patients. Serum netrin-1 and netrin-4 levels might be considered complementary markers for ACS diagnosis in T2DM patients.

Development and analytical characterization of novel tau Simoa assays targeting full‐length tau in CSF and mid‐tau in CSF and plasma

AbstractBackgroundBiofluid markers of neurodegeneration and neural injury have great potential to elucidate disease mechanisms and accelerate development of experimental therapeutics. Cerebrospinal fluid (CSF) tau and phosphorylated tau are established biomarkers for AD, while plasma (N‐terminal) tau and phosphorylated tau (p‐tau) are being evaluated as complementary markers in a more accessible biofluid.Tau is present in CSF and plasma in both full‐length and truncated forms, with great interest in characterizing and advancing these different forms as biomarkers to support clinical development. To contribute to the emerging research on tau fragments as biomarker, novel ultra‐sensitive immunoassays were developed targeting low‐abundant, non‐truncated full‐length (FL) tau in CSF and a mid‐region tau fragment in CSF and plasma.MethodSimoa assays were developed using monoclonal antibodies (mAbs) targeting mid‐region tau epitopes or epitopes on full‐length tau.Resulting assays were qualified and partially validated for analytical performance parameters: measuring range, specificity, repeatability, reproducibility and parallelism were assessed. Reagent and analyte stability were investigated by assessing hold time and freeze/thaw (F/T) stability. Paired clinical routine CSF and plasma samples were analysed (20 controls and 20 AD based upon CSF Aβ1‐42, t‐tau and p‐tau(T181) profile).ResultFL‐ and mid‐tau Simoa assays were analytically characterized, upscaled to bulk volumes and partially validated. Both assays had acceptable repeatability and reproducibility (%CV &lt;20%) for plasma and/or CSF. Parallelism was within acceptance criteria (ACC of 75‐125%; %CV &lt;20%) for FL‐tau in 4 CSF samples and for mid‐tau in 4 CSF and 4 plasma samples. Analyte stability was demonstrated up to 5 F/T cycles and for a hold‐time of 24h at 21°C with a %CV&lt;20%. Testing of clinical samples showed an increased CSF FL‐ (p&lt;0.005) and mid‐Tau (p&lt;0.0001) concentration in AD versus controls, whereas plasma mid‐tau did not increase.ConclusionA novel CSF assay for full length tau and a novel CSF/plasma assay for the mid‐tau fragment was developed, qualified and partially validated. The generated data indicated well‐performing tau assays available as RUO kits in pre‐clinical and clinical use in drug development programs.

Plasma Hemoglobin and Red Blood Cell Mass Levels as Dynamic Prognostic Markers for Progression and Survival in Pancreatic Neuroendocrine Tumors.

There are scarce data on readily available markers enabling immediate risk stratification and personalized management in patients with advanced pancreatic neuroendocrine tumors. This study explores the association of red blood cells-related parameters as prognostic markers in patients harboring pancreatic neuroendocrine tumors. Retrospective analysis of a tertiary medical center database, acquiring data of patients with pancreatic neuroendocrine tumors including demographics, tumor-related parameters and consecutive imaging results, vital status at last follow-up, and red blood cells parameters at baseline, last follow-up, and dynamics (last/baseline ratio). Univariate and multivariable analyses were performed. Sixty-seven patients were identified (mean age at diagnosis of 63±11 years, 56.7% males). Patients with disease progression had lower hemoglobin, red blood cells mass values and hematocrit at the last evaluation (p<0.001 for all comparisons), with red blood cells mass level<3.9 m/μl and a 6% and 9% relative reduction in hemoglobin and hematocrit levels, respectively, associated with an increased risk for disease progression. Similarly, patients deceased during the study period had lower hemoglobin, red blood cells mass values and hematocrit (p<0.03 for all) than those alive, at last follow-up. Eleven percent reduction in hemoglobin level was noted indicating a higher mortality risk (p=0.04). Negative hemoglobin and hematocrit dynamics were independently associated with increased risk for disease progression (p=0.03 and 0.049, respectively). In conclusion, decrease in red blood cells mass, hemoglobin and/or hematocrit levels are all associated with poor prognosis in patients with pancreatic neuroendocrine tumors. We suggest utilizing these parameters as complementary follow-up prognostic markers to radiologic imaging in this patients population.

