| 1. |
- Lundin, Anna-Carin
(författare)
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Tendinosis in Trigger Finger
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Trigger finger is one of the most common hand conditions, with a prevalence of almost 3%. The aetiology remains unclear even though many causes have been suggested. The prevailing paradigm is that the pathogenesis of trigger finger is ascribed to primary changes in the first fibrous condensation of the tendon sheath (A1-pulley). Several studies have investigated pathology in the pulley, but few have investigated the tendon. The general aim of this thesis was to find out if there is pathology in the trigger finger tendon and to define it.We first looked at trigger finger tendon biopsies in a light microscope, and found that they were histologically different from healthy tendons. They showed signs of micro-ruptures, collagen degradation, increased amounts of ground substance, both hyper- and hypo-cellular areas, round active cell nuclei and absence of inflammatory cells, all similar to tendinosis. The histological picture was further assessed by using a scoring system for Achilles tendinosis. The trigger finger tendons scored high, suggesting a similar histopathology.Next, we performed a quantitative real-time polymerase chain reaction (qPCR) on trigger finger tendons. We assessed the mRNA expression of 10 genes, which have been described to be differently expressed in Achilles tendinosis (collagen 1 and 3, versican, decorin, biglycan, aggrecan, MMP-2, MMP-3, ADAMTS-5, and TIMP-3). The overall expression pattern agreed with previous studies on Achilles tendinosis, suggesting that the cellular function in trigger finger tendons is disturbed in a similar way as in Achilles tendinosis.Recent experimental and observational research has suggested potential side effects of statin treatment on tendons, but firm evidence was lacking. We performed an epidemiological study on two large population-based cohorts. Statin use was found to increase the risk of both trigger finger and tendinosis in the shoulder and Achilles tendons, especially among men. This suggests a similar pathology in trigger finger and tendinosis.We have also studied the time to treatment effect after a single injection of glucocorticoid in trigger finger. Our results suggest that 60-80% of patients can expect resolution of the triggering within 14 days, and half of them within seven days. This result allows correct information to be given to the patient and proper planning of follow-ups.In conclusion, the pathology in trigger finger tendons is similar to tendinosis in other tendons.
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| 2. |
- Hellström Ängerud, Karin, et al.
(författare)
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Differences in symptoms in relation to myocardial infarction.
- 2016
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: In myocardial infarction (MI) rapid diagnosis and treatment is crucial for the prognosis. Previous research has found that symptom presentation influence pre hospital delay times but studies about differences in MI symptoms between patients with ST-elevation myocardial infarction (STEMI) and non ST-elevation myocardial infarction (NSTEMI) are sparse and inconclusive. To enhance the understanding of symptom presentation in regard to MI type, we aimed to describe symptoms in relation to MI type and to find predictors of STEMI versus NSTEMI in patients with MI.Methods: Patients with MI (n=694) from the SymTime study were included. SymTime was a multicentre cross-sectional study of symptoms and actions in the prehospital phase of MI and data were collected using a previously validated questionnaire administered to MI patients within 24 h of admission to hospital.Results: Patients with STEMI were younger, more often men and smokers. Patients with NSTEMI were more likely to have a history of hypertension, MI and stroke. Chest pain was the most common symptom in both groups. Pain, discomfort, or pressure located in the jaw or teeth, vertigo/pre-syncope, cold sweat and nausea/vomiting were significantly more frequent in patients with STEMI (Table 1). In a multivariate logistic regression model patients with STEMI were more likely to present with cold sweat (OR 4.13, 95% CI 2.71–6.29) jaw pain (OR 2.14, 95% CI 1.02–4.50), and nausea (OR 2.01, 95% CI 1.20–3.33), and less likely to have a history of stroke (OR 0.35, 95% CI 0.15–0.84), fluctuating symptoms (OR 0.54, 95% CI 0.36–0.83) and anxiety (OR 0.54, 95% CI 0.32–0.92) compared to patients with NSTEMI.Conclusion: Patients with STEMI differed significantly from those with NSTEMI regarding symptom presentation. This knowledge is important for health care personnel to recognize symptoms alarming for STEMI when evaluating patients with MI symptoms.
