| 41. |
|
|
| 42. |
|
|
| 43. |
|
|
| 44. |
- Lindskov, Susanne, et al.
(författare)
-
Weight stability in Parkinson's disease
- 2016
-
Ingår i: Nutritional Neuroscience. - : Maney Publishing. - 1476-8305 .- 1028-415X. ; 19:1, s. 11-20
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Parkinson's disease (PD) has traditionally been associated with weight loss. However, recent studies have not found any evidence of underweight in PD. Nevertheless, few studies have addressed nutritional status changes over time in relation to other clinical PD features. Here, we explore changes in nutritional status and motor and non-motor PD features (including dopaminergic drug therapy) in PD patients after 1 year. Methods: Motor and non-motor PD features, dopaminergic drug therapy, under-nutrition and malnutrition risk, and anthropometric measures (BMI, handgrip strength, triceps skin-fold, mid-arm circumference, and mid-upper arm muscle circumference) were assessed at baseline and 1 year later among 65 people with PD. Results: Disability, PD motor symptoms, dysautonomia, and dopaminergic drug therapy increased. Underweight was uncommon both at baseline (n= 3) and follow-up (n = 2); malnutrition risk was common but stable (88 and 92%), whereas triceps skin-fold increased (P = 0.030); mid-upper arm muscle circumference decreased (P = 0.002); and the proportion of people with low handgrip strength (P = 0.012) increased. Correlations between nutritional variables and motor and non-motor PD features were absent to modest. Multiple linear regression analysis showed that baseline pupillomotor functioning was associated with decreased weight and BMI, and sleep with increased weight and BMI. In addition, increases in anxiety were associated with decreased weight, BMI, and triceps skin-fold. Discussion: During the PD course, there seems to be redistribution in body composition from muscle to fat. Studies are needed to identify possible explanations for the findings. This implies that malnutrition should be regularly screened to identify those at risk of developing reduced muscle mass and increased morbidity.
|
|
| 45. |
- Ling Lundström, Maria, 1977-
(författare)
-
Faecal biomarkers of neutrophil and eosinophil origin in the evaluation of inflammatory bowel disease : Providing insights into the patophysiology
- 2024
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is characterised by chronic inflammation of the gastrointestinal tract. The gold standard for diagnosing and monitoring IBD is by endoscopy, but biomarkers, like the clinically established faecal calprotectin (FC), can function as non-invasive surrogate markers reflecting disease activity. As FC has some known limitations, it is worthwhile to investigate the performance of alternative faecal markers. Therefore, we aimed to evaluate eosinophil and neutrophil granule proteins as potential faecal biomarkers for different aspects of IBD. An additional aim was to study the association of eosinophils with IBD onset.In Paper I, we explored the role of eosinophils in the pathophysiology of IBD by studying faecal eosinophil markers in a cohort of discordant twin pairs. This study showed that, unlike neutrophils, eosinophils are not active in the pre-clinical state of IBD. Thus, activation of eosinophils is a consequence of inflammation rather than a primary event triggering the onset of disease. In Paper II, the diagnostic association and predictive performance of neutrophil and eosinophil faecal markers were evaluated in a cohort of newly-onset IBD patients. We showed that Myeloperoxidase (MPO) and FC have comparable diagnostic capacities in IBD and that combining FC and MPO could enhance diagnostic accuracy. We also demonstrated that neutrophil markers were predictive of an aggressive disease course in UC. Paper III showed that faecal MPO, human neutrophil lipocalin (HNL) and eosinophil-derived neurotoxin (EDN) – similar to FC – are functioning biomarkers for monitoring clinical remission in IBD patients treated with biologics. The study also demonstrated that faecal EDN and HNL are influenced by corticosteroids, indicating a response mechanism different from that of FC and MPO. In Paper IV we proposed that faecal HNL, reflecting both intestinal neutrophils and epithelial cells, can differentiate patients with gastroenteritis (GE) from new-onset IBD patients.This comprehensive exploration of faecal biomarkers suggests interesting alternatives or adjuncts to FC in the diagnostics, monitoring and prediction of disease course in IBD. By studying these biomarkers, we have also uncovered parts of the IBD pathophysiology and increased the knowledge of the eosinophils in the early state of IBD.