TSPO and P2X7 discriminate between amyloid‐ and tau‐induced glial responses

AbstractBackgroundCurrent clinical PET imaging relies on translocator protein (TSPO) to detect neuroinflammation in brain disorders including degenerative conditions such as AD, however this marker lacks cell type‐specificity and offers no information on what type of insult is causing the reaction. An ideal PET tracer would detect both the rise in pro‐inflammatory and loss of anti‐inflammatory glial responses and would discriminate cellular responses to amyloid‐beta from tau. We investigated whether a pair of glial purinergic receptors would provide a better measure of inflammatory status in mouse models of AD than the current standard TSPO.MethodWe studied the expression of P2X7, P2Y12, and TSPO in 5xFAD and PS19 transgenic mice at early and late stages of pathology using quantitative immunohistochemistry. Co‐staining with microglial (Iba1) and astroglial (GFAP) markers was used to identify cell types expressing each receptor.ResultExpression of P2Y12 decreased significantly with the onset of both Aβ and tau pathology. TSPO increased in 5xFAD mice with amyloid pathology, but not in PS19 mice with tau pathology. We observed the opposite pattern in P2X7 signal, which increased in PS19 mice with tau pathology, but less in 5xFAD mice with amyloid plaques.ConclusionOur findings suggest there may be distinct neuroinflammatory responses to Aβ and tau with increased TSPO around amyloid but not tau, and a reciprocal increase in P2X7 around tau but not amyloid. We found that P2Y12 and P2X7 serve as complementary markers reflecting the loss of homeostatic microglia and the rise of a reactive phenotype. Our results support continued investigation of P2Y12 and P2X7 as potential biomarkers of distinct neuroinflammatory responses which may be used in conjunction with TSPO to distinguish AD pathologies in clinical settings.

Neutrophil-lymphocyte, platelet-lymphocyte and lymphocyte-monocyte ratios may not be useful markers to assess disease activity in rheumatoid arthritis: A STROBE-compliant article.

The associations among the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR) and disease activity in rheumatoid arthritis remains unclear.To evaluate these indicators as potential markers of disease activity in patients with rheumatoid arthritis (RA).This cross-sectional study included 547 adult patients with RA. The patients were divided into two groups according to the disease activity score (DAS) system: remission and disease activity. Differences in the NLR, PLR and LMR of the two groups were assessed. Correlations were analyzed using Spearman analysis, and receiver operating characteristic (ROC) curves were used to identify the sensitivity, specificity, and optimal cutoff values to differentiate active RA patients from inactive RA patients.There was a statistically significant difference in the NLR (4.2 ± 3.2 vs 3.4 ± 2.4, P = .034) and PLR (222.3 ± 136.4 vs 176.9 ± 89.8, P = .006) between the two groups, but not for the LMR (3.0 ± 1.8 vs 3.4 ± 2.4, P = .115). In addition, the DAS28 and traditional inflammatory markers, including ESR and CRP, were weakly positively correlated with the NLR and PLR. Based on the ROC curves, the NLR (sensitivity 31.8%, specificity 77.8%) and PLR (sensitivity 57.3%, specificity 63.9%) were less valuable than the ESR (sensitivity 67.2%, specificity 91.7%) and CRP (sensitivity 76.2%, specificity 91.7%) for differentiating inactive RA patients from active RA patients due to low sensitivity and specificity and combining NLR or PLR also cannot significantly improved the diagnostic value of ESR and CRP.NLR, PLR and LMR may not be an useful independent diagnostic or complementary marker for disease activity in RA patients.

