| 1. |
- Klaff, Rami, 1971-
(författare)
-
Disease-Specific Survival in Prostate Cancer Patients : Results from the Scandinavian Prostate Cancer Group (SPCG) Trial No. 5 and Regional Cancer Register Data
- 2016
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- IntroductionProstate cancer (PCa) is the most common cancer among men in Sweden. The clinical course varies considerably, which makes it difficult to predict the prognosis in the individual case. In order to explore the early as well as the late course of the disease, large study groups and population-based cohorts are necessary.AimsTo explore factors that influence the long-term outcome of men with low-risk tumours in a population-based register, to predict the long-term course, and to assess the mortality rate for men with prostate cancer (Paper I)To analyse long-term outcome and to investigate factors associated with long-term survival in patients with metastases to the skeleton (Paper II)To analyse early androgen deprivation treatment (ADT) failure and to define clinical predictors associated with short survival due to early ADT failure in prostate cancer patients with bone metastases (Paper III)To analyse the prognostic significance of the extent of bone metastases in relation to other pretreatment variables in prostate cancer patients, and to explore the impact of bone metastases on quality-of-life (Paper IV)Material and methodsThe study groups were assembled from The South East Region Prostate Cancer Register (SERPCR), and The Scandinavian Prostate Cancer Group (SPCG) Trial No. 5. In the first study, prognostic factors and long-term disease-specific mortality rates of low-risk prostate cancer patients from the early PSA era were analysed. In the second study, patient-related factors, quality-of-life (QoL) and long-term survival in 915 PCa patients with bone metastases (M1b) under ADT, were analysed. In Study III factors predicting primary failure to respond to ADT were identified. Study IV explored the impact of the extent of bone metastases on survival and QoL for these men.Result and conclusionsThe long-term disease-specific mortality of low-risk localised PCa is low, but the annual mortality rate gradually increases. This indicates that some tumours slowly develop into lethal cancer, particularly in men 70 years or older and with a PSA level ≥ 4 μg/L. From the SPCG Trial No. 5, a subgroup of patients with M1b disease and favourable set of predictive factors survived more than 10 years under ADT with an acceptable QoL. Independent predictors of long-term survival were identified as performance status (PS) < 2, limited extent of bone metastases, and a PSA level < 231 μg/L at the time of enrolment in the trial. However, four independent clinical predictors of early ADT failure could be defined. Men exhibiting these features should be considered for an alternative treatment. Patient grouping based on three categories of extent of bone metastases related to PS, haemoglobin, and QoL at presentation, as independent predictors of mortality, may provide improved accuracy of prognosis.
|
|
| 2. |
- Marques, Catarina, 1969-
(författare)
-
Studies on Cervical Artificial Disc Replacement
- 2022
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Artificial disc replacement (ADR) was developed as an alternative to anterior fusion after decompression for cervical degenerative radiculopathy. By preserving motion, it was expected to prevent acceleration of adjacent segment pathology (ASP) associated with fusion, and lead to better clinical outcomes. The aims of this thesis were to evaluate whether ADR surgery leads to better outcomes than fusion surgery, to investigate if it prevents the acceleration of ASP, and to analyze its potential complications. In a multicenter randomized controlled trial (RCT) 153 patients were randomized to ADR (DiscoverTM implant) or fusion surgery (autograft, plate and screws). The outcomes at 5 and 10 years postoperatively were analyzed with Neck Disability Index (NDI) as primary measure. Heterotopic ossification (HO), ASP, and secondary surgery where analyzed. The measurements of radiographic parameters used in the assessment of cervical alignment where validated.To further analyze secondary surgery after ADR, a descriptive register cohort study was done with 42 patients whose data were retrieved from Swespine and completed with medical charts, images, and a telephone interview. There was no difference in NDI scores between groups in the RCT, 5 or 10 years postoperatively. Radiological and clinically significant ASP were similar in both groups. There was more secondary surgery in the ADR group compared with the fusion group, mainly due to device loosening in women. Severe HO was seen in 71% of the ADR implants 5 years postoperatively, and 27% were fused, male sex being a clear risk factor.Normative data for measurement error were provided on the cervical alignment measurements, and the most reliable were the K-line tilt and the cervical sagittal vertical axis (cSVA). In the 42 patients in the register cohort study the most common diagnosis leading to reoperation was loosening of the ADR implant and/or ASP, predominantly treated with fusion surgery. Reoperation resulted in good outcomes in the vast majority of patients. At the long-term, there is no clinical benefit of ADR over fusion surgery after decompression for cervical degenerative radiculopathy. ADR, compared with fusion surgery, does not prevent acceleration of ASP, and results in more reoperations. Revision surgery for failed cervical ADRs is effective and justified.
