Doctoral Theses / Doktorsavhandlingar Institutionen för kliniska vetenskaper

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A methodological platform to study molecular biocompatibility of biomaterials. Experimental and clinical studies
(2016-05-13) Lennerås, Maria
The aim of this project was to develop a methodological platform in order to advance our scientific understanding of the mechanisms of osseointegration. Screw-shaped, titanium implants, with different surface properties, were inserted in the rat tibia, or incubated in mono- or co-culture of human monocytes and MSCs. After different time points, the implant-adherent cells or the peri-implant bone were harvested and processed for different analyses. For in-vivo studies, qPCR, immunohistochemistry, histomorphometry, electron microscopy and removal torque analyses were used. In the in-vitro study, FACS, qPCR, ELISA and protein profiling were applied. Finally, qPCR was employed in a clinical study to analyse the abutment-adherent cells of osseointegrated fixtures. At the early time points in vivo, a higher gene expression of MSC recruitment and adhesion factors (CXCR4 and integrin-β1) was found in cells adhering to the oxidised compared to machined implant. This was corroborated by predominance of MSCs at the oxidised surface, as judged by immunohistochemistry and SEM. At the later time points, cells adhering to oxidised implants retained a higher expression of bone formation (ALP and OC) and bone remodelling (TRAP and CatK) genes. The qPCR findings correlated with histomorphometric, electron microscopy and removal torque measurements, revealing progressively increasing bone-implant contact and bone bonding and, as a result, an increase in the biomechanical stability of the oxidised implant. The enhanced RANKL/OPG expression ratio corresponded to the remodelling phase at the bone-implant interface. The qPCR analysis of FACS-sorted cells showed that the co-existence of monocytes and MSCs on the implant surface, in vitro, upregulates the gene expression of some cytokines in a cell-specific manner. The clinical study showed that bacterial colonisation was frequently detected on the skin, the abutment and in the bone canal. A higher expression of TNF-α was associated with positive cultures of S. aureus, whereas fixture loss was associated with lower expression of OC and IL-10. In conclusion, the present methodological platform enables detailed analyses of the events at the bone-implant interface. Employing this platform demonstrated that implant surface properties elicit a cellular and molecular cascade for rapid cell recruitment and enhanced bone formation and remodelling, which accelerates bone maturation and implant stability. Finally, the results of the thesis provide a first line of information on factors that could affect the performance of percutaneous implants.
Abdominoperineal excision for distal rectal carcinoma. Oncological outcome and aspects of self-assessed quality of life
(2016-09-15) Prytz, Mattias
Abstract: In recent years an adjusted method of performing an abdominoperineal excision (APE) - so called extralevator APE - has been developed and internationally spread. It has been proposed to decrease intraoperative perforations and non-radical surgery and therefor improve local cancer control and decrease rates of local recurrences as compared to standard APE. This thesis aims to investigate if the oncological outcome of ELAPE is superior to standard APE and to explore the association between patient reported intrusive thoughts and QoL as well as to type of surgery performed three years after surgery and to compare outcome to that found in a normative Swedish cohort. Data on all Swedish patients operated with any kind of APE in the years 2007-2009 were collected from the Swedish ColoRectal Cancer Registry and short-term oncological outcome was measured (i.e. perforations and non-radical surgery) as well as short-term complications and mortality. In order to be able to differ between APE and ELAPE, all patients’ operation notes were collected from the hospital charts where they had been operated, and analysed with regard to which operating technique had been used. When 3-years local recurrence data were available in the registry these data were also collected from the registry and analysed with regard to what operation had been performed. Furthermore, a special questionnaire was developed in order to be able to measure a number of health-related QoL parameters specific for this group of patients. The questionnaire was sent to all patients alive 3 years following surgery and data on QoL was compared to data from a Swedish normative population. Short-term oncological results were the same for both groups with regard to perforation and non-radical surgery. There were fewer intraoperative perforations for a subgroup of the most distal tumours in the ELAPE group but not for the entire group. There were more wound infections for the ELAPE-group. Local recurrences after 3 years were significantly more common in the ELAPE group as compared to standard APE but there was no difference between groups in overall survival. Intraoperative perforation was significantly associated with higher risk of local recurrence. A large proportion of survivors after abdominoperineal excision for rectal cancer have a quality of life comparable to a normative population, however many suffer from a symptom of stress, negative intrusive thoughts, which significantly decrease overall quality of life. Oncological outcome following ELAPE is not superior to standard APE. ELAPE is associated with more perineal wound complications. This method should be used in selected patients with high risk of intraoperative perforation.
