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1.
Epithelial ovarian cancer accounts for more than 90% of ovarian tumours and continues as a leading cause of death from gynaecological malignancies. It is often difficult to differentiate a benign ovarian mass from malignant ones. Invasive histopathological biopsy is used as the gold standard diagnostic tool to diagnose cancer in patients with ovarian mass. A wide spectrum of Biomarkers were tried in various studies to develop a non invasive diagnostic tool, out of which HE4 and CA 125 remain the only clinically useful biomarker. Consequently various Biomarker based algorithms i.e. Risk of Malignancy Index, risk of ovarian cancer algorithm, OVA1, risk of malignancy algorithm were generated that have been developed to assess the risk of a mass being malignant. These algorithms help in timely triage of patients. Recently in 2016 FDA cleared Ova1 test (OVERA) with CA 125-II, HE4, apolipoprotein A-1, FSH, and transferring (Sensitivity 91% and Specificity 69%) as a referral or Triage test in patients presenting with ovarian mass. Combination of protein and circulating Micro RNA analysis in blood, could provide a comprehensive screening and diagnostic panel, in management of patients presenting with ovarian mass in one clinical setting.  相似文献   

2.
Non-invasive and accurate access of biomarkers remains a holy grail of the biomedical community. Human eccrine sweat is a surprisingly biomarker-rich fluid which is gaining increasing attention. This is especially true in applications of continuous bio-monitoring where other biofluids prove more challenging, if not impossible. However, much confusion on the topic exists as the microfluidics of the eccrine sweat gland has never been comprehensively presented and models of biomarker partitioning into sweat are either underdeveloped and/or highly scattered across literature. Reported here are microfluidic models for eccrine sweat generation and flow which are coupled with review of blood-to-sweat biomarker partition pathways, therefore providing insights such as how biomarker concentration changes with sweat flow rate. Additionally, it is shown that both flow rate and biomarker diffusion determine the effective sampling rate of biomarkers at the skin surface (chronological resolution). The discussion covers a broad class of biomarkers including ions (Na+, Cl−, K+, NH4+), small molecules (ethanol, cortisol, urea, and lactate), and even peptides or small proteins (neuropeptides and cytokines). The models are not meant to be exhaustive for all biomarkers, yet collectively serve as a foundational guide for further development of sweat-based diagnostics and for those beginning exploration of new biomarker opportunities in sweat.  相似文献   

3.
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4.
Kuczenski RS  Chang HC  Revzin A 《Biomicrofluidics》2011,5(3):32005-3200515
Microfluidic diagnostic devices promise faster disease identification by purifying and concentrating low-abundance analytes from a flowing sample. The diagnosis of sepsis, a whole body inflammatory response often caused by microbial infections of the blood, is a model system for pursuing the advantages of microfluidic devices over traditional diagnostic protocols. Traditional sepsis diagnoses require large blood samples and several days to culture and identify the low concentration microbial agent. During these long delays while culturing, the physician has little or no actionable information to treat this acute illness. We designed a microfluidic chip using dielectrophoresis to sort and concentrate the target microbe from a flowing blood sample. This design was optimized using the applicable electrokinetic and hydrodynamic theories. We quantify the sorting efficiency of this device using growth-based assays which show 30% of injected microbes are recovered viable, consistent with the electroporation of target cells by the dielectrophoretic cell sorters. Finally, the results illustrate the device is capable of a five-fold larger microbe concentration in the target analyte stream compared to the waste stream at a continuous sample flow rate of 35 μl∕h.  相似文献   

5.

Introduction

Presepsin, the circulating soluble form of CD14 subtype (sCD14-ST) is a new emerging early marker for sepsis. Various cutoff levels of presepsin have been proposed, to discriminate between systemic bacterial and nonbacterial infectious diseases. The aim of this work was to define the reference interval for presepsin according to the CLSI C28-A3c approved guideline.

