| 1. |
- Forsgren, Mikael
(författare)
-
The Non-Invasive Liver Biopsy : Determining Hepatic Function in Diffuse and Focal LiverDisease
- 2017
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The liver is one of the largest organs within the human body and it handles many vital tasks such as nutrient processing, toxin removal, and synthesis of important proteins. The number of people suffering from chronic liver disease is on the rise, likely due to the present ‘western’ lifestyle. As disease develops in the liver there are pathophysiological manifestations within the liver parenchyma that are both common and important to monitor. These manifestations include inflammation, fatty infiltration (steatosis), excessive scar tissue formation (fibrosis and cirrhosis), and iron loading. Importantly, as the disease progresses there is concurrent loss of liver function. Furthermore, postoperative liver function insufficiency is an important concern when planning surgical treatment of the liver, because it is associated with both morbidity and mortality. Liver function can also be hampered due to drug-induced injuries, an important aspect to consider in drug-development.Currently, an invasive liver needle biopsy is required to determine the aetiology and to stage or grade the pathophysiological manifestations. There are important limitations with the biopsy, which include, risk of serious complications, mortality, morbidity, inter- and intra-observer variability, sampling error, and sampling variability. Cleary, it would be beneficial to be able investigate the pathophysiological manifestations accurately, non-invasively, and on regional level.Current available laboratory liver function blood panels are typically insufficient and often only indicate damage at a late stage. Thus, it would be beneficial to have access to biomarkers that are both sensitive and responds to early changes in liver function in both clinical settings and for the pharmaceutical industry and regulatory agencies.The main aim of this thesis was to develop and evaluate methods that can be used for a ‘non-invasive liver biopsy’ using magnetic resonance (MR). We also aimed to develop sensitive methods for measure liver function based on gadoxetate-enhanced MR imaging (MRI).The presented work is primarily based on a prospective study on c. 100 patients suffering from chronic liver disease of varying aetiologies recruited due to elevated liver enzyme levels, without clear signs of decompensated cirrhosis. Our results show that the commonly used liver fat cut-off for diagnosing steatosis should be lowered from 5% to 3% when using MR proton-density fat fraction (PDFF). We also show that MR elastography (MRE) is superior in staging fibrosis.Finally we presented a framework for quantifying liver function based on gadoxetate-enhanced MRI. The method is based on clinical images and a clinical approved contrast agent (gadoxetate). The framework consists of; state-of the-art image reconstruction and correction methods, a mathematical model, and a precise model parametrization method. The model was developed and validated on healthy subjects. Thereafter the model was found applicable on the chronic liver disease cohort as well as validated using gadoxetate levels in biopsy samples and blood samples. The liver function parameters correlated with clinical markers for liver function and liver fibrosis (used as a surrogate marker for liver function).In summary, it should be possible to perform a non-invasive liver biopsy using: MRI-PDFF for liver fat and iron loading, MRE for liver fibrosis and possibly also inflammation, and measure liver function using the presented framework for analysing gadoxetate-enhanced MRI. With the exception of an MREtransducer no additional hardware is required on the MR scanner. The liver function method is likely to be useful both in a clinical setting and in pharmaceutical trials.
|
|
| 2. |
- Marcisauskas, Simonas, 1988
(författare)
-
An insight towards food-related microbial sets through metabolic modelling and functional analysis
- 2020
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The dietary food digestion depends on the human gastrointestinal tract, where host cells and gut microbes mutually interact. This interplay may also mediate host metabolism, as shown by microbial-derived secondary bile acids, needed for receptor signalling. Microbes are also crucial in the production of fermented foods, such as wine and dairy. Kefir is fermented milk processed by the symbiotic community of bacteria and yeasts. One such species is a yeast Kluyveromyces marxianus . Its thermotolerance is a desired trait in biotechnology since it may reduce the cooling demands during cultivation. The systems biology tools allow analysing various size microbial communities under the different functional scope. For example, the homology prediction tools can give detailed functional insights when working with metagenomics data. The whole-cell metabolic processes can be summarised in genome-scale metabolic models (GEMs), which enable to predict the metabolic capabilities and allow for the integration of omics data. The work shown in this thesis includes i) in silico analysis of food-related microbes; ii) the development of GEMs and RAVEN. With a focus on bile acid metabolism, hundreds of human gut microbes were annotated based on metagenomics data, thereby suggesting the differences in the potential for bile acid processing between healthy and diseased subjects. These findings may be exploitable once aiming to restore the bile acid metabolism for the patients having inflammatory bowel disease. Also, the metabolism of yeast K. marxianus was characterised in genome-scale. Two K. marxianus strains from kefir grains were isolated, sequenced, assembled, and functionally annotated. They were compared with the other ten strains, providing the core and dispensable physiological features for K. marxianus . Furthermore, the first GEM for K. marxianus , namely iSM996, was reconstructed. It was integrated with transcriptomics data to predict its metabolic capabilities in rich medium and high-temperature conditions. The results might be useful to optimise strain-specific medium for high-temperature applications. The final paper comprises the efforts to improve the usability for RAVEN, a toolbox for GEM reconstruction and analysis. Altogether the outcomes of this thesis suggest the potential applications for medicine and industrial biotechnology, which may be facilitated by the newly upgraded RAVEN toolbox.
|
|
| 3. |
- Marques, Filipe, et al.