Сравнительное исследование хромогранина А и хромогранина В у больных с нейроэндокринными опухолями желудка и поджелудочной железы

Introduction. Immunoenzyme assay of biochemical markers is one of the most important methods for examination of pa- tients with neuroendocrine tumors (NETs). Along with the generally accepted NET marker chromogranin A (CgA), another member of the granin family, chromogranin B (CgB), can serve as a complementary marker. Objectives. Analysis of CgB as an additional to CgA biochemical marker in the blood serum of patients with gastric and pancreatic neuroendocrine tumors. Materials and methods. We examined 79 patients with gastic ( n = 14) and pancretic ( n = 65) NETS, and 42 particularly healthy people, who were included in the control group. CgB and CgA were determined with ELISA method using the Human Chromogranin B (USCN, China) and Chromogranin A NEOLISA (Eurodiagnostica, Sweden) test systems. , Results. CgB levels in gastric and pancreatic NETs were significantly higher than in control group. CgB concentrations were independent of tumor spread and its biological activity. ROC analysis in common group of NETs relative to control group showed AUC for CgB = 0.869 and for CgA AUC = 0.82. According to results in common group of NET patients when used isolated, CgA and CgB have comparable diagnostic sensitivity, which increases in complex use to 82.5 %. In the group of NET patients with low levels of CgA (&lt;100 ng/ml), an increase in CgB concentration above the cut-off level (&gt;15.7 ng/ml) was observed in 53.6 % of cases. Conclusion. The combination of CgB and CgA in gastric and pancreatic NETs could increase the diagnostic efficacy of bio- chemical diagnostics. The received data confirms the significance of CgB as a complementary biomarker of NETs.

Clinical impact of antibodies to Sp100 on a bacterial infection in patients with primary biliary cholangitis.

BackgroundA specific antinuclear antibody for primary biliary cholangitis (PBC) is anti‐Sp100, which was recognized as a serological marker of concurrent urinary tract infection. We sought to determine the clinical characteristics of PBC patients who had anti‐Sp100.Patients and MethodsFifty‐one patients with PBC and 10 healthy controls (HCs) were enrolled. Anti‐Sp100 were determined with an ELISA method. Lipopolysaccharide‐binding protein (LBP) was measured as a serological hallmark for bacterial infection. The correlations of anti‐Sp100 with demographic, laboratory, and pathological parameters were investigated.ResultsSix of the 51 (11.8%) PBC patients had anti‐Sp100, whereas none of the HCs did. There was no significant difference in the frequency of antimitochondrial antibodies (AMAs) between PBC patients with and without anti‐Sp100 (67% vs. 82%, p = 0.5839). Biochemical and immunological parameters were not associated with the emergence of anti‐Sp100 in these patients. The clinical stage by Scheuer classification was not correlated with the existence of anti‐Sp100. No significant difference in the serum LBP levels was found between PBC patients with and without anti‐Sp‐100, although serum LBP levels were significantly higher in PBC patients with anti‐Sp100 than in HCs (8.30 ± 2.24 ng/ml, vs. 5.12 ± 2.48 ng/ml, p = 0.0022). The frequency of granuloma formation was higher in the liver specimens of PBC patients with anti‐Sp100 than in those without anti‐Sp100 (67% vs 29%, p = 0.0710).Conclusionanti‐Sp100 does not become a complementary serological marker for PBC in AMA‐negative patients. A bacterial infection may trigger the production of anti‐Sp100. Another factor is required to initiate the autoantibody production.

CD44v6 Defines a New Population of Circulating Tumor Cells Not Expressing EpCAM.