Acetabular Revisions
(2015-09-15) Mohaddes, Maziar
Hip replacement is a successful intervention when treating patients with hip osteoarthritis. Approximately 10% of all patients undergoing primary hip replacement surgery require further surgical interventions (revisions) during their lifetime. Acetabular component (cup) failure is the most common reason for a revision. Cemented fixation in acetabular revision surgery was a common method until the mid-1980s. Low survival rates reported for cemented revision cups and encouraging results. There are, however, no studies comparing the results of revision surgery based on the method of fixation for the acetabular component. In 2006, a highly porous trabecular metal (TM) tantalum cup was introduced in the Swedish market and, in 2013, this cup was the most commonly used acetabular revision component in Sweden. The primary aim of this thesis was to compare cemented and uncemented fixation in acetabular revisions using radiostereometric analysis (RSA). Further, a comparative analysis of the TM cup and other cup designs frequently used in acetabular revisions was performed. Data from the SHAR, on 18,593 first-time revisions, were used in the first study to analyse differences relating to the risk of re-revision between cemented and uncemented cups. The overall risk of acetabular component failure did not differ between the two modes of fixation. In this analysis, cemented revision cups were re-revised more often due to aseptic loosening but less often due to dislocation. In Paper II, TM cups were compared with the other two cups most frequently used in first-time revisions recorded in the SHAR. The short-term re-revision rate of the TM design did not differ from that of the other two designs. The third paper addressed the influence of proximal migration on the risk of aseptic loosening. An analysis of 312 acetabular revisions followed with RSA for two to 20 years showed that proximal migration measured with RSA can be used a predictor of aseptic loosening of the acetabular component. In the fourth paper, 45 patients (47 hips) undergoing surgery with cemented or uncemented fixation were followed prospectively for 17 years. Radiostereometry was used to monitor the migration and rotation of acetabular components. Cups installed using cemented fixation showed a higher rate of early migration. In a randomised prospective study (Paper V), the RSA migration pattern of the TM cup was compared with that of a cemented cup in hips with large bone defects. The TM design showed less proximal migration compared with the cemented design, indicating a lower risk of aseptic loosening when the TM cup is used in hips with large bone defects. To summarise, there was no difference in the overall risk of re-revision based on the method of fixation, according to data from the SHAR. Proximal migration measured with RSA is a predictor of late aseptic loosening in acetabular revisions. The TM cup shows promising short-term results in the SHAR. The low early proximal migration of the TM design suggests that it has the potential to reduce the risk of late aseptic loosening in revision surgery, but this remains to be demonstrated in clinical studies with longer follow-up.