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| 3. |
- Venetsanos, Dimitrios
(författare)
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Improving management of STEMI patients treated with primary PCI : Pharmacotherapy, renal function estimation and gender perspective
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis focused on the acute management of patients with ST-segment elevation myocardial infarction (STEMI) in an effort to provide information that may improve outcome. The aim was to evaluate the efficacy and safety of bivalirudin versus unfractionated heparin (UFH) in STEMI patients during primary PCI. Furthermore, to provide pharmacodynamic data of novel ways of ticagrelor administration compared to standard tivcagrelor. Additionally, to identify subgroups of patients, such as women who may derive greater benefit from specific antithrombotic strategies due to their risk/benefit profile. Finally, to evaluate current formulas for estimation of renal function in the acute phase of STEMI.In Paper I, all STEMI patients in Sweden between 2008 and 2014, treated with primary PCI and UFH or bivalirudin were included in our analysis. Of the total population of 23 800 patients, 8 783 (36.9%) were included in the UFH group and 15 017 (63.1%) in the bivalirudin group. Concomitant GPI administration was 68.5% in the UFH arm compared to 3.5% in the bivalirudin arm (p<0.01).The adjusted incidence of 30-day mortality was not significant different between the two groups (UFH vs bivalirudin, adjusted HR 0.94; 95% CI 0.82 -1.07). The adjusted risk for 1-year mortality, 30-day and 1-year stent thrombosis and re-infarction did not differ significantly between the two groups. In contrast, patients treated with UFH had a significantly higher incidence of major in-hospital bleeding (adjusted OR 1.62; 95%CI 1.30 -2.03).In Paper II pharmacodynamic data of chewed or crushed ticagrelor compared to standard ticagrelor loading dose (LD) was assessed in 99 patients with stable angina. Platelet reactivity (PR) was assessed with VerifyNow before, 20 and 60 minutes after LD. High Residual platelet reactivity (HRPR) was defined as > 208 P2Y12 reaction units (PRU). Chewed ticagrelor tablets resulted in significantly lower PRU values compared to crushed or integral tablets at 20 and 60 minutes. Crushed ticagrelor LD resulted in significantly lower PRU values compared to integral tablets at 20 minutes whereas no difference was observed at 60 minutes. At 20 minutes, no patients had HRPR with chewed ticagrelor compared to 68% with integral and 30% with crushed ticagrelor LD (p<0.01).In Paper III we presented a pre-specified gender analysis of the ATLANTIC trial including 1 862 STEMI patients that were randomly assigned to pre-hospital versus in-hospital administration of 180mg ticagrelor. Women were older and had higher TIMI risk score. Women had a 3-fold higher risk for all-cause mortality compared to men (5.7% vs 1.9%, HR 3.13, 95% CI 1.78 – 5.51). However, after adjustment for baseline characteristics, the difference was lesser and no longer significant (HR 1.98, 95% CI 0.97 – 4.04). Female gender was not an independent predictor of risk for bleeding after multivariable adjustments (BARC type 3-5 HR 1.52, 95% CI 0.74-3.09). There was no interaction between gender and efficacy or safety of randomised treatment.In Paper IV, forty patients with PCI- treated STEMI were included between November 2011 and February 2013. We validated the performance of the Cockcroft-Gault (CG), the Modification of Diet in Renal Disease (MDRD-IDMS), the Chronic Kidney Disease Epidemiology (CKD-EPI) and the Grubb relative cystatin C (rGCystC) equations for estimation of GFR against measured GFR (mGFR) during the index hospitalisation for STEMI.MDRD-IDMS and CKD-EPI demonstrated a good performance to estimate GFR with accuracy within 30% (P30) 82.5% vs 82.5%, respectively. CKD was best classified by CKD-EPI (Kappa 0.83). CG showed the worst performance with the lowest P30. The rG-CystC equation had a marked bias of -17.8% and significantly underestimated mGFR (p=0.03).Conclusions – In STEMI patients treated with primary PCI, bivalirudin should be preferred in patient at high risk for bleeding. With crushed or chewed ticagrelor tablets a more rapid platelet inhibition may be achieved, compared with standard integral tablets. In STEMI patients, fast and potent platelet inhibition with chewed ticagrelor may reduce the risk of early stent thrombosis and patients treated with a less aggressive antithrombotic strategy, such as UFH or bivalirudin monotherapy, may derive a greater benefit. Although gender differences in adverse outcomes could mainly be explained by older age and clustering of comorbidities in women, a bleedreduction strategy in women with high risk characteristics is warranted in order to improve their outcome. Regardless the choice of antithrombotic strategy, dose adjustment of drugs cleared by kidneys based on GFR estimation is of crucial importance. MDRD and CKD-EPI should be the formulas used for estimation of GFR in STEMI patients
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| 4. |
- Slind Olsen, Renate
(författare)
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Circulating and genetic factors in colorectal cancer : Potential factors for establishing prognosis?
