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Neurologia 2024Availability of adequate normative data is essential when performing neuropsychological evaluation; good methodological quality of the studies that propose these data...
INTRODUCTION
Availability of adequate normative data is essential when performing neuropsychological evaluation; good methodological quality of the studies that propose these data ensures that their conclusions are reliable and valid. We present the methodological characteristics of the Neuronorma Colombia Project in order to analyse its contributions and limitations.
METHOD
We present the characteristics of the normative sample, inclusion and exclusion criteria, statistical analysis, the procedure for obtaining normative data, and the instruments used.
RESULTS
We present graphical profiles of patient performance, based on the Neuronorma Work Unit, to illustrate the interpretation of the results obtained when evaluating patients with the Neuronorma Colombia Battery.
DISCUSSION AND CONCLUSIONS
Our study presents several methodological advantages, such as its multicentre, co-normalised design and the availability of the Neuronorma Work Unit, which allows the creation of graphical profiles of patient performance, a fundamental tool for diagnosis and research. We present the findings of subsequent research based on the proposed normative data, which demonstrate the value of the battery. The contribution of this study is discussed in the context of its immediate background.
Topics: Humans; Aged; Colombia; Reference Values; Educational Status; Geriatric Assessment; Neuropsychological Tests
PubMed: 38056593
DOI: 10.1016/j.nrleng.2023.12.001 -
International Journal of Molecular... Aug 2023Mesenchymal stem cell secretome or conditioned medium (MSC-CM) is a combination of biomolecules and growth factors in cell culture growth medium, secreted by mesenchymal... (Review)
Review
Mesenchymal stem cell secretome or conditioned medium (MSC-CM) is a combination of biomolecules and growth factors in cell culture growth medium, secreted by mesenchymal stem cells (MSCs), and the starting point of several derived products. MSC-CM and its derivatives could be applied after injuries and could mediate most of the beneficial regenerative effects of MSCs without the possible side effects of using MSCs themselves. However, before the clinical application of these promising biopharmaceuticals, several issues such as manufacturing protocols and quality control must be addressed. This review aims to underline the influence of the procedure for conditioned medium production on the quality of the secretome and its derivatives and highlights the questions considering cell sources and donors, cell expansion, cell passage number and confluency, conditioning period, cell culture medium, microenvironment cues, and secretome-derived product purification. A high degree of variability in MSC secretomes is revealed based on these parameters, confirming the need to standardize and optimize protocols. Understanding how bioprocessing and manufacturing conditions interact to determine the quantity, quality, and profile of MSC-CM is essential to the development of good manufacturing practice (GMP)-compliant procedures suitable for replacing mesenchymal stem cells in regenerative medicine.
Topics: Secretome; Culture Media, Conditioned; Quality Control; Mesenchymal Stem Cells; Reference Standards
PubMed: 37628774
DOI: 10.3390/ijms241612594 -
Frontiers in Endocrinology 2023Standard treatment for acromegaly focuses on the achievement of target absolute levels of growth hormone (GH) and insulin-like growth factor (IGF-I). The appropriateness... (Review)
Review
Standard treatment for acromegaly focuses on the achievement of target absolute levels of growth hormone (GH) and insulin-like growth factor (IGF-I). The appropriateness of these targets when measured using modern assay methods is not well defined. This paper reviews biochemical status assessed using methods available at the time and associated clinical outcomes. GH measurements were shown to provide an indication of changes in tumor size, and failure of GH suppression after glucose stimulation is associated with tumor recurrence. IGF-I levels were more closely associated with changes in symptoms and signs. Reduced GH and IGF-I concentrations were shown to be associated with increased longevity, although the degree of increase has only been analyzed for GH. Lowering of GH and IGF-I has consistently been associated with improved outcomes; however, absolute levels reported in previous studies were based on results from methods and reference ranges that are now obsolete. Applying previously described absolute thresholds as targets (e.g. "normal" IGF-I level) when using current methods is best applied to those with active acromegaly symptoms who could benefit from further lowering of biochemical markers. In asymptomatic individuals with mild IGF-I or GH elevations, targeting biochemical "normalization" would result in the need for combination pharmacotherapy in many patients without proven benefit. Measurement of both GH and IGF-I remains an essential component of diagnosis and monitoring the effectiveness of treatment in acromegaly; however, treatment goals based only on previously identified absolute thresholds are not appropriate without taking into account the assay and reference ranges being employed. Treatment goals should be individualized considering biochemical improvement from an untreated baseline, symptoms of disease, risks, burdens and costs of complex treatment regimens, comorbidities, and quality of life.
