| 238581. |
- Simrén, Joel, 1996, et al.
(author)
-
Establishment of reference values for plasma neurofilament light based on healthy individuals aged 5-90 years
- 2022
-
In: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 4:4
-
Journal article (peer-reviewed)abstract
- The recent development of assays that accurately quantify neurofilament light, a neuronal cytoskeleton protein, in plasma has generated a vast literature supporting that it is a sensitive, dynamic, and robust biomarker of neuroaxonal damage. As a result, efforts are now made to introduce plasma neurofilament light into clinical routine practice, making it an easily accessible complement to its cerebrospinal fluid counterpart. An increasing literature supports the use of plasma neurofilament light in differentiating neurodegenerative diseases from their non-neurodegenerative mimics and suggests it is a valuable biomarker for the evaluation of the effect of putative disease-modifying treatments (e.g. in multiple sclerosis). More contexts of use will likely emerge over the coming years. However, to assist clinical interpretation of laboratory test values, it is crucial to establish normal reference intervals. In this study, we sought to derive reliable cut-offs by pooling quantified plasma neurofilament light in neurologically healthy participants (5-90 years) from eight cohorts. A strong relationship between age and plasma neurofilament light prompted us to define the following age-partitioned reference limits (upper 95(th) percentile in each age category): 5-17 years = 7 pg/mL; 18-50 years = 10 pg/mL; 51-60 years = 15 pg/mL; 61-70 years = 20 pg/mL; 70 + years = 35 pg/mL. The established reference limits across the lifespan will aid the introduction of plasma neurofilament light into clinical routine, and thereby contribute to diagnostics and disease-monitoring in neurological practice. Simren et al. report age-stratified cut-offs for plasma neurofilament light, based on a large material of healthy individuals across the ages 5-90 years. The findings will assist clinical implementation of plasma neurofilament light in clinical routine, by simplifying interpretation of concentrations across the lifespan as neurofilament light increases with age.
|
|
| 238582. |
- Simrén, Joel, 1996, et al.
(author)
-
Fluid biomarkers in Alzheimer's disease
- 2022
-
In: Advances in Clinical Chemistry. - : Elsevier. - 0065-2423. ; , s. 249 - 281
-
Book chapter (peer-reviewed)abstract
- Alzheimer's disease (AD) characterization has progressed from being indexed using clinical symptomatology followed by neuropathological examination at autopsy to in vivo signatures using cerebrospinal fluid (CSF) biomarkers and positron emission tomography. The core AD biomarkers reflect amyloid-β plaques (A), tau pathology (T) and neurodegeneration (N), following the ATN schedule, and are now being introduced into clinical routine practice. This is an important development, as disease-modifying treatments are now emerging. Further, there are now reproducible data on CSF biomarkers which reflect synaptic pathology, neuroinflammation and common co-pathologies. In addition, the development of ultrasensitive techniques has enabled the core CSF biomarkers of AD pathophysiology to be translated to blood (e.g., phosphorylated tau, amyloid-β and neurofilament light). In this chapter, we review where we stand with both core and novel CSF biomarkers, as well as the explosion of data on blood biomarkers. Also, we discuss potential applications in research aiming to better understand the disease, as well as possible use in routine clinical practice and therapeutic trials.
|
|
| 238583. |
- Simrén, Joel, 1996, et al.
(author)
-
The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer's disease
- 2021
-
In: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 17:7, s. 1145-1156
-
Journal article (peer-reviewed)abstract
- Introduction: This study investigated the diagnostic and disease-monitoring potential of plasma biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia and cognitively unimpaired (CU) individuals. Methods: Plasma was analyzed using Simoa assays from 99 CU, 107 MCI, and 103 AD dementia participants. Results: Phosphorylated-tau181 (P-tau181), neurofilament light, amyloid-β (Aβ42/40), Total-tau and Glial fibrillary acidic protein were altered in AD dementia but P-tau181 significantly outperformed all biomarkers in differentiating AD dementia from CU (area under the curve [AUC] = 0.91). P-tau181 was increased in MCI converters compared to non-converters. Higher P-tau181 was associated with steeper cognitive decline and gray matter loss in temporal regions. Longitudinal change of P-tau181 was strongly associated with gray matter loss in the full sample and with Aβ measures in CU individuals. Discussion: P-tau181 detected AD at MCI and dementia stages and was strongly associated with cognitive decline and gray matter loss. These findings highlight the potential value of plasma P-tau181 as a non-invasive and cost-effective diagnostic and prognostic biomarker in AD.
|
|
| 238584. |
- Simrén, Magnus, 1966, et al.