|
|
| 3. |
- Aulin, Cecilia, 1979-
(författare)
-
Extracellular Matrix Based Materials for Tissue Engineering
- 2010
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The extracellular matrix is (ECM) is a network of large, structural proteins and polysaccharides, important for cellular behavior, tissue development and maintenance. Present thesis describes work exploring ECM as scaffolds for tissue engineering by manipulating cells cultured in vitro or by influencing ECM expression in vivo. By culturing cells on polymer meshes under dynamic culture conditions, deposition of a complex ECM could be achieved, but with low yields. Since the major part of synthesized ECM diffused into the medium the rate limiting step of deposition was investigated. This quantitative analysis showed that the real rate limiting factor is the low proportion of new proteins which are deposited as functional ECM. It is suggested that cells are pre-embedded in for example collagen gels to increase the steric retention and hence functional deposition. The possibility to induce endogenous ECM formation and tissue regeneration by implantation of growth factors in a carrier material was investigated. Bone morphogenetic protein-2 (BMP-2) is a growth factor known to be involved in growth and differentiation of bone and cartilage tissue. The BMP-2 processing and secretion was examined in two cell systems representing endochondral (chondrocytes) and intramembranous (mesenchymal stem cells) bone formation. It was discovered that chondrocytes are more efficient in producing BMP-2 compared to MSC. The role of the antagonist noggin was also investigated and was found to affect the stability of BMP-2 and modulate its effect. Finally, an injectable gel of the ECM component hyaluronan has been evaluated as delivery vehicle in cartilage regeneration. The hyaluronan hydrogel system showed promising results as a versatile biomaterial for cartilage regeneration, could easily be placed intraarticulary and can be used for both cell based and cell free therapies.
|
|
| 4. |
- Malmgren, Linnea
(författare)
-
Kidney Function During Ageing and its Association with Bone Mass, Fracture and Mortality
- 2020
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Osteoporosis and osteoporosis related fractures are a major health care challenge both in Sweden and globally. The cost and suffering from osteoporosis are expected to increase since the population of elderly is increasing. Bone health can be affected by altered mineral homeostasis, which in its turn can be affected by reduced kidney function. However, the course of age-related decline in kidney function and its association to osteoporosis andfracture in the very elderly need further investigation since longitudinal data are scarce. Therefore, this thesis has two main aims; 1) to investigate kidney function during ageing and 2) its association to bone health in a cohort ofelderly women.Data was collected through the Malmö Osteoporosis Prospective Risk Assessment (OPRA) cohort, a prospective cohort of 1044 community dwelling women, all aged 75 and followed for ten years with reinvestigations at age 80and 85. Data on BMD, fracture and blood biochemistry was available at all three time points.Estimated kidney function greatly depends on which marker and study equation is used. The discrepancies are to such an extent that could affect whether a person is diagnosed with chronic kidney disease (CKD) or not, of particular importance in the elderly. Only women with the worst kidney function, corresponding to CKD stage 3b-5, had continuously increased mortality risk. This indicates that an age-dependent CKD definition would be of valuein elderly women.Kidney function in elderly women was associated with markers of mineral homeostasis, bone loss and BMD, but the effect size was relatively small compared to other risk factors. Also, fracture risk was increased only in womenwith mild-moderate reduction of kidney function (CKD stage 3a) and not in women with the worst kidney function (CKD stage 3b-5). Low BMD was associated with increased fracture risk independent of kidney function. Havingboth reduced kidney function and osteoporosis could present an additional risk increase.In conclusion, estimated kidney function in elderly women greatly depends on method of estimation and the results advocate for an age-adapted CKD definition. Maintaining adequate kidney function is important formaintaining bone health, although in old age it is probable that the effect size of any single specific risk factor is smaller compared with younger individuals.