Topics: Humans; Acromegaly; Growth Hormone; Insulin-Like Growth Factor I; Reference Values; Quality of Life; Human Growth Hormone; Treatment Outcome
PubMed: 38027199
DOI: 10.3389/fendo.2023.1266339 -
Clinical Chemistry and Laboratory... Aug 2023Free thyroxine (FT4) in serum is routinely measured in clinical practice to diagnose and monitor thyroid disease. Due to its concentration in picomolar range and the...
OBJECTIVES
Free thyroxine (FT4) in serum is routinely measured in clinical practice to diagnose and monitor thyroid disease. Due to its concentration in picomolar range and the delicate equilibrium of free and protein-bound T4, accurate measurement is challenging. As a consequence, large inter-method differences in FT4 results exists. Optimal method design and standardization of the FT4 measurement is therefore necessary. The IFCC Working Group for Standardization of Thyroid Function Tests proposed a reference system with a conventional reference measurement procedure (cRMP) for FT4 in serum. In this study, we describe our FT4 candidate cRMP and its validation in clinical samples.
METHODS
This candidate cRMP is based on equilibrium dialysis (ED) combined with determination of T4 with an isotope-dilution liquid chromatography tandem mass-spectrometry (ID-LC-MS/MS) procedure and was developed according to the endorsed conventions. Its accuracy, reliability, and comparability was investigated using human sera.
RESULTS
It was shown that the candidate cRMP adhered to the conventions and its accuracy, precision, and robustness were adequate in serum of healthy volunteers.
CONCLUSIONS
Our candidate cRMP measures FT4 accurately and performs well in serum matrix.
Topics: Humans; Chromatography, Liquid; Thyroxine; Reproducibility of Results; Tandem Mass Spectrometry; Renal Dialysis; Isotopes; Reference Standards
PubMed: 36994743
DOI: 10.1515/cclm-2022-1134 -
PloS One 2023The increasing application of TMS in research and therapy has spawned an ever-growing number of commercial and non-commercial TMS devices and technology development. New...
The increasing application of TMS in research and therapy has spawned an ever-growing number of commercial and non-commercial TMS devices and technology development. New CE-marked devices appear at a rate of approximately one every two years, with new FDA-approved application of TMS occurring at a similar rate. With the resulting complex landscape of TMS devices and their application, accessible information about the technological characteristics of the TMS devices, such as the type of their circuitry, their pulse characteristics, or permitted protocols would be beneficial. We here present an overview and open access database summarizing key features and applications of available commercial and non-commercial TMS devices (http://www.tmsbase.info). This may guide comparison and decision making about the use of these devices. A bibliometric analysis was performed by identifying commercial and non-commercial TMS devices from which a comprehensive database was created summarizing their publicly available characteristics, both from a technical and clinical point of view. In this document, we introduce both the commercial devices and prototypes found in the literature. The technical specifications that unify these devices are briefly analysed in two separate tables: power electronics, waveform, protocols, and coil types. In the prototype TMS systems, the proposed innovations are focused on improving the treatment regarding the patient: noise cancellation, controllable parameters, and multiple stimulation. This analysis shows that the landscape of TMS is becoming increasingly fragmented, with new devices appearing ever more frequently. The review provided here can support development of benchmarking frameworks and comparison between TMS systems, inform the choice of TMS platforms for specific research and therapeutic applications, and guide future technology development for neuromodulation devices. This standardisation strategy will allow a better end-user choice, with an impact on the TMS manufacturing industry and a homogenisation of patient samples in multi-centre clinical studies. As an open access repository, we envisage the database to grow along with the dynamic development of TMS devices and applications through community-lead curation.