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Colorectal cancer (CRC) is defined as a cancer appearing in the colon or in the rectum. In Sweden, ~ 6300 individuals were diagnosed with the disease in 2014 and ~ 2550 individuals diagnosed with CRC die each year due to their cancer. Surgery is the main treatment option of CRC and a survival rate of ~ 10 % is estimated if distant metastases have developed. It is therefore of importance to find factors that may be useful together with tumour, node, metastasis (TNM) stage to establish early CRC diagnosis, prognosis and follow-up of CRC patients. The aim of this thesis was to study the possible association of CD93, PLA2G4C, PDGF-D and inflammatory cytokines with CRC disease progression.In a prospective study approach CD93 and PLA2G4C single nucleotide polymorphisms (SNPs) were of potential importance in CRC prognosis.The T/T genotype of CD93 was associated with an increased CD93 expression in CRC tissue. Further, CRC patients carrying this genotype were associated with disseminated CRC at diagnosis and a lower recurrence-free survival after surgery. The A allele of a SNP of PLA2G4C was a stronger predictor for CRC-specific mortality than the conventional risk factors used in the clinic for selection of TNM stage II patients for adjuvant treatment. This indicates that the T/T genotype of CD93 and the A allele of PLA2G4C may be potential genetic factors related to disease severity and spread. Furthermore, they distinguish CRC patients that may benefit from a more comprehensive follow-up and adjuvant treatment.To study the putative involvement of PDGF-D in CRC the effects of PDGF-D signalling was studied in vitro. PDGF-D signalling altered the expression of genes of importance in CRC carcinogenesis and proliferation which was blocked by imatinib, a tyrosine kinase inhibitor. This indicates that PDGF-D signalling may be an important pathway in CRC progression and a potential target in CRC treatment.The analysis of various inflammatory cytokines in plasma at diagnosis showed an association between high levels and increased total- or CRC-specific mortality two years after surgery. High levels of CCL1 and CCL24 was the only cytokines strongly correlated with a worse CRC prognosis after statistical adjustments and may be of interest for further evaluation.In conclusion, this thesis presents circulating and genetic factors such as CD93, PLA2G4C, PDGF-D, CCL1 and CCL24 that may be of importance in CRC progression and may be of clinical value together with TNM stage in establishing prognosis.