Achilles tendinopathy : evaluation and treatment
(2006) Grävare Silbernagel, Karin
Abstract. Background: Achilles tendinopathy is considered to be one of the most common overuse injuries in elite and recreational athletes. There are, however, only a few randomized studies of treatment and there is a need for standardized outcome measures for the patients’ symptoms and function. Purpose: The overall purpose of this thesis was to develop and evaluate outcome measures and treatment protocols for patients with Achilles tendinopathy. Material, Methods and Results: Initially, a method was developed to evaluate both symptoms and function in Studies I and II. The method was shown to have good reliability in 10 patients with acute Achilles tendon injuries and in 32 patients with chronic Achilles tendinopathy. We questioned, however, the validity of the methods since only small changes were detected while symptoms improved. At that time there was no standardized symptom questionnaire for the assessment of patients with Achilles tendinopathy. A questionnaire of this kind became available in 2001 in English. In Study III this questionnaire, the Victorian Institute of Sports Assessment – Achilles questionnaire (VISA-A), was cross-culturally adapted and evaluated for reliability, validity and structure on 15 healthy subjects and 51 patients. The Swedish version of the VISA-A questionnaire (VISA-A-S), which measured two factors, pain/symptoms and physical activity, was shown to have good reliability and to be a valid instrument, fully comparable to the original version. The VISA-A-S can be used in both research and clinical settings. A test battery for lower leg muscle/tendon function, including jump and strength tests, was developed and evaluated on 42 patients in Study IV. The purpose of the test battery was to evaluate, in more detail than had previously been possible, whether Achilles tendinopathy caused functional deficits on the injured side compared with the non-injured side. The test battery was found to be reliable and able to detect clinically relevant differences in lower leg function between the injured or “most symptomatic” and non-injured or “least symptomatic” sides in patients with Achilles tendinopathy. The test battery imposed more rigorous demands on patient function compared with each individual test. Treatment comprising iontophoresis using dexamethazone combined with exercise for patients with acute Achilles tendinopathy was evaluated on 25 patients in a randomized, double-blind design in Study II. Positive effects on symptoms were found from using iontophoresis with dexamethazone, compared with a control group in patients with acute Achilles tendon pain. Achilles tendon and calf muscle strengthening exercises (intensity modified with the use of a pain-monitoring model) as treatment for patients with chronic (symptoms for more than 2-3 months) Achilles tendinopathy was evaluated in 40 patients in Study I and in 38 patients in Study V. Furthermore, the effect of continued running and jumping on treatment outcome was evaluated in Study V. A treatment protocol which includes Achilles tendon and calf muscle exercises resulted in significant improvements in patients with chronic Achilles tendinopathy. When the pain-monitoring model was used, no negative effects could be demonstrated from continuing Achilles tendon loading activity (such as running and jumping) during treatment. Conclusion: The VISA-A-S questionnaire can be used to evaluate the clinical severity of patients with Achilles tendinopathy and it is useful in both research and clinical settings. Patients with Achilles tendinopathy reports not only pain, but also demonstrate deficits in lower leg function. In the acute phase, the use of iontophoresis with dexamethazone could potentially be beneficial. For patients with both acute and chronic Achilles tendinopathy, the performance of Achilles tendon and calf muscle strengthening exercises with the use of a pain-monitoring model for 6 months can be recommended. A training regimen of continued, pain monitored, Achilles tendon loading physical activity, such as running and jumping, might represent a valuable option for patients with Achilles tendinopathy.
Achilles tendon rupture: the evaluation and outcome of percutaneous and minimally invasive repair
(2017-11-17) Carmont, Michael R
Acute Achilles tendon rupture is common and has increasing incidence. This is thought to be due to increasing activity and sports participation in middle age. Sustaining an Achilles tendon rupture means a long rehabilitation period and many patients do not achieve full recovery of strength and function. One of the reasons for this reduced function is considered to be due to tendon elongation. The reasons for the lack of recovery has been discussed in earlier studies comparing operative and non-operative treatments. Operative treatment can be divided into open, minimally-invasive and percutaneous technique. Proponents for operative treatment consider open technique to prevent tendon elongation and reduce the re-rupture rate compared with non-operative treatment. Percutaneous repair is considered to lead to an increasing incidence of iatrogenic nerve damage and reduced repair strength compared with open repair but is considered to be advantageous because of lower risk of infections and wound problems. The purpose of this dissertation was to evaluate and optimise the results of percutaneous and minimally-invasive technique for an Achilles tendon rupture. Moreover, evaluation instruments were developed and an already existing validated questionnaire was culturally adapted in English to be used in the United Kingdom. Achilles Tendon Resting Angle (ATRA) is an indirect measure of tendon elongation. The method has been developed and validated in one of the studies in the dissertation. ATRA has subsequently been used to evaluate the clinical outcomes. The ATRA angle increases after an Achilles tendon rupture, then decreases after operative intervention to finally increase again during the first rehabilitation phase. The ATRA angle was shown to correlate with patient-reported symptoms and function as measured by heel rise height one year after injury. Thus, ATRA can provide an indication of function achieved after treatment of an Achilles tendon rupture. Achilles Tendon Total Rupture Score (ATRS) is a validated patient-reported questionnaire for evaluating limitations and physical activity after an Achilles tendon rupture. ATRS was originally developed for a Swedish population but has now been translated and culturally adapted to an English population in one of the studies. ATRS has also been used for evaluating patient-reported outcomes. Percutaneous and minimally-invasive operative techniques have been evaluated in 169 patients treated for an Achilles tendon rupture. Percutaneous technique was found to be more cost-effective in comparison to open procedure, with similar results regarding function and patient-reported symptoms. Minimally invasive repairs produced similar outcome to percutaneous repair but with a lower complication rate. Based on these results, minimally invasive repair is recommended for the operative treatment of an acute Achilles tendon rupture. In order to compare the strength of different suture materials after repair of the Achilles tendon, a cadaveric study was performed, in which the tendon was cyclically loaded. The result from this study shows that repair with non-absorbable suture has better strength in comparison to an absorbable one. However, there is still a lack of knowledge of why a patient suffering from an Achilles tendon rupture does not fully recover. Further studies involving how treatment and rehabilitation can be optimised is of value.