(författare)
-
New through-the-needle brush for pancreatic cysts assessment : a randomized control trial
- 2023
-
Ingår i: iGIE. - : Elsevier BV. - 2949-7086.
-
Tidskriftsartikel (refereegranskat)abstract
- AbstractObjectiveCurrent endoscopic ultrasound technologies (EUS) are suboptimal in the assessment of pancreatic cystic lesions (PCLs). We developed a new through-the- needle brush, the "loop brush", to improve the cellular yield, and thereby sensitivity,of EUS fine needle aspiration (EUS-FNA) of pancreatic cysts. In this study, we aim to evaluate its safety and efficacy.DesignWe performed an in-vivo randomized controlled trial in pigs using artificial cysts. In one group, the loop brush was deployed through a 22G EUS-FNA needle into the cysts. In the control group, cystic punction was performed with standard EUS- FNA. Loop brushes were visually inspected post-procedure. Cytological assessment, cell counting, and hemoglobin analysis were performed in samples from both groups.ResultsArtificial cysts (n=114) were punctured in six pigs, 57 in each group. Neither adverse events nor significant device malfunction occurred during loop brushing. Samples collected with the brush had non-detectable concentrations of hemoglobin in 72% (41/57) of cases, and 26% (16/57) had less than 0.6 g/dL, with no significant difference to the controls (p=0.32). Brushing cell counts were associated with significantly increased cell counts (11.7× median difference, p<.0001). Cytological smears were diagnostic in 77% of cases in the brushing group, while 54% in the control group (p=0.01, Fisher’s exact test; p=0.006, Chi-square test).ConclusionsThe new loop brush procedure appears to be safe, causing neither significant bleeding nor device malfunction. Samples obtained with the loop brush were suitable for cytological analysis and showed significantly higher cell yield than controls. Further clinical studies are warranted.
|
|
| 4. |
- Leenhardt, R., et al.
(författare)
-
Key research questions for implementation of artificial intelligence in capsule endoscopy
- 2022
-
Ingår i: Therapeutic Advances in Gastroenterology. - : SAGE Publications. - 1756-283X .- 1756-2848. ; 15
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Artificial intelligence (AI) is rapidly infiltrating multiple areas in medicine, with gastrointestinal endoscopy paving the way in both research and clinical applications. Multiple challenges associated with the incorporation of AI in endoscopy are being addressed in recent consensus documents. Objectives: In the current paper, we aimed to map future challenges and areas of research for the incorporation of AI in capsule endoscopy (CE) practice. Design: Modified three-round Delphi consensus online survey. Methods: The study design was based on a modified three-round Delphi consensus online survey distributed to a group of CE and AI experts. Round one aimed to map out key research statements and challenges for the implementation of AI in CE. All queries addressing the same questions were merged into a single issue. The second round aimed to rank all generated questions during round one and to identify the top-ranked statements with the highest total score. Finally, the third round aimed to redistribute and rescore the top-ranked statements. Results: Twenty-one (16 gastroenterologists and 5 data scientists) experts participated in the survey. In the first round, 48 statements divided into seven themes were generated. After scoring all statements and rescoring the top 12, the question of AI use for identification and grading of small bowel pathologies was scored the highest (mean score 9.15), correlation of AI and human expert reading-second (9.05), and real-life feasibility-third (9.0). Conclusion: In summary, our current study points out a roadmap for future challenges and research areas on our way to fully incorporating AI in CE reading.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Cock, C., et al.