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| 5. |
- Åkerman, Linda, 1983-
(författare)
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Aspects of the Pre-Diabetic Period in Type 1 Diabetes
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Type 1 diabetes (T1D) is an autoimmune disease characterized by insulin deficiency, due to immune-mediated destruction of beta cells. Current knowledge regarding the period preceding disease onset comes, to a large extent, from studying risk cohorts based on relatives of T1D-patients, as they have an increased disease risk. Among T1D patients in general, however, few have the disease in their immediate family. It is therefore important to study risk cohorts from the general population as well. An ongoing autoimmune reaction can often be seen in the blood long before disease onset, by detection of autoantibodies directed towards beta cell antigens. By autoantibody screening among participants in the ABIS (All Babies in the South-east of Sweden) cohort, we could identify a group of children from the general population with increased risk for T1D, positive for multiple autoantibodies. They were enrolled in a 2-year prospective follow-up aiming to characterize the prediabetic period and to identify factors indicative of progression/non-progression to T1D. We assessed glucose homeostasis and autoantibody titers over time, and searched for risk-biomarkers by analyzing the expression of immune-related genes (Th1-Th2-Th3) in peripheral blood mononuclear cells (PBMC) from these children, in comparison to healthy children and newly diagnosed T1D patients. In the same groups we also compared serum micro RNA (miRNA) profiles, knowing that miRNA molecules have desirable biomarker properties. We found that two specific autoantibodies, IA2A and ZnT8A, were detected at higher concentrations in risk-individuals who progressed to overt T1D during or after the follow-up period, compared to those who still have not. We also observed disturbed glucose homeostasis long before onset in the progressors, but it was seen among those who remain symptom free as well. Further, we found support for the possible role of insulin resistance as an accelerator of the disease process. For gene expression and serum miRNA, few differences were observed between risk-individuals and healthy children overall. However, for PBMC gene expression and serum miRNA both, there were associations to beta cell function and glucose homeostasis, and for miRNA also to islet autoantibodies. Although specific profiles for prediction of disease onset or identification of risk-individuals could not be found, these results are interesting and deserve to be evaluated further. As part of another sub-study within ABIS, the effects of physical activity on glucose homeostasis were assessed in healthy schoolchildren. The level of physical activity, measured by pedometers, was related to insulin resistance and beta cell-stress, and decreased physical activity was associated with increased insulin resistance and load on the insulin-producing beta cells, already at school-age.
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| 6. |
- Aljabery, Firas
(författare)
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Staging and tumor biological mechanisms of lymph node metastasis in invasive urinary bladder cancer
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aim: To study the possibility of detecting lymph node metastasis in locally advanced urinary bladder cancer (UBC) treated with radical cystectomy (RC) by using preoperative positron emission tomography/computed tomography (PET/CT) and peroperative sentinel node biopsy (SNB) technique. We also investigate the clinical significance of macrophage traits expression by cancer cells, M2-macrophage infiltration (MI) in tumor stroma and the immunohistochemical expression of biomarkers in cancer cells in relation to clinicopathologic data.Patients and Methods: We studied prospectively 122 patients with UBC, pathological stage pT1–pT4 treated with RC and pelvic lymph node dissection (PLND) during 2005–2011 at the Department of Urology, Linköping University Hospital. In the first study, we compared the results of preoperative PET/CT and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes (LNs). In the second study we investigated the value of SNB technique for detecting pathological LNs during RC in patients with UBC. W also examined the significance of the primary tumor location in the bladder in predicting the site of LN metastases, and the prognostic significance of lympho-vascular invasion (LVI) and lymph node metastasis density (LNMD) on survival. In the third study, we investigate the clinical significance of macrophage infiltration (MI) in tumor stroma and macrophage-traits expression by tumor cells. In the fourth study, we investigate the cell cycle suppression proteins p53, p21, pRb, p16, p14 ARF as well as tumors proliferative protein Ki67 and DNA repair protein ERCC1 expression in cancer cells. The results were compared with clinical and pathological characteristics and outcome.Results: Prior to RC, PET/CT was used to detect LN metastasis in 54 patients. PET/CT had 41% sensitivity, 86% specificity, 58% PPV, and 76% NPV, whereas the corresponding figures for conventional CT were 41%, 89%, 64%, and 77%. SNB was performed during RC in 103 patients. A median number of 29 (range 