|
|
| 46. |
- Lundgren, David, 1966-
(författare)
-
The significance of low-grade inflammation in the gastrointestinal tract
- 2021
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundGastrointestinal (GI) symptoms are commonly reported in a normal population. Mostly, the symptoms are of benign cause but occasionally the symptoms can be signs of a more harmful disease. In general, it is difficult to distinguish whether the reported symptoms are caused by a benign (functional) or organic (i.e., inflammatory) disease. To make this distinction, the tools available in clinical practice are medical history, blood and faecal tests, radiology, endoscopy and histological evaluation. Mucosal inflammation usually separates organic from functional disease and, in patients with inflammatory bowel disease (IBD), mucosal inflammation correlates with disease activity. Faecal calprotectin (FC) corresponds well with mucosal inflammation and is in clinical practice often used as the first line non-invasive test for gut inflammation. Although the sensitivity of the FC test to detect gut inflammation is good, there are uncertainties in how to interpret a modestly elevated FC level (i.e., in the span of 50-200µg/g) and in patients with IBD, there is a disagreement into which degree of inflammatory remission it is sufficient to reach.AimThe overall aim of this thesis was to study factors associated with low-grade inflammation based on biochemical markers, and to study the clinical significance of low-grade inflammation in patients with IBD and other patients with elevated FC levels. Is low-grade inflammation associated with reported gastrointestinal symptoms in patients with IBD and could low-grade inflammation be detected in the pre-clinical phase of IBD? How should an elevated FC level in patients with a normal colonoscopy be interpreted and could it be a risk factor for gastrointestinal disease or associated with other factors? Could low-grade inflammation cause IBS-like symptoms in patients with IBD?Methods and resultsThree of the manuscripts on which this thesis is based are from the Faecal and Endoscopic Colorectal Study in Umeå Sweden (FECSU) which consists of 1263 patients that underwent colonoscopy during the period of May 2007 to February 2013. The patients that accepted to participate in the FECSU study performed a FC test the day before the bowel preparation for the colonoscopy and simultaneously filled in questionnaires of gastrointestinal symptoms (GSRS), symptoms of anxiety and depression (HADS) and current medications. A thorough medical chart review that focused on endoscopic evaluations, histological judgements and medical history was performed. The included patients with IBD (n=157) in the FECSU study were analysed separately. Patients with ulcerative colitis (UC) in endoscopic remission reported lower total scores on GSRS-irritable bowel syndrome (GSRS-IBS) than controls (6 vs 10.5; p=0.062). However there was a moderate, yet significant association between GSRS-diarrhoea score and FC levels in the span £ 200 µg/g (rho 0.38;p=0.004) in patients with UC. To investigate pre-clinical biomarkers of IBD we identified 96 patients with IBD in the “Västerbotten Intervention Program (VIP)” and the “Mammography screening project” (MA). In the pre-clinical study in patients with IBD we found that patients who later developed UC had lower plasma albumin levels and patients who later developed Crohn’s disease (CD) had higher levels of CRP in plasma, reflecting signs of a low-grade systemic inflammation years before diagnosis. Plasma calprotectin levels were not elevated before IBD-diagnosis. In the FECSU study, all non-IBD patients with a normal colonoscopy were studied for factors associated with an elevated FC level. Patients with a FC > 50 µg/g more often used Proton-pump inhibitors (PPI) (multivariate OR: 3.843; CI: 2.338-6.316), Non-steroidal anti-ivinflammatory drugs (NSAID) (multivariate OR: 2.411; CI: 1.162-5.002) and acetylsalicylic acid (ASA) (multivariate OR: 2.934; CI: 1.085-3.448). One third of the patients with a normal colonoscopy had elevated FC levels (> 50 µg/g) and these patients were observed three years after the colonoscopy. There was no increased risk for developing gastrointestinal disease in the patients with an increased baseline FC level and a normal colonoscopy during the observation period.ConclusionPatients with longstanding UC in remission did not experience more IBS-like symptoms than controls. In patients with UC in remission, the FC levels in the lower span were moderately associated with symptoms of diarrhoea. Patients with IBD had elevated inflammatory biochemical markers in blood in the pre-clinical phase. P- CRP and P-albumin were more sensitive to detect a low grade systemic inflammation than P-calprotectin in the pre-clinical phase of IBD. More than one-third of the patients with a normal colonoscopy had a slightly elevated FC. In patients with a normal colonoscopy, the use of PPI, NSAID and ASA was associated with an increased FC level. No significant gastrointestinal disease developed in the patients with an increased FC level together with a normal colonoscopy during the three-year period following colonoscopy.
|
|
| 47. |
- Lushnikova, Alexandra, et al.
