Perspective non-invasive biomarkers: intestinal proteins in the diagnosis for diagnosis and control of intestinal mucosal damage

The aim of this literature review was to consider the diagnostic value of potential biomarkers detection: citrulline and intestinal proteins, designed to detect intestinal mucosa damage.Conclusion: determination of I-FABP and I-BABP in blood are promising methods for non-invasive diagnosis of the intestinal damage, since these proteins are released from the damaged enterocytes. However, the determination of intestinal proteins is important in combination with the determination of citrulline. Several studies have shown that citrulline can be measured in animal models, in adult and pediatric patients. It is easily detectable, consistently measured and capable of detecting inflammation of the intestinal mucosa. The limitation of most studies was the small sample size. Non-invasive diagnostic and therapeutic monitoring techniques remain an important area of further research.

Download Full-text

Abstract W P20: A Model to Calculate the Expected Treatment Effect in Acute Endovascular Stroke Trials

Stroke ◽

10.1161/str.45.suppl_1.wp20 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Maarten G Lansberg ◽

Robin Lemmens ◽

Soren Christensen ◽

Nishant K Mishra ◽

Gregory W Albers

Keyword(s):

Literature Review ◽

Sample Size ◽

Endovascular Therapy ◽

Treatment Effect ◽

Small Sample Size ◽

Small Sample ◽

Absolute Difference ◽

Sample Size Calculations ◽

And Control ◽

Larger Sample

Background: Recent trials have shown no benefit of endovascular therapy. This may, in part, be explained by inaccurate estimates of the treatment effect used in the sample size calculations of these trials. A predictive model which includes variables that modify the expected treatment effect might yield more accurate estimates, and could be valuable in the design of future acute stroke trials. Methods: We conducted a literature review to obtain estimates of parameters that are associated with good functional outcome (GFO) following recanalization. We developed a model to estimate the treatment effect in endovascular stroke trials and applied this model to two recently published endovascular stroke trials. Results: We estimated a 40% absolute difference in the proportion of GFO (mRS 0-2 at 90 days) associated with reperfusion in patients with ICA or M1 occlusions who have a substantial ischemic penumbra at baseline. To estimate the effect size in trials, this value was multiplied by: 1) the proportion of patients undergoing endovascular therapy in the active treatment arm; 2) the proportion of patients with occlusions of the ICA or MCA-M1; 3) the proportion of patients with a substantial penumbra and a DWI lesion <50mL; and 4) the absolute difference in the proportion of patients with reperfusion, defined as TICI 2B-3, between the endovascular treatment and control arms. Based on literature review we assumed a reperfusion rate of 20% in the control arms of IMS III and MR Rescue, a 50% prevalence of patients with substantial penumbra and DWI lesions<50 mL in IMS III, and a 75% prevalence in the penumbral arms of MR Rescue. Based on these model inputs, a 2.2% increase in GFO with endovascular therapy was expected in IMS III, which closely matches the observed 2.1% increase. For MR Rescue, the model predicted a 1.5% increase in GFO with endovascular therapy. Considering the small sample size, this equates to 0.5 additional patients with GFO which closely matches the observed result of 3 fewer patients with GFO. Conclusion: A simple model shows promise for estimating the treatment effect of endovascular stroke trials. It may be useful for the design of future trials and could lead to different inclusion criteria or larger sample sizes compared to the recently conducted studies.