7–68) nodes per patient were examined. SNs were detected in 83 out of 103 patients (81%). The sensitivity and specificity for detecting metastatic disease by SNB varied among LN stations, with average values of 67% -90%. LNMD or ≥8% and LVI were significantly related to shorter survival. In 103 patients, MI was high in 33% of cases, while moderate and low infiltration occurred in 42% and 25% of tumors respectively. Patients with tumors containing high and moderate compared to low MI had low rate of LN metastases (P=0.06) and improved survival (P=0.06), although not at significant level. The expression of different tumor suppression proteins was altered in 47-91% of the patients. There were no significant association between cancer specific survival (CSS) and any of the studied biomarkers. In case of altered p14ARF, ERCC1 or p21, CSS was low in case of low p53 immunostaining but increased in case of p53 accumulation, although not at a significant level, indicating a possible protective effect of p53 accumulation in these cases.Conclusion: PET/ CT provided no improvement over conventional CT in detection and localization of regional LN metastases in bladder cancer. It is possible to detect the SN but the technique is not a reliable for perioperative localization of LN metastases; however, LVI and LNMD at a cut-off level of 8% had significant prognostic values. MI in the tumor microenvironment but not CD163 expression in tumor cells seems to be synergistic with the immune response against urinary bladder cancer. Our results further indicate that altered p53 might have protective effect on survival in case of altered p14ARF, p21, or ERCC1 indicating an interaction between these biomarkers.
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| 7. |
- Loftås, Per, 1964-
(författare)
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Response to neoadjuvant treatment in rectal cancer surgery
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rectal cancer is one of the three most common malignancies in Sweden with an annual incidence of about 2000 cases. Current treatment consists of surgical resection of the rectum including the loco-regional lymph nodes in the mesorectum. In advanced cases, neoadjuvant chemo-radiotherapy (CRT) prior to the operative treatment reduces local recurrences and enables surgery. The neoadjuvant treatment can also eradicate the tumour completely, i.e. complete response. This research project was designed to investigate the effects of preoperative radiotherapy/ CRT and analyze methods to predict response to CRT.Study I investigated the expression of the FXYD-3 protein with immunohistochemistry in rectal cancer, with or without preoperative radiotherapy. The results from the total cohort showed that, strong FXYD-3 expression was correlated to infiltrative tumour growth (p = 0.02). In the radiotherapy group, strong FXYD-3 expression was related to an unfavourable prognosis (p = 0.02). Tumours with strong FXYD-3 expression had less tumour necrosis (p = 0.02) after radiotherapy. FXYD-3 expression in the primary tumour was increased compared to normal mucosa (p=0.008). We concluded that FXYD-3 expression was a prognostic factor in patients receiving preoperative radiotherapy for rectal cancer.Study II investigated FXYD-3 expression in tumours that developed local recurrences following surgery and compared this with expression in tumours that did not develop local recurrences. There was no difference in the expression of FXYD-3 between the group that developed local recurrences and the group that did not develop local recurrences. There was no difference in survival between those with strong or weak FXYD-3 expression. We concluded that this study could not confirm the findings from study 1 i.e. that FXYD-3 expression has prognostic significance in rectal cancer.Study III was a register-based study on the incidence and effects of complete response to neoadjuvant treatment. Eight per cent of the patients with adequate CRT to achieve complete response also had a complete histological response of the luminal tumor in the resected bowel. Sixteen per cent of that group had remaining lymph node metastases in the operative specimen. Chemotherapy together with radiotherapy doubled the chance of complete response in the luminal tumour. Patients with remaining lymph node metastases had a lower survival rate compared to those without. We concluded that residual nodal involvement after neoadjuvant treatment was an important factor for reduced survival after complete response in the luminal tumour.Study IV followed up the results from the previous study by re-evaluating magnetic resonance imaging (MRI)- images in patients with complete tumour response. Two experienced MRI radiologists performed blinded re-staging of post CRT MR- images from patients with complete response in the luminal tumour. One group with lymph node metastases and another one without were studied and the results compared with the pathology reports. The sensitivity, specificity, and positive and negative predicted values for correct staging of positive lymph nodes was 37%, 84%, 70% and 57%. The size of the largest lymph node (4.5 mm, p=0.04) seemed to indicate presence of a tumour positive lymph node. We concluded that MRI couldn’t correctly stage patients for lymph node metastases in patients with complete response to CRT in the luminal tumour.