Materials and methods

Reference individuals (N = 200; 120 females) aged 18-75 years (median 39 years), free from inflammatory diseases, were selected for the study. Presepsin concentrations were measured by a commercially available chemiluminescent enzyme immunoassay (PATHFASTTM, Mitsubishi Chemical Europe GmbH, Düsseldorf, Germany). Reference limits were calculated using the non-parametric percentile method.

Results

Overall, the reference limits for the presepsin were 55–184 pg/mL (90% confidence intervals, CI, were 45 to 58 and 161 to 214, respectively). There were no significant differences between males and females and the presepsin concentrations were not even particularly influenced by age. The upper reference limit for the presepsin is much lower than every cut-off limit so far proposed, both for sepsis and also for systemic inflammatory response syndrome.

Conclusion

Specific decision levels are required to define the diagnostic and prognostic roles of presepsin in different settings of inflammatory and infectious diseases. Reference values can help to distinguish and quickly rule out healthy subjects or patients with other pathologies.Key words: CD14 Antigen, presepsin, reference values, male, female, Clinical and Laboratory Standard Institute  相似文献   

6.
Pleural tuberculosis accounts for nearly 20% of Extra pulmonary tuberculosis. Adenosine deaminase, commonly used biomarker for the diagnosis, is non specific and there is paucity of literature on its correlation with conventional or newer methods for the diagnosis of extra pulmonary forms of TB. The aim of the study was to assess diagnostic potential of T cell function markers [interferon (IFN-γ), interleukin (IL-2) and IFN-γ/IL-2 ratio]; macrophage activation marker [neopterin]; and oxidative stress markers [protein carbonyl and malondialdehyde (MDA)] in pleural tuberculosis. 26 pleural TB cases diagnosed on the basis of suggestive chest X-ray and raised serum ADA levels and healthy controls were included in the study. Pleural fluid specimens were subjected to Zeihl Neelsen staining and culture on Lowenstein Jensen medium. Serum IFN-γ, IL-2, neopterin and protein carbonyl levels detection were done by ELISA and MDA levels were determined by measuring the thiobarbituric acid reactive substances. Median serum levels of IFN-γ, IL-2, IFN-γ/IL-2 ratio, neopterin, protein carbonyl and MDA were significantly different between cases and controls. Levels of all biomarkers except IL-2 were significantly higher in cases with contact history. Mean levels of ADA and ESR were 46.27 U/L and 46.62 mm/hr in PTB cases. AUC for IFN-γ, IL-2, IFN-γ/IL-2 ratio, neopterin, protein carbonyl and MDA were significantly discriminative for cases and controls. IFN-γ/IL-2 ratio was best discriminatory biomarker with highest area under ROC curve. Though no correlation was seen between ADA and any of the six biomarkers, ESR levels correlated significantly with all biomarkers except IL-2 by spearman’s correlation coefficient. Though all the circulating biomarkers under study provide useful supportive evidence for the diagnosis of PTB, further studies involving diverse control groups particularly non-PTB effusion are needed to validate these results.  相似文献   

7.
IntroductionThe prognostic value of D-dimer (DD) in sepsis remains controversial. This study aimed to investigate the performance of DD for predicting sepsis mortality in the hospital and for identifying its potential correlates.Materials and methodsThe clinical and laboratory data of adult sepsis patients were extracted from the Medical Information Mart for Intensive Care III (MIMIC III, v1.4) database using the structured query language (SQL). The database contains critical illness admitted to the intensive care unit at Beth Israel Deaconess Medical Center between June 2001 and October 2012. The association between DD and mortality was investigated with receiver operating characteristic (ROC) curve, restricted cubic spline and logistic regression analysis. Subgroup analysis was also used for identifying DD correlates.ResultsThe study population consisted of 358 sepsis patients. Those who died during hospital stay (N = 160) had significantly higher DD values than those who survived (N = 198). The area under the ROC curve (AUC) of DD was 0.59 (P < 0.010). In subgroup analysis, white blood cell (WBC) count > 18 x109/L and vasopressor therapy significantly decreased DD diagnostic performance. Categorical DD value was independently associated with hospital mortality after sequential organ failure score (SOFA) and blood lactate adjustment. Restricted cubic spline analysis revealed a U-shape relationship between DD and in-hospital mortality.DiscussionWe conclude that the accuracy of DD for predicting in-hospital sepsis mortality depends on WBC count and vasopressor therapy. Both low and extremely elevated DD values are associated with higher risk of death.  相似文献   