(författare)
-
Altered levels of immune checkpoint molecules in colon biopsies and sera from microscopic colitis and ulcerative colitis patients compared to controls
- 2021
-
Ingår i: Journal of Immunology. - : American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 206:Suppl.
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Microscopic colitis (MC), comprising lymphocytic colitis (LC) and collagenous colitis (CC), is an inflammatory bowel disorder. MC patients have a lower risk of developing colorectal cancer (CRC) than ulcerative colitis (UC) patients. We hypothesize that the immune response in MC is geared more towards immune surveillance of tumor cells than that of UC, which instead contributes to inflammation-associated CRC.Methods: Using Luminex, protein levels of 14 immune checkpoints (TIM-3, CD28, CD137, CD27, CD152, HVEM, IDO, LAG-3, BTLA, GITR, CD80, PD-1, PD-L1, PD-L2) in protein lysates from colon biopsies (controls, n = 9; diarrhea controls, n = 7; LC, n = 14; CC, n = 15; UC, n = 17) were analyzed. Soluble checkpoints were analyzed in serum (23 controls, 17 LC, 36 CC and 2 UC).Results: In patients with active LC and CC, CD137, IDO, and CD80 levels were increased compared with one or both control groups. CD152 and PD-1 levels were increased in patients with active CC compared with both control groups. In patients with active UC, levels of CD137, CD152, BTLA, PD-1, and PD-L2 were increased compared with both control groups, IDO levels were increased compared with controls, and CD80 levels were raised compared with diarrhea controls.In sera, CD27, IDO, CD80, PD-1, and PD-L2 levels were decreased in LC patients compared to controls.Conclusions: Increased levels of immune checkpoint molecules in colon biopsies from UC and MC patients are likely a sign of inflammation and may indicate what kind of homeostatic feed-back mechanisms are active to balance inflammation. Lowered concentrations of soluble immune checkpoint molecules in sera from patients with LC indicate a different level of homeostatic balance systemically in LC patients versus controls.
|
|
| 48. |
- Lushnikova, Alexandra, et al.
(författare)
-
Patients With Microscopic Colitis Have Altered Levels of Inhibitory and Stimulatory Biomarkers in Colon Biopsies and Sera Compared to Non-inflamed Controls
- 2021
-
Ingår i: Frontiers in Medicine. - Lausanne, Switzerland : Frontiers Media S.A.. - 2296-858X. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Microscopic colitis (MC) is an inflammatory bowel condition with two subtypes, lymphocytic colitis (LC) and collagenous colitis (CC). Unlike patients with ulcerative colitis (UC) and non-inflamed individuals, MC patients have reduced risk of developing colorectal cancer, possibly due to increased immune surveillance in MC patients.Aim: To examine differences in levels of immunomodulatory molecules, including those involved in immune checkpoint mechanisms, in sera from patients with MC and in colonic biopsies from patients with MC and UC compared with controls.Methods: Using Luminex, 23 analytes (4-1BB, 4-1BBL, APRIL, BAFF, BTLA, CD27, CD28, CD80, CTLA-4, E-cadherin, Galectin-3, GITR, HVEM, IDO, IL-2Rα, LAG-3, MICA, MICB, PD-1, PD-L1, PD-L2, sCD40L and TIM-3) were studied in serum from patients with active MC (n = 35) and controls (n = 23), and in colonic biopsies from patients with active LC (n = 9), active CC (n = 16) and MC in histological remission (LC n = 6, CC n = 6), active UC (n = 15) and UC in remission (n = 12) and controls (n = 58).Results: In serum, IDO, PD-1, TIM-3, 4-1BB, CD27, and CD80 were decreased whereas 4-1BBL and IL-2Rα were increased in MC patients compared with controls. In contrast, in biopsies, levels of PD-L2 and 4-1BB were increased in MC and UC patients with active disease. Furthermore, in biopsies from CC and UC but not LC patients with active disease, CTLA-4, PD-1, APRIL, BAFF, and IL-2Rα were increased compared with controls. PD-L1 was increased in CC but not UC or LC patients. CD27 and TIM-3 were decreased in biopsies from MC patients in comparison to controls whereas levels of MICB were decreased in patients with active UC compared with controls.Conclusions: Compared with non-inflamed controls, levels of soluble and membrane-bound immunomodulatory molecules were systemically and locally altered in MC and UC patients, with most analytes being decreased in serum but enhanced in colonic biopsies. These findings contribute to knowledge about checkpoint molecules and their role as biomarkers in MC and may also contribute to knowledge about possible mechanisms behind the seemingly protective effects of MC against colorectal cancer.