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| 8. |
- Nord, Maria
(författare)
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Levodopa pharmacokinetics -from stomach to brain : A study on patients with Parkinson’s disease
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Parkinson’s disease (PD) is one of the most common neurodegenerative disorders and it is caused by a loss of dopamine (DA) producing neurons in the basal ganglia in the brain. The PD patient suffers from motor symptoms such as tremor, bradykinesia and rigidity and treatment with levodopa (LD), the precursor of DA, has positive effects on these symptoms. Several factors affect the availability of orally given LD. Gastric emptying (GE) is one factor and it has been shown to be delayed in PD patients resulting in impaired levodopa uptake. Different enzymes metabolize LD on its way from the gut to the brain resulting in less LD available in the brain and more side effects from the metabolites. By adding dopa decarboxylase inhibitors (carbidopa or benserazide) or COMT-inhibitors (e.g. entacapone) the bioavailability of LD increases significantly and more LD can pass the blood-brain-barrier and be converted to DA in the brain. It has been considered of importance to avoid high levodopa peaks in the brain because this seems to induce changes in postsynaptic dopaminergic neurons causing disabling motor complications in PD patients. More continuously given LD, e.g. duodenal or intravenous (IV) infusions, has been shown to improve these motor complications. Deep brain stimulation of the subthalamic nucleus (STN DBS) has also been proven to improve motor complications and to make it possible to reduce the LD dosage in PD patients.In this doctoral thesis the main purpose is to study the pharmacokinetics of LD in patients with PD and motor complications; in blood and subcutaneous tissue and study the effect of GE and PD stage on LD uptake and the effect of continuously given LD (CDS) on LD uptake and GE; in blood and cerebrospinal fluid (CSF) when adding the peripheral enzyme inhibitors entacapone and carbidopa to LD infusion IV; in brain during STN DBSand during oral or IV LD treatment.To conclude, LD uptake is more favorable in PD patients with less severe disease and GE is delayed in PD patients. No obvious relation between LD uptake and GE or between GE and PD stage is seen and CDS decreases the LD levels. Entacapone increases the maximal concentration of LD in blood and CSF. This is more evident with additional carbidopa and important to consider in avoiding high LD peaks in brain during PD treatment. LD in brain increases during both oral and IV LD treatment and the DA levels follows LD well indicating that PD patients still have capacity to metabolize LD to DA despite probable pronounced nigral degeneration. STN DBS seems to increase putaminal DA levels and together with IV LD treatment also increases LD in brain possibly explaining why it is possible to decrease LD medication after STN DBS surgery.