(author)
-
Cumulative Effects of Psychologic Distress, Visceral Hypersensitivity, and Abnormal Transit on Patient-reported Outcomes in Irritable Bowel Syndrome
- 2019
-
In: Gastroenterology. - : Elsevier BV. - 0016-5085. ; 157:2, s. 391-402
-
Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: Little is known about the link between pathophysiologic factors and symptoms of irritable bowel syndrome (IBS), or whether these factors have cumulative effects on patient-reported outcomes (PROs). We investigated whether pathophysiologic alterations associated with IBS have cumulative or independent effects on PROs. METHODS: We performed a retrospective analysis of data from 3 cohorts of patients with IBS (n = 407; 74% female; mean age, 36 +/- 12 years), based on Rome II or Rome III criteria, seen at a specialized unit for functional gastrointestinal disorders in Sweden from 2002 through 2014. All patients underwent assessments of colonic transit time (radiopaque markers); compliance, allodynia, and hyperalgesia (rectal barostat); anxiety and depression (Hospital Anxiety and Depression scale), as pathophysiologic factors. Dysfunction was defined by available normal values. PROs included IBS symptom severity, somatic symptom severity, and disease-specific quality of life. RESULTS: Allodynia was observed in 36% of patients, hyperalgesia in 22%, accelerated colonic transit in 18%, delayed transit in 7%, anxiety in 52%, and depression in 24%: each of these factors was associated with severity of at least 1 symptom of IBS. Rectal compliance was not associated with more severe symptoms of IBS. At least 3 pathophysiologic factors were present in 20% of patients, 2 in 30%, 1 in 31%, and none in 18%. With increasing number of pathophysiologic abnormalities, there was a gradual increase in IBS symptom severity (P < .0001) and somatic symptom severity (P < .0001), and a gradual reduction in quality of life (P < .0001). CONCLUSION: Visceral hypersensitivity, including allodynia and hyperalgesia, abnormal colonic transit, and psychologic factors are all associated with IBS symptoms. These factors have a cumulative effect on gastrointestinal and non-gastrointestinal symptoms, as well as on quality of life, in patients with IBS and are therefore relevant treatment targets.
|
|
| 238585. |
- Simrén, Magnus, 1966, et al.
(author)
-
General management of irritable bowel syndrome
- 2013
-
In: Clinical Insights: Irritable Bowel Syndrome: Diagnosis and Management. - : Future Medicine. - 9781780843513 ; , s. 195-200
-
Book chapter (other academic/artistic)
|
|
| 238586. |
- Simrén, Magnus, 1966, et al.
(author)
-
New treatments and therapeutic targets for IBS and other functional bowel disorders
- 2018
-
In: Nature Reviews Gastroenterology & Hepatology. - : Springer Science and Business Media LLC. - 1759-5045 .- 1759-5053. ; 15:10, s. 589-605
-
Journal article (peer-reviewed)abstract
- Functional bowel disorders (FBDs) are a spectrum of disorders characterized by combinations of symptoms attributable to the lower gastrointestinal tract. Most current first-line therapies for IBS and other FBDs target the predominant symptom and mainly affect one symptom in the symptom complex. Additional broadly effective treatment alternatives targeting the entire symptom complex are needed. New drugs for FBDs (such as lubiprostone, linaclotide, plecanatide, prucalopride, eluxadoline and rifaximin) target key mechanisms in the pathophysiology of these disorders and improve both the abnormal bowel habit and other key symptoms, such as abdominal pain and bloating. The current development of new treatment alternatives is focusing on different aspects of the complex pathophysiology of IBS and other FBDs: gut microenvironment (via diet and modulation of gut microbiota), enterohepatic circulation of bile acids, gastrointestinal secretion, motility and sensation, gut-brain interactions, gut barrier function and the immune system within the gastrointestinal tract. Studies also suggest that personalized treatment of IBS and other FBDs is possible using various diagnostic markers.
|
|
| 238587. |
|
|
| 238588. |
- Simrén, Magnus, 1966, et al.
(author)
-
Visceral hypersensitivity is associated with GI symptom severity in functional GI disorders: consistent findings from five different patient cohorts
- 2018
-
In: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 67:2, s. 255-262
-
Journal article (peer-reviewed)abstract
- Objective Our aim was to evaluate the association between visceral hypersensitivity and GI symptom severity in large cohorts of patients with functional GI disorder (FGID) and to adjust for psychological factors and general tendency to report symptoms. Design We included five cohorts of patients with FGIDs (IBS or functional dyspepsia; n=1144), who had undergone visceral sensitivity testing using balloon distensions (gastric fundus, descending colon or rectum) and completed questionnaires to assess GI symptom severity, non-GI somatic symptoms, anxiety and depression. Subjects were divided into sensitivity tertiles based on pain/discomfort thresholds. GI symptom severity was compared between sensitivity tertiles in each cohort and corrected for somatisation, and anxiety and depression. Results In all five cohorts, GI symptom severity increased gradually with increasing visceral sensitivity, with significant differences in GI symptom severity between the sensitivity tertiles (p<0.0001), with small to medium effect sizes (partial eta(2): 0.047-0.11). The differences between sensitivity tertiles remained significant in all cohorts after correction for anxiety and depression, and also after correction for non-GI somatic symptom reporting in all of the cohorts (p<0.05). Conclusions A gradual increase in GI symptom severity with increasing GI sensitivity was demonstrated in IBS and functional dyspepsia, which was consistent across several large patient groups from different countries, different methods to assess sensitivity and assessments in different parts of the GI tract. This association was independent of tendency to report symptoms or anxiety/depression comorbidity. These findings confirm that visceral hypersensitivity is a contributor to GI symptom generation in FGIDs.