|
|
| 49. |
- Munkvold, Bodil Karoline Ravn, et al.
(författare)
-
Variations in the management of diffuse low-grade gliomas : A Scandinavian multicenter study
- 2021
-
Ingår i: Neuro-Oncology Practice. - : Oxford University Press. - 2054-2577 .- 2054-2585. ; 8:6, s. 706-717
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Early extensive surgery is a cornerstone in treatment of diffuse low-grade gliomas (DLGGs), and an additional survival benefit has been demonstrated from early radiochemotherapy in selected "high-risk" patients. Still, there are a number of controversies related to DLGG management. The objective of this multicenter population-based cohort study was to explore potential variations in diagnostic work-up and treatment between treating centers in 2 Scandinavian countries with similar public health care systems.Methods. Patients screened for inclusion underwent primary surgery of a histopathologically verified diffuse WHO grade II glioma in the time period 2012 through 2017. Clinical and radiological data were collected from medical records and locally conducted research projects, whereupon differences between countries and inter-hospital variations were explored.Results. A total of 642 patients were included (male:female ratio 1:4), and annual age-standardized incidence rates were 0.9 and 0.8 per 100 000 in Norway and Sweden, respectively. Considerable inter-hospital variations were observed in preoperative work-up, tumor diagnostics, surgical strategies, techniques for intraoperative guidance, as well as choice and timing of adjuvant therapy.Conclusions. Despite geographical population-based case selection, similar health care organizations, and existing guidelines, there were considerable variations in DLGG management. While some can be attributed to differences in clinical implementation of current scientific knowledge, some of the observed inter-hospital variations reflect controversies related to diagnostics and treatment. Quantification of these disparities renders possible identification of treatment patterns associated with better or worse outcomes and may thus represent a step toward more uniform evidence-based care.
|
|
| 50. |
- Nyberg, Lisa, et al.
(författare)
-
Sclerosing mesenteritis and mesenteric panniculitis - clinical experience and radiological features
- 2017
-
Ingår i: BMC Gastroenterology. - : Springer Science and Business Media LLC. - 1471-230X. ; 17:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Sclerosing mesenteritis (SM) is sometimes used as an umbrella-term for idiopathic inflammatory conditions in the mesentery. Mesenteric panniculitis (MP) is a radiological finding and its relation to clinical SM is not fully understood. The aims of this study were to determine whether any correlation could be found between the radiological findings and the clinical disease course. Methods: Patients observed due to idiopathic inflammation of the mesentery were identified. If SM could be verified histologically or MP radiologically, the patients were included in this descriptive retro perspective study. Results: Typical radiological changes were observed in 27 patients. A majority (23/27) of these patients had mild to moderate symptoms. This group with typical radiology was labelled MP. Four patients were included due to histologically verified disease but had uncharacteristic radiology involving multiple compartments of the abdomen. All four had marked systemic inflammation, fever and fluctuating radiologic findings. Three had severe disease with multiple hospitalisations and complications but responded promptly to corticosteroids. This group was denoted SM. Conclusions: We have identified two subgroups of patients; firstly, MP with stable and characteristic radiologic changes and secondly SM with atypical radiology and a more aggressive clinical course. We propose that the term SM should be reserved for this latter condition.
|
|
