To determine whether a panel of blood-based biomarkers can discriminate between patients with suspected mild traumatic brain injury (mTBI) with and without neuroimaging findings (CT and MRI).
Study ...participants presented to the emergency department with suspected mTBI (n = 277) with a CT and MRI scan and healthy controls (n = 49). Plasma concentrations of tau, glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase L1, and neurofilament light chain (NFL) were measured using the single-molecule array technology.
Concentrations of GFAP, tau, and NFL were higher in patients with mTBI, compared with those of controls (
's < 0.01). GFAP yielded an area under the curve (AUC) of 0.93 (95% confidence interval CI 0.90-0.96), confirming its discriminatory power for distinguishing mTBI from controls. Levels of GFAP, tau, and NFL were higher in patients with trauma-related intracranial findings on CT compared with those with normal CT, with the only significant predictor being GFAP (AUC 0.77, 95% CI 0.70-0.84). Among patients with mTBI, tau, NFL, and GFAP differentiated subjects with and without MRI abnormalities with an AUC of 0.83, with GFAP being the strongest predictor. Combining tau, NFL, and GFAP showed a good discriminatory power (AUC 0.80, 95% CI 0.69-0.90) for detecting MRI abnormalities, even in patients with mTBI with a normal CT.
Our study confirms GFAP as a promising marker of brain injury in patients with acute mTBI. A combination of various biomarkers linked to different pathophysiologic mechanisms increases diagnostic subgroup accuracy. This multimarker strategy may guide medical decision making, facilitate the use of MRI scanning, and prove valuable in the stratification of patients with brain injuries in future clinical trials.
Class I evidence that blood concentrations of GFAP, tau, and NFL discriminate patients with mTBI with and without neuroimaging findings.
In order to improve assessment and outcome prediction in patients suffering from traumatic brain injury (TBI), cerebral protein levels in serum have been suggested as biomarkers of injury. However, ...despite much investigation, biomarkers have yet to reach broad clinical utility in TBI. This study is a 9-year follow-up and clinical experience of the two most studied proteins, neuron-specific enolase (NSE) and S100B, in a neuro-intensive care TBI population. Our aims were to investigate to what extent NSE and S100B, independently and in combination, could predict outcome, assess injury severity, and to investigate if the biomarker levels were influenced by extracranial factors.
All patients treated at the neuro-intensive care unit at Karolinska University Hospital, Stockholm, Sweden between 2005 and 2013 with at least three measurements of serum S100B and NSE (sampled twice daily) were retrospectively included. In total, 417 patients fulfilled the criteria. Parameters were extracted from the computerized hospital charts. Glasgow Outcome Score (GOS) was used to assess long-term functional outcome. Univariate, and multivariate, regression models toward outcome and what explained the high levels of the biomarkers were performed. Nagelkerke's pseudo-R(2) was used to illustrate the explained variance of the different models. A sliding window assessed biomarker correlation to outcome and multitrauma over time.
S100B was found a better predictor of outcome as compared to NSE (area under the curve (AUC) samples, the first 48 hours had Nagelkerke's pseudo-R(2) values of 0.132 and 0.038, respectively), where the information content of S100B peaks at approximately 1 day after trauma. In contrast, although both biomarkers were independently correlated to outcome, NSE had limited additional predictive capabilities in the presence of S100B in multivariate models, due to covariance between the two biomarkers (correlation coefficient 0.673 for AUC 48 hours). Moreover, NSE was to a greater extent correlated to multitrauma the first 48 hours following injury, whereas the effect of extracerebral trauma on S100B levels appears limited to the first 12 hours.
While both biomarkers are independently correlated to long-term functional outcome, S100B is found a more accurate outcome predictor and possibly a more clinically useful biomarker than NSE for TBI patients.