Topics: Humans; Transcranial Magnetic Stimulation; Electronics; Reference Standards
PubMed: 38015924
DOI: 10.1371/journal.pone.0292733 -
BMJ Open Jul 2023Two blood brain-derived biomarkers, glial fibrillar acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), can rule out intracranial lesions in...
Study protocol for investigating the clinical performance of an automated blood test for glial fibrillary acidic protein and ubiquitin carboxy-terminal hydrolase L1 blood concentrations in elderly patients with mild traumatic BRAIN Injury and reference values (BRAINI-2 Elderly European study): a...
INTRODUCTION
Two blood brain-derived biomarkers, glial fibrillar acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), can rule out intracranial lesions in patients with mild traumatic brain injury (mTBI) when assessed within the first 12 hours. Most elderly patients were excluded from previous studies due to comorbidities. Biomarker use in elderly population could be affected by increased basal levels. This study will assess the performance of an automated test for measuring serum GFAP and UCH-L1 in elderly patients to predict the absence of intracranial lesions on head CT scans after mTBI, and determine both biomarkers reference values in a non-TBI elderly population.
METHODS AND ANALYSIS
This is a prospective multicentre observational study on elderly patients (≥65 years) that will be performed in Spain, France and Germany. Two patient groups will be included in two independent substudies. (1) A cohort of 2370 elderly patients (1185<80 years and 1185≥80 years; BRAINI2-ELDERLY DIAGNOSTIC AND PROGNOSTIC STUDY) with mTBI and a brain CT scan that will undergo blood sampling within 12 hours after mTBI. The primary outcome measure is the diagnostic performance of GFAP and UCH-L1 measured using an automated assay for discriminating between patients with positive and negative findings on brain CT scans. Secondary outcome measures include the performance of both biomarkers in predicting early (1 week) and midterm (3 months) neurological status and quality of life after trauma. (2) A cohort of 480 elderly reference participants (BRAINI2-ELDERLY REFERENCE STUDY) in whom reference values for GFAP and UCHL1 will be determined.
ETHICS AND DISSEMINATION
Ethical approval was obtained from the Institutional Review Boards of Hospital 12 de Octubre in Spain (Re#22/027) and Southeast VI (Clermont Ferrand Hospital) (Re# 22.01782.000095) in France. The study's results will be presented at scientific meetings and published in peer-review publications.
TRIAL REGISTRATION NUMBER
NCT05425251.
Topics: Humans; Aged; Brain Concussion; Prospective Studies; Glial Fibrillary Acidic Protein; Ubiquitin Thiolesterase; Quality of Life; Reference Values; Biomarkers; Hematologic Tests; Brain Injuries, Traumatic; Observational Studies as Topic; Multicenter Studies as Topic
PubMed: 37460257
DOI: 10.1136/bmjopen-2022-071467 -
Nuclear Medicine Communications Jan 2024
Topics: Nuclear Medicine; Reference Standards; United Kingdom; Positron-Emission Tomography
PubMed: 37901922
DOI: 10.1097/MNM.0000000000001779 -
Frontiers in Endocrinology 2023Septic patients with diabetes mellitus (DM) are more venerable to subsequent complications and the resultant increase in associated mortality. Therefore, it is important...
BACKGROUND
Septic patients with diabetes mellitus (DM) are more venerable to subsequent complications and the resultant increase in associated mortality. Therefore, it is important to make tailored clinical decisions for this subpopulation at admission.
METHOD
Data from large-scale real-world databases named the Medical Information Mart for Intensive Care Database (MIMIC) were reviewed. The least absolute selection and shrinkage operator (LASSO) was performed with 10 times cross-validation methods to select the optimal prognostic factors. Multivariate COX regression analysis was conducted to identify the independent prognostic factors and nomogram construction. The nomogram was internally validated the bootstrapping method and externally validated by the MIMIC III database with receiver operating characteristic (ROC), calibration curves, decision curve analysis (DCA), and Kaplan-Meier curves for robustness check.