8.
Pleural effusion is one of the commonest presentations of tuberculosis, the clinical manifestations being typically abrupt resembling bacterial pneumonia. Since delayed hypersensitivity is the underlying immune response, bacterial load is very low. Owing to these facts, tuberculous pleurisy as an extra-pulmonary disease poses a diagnostic dilemma. The conventional bacteriological methods rarely detect Mycobacterium tuberculosis in pleural fluid and are of limited use in diagnosis of tuberculous pleurisy. We evaluated the efficacy of polymerase chain reaction (PCR) in the diagnosis of tuberculous pleurisy by targeting the gene segment coding for MPB64 protein specific forMycobacterium tuberculosis. Based on the clinical criteria, 82 patients with lymphocytic exudative pleural effusion were included in the study. Patients were analyzed in two groups; one group consisting of 48 patients of tubercular pleural effusion confimed by various diagnostic procedures and another group of 34 patients comprising of non-tubercular pleural effusion. There were no false positive results by PCR and the specificity worked out to be 100%. Twenty two patients tested positive for Mantoux with a sensitivity of 45%. ZN-staining for AFB was found in samples from 15 patients (20% sensitivity). ADA was positive for 28 patients with a sensitivity of 53%. PCR was positive for 32/48 patients (67% sensitivity). Thus, PCR was found to be more sensitive than any other conventional method in diagnosis of clinically suspected tubercular pleurisy.  相似文献   

9.
The discovery of protein biomarkers that reflect the biological state of the body is of vital importance to disease management. Urine is an ideal source of biomarkers that provides a non-invasive approach to diagnosis, prognosis and prediction of diseases. Consequently, the study of the human urinary proteome has increased dramatically over the last 10 years, with many studies being published. This review focuses on urinary protein biomarkers that have shown potential, in initial studies, for diseases affecting the urogenital tract, specifically chronic kidney disease and prostate cancer, as well as other non-urogenital pathologies such as breast cancer, diabetes, atherosclerosis and osteoarthritis. PubMed was searched for peer-reviewed literature on the subject, published in the last 10 years. The keywords used were “urine, biomarker, protein, and/or prostate cancer/breast cancer/chronic kidney disease/diabetes/atherosclerosis/osteoarthritis”. Original studies on the subject, as well as a small number of reviews, were analysed including the strengths and weaknesses, and we summarized the performance of biomarkers that demonstrated potential. One of the biggest challenges found is that biomarkers are often shared by several pathologies so are not specific to one disease. Therefore, the trend is shifting towards implementing a panel of biomarkers, which may increase specificity. Although there have been many advances in urinary proteomics, these have not resulted in similar advancements in clinical practice due to high costs and the lack of large data sets. In order to translate these potential biomarkers to clinical practice, vigorous validation is needed, with input from industry or large collaborative studies.Key words: urine, protein, biomarker  相似文献   