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| 9. |
- Ranebo, Mats, 1970-
(författare)
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Rotator Cuff Tears : Short- and long-term aspects on treatment outcome
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rotator cuff tear is a common disorder and there is a lack of knowledge of appropriate treatment and consequences of different treatment modalities. The overall aim of this thesis was to examine short- and long-term results of rotator cuff tear treatment.In Paper I we did a retrospective 21 to 25-year follow-up of a consecutive series of patients with partial and full-thickness rotator cuff tears, treated with acromioplasty without cuff repair. The cuff status had been documented in a specific perioperative protocol in all patients at the index operation. We did x-ray, ultrasonography and clinical scores with Constant score and Western Ontario Rotator Cuff index (WORC) at follow-up. We identified 111 patients with either a partial or a full-thickness tear, but at follow-up 21 were deceased and 11 were too ill from medical conditions unrelated to their shoulder. Out of the remaining 78 eligible patients, 69 were examined (follow-up rate 88 %) and they had a mean age at the index operation of 49 years (range 19-69 years). Forty-five had a partial tear and 24 a full-thickness tear at the index operation. At follow-up, 74% of patients with full-thickness tear had cuff tear arthropathy grade 2 or more according to the arthropathy classification of Hamada (grade 1 to 5) and 87% had developed tear progression (i.e. a larger tear). Corresponding numbers in those with a partial tear was 7 % arthropathy and 42 % tear progression, and the differences between the full-thickness group and the partial tear group was significant for both outcome measures (P<0.001 for both analyses). In those with arthropathy, the mean Constant score was 47 (standard deviation [SD], 23), the mean age and gender-adjusted Constant score 62 (SD, 27) and the mean WORC 58 % (SD, 26). Patients with a partial tear at follow-up had mean Constant score and WORC within the normal range. In multivariable analysis with logistic regression, having a full-thickness tear at the index operation was a risk factor for arthropathy (odds ratio [OR] 37.8; 95% confidence interval [CI], 8.2-175.0) and for tear progression (OR 6.09; 95% CI, 1.41-26.29).In Paper II we examined the contralateral shoulder in the same patients as in paper I and with the same methodology. Sixty-one patients were examined and 38 had had a partial tear at the index operation 21-25 years ago and 23 a full-thickness tear. The overall rate of contralateral full-thickness tears was 50.8 %, which is higher than the 16-35 % rate found in previous studies of newly diagnosed cuff patients. The rate of contralateral full-thickness tear ranged from 13.6 % in patients with a partial tear in the index shoulder at follow-up, to 90 % in patients with a full-thickness tear and arthropathy in the index shoulder. There was a significant correlation regarding conditions between shoulders in the same patient, with a Spearman coefficient of 0.72 for the number of ten-dons with a full-thickness tear, 0.31 for Hamada grade of arthropathy and 0.65 for Constant score. The number of tendons with a full-thickness tear in the index shoulder at follow-up was a risk factor for a contralateral full-thickness tear (OR 3.28; 95% CI, 1.67-6.44) in a multi-variable logistic regression model. We also found that cuff tear arthropathy was significantly more common in patients who had undergone an acromioplasty (P<0.001), a finding which is not confirmatory but may generate a hypothesis.Paper III addressed 17 to 20-year results after operation with a synthetic interposition graft for irreparable cuff tears. We used X-ray, ultrasonography and clinical scores at follow-up. We identified a consecutive series of 13 patients, one of whom was deceased at follow-up. Ten of the remaining 12 participated in a complete follow-up and 2 did only x-ray examination. Nine out of 12 (75 %; 95% CI, 43-95 %) had cuff tear arthropathy Hamada grade 2 or more in the index shoulder at follow-up. The mean Constant score was 46 (SD, 26) and the mean WORC 59 % (SD, 20). Seven out of 12 had contralateral cuff tear arthropathy, and the difference in frequency of arthropathy between shoulders was not statistically significant (P=0.667).In Paper IV we tested whether early repair of small cuff tears, involving mainly supraspinatus, would give a superior clinical result com-pared to physiotherapy without repair in a prospective randomised trial with 12 months follow-up. We used Constant score as the primary out-come, and WORC, EQ-VAS and Numerical Rating Scale for pain (NRS) as secondary outcomes. We also aimed at assessing the rate of tear progression in unrepaired shoulders and the healing rate in repaired shoulders by Magnetic Resonance Imaging (MRI) performed at 12 months. With a high grade of follow-up (100 % for 12 months Constant score and 95 % for 12 months MRI), the repair group had a 12 months median Constant score of 83 (Quartile range [QR], 25) and the conservative group 78 (QR, 22). This between-group difference in medians of 4.5 (95% CI,-5 to 9; P=0.68) was not statistically significant and we did not detect any significant differences in the secondary outcomes at 12 months. The retear rate was 6.5 % in repaired patients and 29 % of unrepaired patients had a tear enlargement >5 mm.The results in this thesis indicate that patients with small, traumatic, full-thickness tears of mainly supraspinatus have no clinical benefit of early surgical repair compared to physiotherapy alone, but in the long-term, patients with full-thickness tears have an increased risk of tear progression, cuff tear arthropathy and low clinical scores. These results are especially important in the treatment decision of repair or not in younger patients. Having a full-thickness tear is also a risk factor for having a contralateral cuff tear, a phenomenon that underlines the importance of endogenous factors in the development of rotator cuff tears. If a cuff tear is not repairable to bone, the addition of a synthetic inter-position graft does not seem to prevent cuff tear arthropathy.