Download Full-text

Abstract 276: Asymmetric Dimethylarginine Is A Potential Risk Factor For Transient Ischemic Attack

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.7.suppl_1.276 ◽

2014 ◽

Vol 7 (suppl_1) ◽

Author(s):

Yuanjin Zhang ◽

Daniel Laskowitz ◽

Dongsheng Fan

Keyword(s):

Growth Factor ◽

Transient Ischemic Attack ◽

Asymmetric Dimethylarginine ◽

Small Sample Size ◽

Small Sample ◽

Control Group ◽

Acute Infarction ◽

Abcd2 Score ◽

Ischemic Attack ◽

And Control

Objective: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase which has been shown to be involved in the pathogens of atherosclerosis. Vascular endothelial growth factor (VEGF) is apleiotropic growth factor involved in neurovascular remodeling in the cerebral ischemia disease. ADMA has been validated to be a risk marker of stroke and transient ischemic attack (TIA). VEGF has been demonstrated associated with risk of stroke. This pilot study aimed to verify the correlation between serum ADMA, VEGF levels and ABCD2 score which has been validated to predict short term risk of stroke following transient ischemic attack (TIA). Methods: TIA was defined as a transient episode of neurologic dysfunction caused by focal brain, spinal cord or retinal ischemia, without acute infarction even the focal transient neurologic symptoms last less than one hour. We enrolled 40 TIAs and 40 healthy controls in Peking University Third Hospital Neurology wards and clinics since May to July 2013. The TIA diagnosis and ABCD2 score evaluation is conducted by the same neurology physician. The mean age of TIAs and controls was 61.9±12.9yrs and 63.4±10.9yrs respectively (P=0.544). Blood samples were drawn within 24 hours after the TIA diagnosis clarified. ADMA and VEGF levels were measured by ELISA. Result: The ADMA levels in TIAs and control group are 0.52±0.06mmol/L and 0.23±0.04mmol/L (t=24.14, P<0.01). The VEGF levels in TIAs and control group are 272.01±26.36mmol/L and 148.87±21.05mmol/L (t=24.65, P<0.01). In the non-stroke history TIAs (23 cases) sub-group the spearman correlation coefficient between ADMA and ABCD2 score is 0.6(P=0.002). Conclusion: ADMA and VEGF are absolutely increased in TIAs. There is no correlation between ADMA, VEGF, age, sex, blood pressure, glucose and ABCD2 in this small sample size population. But ADMA is probably associated with risk of TIA with no-stroke history. Thus, these findings reveal a possibly new challenging potential of the ADMA and VEGF role in the pathogenesis of TIA.

Download Full-text

Maternally and Paternally Silenced Imprinted Genes Differ in Their Intron Content

Comparative and Functional Genomics ◽

10.1002/cfg.437 ◽

2004 ◽

Vol 5 (8) ◽

pp. 572-583 ◽

Cited By ~ 2

Author(s):

Marie E. Fahey ◽

Walter Mills ◽

Desmond G. Higgins ◽

Tom Moore

Keyword(s):

Small Sample Size ◽

Small Sample ◽

Control Group ◽

Imprinted Genes ◽

Intronless Genes ◽

Intron Content ◽

Group A ◽

Control Set ◽

And Control ◽

Human And Mouse

Imprinted genes exhibit silencing of one of the parental alleles during embryonic development. In a previous study imprinted genes were found to have reduced intron content relative to a non-imprinted control set (Hurstet al., 1996). However, due to the small sample size, it was not possible to analyse the source of this effect. Here, we re-investigate this observation using larger datasets of imprinted and control (non-imprinted) genes that allow us to consider mouse and human, and maternally and paternally silenced, imprinted genes separately. We find that, in the human and mouse, there is reduced intron content in the maternally silenced imprinted genes relative to a non-imprinted control set. Among imprinted genes, a strong bias is also observed in the distribution of intronless genes, which are found exclusively in the maternally silenced dataset. The paternally silenced dataset in the human is not different to the control set; however, the mouse paternally silenced dataset has more introns than the control group. A direct comparison of mouse maternally and paternally silenced imprinted gene datasets shows that they differ significantly with respect to a variety of intron-related parameters. We discuss a variety of possible explanations for our observations.