|
|
| 238589. |
- Simrén, Yvonne, 1966, et al.
(author)
-
Diffusion weighted imaging is a promising method to detect acute pyelonephritis in non-sedated free breathing infants
- 2020
-
In: Journal of Pediatric Urology. - : Elsevier BV. - 1477-5131. ; 16, s. 320-325
-
Journal article (peer-reviewed)abstract
- Introduction: Urinary tract infection (UTI) is a common disease in infants. The initial evaluation includes imaging to identify risk factors for permanent renal damage, such as malformation and renal parenchymal involvement of the infection i.e. pyelonephritis. 99mTc-Dimercaptosuccinic acid (DMSA) scintigraphy is a well-established method for detection of pyelonephritis and renal damage, but has limitations in availability, spatial resolution, and detection of congenital malformations. Diffusion weighted magnetic resonance imaging (DWI) has been shown to have a high sensitivity for detection of pyelonephritis in children without the use of invasive procedures, contrast agents or ionizing radiation. How this method performs in young infants during non-sedated free breathing remains, however, to be investigated. Objective: To prospectively assess the feasibility and performance of DWI for detection of pyelonephritis in non-sedated free breathing infants. Methods: 32 children <6 months of age with first-time symptomatic UTI were examined with DWI and DMSA scintigraphy. The DWI examination was performed using a free breathing protocol without the use of sedation. Pyelonephritic lesions were registered for both methods by independent observers. Agreement between DWI and DMSA was evaluated. Consensus diagnosis was determined and compared to the DWI findings. Results: The MRI and DMSA examinations were completed in 25 infants, with a median age of 1.7 (0.7–5.5) months. Focal uptake reductions were detected on the DMSA images in 12 (24%) of the 50 kidneys. The DWI method demonstrated a fair to good agreement with DMSA, k = 0.50 (p < 0.0001). The consensus diagnosis was pyelonephritis in eight (16%) of the 50 kidneys. DWI detected seven of the eight kidneys with pyelonephritis. No false positive findings were detected with DWI compared to consensus diagnosis. Discussion: This study has shown an agreement between DWI and DMSA scintigraphy in the detection of pyelonephritis. Further validation of the performance of DWI, using a consensus diagnosis as a reference, confirmed the potential of the method. This feasibility study included a limited number of patients and the results need to be confirmed in a prospective study of a larger cohort. Conclusion: Free breathing DWI is a promising method for detection of pyelonephritic lesions in non-sedated infants.[Formula presented] © 2020 Journal of Pediatric Urology Company
|
|
| 238590. |
- Simrén, Yvonne, 1966, et al.
(author)
-
Ultrasound is an effective and noninvasive method of evaluating renal swelling in infants with their first urinary tract infection
- 2017
-
In: Acta Paediatrica. - : Wiley. - 0803-5253. ; 106:11, s. 1868-1874
-
Journal article (peer-reviewed)abstract
- Aim: This study evaluated renal swelling in infants with a first urinary tract infection (UTI) by correlating renal length and volume with C-reactive protein (CRP) and body temperature. Methods: Ultrasounds were carried out on 104 infants at The Queen Silvia Children's Hospital, Gothenburg, Sweden - 58 boys (mean age 3.3 months) and 46 girls (mean age 4.8 months) - during the acute phase of their UTI. A second scan was performed on 94 of them 4 weeks later. Renal length and volume were computed to standard deviation scores (SDS). Results: The mean renal length and volume at the first ultrasound were 1.90 SDS (1.54) and 1.67 SDS (+/- 1.13) for the larger kidney and 0.86 SDS (+/- 1.01) and 0.84 SDS (+/- 0.90) for the smaller kidney. There was a significant decrease in renal length and volume between the two ultrasounds, with a mean difference of 0.96 SDS (+/- 1.24) and 1.07 SDS (+/- 1.10) for the larger kidney (p < 0.0001). The length and volume of the larger kidney correlated with CRP (p < 0.001), but only the renal length correlated with fever (p < 0.001). Conclusion: Early ultrasound determined renal swelling in infants with a UTI and may be a valuable noninvasive way of identifying infants with renal parenchymal involvement.
|
|