10.
Hemophagocytic lymphohistiocytosis (HLH) is an inflammatory condition that may run a rapid fatal course and calls for prompt diagnosis. Early intervention with steroids and other immunosuppressive drugs can contain the disease process and favours positive outcome. Ferritin ≥500 ng/ml is a HLH diagnostic criterion. We evaluated the diagnostic potential of admission ferritin, in children with HLH. Pediatric patients of a referral teaching hospital from Feb 2010–Oct 2013 having been investigated for ferritin on admission were included. HLH was confirmed when patients had clinical features and met 5/8 diagnostic criteria of the revised 2004 HLH guidelines. Ferritin was estimated on Cobas e411 by electrochemiluminiscence, with a measuring range of 0.5–2000 ng/ml. Dilutions were made when linearity exceeded and absolute values were reported. 905 on-admission ferritin investigations were reviewed out of which 346 values ≥500 ng/ml. Hyperferritinemia was seen in HLH/MAS (macrophage activation syndrome) [HLH group, median age 4 year 4 month, 59% male] and in systemic lupus erythematosus, sepsis, juvenile idiopathic arthritis, impending HLH, haemolytic anemias and malignancy [non-HLH group, median age 4 year 6 month, 60% male]. Of 346, 72 cases of hyperferritinemia were diagnosed with secondary HLH while one patient had primary HLH. 13/73 patients expired. The median ferritin level of the HLH group was significantly higher [6556 (2402–11,734) ng/ml] compared to non-HLH group [median 1175 (943–2000) ng/ml] (p < 0.0001). Receiver operator characteristics curve analysis revealed optimal admission ferritin of 3120 ng/ml as the cut-off with sensitivity of 70% and specificity of 88.9% for HLH diagnosis, exceeding the currently prescribed cut-off of 500 ng/ml. Hyperferritinemia below 3120 ng/ml has higher negative predictive value to rule out secondary HLH on admission in the study population of children predominantly diagnosed with infection associated HLH than the prescribed cut-off as per the 2004 guidelines. This may prove to be beneficial to alert physicians for prompt intervention which considerably decreases mortality in this often fatal condition.  相似文献   

11.
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12.
CD40-CD40L interaction plays a significant role in the pathogenesis of atherosclerosis and coronary artery disease. The clinical predictive value of Soluble CD40 Ligand (sCD40L) was evaluated in patients with Acute Coronary Syndrome (ACS) and Non-Cardiac Chest Pain (NCCP). The levels of serum soluble CD 40 ligand were measured by ELISA in 485 patients admitted to emergency care unit, of which 89 patients were diagnosed as NCCP. The levels of sCD40L were significantly increased in patients with ACS when compared to controls and NCCP. Receiver Operator Characteristic (ROC) Curve analysis showed sCD40L to be a good discriminator between patients with ischemic heart disease and patients without ischemic heart disease. The area under the curve was found to be 0.940 with 95% CI (0.915 to 0.960) (P<0.0001). The cut off value from the ROC curve was 2.99 ng/ml, above which sCD40L was considered to be positive. Combined assessment of sCD40L, Troponin I and CK-MB enhanced the risk prediction and early classification of patients. sCD40L seems to be a promising biomarker for identification and risk stratification for patients with acute coronary syndrome.  相似文献   

13.

Introduction:

Zonulin is a eukaryotic protein structurally similar to Vibrio cholerae’s zonula occludens toxin. It plays an important role in the opening of small intestine tight junctions. The loss of gut wall integrity during sepsis might be pivotal and has been described in various experimental as well as human studies. Increased levels of zonulin could be demonstrated in diseases associated with increased intestinal inflammation, such as celiac disease and type 1 diabetes. We therefore investigated the role of plasma levels of zonulin in patients with sepsis as a non-invasive marker of gut wall integrity.

Materials and methods:

Plasma level of zonulin was measured in 25 patients with sepsis, severe sepsis or septic shock according to ACCP/SCCM criteria at the first day of diagnosed sepsis. 18 non-septic post-surgical ICU-patients and 20 healthy volunteers served as control. Plasma levels were determined by using commercially available ELISA kit. Data are given as median and interquartile range (IQR).