Download Full-text

Changes of biochemical parameters in rat intestinal mucosa induced by methotrexate and effects of enteral administration of glutamine

Archive of oncology ◽

10.2298/aoo0401035b ◽

2004 ◽

Vol 12 (1) ◽

pp. 35-38 ◽

Cited By ~ 3

Author(s):

Katica Bajin-Katic ◽

Karmen Stankov ◽

Zoran Kovacevic

Keyword(s):

Intestinal Mucosa ◽

Biochemical Parameters ◽

Intraperitoneal Administration ◽

Mucosal Damage ◽

Control Group ◽

Intestinal Damage ◽

Sprague Dawley ◽

Regeneration Time ◽

Sprague Dawley Rats ◽

Previously Treated

BACKGROUND: Rapidly proliferating crypt cells of the intestinal epithelium, the precursors of the mature enterocytes, are extremely sensitive to the effects of cytostatic agents. We investigated the effects of the methotrexate on rat intestinal mucosa in order to get the information on biochemical indicators of intestinal damage. METHODS: Biochemical parameters were investigated in isolated intestinal mucosa of Sprague-Dawley rats, previously treated with methotrexate by intraperitoneal administration. Glutamine was dissolved in water and administered orally. RESULTS: The activity of glutaminase and alkaline phosphatase showed the enzymatic response to different doses of methotrexate. The activity of both enzymes was significantly lower in the mucosa of treated animals, compared to control group. CONCLUSION: Minimal mucosal damage and regeneration time is dose dependent and influenced by the dosage schedule of antitumor therapy.

Download Full-text

Simple and rapid liquid chromatography method for simultaneous determination of isoniazid and pyrazinamide in plasma

SAARC Journal of Tuberculosis Lung Diseases and HIV/AIDS ◽

10.3126/saarctb.v9i1.6960 ◽

2012 ◽

Vol 9 (1) ◽

pp. 13-18 ◽

Cited By ~ 13

Author(s):

AK Kumar Hemanth ◽

V Sudha ◽

G Ramachandran

Keyword(s):

Simultaneous Determination ◽

High Performance ◽

Small Sample Size ◽

Accurate Method ◽

Reversed Phase ◽

Small Sample ◽

Pharmacokinetic Studies ◽

Chromatography Method ◽

Relative Standard

Introduction: Treatment of tuberculosis (TB) requires a combination of drugs. Isoniazid (INH) and pyrazinamide (PZA) are key components of the fi rst-line regimen used in the treatment of TB and monitoring these drug levels in plasma would help in better patient care. The objective of the study is to develop and validate a simple and rapid high performance liquid chromatographic method for simultaneous determination of INH and PZA in human plasma. Methodology: The method involved deproteinisation of plasma with para hydroxy benzaldehyde and trifl uoroacetic acid and analysis using a reversed-phase C8 column and UV detection at 267nm. The fl ow rate was set at 1.5 ml/min at ambient temperature. The accuracy, linearity, precision, specifi city, stability and recovery of the method were evaluated. The method was applied to estimate plasma INH and PZA collected from six children with TB. Results: Well resolved peaks of PZA and INH at retention times of 3.2 and 6.1 minutes respectively were obtained. The assay was linear from 0.25 - 10.0 ìg/ml for INH and 1.25 – 50.0 ìg/ml for PZA. The within-day and between-day relative standard deviation for standards were below 10%. The average recoveries of INH and PZA from plasma were 104 and 102% respectively. Conclusions: A rapid and accurate method for simultaneous determination of INH and PZA in plasma was validated. The assay spans the concentration range of clinical interest. The easy sample preparation and small sample size makes this assay highly suitable for pharmacokinetic studies of INH and PZA in TB patients. SAARC Journal of Tuberculosis, Lung Diseases & HIV/AIDS 2012; IX (1) 13-18 DOI: http://dx.doi.org/10.3126/saarctb.v9i1.6960

Download Full-text

Appropriateness of Apixaban Dosing to Prevent Stroke in Patients with Atrial Fibrillation: A Pilot Study

The Canadian Journal of Hospital Pharmacy ◽

10.4212/cjhp.v69i6.1607 ◽

2016 ◽

Vol 69 (6) ◽

Author(s):