|
|
| 5. |
- Lammi, Mikko, 1961-
(författare)
-
Influences of in vivo and in vitro loading on the proteoglycan synthesis of articular cartilage chondrocytes
- 1993
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this study, the biosynthesis of proteoglycans (PGs) was examined in articular cartilage of canine hip joint after long-distance running experiment and in bovine chondrocyte cultures during in vitro loading with hydrostatic pressure. In addition, new assays were developed for more sensitive quantitation of glycosaminoglycans (GAGs) and PGs.Anterior (weight-bearing) and posterior (less weight-bearing) areas of the femoral head from young beagles were labeled after long-term, longdistance running exercise. Total sulpahte incorporation rates were determined and distribution of of the incorporated sulphate in the tissue was localized by quantitative autoradiography. Concentration and extractability of the PGs were determined, and PG structures were studied by gel filtration, agarose gel electrophoresis, and chemical determinations. In the less weight-bearing area, the amount of extractable PGs was decreased, simultaneously with an increased concentration of residual GAGs in the tissue after 4M GuCl extraction. In the weight-bearing area, no marked alterations were noticed. The congruency of the femoral head seems to protect the cartilage from untoward alterations that occur in the femoral head condyles subjected to the same running program.The effect of hydrostatic pressure on PG metabolism of chondrocyte cultures was examined during 20 hours' exposure of chondrocytes to 5 and 30 MPa pressures. The continuous 30 MPa pressure reduced total PG synthesis by 37 % as measured by [35S]sulphate incorporation, in contrast to the 5 MPa which had no effect. Continuous 30 MPa hydrostatic pressure also reduced the steady-state mRNA level of aggrecan. The cyclic pressures showed a frequency dependent stimulation (0.5 Hz, + 11 %) or inhibition (0.017 Hz, -17 %). Aggrecans secreted under continuous 30 MPa pressure showed a retarded migration in 0.75 % SDS-agarose gel electrophoresis and also eluted earlier on Sephacryl S-1000 gel filtration, indicative of larger molecular size. The results demonstrate that high hydostatic pressure can influence the synthesis of PGs in chondrocytes both at the transcriptionl and translational/posttranslational levels.
|
|
| 6. |
- Pettersson, Ulrika, 1970-
(författare)
-
Bone mass in the young athlete
- 1999
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bone mass and bone size accumulate during childhood and adolescence and peak in the twenties. The obtained peak bone mass has been suggested to be a major determinant of bone mass even in the very elderly. Although, genetic factors are the main determinants, environmental and lifestyle factors also play a crucial role in modulating maximal bone mass. Assessing these lifestyle factors would be of great importance for the intervention strategies against osteoporosis. The first aim of this thesis was to compare the bone mass and bone size in male and female young adults on a high level of physical activity with males or females on a low level of physical activity. Furthermore, it also aimed to investigate the influence of pubertal maturity, menstrual disturbances, and different body constitutional factors on bone mass and size during adolescence and young adulthood. The female activity groups consisted of cross-county skiers, soccer players, and rope skippers. Compared to their age-matched inactive controls, all these athletic groups demonstrated a significantly higher bone mineral density (BMD) at those sites subjected to the sport-specific loading. Rope-skipping, a very high impact activity was associated with a higher bone size, preferentially in the lower extremity, suggesting an effect of weight-bearing activity also on bone geometry. The effect of menstrual disturbances was evaluated in a group of long-distance runners, where amenorrheic runners had significantly lower BMD in both trabecular and also cortical bone in the lower extremity compared to eumenorrheic runners, suggesting that weight-bearing activity cannot compensate for the shortfall of reduced estrogen levels. The male activity groups consisted of ice hockey players and badminton players. Compared to their age-matched controls, both athletic groups demonstrated a significantly higher BMD at those sites subjected to the sport-specific loading. Especially badminton was associated with a high BMD, suggesting that physical activity, including jumps in unusual directions has a great osteogenic potential. The main determinants of BMD in both male and females were, except for type of physical activity, activity, muscle strength, height, and different body constitutional factors. However, the relationships with muscle strength and body constitution were somewhat weaker in the athletic groups, especially in the males, indicating that impact forces may be of greater importance in regulating bone mass in highly trained athletes. Yet bone size was largely determined by parameters related to body size and less strongly to physical activity. In a prospective study on adolescent boys, the changes in bone mass during late puberty were mainly accounted for by growth and development, including height and pubertal maturation, and less to physical activity level. Thus, the osteogenic effect from physical activity seems to be of importance for bone mass achievement predominantly before late puberty.