Results:

Significantly higher plasma concentration of zonulin were found in the sepsis group: 6.61 ng/mL (IQR 3.51–9.46), as compared to the to the post-surgical control group: 3.40 ng/mL (IQR 2.14–5.70) (P = 0.025), as well as to the healthy group: 3.55 ng/mL (IQR 3.14–4.14) (P = 0.008).

Conclusion:

We were able demonstrate elevated levels of plasma zonulin, a potential marker of intestinal permeability in septic patients. Increased zonulin may serve as an additional mechanism for the observed increased intestinal permeability during sepsis and SIRS.  相似文献   

14.
Sepsis suffers from lack of specific clinical symptoms which contribute to one of the major causes of mortality. In the present study, our aim was to evaluate the role of a recent biomarker Procalcitonin (PCT) in predicting organ dysfunction. 71 patients admitted with sepsis were included in the study. PCT levels were measured at 0, 24, 72 h and 7th day and sequential organ failure assessment score (SOFA) scores were calculated. PCT levels significantly decreased (p < 0.001) in 89.3 % of surviving patients, whereas, in 60 % non surviving patients the PCT level increased significantly (p < 0.001). A significant positive correlation between PCT and SOFA score was observed in survivors at each hour. These observations indicate that PCT concentration is significantly associated with severity of multi organ dysfunction and also helps in determining the prognosis of septic patients.  相似文献   

15.
Inflammatory bowel disease (IBD) is a heterogeneous group of chronic inflammatory disorders of the gastrointestinal tract with two main distinguishable entities, Crohn’s disease (CD) and ulcerative colitis (UC). IBD-unclassified (IBD-U) is a diagnosis that covers the “grey” zone of diagnostic uncertainty between UC and CD. Current diagnosis of IBD relies on the clinical, endoscopic, radiological, histological and biochemical features, but this approach has shortcomings especially in cases of overlapping symptoms of CD and UC. The need for a diagnostic tool that would improve the conventional methods in IBD diagnosis directed the search towards potential immunological markers, since an aberrant immune response against microbial or endogenous antigens in a genetically susceptible host seems to be implicated in IBD pathogenesis. The spectrum of antibodies to different microbial antigens and autoantibodies associated with IBD is rapidly expanding. Most of these antibodies are associated with CD like anti-glycan antibodies: anti-Saccharomices cerevisiae (ASCA) and the recently described anti-laminaribioside (ALCA), anti-chitobioside (ACCA), anti-mannobioside (AMCA), anti-laminarin (anti-L) and anti-chitin (anti-C) antibodies; in addition to other antibodies that target microbial antigens: anti-outer membrane porin C (anti-OmpC), anti-Cbir1 flagellin and anti-I2 antibody. Also, autoantibodies targeting the exocrine pancreas (PAB) were shown to be highly specific for CD. In contrast, UC has been associated with anti-neutrophil cytoplasmic autoantibodies (pANCA) and antibodies against goblet cells (GAB). Current evidence suggests that serologic panels of multiple antibodies are useful in differential diagnosis of CD versus UC and can be a valuable aid in stratifying patients according to disease phenotype and risk of complications.  相似文献   

16.
Cardiac markers are used to evaluate functions of heart. However, there are no satisfactory cardiac biomarkers for the diagnosis of acute myocardial infarction (AMI) within 4 h of onset of chest pain. Among novel cardiac markers, glycogen phosphorylase BB (GPBB) is of particular interest as it is increased in the early hours after AMI. The present study was conducted with the objective to find out the sensitivity and specificity of GPBB over other cardiac markers i.e. myoglobin and CKMB in patients of AMI within 4 h after the onset of chest pain. The study includes 100 AMI patients and 100 normal healthy individuals as controls. In all the cases and controls, serum GPBB and myoglobin concentrations were measured by ELISA where as CK-MB was measured by diagnostic kit supplied by ERBA. The sensitivity and specificity of glycogen phosphorylase BB (GPBB) were greater than CK-MB and myoglobin in patients of AMI within 4 h after the onset of chest pain. Hence, glycogen phosphorylase BB (GPBB) can be used as additional biomarker for the early diagnosis of AMI.  相似文献   