Achilles Tendon Ruptures Predictors; functional and economic impact
(2018-11-22) Westin, Olof
Acute Achilles tendon rupture is a common injury, which leads to significant morbidity in patients. Many patients never recover their full function even after long rehabilitation, whereas others make a good recovery. The factors behind this are unknown. The optimal treatment strategy, whether or not to treat surgically, is still controversial. This thesis consists of six studies with the overall aim of finding predictors of outcome, examining the long-term follow-up of re-ruptures and comparing the cost efficiency of two different management strategies. Study I is a cohort study of 45 patients who underwent acute ultrasonography within 72 hours of the index injury. They were randomly allocated to either surgical or non-surgical treatment. Three of four (75%) patients with a diastasis of more than 10 mm treated non-surgically sustained a re-rupture and these were the only re-ruptures in the study group. The patients with a diastasis of more than 5 mm displayed poorer heel-rise function and patient-re-ported outcome if treated non-surgically. Study II is a cross-sectional observational cohort study comprising 256 prospectively randomised patients. At two weeks post-operatively, patients underwent a micro-dialysis investiga-tion and six metabolites were collected. Patients were followed up at three, six and 12 months and the duration of surgery was examined. The results showed that glycerol and glutamate were higher with a longer duration of sur-gery. Interestingly, a longer duration of surgery was correlated with an improved clinical and functional outcome. Study III is a long-term follow-up of patients with an Achilles tendon re-rupture, where validated outcome meas-urements were used to assess lower extremity function and symptoms. Twenty patients with a mean (SD) follow-up of 50.9 (38.1) months were included. This cohort was compared with patients (n=87) treated for primary ruptures. The injured side was significantly worse compared with the healthy side in terms of heel-rise tests. The most inter-esting finding in this study was that patients treated for a re-rupture reported a poorer patient-reported outcome compared with those treated for primary ruptures. Study IV is a health-economic evaluation comparing the cost-effectiveness of surgical and non-surgical treatments. The data were collected prospectively from a randomised controlled trial comprising 100 patients. This study showed that the cost per quality-adjusted life year (QALY) gained is € 45,855 and that surgical treatment is 57% likely to be cost efficient at a willingness to pay per QALY of € 50,000. Study V is a mapping study that develops an algorithm, which converts the Achilles tendon total rupture score (ATRS) to the European Quality of Life-5 dimensions Questionnaire (EQ-5D), which enables detailed health-economic studies related to Achilles tendon injuries. It concludes that the algorithm has a high goodness of fit and can be used in future studies. Study VI comprised 391 patients from five different randomised controlled trials pre-dicting functional and patient-reported outcome one year after an acute Achilles tendon rupture. This study re-vealed that older age is a predictor of poorer outcome and that surgically treated patients have a tendency towards superior recovery in terms of heel-rise height. Taken together, this thesis shows that ultrasonography could be potentially useful in predicting the risk of re-rup-ture and outcome in acute Achilles tendon rupture. It also demonstrates that a longer duration of surgery leads to the upregulation of healing metabolites. Patients who have sustained a re-rupture have long-term deficits in terms of function and a poorer patient-reported outcome than those with primary ruptures. Moreover, it provides the first cost-effectiveness analysis in this field of research and develops an algorithm for future health-economic studies. Finally, it concludes that older age is a strong predictor of poorer heel-rise height at one year.