|
|
| 7. |
|
|
| 8. |
- Hedin, Hanne, 1948-
(författare)
-
External Fixation of Femoral Fractures in Children : Clinical, radiological and functional outcome and cost analysis
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis was to evaluate the outcome when treating children for displaced femoral fractures with external fixation.In a consecutive and prospective study during the period 1993-2000, 96 children aged 3-15 years with 98 displaced femoral fractures were treated with external fixation and early mobilisation. The mean age was 8.1 years, the mean hospital stay was 8.7 days and the mean treatment time was 61 days. All fractures healed. Minor complications included pin tract infections (18%), clinical insignificant malunions, heterotopic ossification and two re-reductions. Major complications (6%) included two re-fractures after significant trauma and three plastic deformations after premature fixator removal leading to an osteotomy.Radiological evaluation was performed up to one year for the whole group and for a subgroup up to two years. The evaluation showed that malunions were few and prone to remodelling almost completely. Although the fractures were fixated without shortening, as recommended earlier, the overgrowth was far less than expected.Isokinetic muscle strength was measured in both hamstrings and quadriceps in 31 of the patients and compared with 31 matched children without previous injury to the legs. Early mobilisation seems to prevent residual muscle weakness previously shown after treatment with traction or cast for femoral fractures in children.A cost analysis was performed, comparing three different treatment modalities of femoral shaft fractures: traction in hospital, traction in hospital/at home and external fixation. The analysis included both total medical costs and costs for the care provider. The most important factors were days spent at the hospital and the sick leave for the care provider. Treatment that can minimise these factors will contribute strongly to a lowering of health care costs.Conclusion: External fixation of displaced femoral fractures in children can be used as standard treatment in children aged 3-15 years. The treatment provides satisfactory results with a low rate of major complications. Early mobilisation seems to prevent residual muscle weakness. The treatment reduce the number of days in hospital and the number of days of sick leave for the care provider and contributes strongly to lowering health care costs.