This study aims to provide a detailed clinical characterization of a large cohort of myotonic dystrophy type 2 (DM2) patients investigating the influence of age and gender as modifying factors of DM2 ...phenotype. A retrospective study was conducted on 307 patients with genetically confirmed DM2. The following data were analyzed: (1) demographics, (2) clinical features (first symptom, muscular complaints, and multisystemic involvement), (3) diagnostics (serological tests, electromyography, and muscle biopsy). In this cohort (186 females, 121 males), a proximal weakness was the leading symptom at onset (55.4%), followed by myalgia (35.5%) and myotonia (25.4%). Proximal weakness was more common in women than men (64.9 vs. 43.8%,
p
= 0.0006), whereas being male was associated with higher odds for developing myalgia OR 2.94 (95% CI 1.53–5.67). Patients with muscle weakness at onset were older than those with myalgia and myotonia (
p
< 0.0001), while each additional disease year was associated with 10% decrease in the odds of developing myotonia OR 0.9 (95% CI 0.87–0.93) and 6% decrease of myalgia OR 0.94 (95% CI 0.91–0.97). Cataract and thyroid diseases occurred more frequently in women (
p
= 0.002 and
p
= 0.002, respectively). Early onset of DM2 is an independent risk factor for the occurrence of multisystemic involvement OR 0.94 (95% CI 0.90–0.98). In this updated clinical description of DM2 emerges a profound gender and age influence on the phenotype, emphasizing that female gender and ageing may be associated with a higher disease burden. These age- and gender-specific differences should be considered in diagnostics, management, and future clinical studies of DM2.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Neurological diseases affect millions of peopleochemistryorldwide and are continuously increasing due to the globe’s aging population. Such diseases affect the nervous system and are characterized by ...a progressive decline in brain function and progressive cognitive impairment, decreasing the quality of life for those with the disease as well as for their families and loved ones. The increased burden of nervous system diseases demands a deeper insight into the biomolecular mechanisms at work during disease development in order to improve clinical diagnosis and drug design. Recently, evidence has related glycosylation to nervous system diseases. Glycosylation is a vital post-translational modification that mediates many biological functions, and aberrant glycosylation has been associated with a variety of diseases. Thus, the investigation of glycosylation in neurological diseases could provide novel biomarkers and information for disease pathology. During the last decades, many techniques have been developed for facilitation of reliable and efficient glycomic analysis. Among these, mass spectrometry (MS) is considered the most powerful tool for glycan analysis due to its high resolution, high sensitivity, and the ability to acquire adequate structural information for glycan identification. Along with MS, a variety of approaches and strategies are employed to enhance the MS-based identification and quantitation of glycans in neurological samples. Here, we review the advanced glycomic tools used in nervous system disease studies, including separation techniques prior to MS, fragmentation techniques in MS, and corresponding strategies. The glycan markers in common clinical nervous system diseases discovered by utilizing such MS-based glycomic tools are also summarized and discussed.
IntroductionBehavioural variant frontotemporal dementia (bvFTD) characterisation has evolved, but diagnosis remains challenging, relying on clinical diagnostic criteria that have undergone revisions ...over time. In this systematic review, our aims are to evaluate the accuracy of clinical diagnostic criteria for bvFTD by comparing them against pathological diagnoses and determine potential improvement in performance over the years.Methods and analysisThis systematic review protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 guidelines and is registered on PROSPERO. We will search four databases (MEDLINE-PubMed, Web of Science, Embase and LILACS) using tailored search terms on May 1st 2024. Inclusion criteria encompass peer-reviewed articles reporting diagnostic parameters or raw data regarding bvFTD clinical diagnosis based on well-defined criteria. Screening and selection of relevant articles will be independently performed by two reviewers using the Covidence systematic review manager. Discrepancies will be resolved by a third researcher. Pathologic and genetic diagnosis will be the main gold standard, but we will also consider refined diagnoses after a follow-up period. Data will be collected on study design, baseline demographics and sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy. Study quality will be assessed with Quality Assessment of Diagnostic Accuracy Studies-2. If possible, we will conduct a meta-analysis using bivariate random-effect models. Subgroup analyses will consider study settings, gold standards, disease stages and bias.Ethics and disseminationEthics approval will not be needed because the data used in this systematic review will be extracted from published studies. Findings will be disseminated through peer-reviewed publications and presentations at relevant scientific conferences, potentially enhancing our understanding of bvFTD clinical diagnosis reliability and guiding future criteria refinements.PROSPERO registration numberCRD42023389063.
Serum biomarkers are promising tools for evaluating patients following traumatic brain injury (TBI). However, their relationship with diffuse histopathology remains unclear. Additionally, ...translatability is a focus of neurotrauma research, however, studies using translational animal models are limited. Here, we evaluated associations between circulating biomarkers and acute thalamic histopathology in a translational micro pig model of mTBI. Serum samples were collected pre-injury, and 1 min-6 h following mTBI. Markers of neuronal injury (Ubiquitin Carboxy-terminal Hydrolase L1 UCH-L1), microglial/macrophage activation (Ionized calcium binding adaptor molecule-1 Iba-1) and interleukin-6 IL-6) and astrogliosis/astrocyte damage (glial fibrillary acidic protein GFAP) were measured. Axonal injury and histological features of neurons and glia were also investigated using immunofluorescent labeling and correlated to serum levels of the associated biomarkers. Consistent with prior experimental and human studies, GFAP, was highest at 6 h post-injury, while no substantial changes were observed in UCH-L1, Iba-1 or IL-6 over 6 h. This study also found promising associations between thalamic glial histological signatures and ensuing release of Iba-1 and GFAP into the circulation. Our findings suggest that in diffuse injury, monitoring serum Iba-1 and GFAP levels can provide clinically relevant insight into the underlying acute pathophysiology and biomarker release kinetics following mTBI, providing previously underappreciated diagnostic capability.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Traumatic brain injury (TBI) is a major global health issue, with outcomes spanning from intracranial bleeding, debilitating sequelae, and invalidity with consequences for individuals, families, and ...healthcare systems. Early diagnosis of TBI by testing peripheral fluids such as blood or saliva has been the focus of many research efforts, leading to FDA approval for a bench-top assay for blood GFAP and UCH-L1 and a plasma point-of-care test for GFAP. The biomarker S100B has been included in clinical guidelines for mTBI (mTBI) in Europe. Despite these successes, several unresolved issues have been recognized, including the robustness of prior data, the presence of biomarkers in tissues beyond the central nervous system, and the time course of biomarkers in peripheral body fluids. In this review article, we present some of these issues and provide a viewpoint derived from an analysis of existing literature. We focus on two astrocytic proteins, S100B and GFAP, the most commonly employed biomarkers used in mTBI. We also offer recommendations that may translate into a broader acceptance of these clinical tools.