Simple SummaryIn the present work, we describe (for the first time) the use of the transmembrane protein, CD44v6, to detect CTCs from blood samples of several patients with colorectal or breast cancer. We used CD44v6 antibodies to demonstrate that live CTCs can be specifically purified from CRC patient blood samples via magnetic bead- or FACS-based isolation techniques. Finally, we demonstrated that CD44v6-positive CTCs rarely expressed EpCam, which is currently the gold standard to enumerate CTCs, suggesting the need to use a combination of markers for a more comprehensive view of CTC heterogeneity.Circulating tumor cells (CTCs) are promising diagnostic and prognostic tools for clinical use. In several cancers, including colorectal and breast, the CTC load has been associated with a therapeutic response as well as progression-free and overall survival. However, counting and isolating CTCs remains sub-optimal because they are currently largely identified by epithelial markers such as EpCAM. New, complementary CTC surface markers are therefore urgently needed. We previously demonstrated that a splice variant of CD44, CD44 variable alternative exon 6 (CD44v6), is highly and specifically expressed by CTC cell lines derived from blood samples in colorectal cancer (CRC) patients. Two different approaches—immune detection coupled with magnetic beads and fluorescence-activated cell sorting—were optimized to purify CTCs from patient blood samples based on high expressions of CD44v6. We revealed the potential of the CD44v6 as a complementary marker to EpCAM to detect and purify CTCs in colorectal cancer blood samples. Furthermore, this marker is not restricted to colorectal cancer since CD44v6 is also expressed on CTCs from breast cancer patients. Overall, these results strongly suggest that CD44v6 could be useful to enumerate and purify CTCs from cancers of different origins, paving the way to more efficacious combined markers that encompass CTC heterogeneity.

Reduction in hypermetabolic state on midazolam stewards anticonvulsive treatment for interictal patterns in severe acute brain injury: A pilot MR perfusion study

Small Cohorts have utilized PET and SPECT scans as complementary markers of metabolic activity in status epilepticus in patients with ictal-interictal EEG patterns (IIC). While some rhythmic/periodic discharges mandate termination, other IIC patterns reflect underlying stable brain lesions with no superimposed cerebral injury. We realize that perfusion mapping is not the greatest surrogate; however, it is more readily available. We suggest severe brain injury patients be treated with aggressive anticonvulsive treatment only when they fulfill all the following criteria: 1) altered mental status, 2) IIC EEG patterns, 3) periodic/rhythmic discharges colocalizing with hypermetabolism detected by loco-regional hyperperfusion and 4) significant decrease in hyperperfusion during a midazolam (MDZ) test.

Immune Profiling Demonstrates a Common Immune Signature of Delayed Acquired Immunodeficiency in Patients With Various Etiologies of Severe Injury.

The host response plays a central role in the pathophysiology of sepsis and severe injuries. So far, no study has comprehensively described the overtime changes of the injury-induced immune profile in a large cohort of critically ill patients with different etiologies. Prospective observational cohort study. Adult ICU in a University Hospital in Lyon, France. Three hundred fifty-three septic, trauma, and surgical patients and 175 healthy volunteers were included in the REAnimation Low Immune Status Marker study. None. Extensive immune profiling was performed by assessing cellular phenotypes and functions, protein, and messenger RNA levels at days 1-2, 3-4, and 5-7 after inclusion using a panel of 30 standardized immune markers. Using this immunomonitoring panel, no specificity in the immune profile was observed among septic, trauma, and surgical patients. This common injury-induced immune response was characterized by an initial adaptive (i.e., physiologic) response engaging all constituents of the immune system (pro- and anti-inflammatory cytokine releases, and innate and adaptive immune responses) but not associated with increased risk of secondary infections. In contrary, the persistence in a subgroup of patients of profound immune alterations at the end of the first week after admission was associated with increased risk of secondary infections independently of exposure to invasive devices. The combined monitoring of markers of pro-/anti-inflammatory, innate, and adaptive immune responses allowed a better enrichment of patients with risk of secondary infections in the selected population. Using REAnimation Low Immune Status Marker immunomonitoring panel, we detected delayed injury-acquired immunodeficiency in a subgroup of severely injured patients independently of primary disease. Critically ill patients' immune status could be captured through the combined monitoring of a common panel of complementary markers of pro-/anti-inflammatory, innate, and adaptive immune responses. Such immune monitoring needs to be incorporated in larger study cohorts with more extensive immune surveillance to develop specific hypothesis allowing for identification of biological systems affecting altered immune function related to late infection in the setting of acute systemic injury.