Stephanie Carlin ◽

Jennifer Pickering ◽

Sam Schulman

Keyword(s):

Atrial Fibrillation ◽

Stroke Prevention ◽

Small Sample Size ◽

Retrospective Chart Review ◽

Small Sample ◽

Centre Hospitalier Universitaire ◽

Product Monograph ◽

Fibrillation Auriculaire ◽

Full Dosage

ABSTRACTBackground: The ARISTOTLE study investigated apixaban, at a dose of 5 mg PO bid, for the prevention of stroke in patients with atrial fibrillation; however, it has been noted anecdotally that many patients are receiving 2.5 mg PO bid, despite being eligible for the full dosage. A recent study examining the use of dabigatran and rivaroxaban found that many patients were receiving these medications inappropriately; however, a literature search conducted in April 2016 showed that apixaban had not been formally studied in this context.Objective: To evaluate the appropriateness of apixaban dosing for stroke prevention in patients with atrial fibrillation, relative to the dose used in the ARISTOTLE study and recommendations in the product monograph.Methods: This retrospective chart review was conducted at a 300-bed Canadian teaching hospital. All inpatients with atrial fibrillation for whom apixaban was prescribed for stroke prevention in March 2015 were considered for inclusion. The appropriateness of apixaban dosing was determined in relation to the ARISTOTLE methodology and product monograph recommendations (i.e., 5 mg PO bid, with a lower dosage of 2.5 mg PO bid if warranted on the basis of age, weight, or serum creatinine level).Results: A total of 47 patients were included, of whom 25 (53%) were receiving apixaban inconsistent with the ARISTOTLE study and the product monograph. Limitations of the current study included small sample size, single-centre setting, and retrospective design, which precluded determination of each prescriber’s rationale for dosage choice.Conclusions: Pharmacists and physicians should be vigilant in ensuring that patients with atrial fibrillation are receiving the appropriate dosage of apixaban to optimize the risk–benefit ratio of this therapy.RÉSUMÉContexte : L’étude ARISTOTLE portait sur l’utilisation de l’apixaban pour la prévention des accidents vasculaires cérébraux (AVC) chez les patients souffrant de fibrillation auriculaire à raison d’une dose de 5 mg par voie orale deux fois par jour. Or, des observations empiriques montrent que bon nombre de patients reçoivent une dose de 2,5 mg par voie orale deux fois par jour, même s’ils se qualifient pour la pleine dose. Une étude récente portant sur l’utilisation du dabigatran et du rivaroxaban a relevé que bon nombre de patients recevaient ces médicaments de façon inappropriée. Or, une recherche bibliographique effectuée en avril 2016 a révélé que l’apixaban n’a pas été officiellement étudié dans ce contexte.Objectif : Évaluer la pertinence du schéma posologique d’apixaban pour la prévention des AVC chez les patients souffrant de fibrillation auriculaire comparativement à la dose utilisée dans l’étude ARISTOTLE et aux recommandations contenues dans la monographie de produit.Méthodes : La présente analyse rétrospective de dossiers médicaux a été menée dans un seul centre hospitalier universitaire canadien de 300 lits. Tous les patients hospitalisés atteints de fibrillation auriculaire pour qui l’on a prescrit de l’apixaban afin de prévenir l’AVC en mars 2015 ont été pris en considération. La pertinence du schéma posologique d’apixaban était établie par rapport à la méthodologie de l’étude ARISTOTLE et aux recommandations de la monographie de produit (c’est-à-dire une dose de 5 mg par voie orale deux fois par jour et une dose réduite de 2,5 mg par voie orale deux fois par jour si l’âge, le poids et le taux de créatinine sérique la justifiaient).Résultats : Au total, 47 patients ont été admis. L’administration de l’apixaban n’était pas conforme à l’étude ARISTOTLE et à la monographie de produit chez 25 (53 %) d’entre eux. Parmi les limites de la présente étude, on comptait la petite taille de l’échantillon, son déroulement dans un seul centre et l’utilisation d’un plan d’étude rétrospectif qui empêchait de comprendre les raisons motivant le choix de posologie de chaque prescripteur.Conclusions : Les pharmaciens et les médecins doivent être vigilants et s’assurer que les patients atteints de fibrillation auriculaire reçoivent la posologie appropriée d’apixaban permettant d’optimiser le rapport bénéfice-risque de ce traitement.

