Coming dissertations at Uppsala university
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Glucose – friend and foe : Glucose alterations and dietary intake in patients undergoing bariatric surgery
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-539013
Hypocaloric diets, varying in energy content and duration, are used before bariatric surgery (BS) to reduce liver volume and facilitate the surgical procedure. After BS, fasting glucose concentration is lowered and the risk for hypoglycemia increased. This thesis is based on studies that investigated the effectiveness of different hypocaloric diets before BS, glucose alterations before and after bariatric surgery, and the relationships between dietary factors and glucose variability.
Paper I was a systematic review examining the effectiveness of different preoperative hypocaloric diets on body weight, liver volume and glucose concentrations. Two to four weeks following a low-energy diet (LED, 800-1200 kcal/day) or very low-energy diet (VLED, 450-<800 kcal/day) resulted in similar median total body weight loss (4-6%). LED over 2-4 weeks reduced liver volume by 13%, glucose concentration by 9%, and HOMA Index IR by 33%. Papers II and III included patients without diabetes accepted for BS. Continuous glucose monitoring (CGM) and food recording were performed in 4 study periods: 10 weeks preoperatively, during preoperative LED, and 6 and 12 months after gastric bypass and sleeve gastrectomy. LED lowered the mean 24-hour glucose concentration significantly, with similar levels being maintained after surgery. Postoperatively, glucose variability and episodes of hypoglycemia (<3.9 mmol/L) increased significantly. Self-reported daily dietary fibre intake and breakfast glycemic index related significantly to the glucose variability preoperatively, while daily carbohydrate intake related significantly to the glucose variability postoperatively. The mean daily dietary fibre intake and step counts were low at all study periods. In Paper IV, CGM and food recording were performed in gastric bypass and duodenal switch treated patients without diabetes. Mean 2-hour postprandial concentrations were significantly higher after gastric bypass compared to duodenal switch. Meal frequency was similar between the two groups, with a mean of 7-8 meals per day.
In conclusion, LED over 2-4 weeks produced similar weight loss as VLED, and LED decreased liver volume and glucose levels. Glucose variability and the frequency of hypoglycemia increased after gastric bypass and sleeve gastrectomy, while postprandial glucose response was less pronounced after duodenal switch. Carbohydrate quality was related to the glucose variability before surgery, while carbohydrate amount was related to the glucose variability after surgery. The clinical implications of our findings are that a preoperative LED-regimen over 2-4 weeks might be sufficient for most patients undergoing BS, screening for hypoglycemia should be considered after BS along with focus on healthy dietary habits with individual adaptions.
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Motion Estimation from Temporally and Spatially Sparse Medical Image Sequences
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-538082
Motion is a fundamental aspect of human life. Even during low-intensity activities, we move. The lungs absorb oxygen when inhaling and desorb carbon dioxide when exhaling. The heart pumps oxygenated blood to the body's organs. Wave-like contractions help us process food. All such events cause motion within the body. Being able to describe motion offers benefits in medical health, e.g., analysis of organ functions and guidance during ongoing treatments. The motion can be captured by acquiring medical images in real-time. However, in several cases, the resolution of the medical images is limited by the acquisition time, and the images suffer from low temporal and spatial resolution. One such example appears in radiotherapy, e.g., by acquiring 2D cine-MRIs for monitoring ongoing treatment sessions. An accurate estimation of the entire 3D motion provides a more realistic estimate of the actual delivery outcome and is a necessary feature for more advanced procedures, like real-time beam adaptation.
In this thesis, we develop methods to estimate the motion from temporally and spatially sparse medical image sequences. We start by extracting knowledge from optimization-based medical image registration methods and showing how deep learning can reduce execution time. Then, we model the motion dynamics as a sequence of deformable image registrations. Due to the high dimensionality of the medical image, we model the dynamics in a lower dimensional space. For this, we apply dimension reduction techniques like principal component analysis and variational auto-encoders. The dynamic is then modeled using state-space representations and diffusion probabilistic models to solve the two inference problems of forecasting and simulating the state processes.
The main contribution lies in the five presented scientific articles, where we deal with the problem of temporally and spatially sparse sequences separately and then combine them into a uniform solution. The proposed methods are evaluated on medical images of several modalities, such as MRI, CT, and ultrasound, and finally demonstrated on the use case in the radiotherapy domain, where more accurate motion estimates could spare healthy tissues from being exposed to radiation dose.
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Periprosthetic bone and uncemented total hip arthroplasty
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-539036
Uncemented total hip arthroplasty (THA) has continuously increased in recent decades. Biological fixation of the implant is achieved initially by press-fit and secondary by osseointegration. However, uncemented THA is associated with loss of periprosthetic bone mineral density (pBMD), reduced mechanical strength and increased risk of periprosthetic fractures. The goals of this thesis were to study the short-term results of treatment with an antiresorptive drug for an uncemented THA (studies I and II) and the 8-year follow-up of an uncemented acetabular implant (study III). In addition, the reliability, agreement and precision for the periprosthetic standardized uptake value (pSUV) with [18F] fluoride PET/CT (F-PET) were evaluated (study IV).
We conducted a randomized controlled trial (RCT) to investigate the effect of 2 subcutaneous injections of denosumab, 6 months apart postoperatively, on pBMD by dual-energy x-ray absorptiometry (DXA), pSUV by F-PET and serum markers for bone turnover for an uncemented THA with the collum femoris preserving (CFP) stem and the Continuum cup. Our results show that denosumab prevents early pBMD loss around the stem (study I) and the cup (study II), but the effect is transient upon treatment discontinuation. Additionally, denosumab reduces periprosthetic and systemic bone turnover, but the effect is unsustainable.
Study III is a prospective study to evaluate the 8-year results of the trabeculae-oriented pattern (TOP) cup in terms of implant survival, pBMD measured by DXA and clinical outcomes. We found an overall implant survival for the TOP cup of 83% and that pBMD continued to decrease in the proximal regions around the cup. The clinical outcome in patients with unrevised cups was excellent.
Study IV is a methodological study investigating F-PET's reliability, agreement and precision. 2 independent observers analyzed all F-PET scans from study II on 2 occasions, with a minimum interval of 3 weeks between each analysis. We found good reliability, high agreement and moderate precision between and within observers.
This thesis concludes that 2 doses of denosumab effectively prevent pBMD loss around the CFP stem and the Continuum cup while also reducing bone turnover. However, the effect on pBMD is not enduring, and a rebound effect on bone turnover markers appears after treatment discontinuation. Moreover, the TOP cup shows inferior 8-year survival rates compared to other uncemented implants and continuous pBMD loss proximally. Finally, the F-PET of acetabular cups can be reliably performed with strong agreement and moderate precision.