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| 10. |
- Hadimeri, Ursula
(författare)
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Factors affecting the physical characteristics of arterio-venous fistula in patients with renal failure
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background and PurposeA patent access is vital for a dialysis patient. The arterio-venous fistula (AVF), the most important access for haemodialysis (HD), is frequently affected by extensive complications such as stenosis and occlusions.Study I: To investigate whether the dimensions of AVFs used for performing haemodialysis were affected by the original disease.Study II: To investigate if the diameter of the distal radiocephalic fistula could influence left ventricular variables in stable haemodialysis patients.Study III: To investigate whether a single Far Infrared (FIR) light treatment could alter blood velocity, AVF diameter or inflammatory markers.Study IV: To evaluate in what extent the renal diagnosis and radiological interventions affected the dysfunction of AVF and results of percutaneous transluminal angioplasty (PTA).Materials and methodsStudy I: The lumen diameter of the AVF was studied by ultrasound in 19 patients with autosomal dominant polycystic kidney disease (ADPKD) and in 19 control patients. The monitoring was performed along the forearm part of the vein, the maximal diameter was measured. The diameters of the two needle insertion sites were also measured.Study II: Nineteen patients were investigated with echocardiography, using M-mode recordings and measurements in the 2D image. Ultrasound and doppler ultrasound were performed. Transsonic measurements were performed after the ultrasound investigation. Measurements of the diameter of the AVF were performed in four locations. Heart variables were analysed regarding left ventricular (LV) criteria.Study III: Thirty patients with native AVF in the forearm were included. Each patient was his/her own control. Ultrasound examinations of the AVF diameter and blood flow velocity were performed before and after a single Far Infrared light (FIR) treatment.Study IV: 522 radiological investigations and endovascular treatments between January 1, 2006 and December 31, 2014 were analysed in 174 patients, retrospectively. All investigations had been performed due to clinical suspicion of impaired AVF function. All stenoses were evaluated and the number, degree, length, location and relation to anastomosis were recorded. After PTA the remaining stenoses were evaluated again and complications were recorded.ResultsStudy I: The diameter of the AVF at the maximal site in patients with ADPKD was significantly wider than that for the control patients.Study II: A larger AVF mean and maximal diameter worsened left ventricular characteristics.Study III: A single FIR treatment resulted in a significant increase in blood velocity over the AV fistula from a mean of 2.1±1.0 m/s to 2.3±1.0 m/s. The diameter of the arterialized vein became wider, i.e. 0.72±0.02 to 0.80±0.02 cm. The increase in fistula blood velocity correlated positively with baseline serum-urate and the increase in venous diameter correlated positively with the baseline plasma orosomucoid concentration.Study IV: The degree of AVF stenosis before PTA correlated significantly with the degree of remaining stenosis after intervention. Arterial stenosis was significantly more frequent among patients with diabetic nephropathy and interstitial nephritis. A shorter life span between PTAs was related to diabetic nephropathy.ConclusionsStudy I: The receiving veins of AVF in patients with ADPKD have an abnormality that causes a greater than normal dilatation in response to the arterialization.Study II: The maximal diameter of the distal AVF seems to be a sensitive marker of LV impairment in stable haemodialysis patients.Study III: A single FIR treatment increased AVF blood velocity and vein diameter. Thus, one FIR treatment can help maturation of AVF in the early postoperative course.Study IV: Repeated PTA was performed significantly more often in patients with diabetic nephropathy. Clinically significant stenosis should be dilated as soon as possible. Occlusion of the AVF should be thrombolyzed and/or dilated when diagnosed.
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