Download Full-text

Fecal calprotectin in inflammatory bowel diseases: update and perspectives

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2016-0522 ◽

2017 ◽

Vol 55 (4) ◽

Cited By ~ 29

Author(s):

Hana Manceau ◽

Valérie Chicha-Cattoir ◽

Hervé Puy ◽

Katell Peoc’h

Keyword(s):

Inflammatory Bowel Diseases ◽

Therapeutic Response ◽

Fecal Calprotectin ◽

Intestinal Wall ◽

Therapeutic Monitoring ◽

Non Invasive ◽

Bowel Diseases ◽

Calprotectin Level ◽

Inflammatory Bowel

AbstractInflammatory bowel diseases (IBDs) are chronic diseases that result from the inflammation of the intestinal wall, suspected in any patient presenting with intestinal symptoms. Until recently, the diagnosis was mainly based on both clinical and endoscopic arguments. The use of an easy, fast, reliable, non-invasive, and inexpensive biological assay is mandatory not only in diagnosis but also in evolutionary and therapeutic monitoring. To date, the fecal calprotectin is the most documented in this perspective. This marker allows the discrimination between functional and organic bowel processes with good performance. The determination of the fecal calprotectin level contributes to the evaluation of the degree of disease activity and to monitoring of therapeutic response.

Download Full-text

A novel technology to integrate imaging and clinical markers for non-invasive diagnosis of lung cancer

Scientific Reports ◽

10.1038/s41598-021-83907-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ahmed Shaffie ◽

Ahmed Soliman ◽

Xiao-An Fu ◽

Michael Nantz ◽

Guruprasad Giridharan ◽

...

Keyword(s):

Lung Cancer ◽

Small Sample Size ◽

Pulmonary Nodules ◽

Small Sample ◽

Appearance Model ◽

Exhaled Breath ◽

Clinical Markers ◽

Imaging Data ◽

Non Invasive ◽

Diagnosis Of Lung Cancer

AbstractThis study presents a non-invasive, automated, clinical diagnostic system for early diagnosis of lung cancer that integrates imaging data from a single computed tomography scan and breath bio-markers obtained from a single exhaled breath to quickly and accurately classify lung nodules. CT imaging and breath volatile organic compounds data were collected from 47 patients. Spherical Harmonics-based shape features to quantify the shape complexity of the pulmonary nodules, 7th-Order Markov Gibbs Random Field based appearance model to describe the spatial non-homogeneities in the pulmonary nodule, and volumetric features (size) of pulmonary nodules were calculated from CT images. 27 VOCs in exhaled breath were captured by a micro-reactor approach and quantied using mass spectrometry. CT and breath markers were input into a deep-learning autoencoder classifier with a leave-one-subject-out cross validation for nodule classification. To mitigate the limitation of a small sample size and validate the methodology for individual markers, retrospective CT scans from 467 patients with 727 pulmonary nodules, and breath samples from 504 patients were analyzed. The CAD system achieved 97.8% accuracy, 97.3% sensitivity, 100% specificity, and 99.1% area under curve in classifying pulmonary nodules.

Download Full-text

Effect of Expanded Hemodialysis with Theranova® in Patients with COVID-19

Blood Purification ◽

10.1159/000520891 ◽

2022 ◽

pp. 1-9

Author(s):

María Luisa Serrano Salazar ◽

Jose Portolés ◽

Maria de Valdenebro Recio ◽

Silvia Rosado Garcia ◽

Maria del Rosario Llópez Carratalá ◽

...