RESULTS
A total of 3,291 septic patients with DM were included in this study, 2,227 in the MIMIC IV database and 1,064 in the MIMIC III database, respectively. In the training cohort, the 28-day all-cause mortality rate is 23.9% septic patients with DM. The multivariate Cox regression analysis reveals age (hazard ratio (HR)=1.023, 95%CI: 1.016-1.031, p<0.001), respiratory failure (HR=1.872, 95%CI: 1.554-2.254, p<0.001), Sequential Organ Failure Assessment score (HR=1.056, 95%CI: 1.018-1.094, p=0.004); base excess (HR=0.980, 95%CI: 0.967-0.992, p=0.002), anion gap (HR=1.100, 95%CI: 1.080-1.120, p<0.001), albumin (HR=0.679, 95%CI: 0.574-0.802, p<0.001), international normalized ratio (HR=1.087, 95%CI: 1.027-1.150, p=0.004), red cell distribution width (HR=1.056, 95%CI: 1.021-1.092, p=0.001), temperature (HR=0.857, 95%CI: 0.789-0.932, p<0.001), and glycosylated hemoglobin (HR=1.358, 95%CI: 1.320-1.401, p<0.001) at admission are independent prognostic factors for 28-day all-cause mortality of septic patients with DM. The established nomogram shows satisfied accuracy and clinical utility with AUCs of 0.870 in the internal validation and 0.830 in the external validation cohort as well as 0.820 in the septic shock subpopulation, which is superior to the predictive value of the single SOFA score.
CONCLUSION
Our results suggest that admission characteristics show an optimal prediction value for short-term mortality in septic patients with DM. The established model can support intensive care unit physicians in making better initial clinical decisions for this subpopulation.
Topics: Humans; Diabetes Mellitus; Albumins; Area Under Curve; Calibration; Sepsis
PubMed: 37608790
DOI: 10.3389/fendo.2023.1237866 -
Clinical Chemistry and Laboratory... Oct 2023
Topics: Humans; Reference Standards; Calibration
PubMed: 37540784
DOI: 10.1515/cclm-2023-0753 -
Journal of Translational Medicine May 2024The appropriate use of predictive equations in estimating body composition through bioelectrical impedance analysis (BIA) depends on the device used and the subject's... (Review)
Review
The appropriate use of predictive equations in estimating body composition through bioelectrical impedance analysis (BIA) depends on the device used and the subject's age, geographical ancestry, healthy status, physical activity level and sex. However, the presence of many isolated predictive equations in the literature makes the correct choice challenging, since the user may not distinguish its appropriateness. Therefore, the present systematic review aimed to classify each predictive equation in accordance with the independent parameters used. Sixty-four studies published between 1988 and 2023 were identified through a systematic search of international electronic databases. We included studies providing predictive equations derived from criterion methods, such as multi-compartment models for fat, fat-free and lean soft mass, dilution techniques for total-body water and extracellular water, total-body potassium for body cell mass, and magnetic resonance imaging or computerized tomography for skeletal muscle mass. The studies were excluded if non-criterion methods were employed or if the developed predictive equations involved mixed populations without specific codes or variables in the regression model. A total of 106 predictive equations were retrieved; 86 predictive equations were based on foot-to-hand and 20 on segmental technology, with no equations used the hand-to-hand and leg-to-leg. Classifying the subject's characteristics, 19 were for underaged, 26 for adults, 19 for athletes, 26 for elderly and 16 for individuals with diseases, encompassing both sexes. Practitioners now have an updated list of predictive equations for assessing body composition using BIA. Researchers are encouraged to generate novel predictive equations for scenarios not covered by the current literature.Registration code in PROSPERO: CRD42023467894.
Topics: Electric Impedance; Humans; Body Composition; Male; Female; Reference Standards; Adult; Middle Aged
PubMed: 38812005
DOI: 10.1186/s12967-024-05272-x