17.
Over the past three decades, the goal of many researchers is analysis of exhaled breath condensate (EBC) as noninvasively obtained sample. A total quality in laboratory diagnostic processes in EBC analysis was investigated: pre-analytical (formation, collection, storage of EBC), analytical (sensitivity of applied methods, standardization) and post-analytical (interpretation of results) phases. EBC analysis is still used as a research tool. Limitations referred to pre-analytical, analytical, and post-analytical phases of EBC analysis are numerous, e.g. low concentrations of EBC constituents, single-analyte methods lack in sensitivity, and multi-analyte has not been fully explored, and reference values are not established. When all, pre-analytical, analytical and post-analytical requirements are met, EBC biomarkers as well as biomarker patterns can be selected and EBC analysis can hopefully be used in clinical practice, in both, the diagnosis and in the longitudinal follow-up of patients, resulting in better outcome of disease.  相似文献   

18.
Suspicion of inflammatory bowel disease should be raised in any patient with chronic or recurrent abdominal pain and diarrhoea. However, symptoms of inflammatory bowel disease (IBD) overlap with functional gastrointestinal disorders and those patients may not need endoscopy. Currently, colonoscopy with multiple biopsies is considered the gold standard to establish the diagnosis of IBD. Unfortunately, patient selection for endoscopy based on symptoms is not reliable. The use of guidelines of appropriateness for endoscopy yields significantly more significant findings but the selection criteria suffer from low specificity. Calprotectin is a calcium binding protein of neutrophil granulocytes that correlates well with neutrophil infiltration of the intestinal mucosa when measured in faeces. In the last decade, a large body of evidence on the diagnostic value of faecal calprotectin has accumulated and measurement of calprotectin in faeces has been suggested as a surrogate marker of intestinal inflammation. Testing of faecal calprotectin has been highly useful to distinguish organic from functional intestinal disorders in patients with abdominal complaints. Additionally, faecal calprotectin has reliably identified colonic inflammation in patients with suspected IBD. The use of this inexpensive and widely available test in the evaluation and risk stratification in patients with abdominal complaints is likely to increase in the future.  相似文献   

19.
Section identification is an important task for library science, especially knowledge management. Identifying the sections of a paper would help filter noise in entity and relation extraction. In this research, we studied the paper section identification problem in the context of Chinese medical literature analysis, where the subjects, methods, and results are more valuable from a physician's perspective. Based on previous studies on English literature section identification, we experiment with the effective features to use with classic machine learning algorithms to tackle the problem. It is found that Conditional Random Fields, which consider sentence interdependency, is more effective in combining different feature sets, such as bag-of-words, part-of-speech, and headings, for Chinese literature section identification. Moreover, we find that classic machine learning algorithms are more effective than generic deep learning models for this problem. Based on these observations, we design a novel deep learning model, the Structural Bidirectional Long Short-Term Memory (SLSTM) model, which models word and sentence interdependency together with the contextual information. Experiments on a human-curated asthma literature dataset show that our approach outperforms the traditional machine learning methods and other deep learning methods and achieves close to 90% precision and recall in the task. The model shows good potential for use in other text mining tasks. The research has significant methodological and practical implications.  相似文献   

20.
This study examines the effects of different product presentation strategies (i.e., alternative- vs. attribute-based) on consumer responses to diagnostic and serendipitous website experiences. Drawing on the accessibility-diagnosticity framework, we propose that different types of information presentation strategies lead consumers to differently evaluate a website as being diagnostic and serendipitous. The findings from three studies suggest that attribute-based presentations effectively increase consumer perceptions of website diagnosticity and serendipity compared with an alternative-based format. Both perceived diagnosticity and serendipity significantly contribute to consumers’ overall satisfaction with a website. Theoretical and practical implications are discussed.  相似文献   

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