|
|
| 9. |
- Crnalic, Sead, 1960-
(författare)
-
Metastatic spinal cord compression in prostate cancer : clinical and morphological studies
- 2012
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Bone metastases occur in most patients with advanced hormone-refractory prostate cancer causing pain, pathologic fractures, and spinal cord compression. Few studies specifically address surgical treatment of metastatic spinal cord compression (MSCC) in prostate cancer. Criteria for identifying patients who may benefit from surgery are poorly defined. Most of the current knowledge regarding tumor biology in prostate cancer is based on studies of primary tumors or soft tissue metastases. The mechanisms regulating growth of bone metastases are not fully established. Aims: a) to evaluate outcome after surgery for MSCC in prostate cancer and to identify prognostic factors for survival and functional recovery; b) to evaluate current practice for referral of prostate cancer patients with MSCC; c) to analyze expression of androgen receptor (AR), cell proliferation, apoptosis, and prostate-specific antigen (PSA) in bone metastases with regard to survival after surgery for complications of bone metastases. Patients and Methods: We retrospectively evaluated the hospital records of 68 consecutive patients operated for metastatic spinal cord compression. Tumor tissue from bone metastases was obtained on spinal surgery (54 patients), fracture surgery (4 patients) and biopsy (2 patients), and analyzed by immunohistochemistry. Results: Study I: Mortality and complication rate after surgery was high. Patients with hormone-naïve disease and those with hormone-refractory disease with good performance status and without visceral metastases had more favorable survival. The ability to walk after surgery was related to better survival. Study II: A new score for prognosis of survival after surgery for spinal cord compression includes: hormone status of prostate cancer, Karnofsky performance status, evidence of visceral metastasis, and preoperative serum PSA. The score is simple, tumor specific, and easy to apply in clinical practice. Study III: Our results suggest that delays in diagnosis and treatment may have negative impact on functional outcome. Pretreatment ability to walk, hormone status of prostate cancer, and time from loss of ambulation influenced neurological recovery after surgery for spinal cord compression. Study IV: High nuclear AR immunostaining in bone metastases and high preoperative serum PSA were associated with a poor outcome after metastasis surgery in patients with hormone-refractory prostate cancer. Short-term effect of castration therapy disclosed that nuclear AR immunostaining was decreased and apoptosis was increased, but cell proliferation remained largely unaffected. Conclusion: Prostate cancer patients with metastatic spinal cord compression represent a heterogeneous group. We identified prognostic factors for survival and functional outcome, which may help clinicians in making decisions about treatment. Our results also implicate the need for development of local and regional guidelines for treatment of patients with spinal cord compression, as well as the importance of information to patients at risk.
|
|
| 10. |
- Bernhoff, Karin, 1972-
(författare)
-
Orthopaedic Patients with Lower Limb Vascular Injuries
- 2016
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Vascular injuries in lower limbs are rare but serious events. If not detected and managed correctly and timely they can lead to permanent functional impairment and even limb loss. The increasing number of orthopaedic interventions, worldwide, makes awareness of this problem among orthopaedic surgeons important.The overall aim of this thesis was to describe lower limb orthopaedic injuries with associated concomitant arterial injuries, especially to the popliteal artery. Epidemiology, mechanisms of injury, management, outcomes and the patient perspective were all addressed. The research questions were generated from clinical praxis. Vascular injuries are rare events, but by using as the National Patient (NPR) and National Vascular registries (Swedvasc) a relatively speaking large cohort was studied. Deep interviews with qualitative study method were used to investigate the patients’ perspective.In papers I and II iatrogenic popliteal artery injuries (PAI) in knee-replacements, and in non-knee-replacements, were investigated. The number of knee arthroplasties in Sweden increased 1987-2008, but not the frequency of iatrogenic PAI. The most common mechanism of injury was sharp, directly to the artery. One third of the injuries resulted in pseudo-aneurysms. This was an unexpected and important finding, since these patients were often diagnosed late, resulting in poor outcome.Paper III. The interviewed patients narrated substantial functional, cosmetic and psychological impairments,4-17 years after their accidents, yet they described their lives as “normal”. Patients with saved limbs reported a need for better interpersonal support in their rehabilitation and adaptation back to “normal” life.Paper IV. Popliteal artery injury is feared in knee dislocations and fractures. The proportion incidence of vascular injury was previously reported to be 2-60%. In this large population-based study, the incidence proportion in knee dislocations was 3.4-8.2%, depending on the definition of dislocation/ligamentous injury. In knee fractures the incidence proportion was lower, only 0.2%. The dominating cause of arterial injury in knee dislocations was fall, in knee fractures it was motor vehicle accidents. Amputation- free survival after arterial injury was inferior in knee fractures compared with knee dislocations.In conclusion, PAI is a serious injury but on sequences can be limited by awareness and timely action.
|
|