The effects of night shift work on health status have been widely studied. Night workers seem to smoke more, eat badly and show a low propensity to physical activity. Night work can be associated ...with an increase in cardiovascular and gastrointestinal disorders, alterations in immune response, diabetes, aging, hormonal imbalance, and premature death; alteration of circadian rhythm is also regarded as a risk factor for breast cancer and neuropsychiatric disorders. Moreover, several studies have highlighted the effects of sleep deprivation on clinical performance, quality of care and personal safety of healthcare personnel. No studies have investigated the effects of night work on Italian resident physicians and compared its effect across specialties. This study aims to assess the prevalence of sleep disorders, possible cognitive impairment and mood states, in relation to night shift work among resident physicians.
80 resident physicians, attending the postgraduate training into an Hospital located in the South of Italy, were divided into 4 areas (medical, surgical, services and anaesthesia). They were recruited from July 2017 to June 2018 and participated to a survey consisting of 4 questionnaires to investigate the presence of sleep deprivation and sleep quality (Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index), their cognitive status (Mini Mental State examination) and mood profiles (Profile of Mood States, POMS). Analysis of variance was used for comparison of questionnaires scores across specialties.
Authors reported no sleep deprivation, no sleep disorders and their outcomes, no changes in intellectual efficiency and no cognitive impairment in this population, neither in the areas performing night shifts nor in those involving only day shifts. Mood states measured by POMS showed a borderline level of Anger-Hostility (A) value among the residents of the medical area and services, and an increase slightly beyond the physiological levels of the T-score 50 of Fatigue-Inertia (F) always in the same groups. An increase in the Vigour-Activity (V) value beyond T-score 50 levels was also observed among residents of all the areas considered.
Emotional involvement could be attributed to the gap between high professional demand and lack of experience and knowledge among trainees. Tutors should help their students in order to identify earlier changes in the mood. Improvement in the organization of the trainee's activity could reduce the emotional overload.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The proteins S100B, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and neurofilament light (NF-L) have been serially sampled ...in serum of patients suffering from traumatic brain injury (TBI) in order to assess injury severity and tissue fate. We review the current literature of serum level dynamics of these proteins following TBI and used the term "effective half-life" (
) in order to describe the "fall" rate in serum.
Through searches on EMBASE, Medline, and Scopus, we looked for articles where these proteins had been serially sampled in serum in human TBI. We excluded animal studies, studies with only one presented sample and studies without neuroradiological examinations.
Following screening (10,389 papers),
= 122 papers were included. The proteins S100B (
= 66) and NSE (
= 27) were the two most frequent biomarkers that were serially sampled. For S100B in severe TBI, a majority of studies indicate a
of about 24 h, even if very early sampling in these patients reveals rapid decreases (1-2 h) though possibly of non-cerebral origin. In contrast, the
for NSE is comparably longer, ranging from 48 to 72 h in severe TBI cases. The protein GFAP (
= 18) appears to have
of about 24-48 h in severe TBI. The protein UCH-L1 (
= 9) presents a
around 7 h in mild TBI and about 10 h in severe. Frequent sampling of these proteins revealed different trajectories with persisting high serum levels, or secondary peaks, in patients with unfavorable outcome or in patients developing secondary detrimental events. Finally, NF-L (
= 2) only increased in the few studies available, suggesting a serum availability of >10 days. To date, automated assays are available for S100B and NSE making them faster and more practical to use.
Serial sampling of brain-specific proteins in serum reveals different temporal trajectories that should be acknowledged. Proteins with shorter serum availability, like S100B, may be superior to proteins such as NF-L in detection of secondary harmful events when monitoring patients with TBI.
Cancer anorexia-cachexia syndrome (CACS) is the most frequent paraneoplastic syndrome occurring in half of all oncologic patients and is considered as a poor prognosticator. Patients usually present ...with weight loss, lipolysis, muscle wasting, anorexia, chronic nausea, inflammation, and asthenia. The etiopathogenesis of CACS is still poorly understood, although several factors and biological pathways are known to be involved. Because of the complexity of this multifactorial condition, a single agent therapy may not be sufficient. Indeed, there is a tendency toward an integrated multiple approach including nonpharmacological and pharmacological treatments. However, despite encouraging preliminary results, currently there is not enough evidence to support a change in clinical practice. This review provides a brief and practical summary of the diagnosis, pathogenesis, and treatment of CACS. Future perspectives will also be discussed.
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DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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