Keyword(s):

Small Sample Size ◽

Statistical Significance ◽

Immunosuppressive Treatment ◽

Kidney Injury ◽

Small Sample ◽

Control Group ◽

Β2 Microglobulin ◽

Cytokine Levels ◽

To Come ◽

And Control

Introduction: Cytokine storm control is the main target for improving severe COVID-19 by using immunosuppressive treatment. Effective renal replacement therapy (RRT) could give us an advantage removing cytokines in patients with RRT requirements superimposed on COVID-19. Methods: This is a prospective observational study in COVID-19 patients who required hemodialysis (HD). Patients were assigned to online hemodiafiltration (OL-HDF) and expanded HD (HDx) according to Brescia group recommendations. We measured several cytokines, β2 microglobulin and albumin levels pre/post-dialysis and on 1st–2nd week. We compared levels among both techniques and control group (HD without COVID-19). Results: We included 26 patients: 18 with COVID-19 on RRT (5 of them had acute kidney injury [AKI]) and 8 controls. We confirm higher cytokine levels in COVID-19 patients than controls and even higher in patients with AKI than in those with chronic kidney disease. Most cytokines raised during HD session, except IL-10 and TNFα. IL-10 was eliminated by any dialysis technique, while clearance of TNFα was higher in the HDx group. HDx achieved a deeper normalization of cytokines and β2 microglobulin reduction. Mortality was higher in the OL-HDF group than the HDx group. Discussion: Not all cytokines behave equally along HD session. The following characteristics should be taken into account, such as intrinsic kinetic profile during a HD session. HDx seems to get better performance, probably due to the combination of different factors; however, we did not reach statistical significance due to the small sample size, dropout, and reduction of AKI incidence during the 2nd pandemic wave. Conclusion: HDx appears to provide better clearance for TNFα and β2 microglobulin during HD session and associates lower mortality. We propose the HDx technique for COVID-19 patients with RRT requirements since it seems to be safe and more effective than OL-HDF. Further studies are still needed, but we hope that our preliminary data may help us in future pandemic waves of SARS-CoV-2 or other viruses still to come.

Download Full-text

Diagnostic and prognostic value of microRNAs for Alzheimer’s disease: a comprehensive meta-analysis

Medicine and Pharmacy Reports ◽

10.15386/mpr-1393 ◽

2020 ◽

Author(s):

Cristina-Sorina Cătană ◽

Cătălina-Angela Crișan ◽

Dana Opre ◽

Ioana Berindan-Neagoe

Keyword(s):

English Language ◽

Small Sample Size ◽

Meta Analysis ◽

Diagnostic Value ◽

Small Sample ◽

Future Perspective ◽

Sufficient Information ◽

Novel Biomarkers ◽

The Right ◽

Statistical Indicators

Background and aims. Recent research has shown that microRNAs (miRNAs), a class of sequences regulating gene expression without undergoing translational processes, have been accepted as novel biomarkers of diseases. In the present meta-analysis, our main objective was to evaluate the diagnostic value of miRNAs expressed in different body fluids for AD, more exactly to analyze the discriminative value of miRNAs between AD and control subjects. Methods. Medline and EMBASE were searched for articles written in English language and because the result reporting modalities were extremely different in the studies included in the analysis, the current article comprises 2 meta-analysis studies, each of them using different statistical indicators. The first meta-analysis reviewed 10 studies, which were required to provide sufficient information to allow the calculation of AUC or Cohen’s d for size effect. We proposed a second meta-analysis, starting from the drawbacks identified in this first approach, which used different statistical indicators (fold change) provided by other studies (8 studies). Results. The present study offers an encouraging role of miRNA families in diagnosing AD. The heterogeneity of miRNA expression between the hippocampus, CSF and peripheral blood, the small sample size of each research study, as well as the different methods for miRNA detection remain the main obstacles in interpreting these results. Conclusions.There is a need (in a future perspective) to establish the right miRNA combinations as potent diagnostic biomarkers for AD.

Download Full-text