(författare)
-
Effects of remifentanil on esophageal and esophagogastric junction (EGJ) bolus transit in healthy volunteers using novel pressure-flow analysis
- 2018
-
Ingår i: Neurogastroenterology and Motility. - : John Wiley & Sons. - 1350-1925 .- 1365-2982. ; 30:2
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Remifentanil is associated with subjective dysphagia and an objective increase in aspiration risk. Studies of opioid effects have shown decreased lower esophageal sphincter relaxation. We assessed bolus transit through the esophagus and esophagogastric junction (EGJ) during remifentanil administration using objective pressure-flow analysis.METHODS: Data from 11 healthy young participants (23±3 years, 7 M) were assessed for bolus flow through the esophagus and EGJ using high-resolution impedance manometry (Manoscan™, Sierra Scientific Instruments, Inc., LES Angeles, CA, USA) with 36 pressure and 18 impedance segments. Data were analyzed for esophageal pressure topography and pressure-flow analysis using custom Matlab analyses (Mathworks, Natick, USA). Paired t tests were performed with a P-value of < .05 regarded as significant.KEY RESULTS: Duration of bolus flow through (remifentanil/R 3.0±0.3 vs baseline/B 5.0 ± 0.4 seconds; P < .001) and presence at the EGJ (R 5.1 ± 0.5 vs B 7.1 ± 0.5 seconds; P = .001) both decreased during remifentanil administration. Distal latency (R 5.2 ± 0.4 vs B 7.5 ± 0.2 seconds; P < .001) and distal esophageal distension-contraction latency (R 3.5 ± 0.1 vs B 4.7 ± 0.2 seconds; P < .001) were both reduced. Intrabolus pressures were increased in both the proximal (R 5.3 ± 0.9 vs B 2.6 ± 1.3 mm Hg; P = .01) and distal esophagus (R 8.6 ± 1.7 vs B 3.1 ± 0.8 mm Hg; P = .001). There was no evidence of increased esophageal bolus residue.CONCLUSIONS AND INFERENCES: Remifentanil-induced effects were different for proximal and distal esophagus, with a reduced time for trans-sphincteric bolus flow at the EGJ, suggestive of central and peripheral μ-opioid agonism. There were no functional consequences in healthy subjects.
|
|
| 8. |
- Marques, Filipe
(författare)
-
Overcoming the Barriers of Fine-Needle Aspiration
- 2023
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cysts, closed sac-like structures filled with fluid or air, can form anywhere in the body. In the majority of cases, cysts are benign (not cancerous). However, these structures can also be precursors of cancer, pointing to the location where cancer can originate. This makes cysts a prime location for examination, especially when they occur in the pancreas. Pancreatic cancer has the lowest survival rate after five years in 2023 (12%) due to the late diagnosis, limiting treatment options. Fine-Needle Aspiration (FNA) is a diagnostic technique used to aspirate the liquid content of cysts. The liquid may possess cells used to determine cyst malignancy, yet up to 66% of samples have little to no cells.Firstly, we introduce a new concept of brush: the loop brush. Unlike traditional brushes with a handle and a block of bristles, the loop brush consists of a handle and a loop-shaped wire. The loop of loop brushes can be compressed within the inner diameter of an FNA needle and autonomously expanded to the size of cysts. Loops can be made of nitinol or commercially available absorbable sutures such as Monocryl, PDS II, and Catgut. Loop brushes increase the cell yield of modeled cysts by an order of magnitude and are, apparently, as safe as standard FNA (FNA without a loop brush). Such brushes could present a promising solution to the lack of cells in liquid samples of cysts, increasing treatment options and producing better, cost-effective care for patients.Secondly, we present a hand-sized microfluidic device to prepare rapid on-site evaluation(ROSE) of FNA samples. During ROSE, FNA samples are prepared by cytopathologists in the operating room for further inspection with a microscope. However, cytopathologists are often time-limited, preventing the dissemination of ROSE. Our device allows sample preparation with minimum chemical quantities and the potential to be implemented by all healthcare providers. This microfluidic device would allow the dissemination of ROSE, preventing the need for patients to return to the OR and accelerating diagnosis.
|
|
| 9. |
- Fischer, Hans, et al.
(författare)
-
Altered microbiota in microscopic colitis
- 2015
-
Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 64:7, s. 1185-1186
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 10. |
- Ciuti, Gastone, et al.
(författare)
-
Frontiers of robotic colonoscopy : A comprehensive review of robotic colonoscopes and technologies
- 2020
-
Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 9:6
-
Forskningsöversikt (refereegranskat)abstract
- Flexible colonoscopy remains the prime mean of screening for colorectal cancer (CRC) and the gold standard of all population-based screening pathways around the world. Almost 60% of CRC deaths could be prevented with screening. However, colonoscopy attendance rates are affected by discomfort, fear of pain and embarrassment or loss of control during the procedure. Moreover, the emergence and global thread of new communicable diseases might seriously affect the functioning of contemporary centres performing gastrointestinal endoscopy. Innovative solutions are needed: artificial intelligence (AI) and physical robotics will drastically contribute for the future of the healthcare services. The translation of robotic technologies from traditional surgery to minimally invasive endoscopic interventions is an emerging field, mainly challenged by the tough requirements for miniaturization. Pioneering approaches for robotic colonoscopy have been reported in the nineties, with the appearance of inchworm-like devices. Since then, robotic colonoscopes with assistive functionalities have become commercially available. Research prototypes promise enhanced accessibility and flexibility for future therapeutic interventions, even via autonomous or robotic-assisted agents, such as robotic capsules. Furthermore, the pairing of such endoscopic systems with AI-enabled image analysis and recognition methods promises enhanced diagnostic yield. By assembling a multidisciplinary team of engineers and endoscopists, the paper aims to provide a contemporary and highly-pictorial critical review for robotic colonoscopes, hence providing clinicians and researchers with a glimpse of the major changes and challenges that lie ahead.
|
|