Acute Achilles tendon rupture - The impact of calf muscle performance on function and recovery
(2017-11-17) Brorsson, Annelie
There is an ongoing debate about the optimal treatment for patients with an acute Achilles tendon rupture. The overall purpose of this thesis was to acquire a greater knowledge of the way patients recover at different time points after the injury when treated with the currently recommended treatment protocols. This knowledge will then form the basis of the further development of treatment strategies with the ultimate goal of minimizing the risk of permanent disability after an Achilles tendon rupture. In Study I, a long-term follow-up of 66 patients included in a randomized, controlled trial revealed that, 7 years after the injury, there were continuing deficits in calf muscle endurance and strength. There was no continued improvement in calf muscle performance after the 2-year follow-up, apart from heel-rise height. Study II, a clinical prospective comparative study of a cohort of 93 patients, performed 3 months after the injury, concluded that standardized seated heel-rises were a safe and useful tool for evaluating calf muscle endurance and predicting future function and patient-reported symptoms. No differences in early calf muscle recovery were found between patients treated with surgery and patients treated with non-surgery, but the question of whether women recovered in the same way as men remained unanswered. In Study III, a clinical retrospective comparative study comprising 182 patients, it was found that female patients had a greater degree of deficit in heel-rise height compared with males, irrespective of treatment. Females had more symptoms after surgery, at both 6 and 12 months, but this difference was not found in non-surgically treated female patients. In Study IV, the effect of continued heel-rise height deficits on biomechanics during walking, running and jumping was further evaluated. This study revealed that heel-rise height, obtained during the single-leg standing heel-rise test, performed 1 year after the injury, was related to the long-term ability to regain normal ankle biomechanics. In this cross-sectional study, comprising 34 patients, the conclusion was drawn that minimizing tendon elongation and regaining heel-rise height may be important for the long-term recovery of ankle biomechanics, particularly during more demanding activities such as jumping. This thesis shows that the early recovery of heel-rise height and calf muscle endurance has a significant impact on lower leg function and patient-reported outcome in the long term after an acute Achilles tendon rupture. No differences in early or late calf muscle recovery were found between patients treated with surgery and patients treated with non-surgery. Furthermore, it is concluded that females have more symptoms after surgery, but this difference is not found in non-surgically treated female patients. This knowledge could now form a new basis for developing more effective, individualized treatment protocols with the aim of optimizing the treatment after an acute Achilles tendon rupture.
Acute achilles tendon rupture. Evaluation of treatment and complications
(2009-04-17T12:29:29Z) Nilsson Helander, Katarina
The overall purpose of this thesis was to evaluate the treatment of patients with an acute Achilles tendon rupture with regard to complications, function and patient-reported outcome. Moreover, the purpose was to develop and evaluate new outcome measurements. Introduction: Controversy still remains about whether surgical or non-surgical treatment is the best option to treat patients with Achilles tendon ruptures. There are only a few randomised, controlled studies that compare surgical and non-surgical treatment, when both groups receive early mobilisation. Many outcome measurements found in the current literature are non-validated and based on a mixture of assessments and there is a need for patient-reported instruments. In patients with a chronic rupture or a re-rupture of the Achilles tendon, the recommended treatment is surgical. Various surgical techniques have been reported in the literature; however, the outcome is rarely evaluated with a sufficiently long follow-up, using appropriate end-points. Venous thromboembolism (VTE) is a major complication and a high incidence of VTE has been reported in previous studies of patients treated for an Achilles tendon rupture. The majority of patients with an Achilles tendon rupture have strength deficits and it is therefore desirable to evaluate function with valid, reliable methods, which are sensitive enough to detect possible differences between treatment groups. Ma terial and Methods: In Study I, a new patient-reported instrument, the Achilles tendon Total Rupture Score (ATRS), was developed for measuring outcome, related to symptoms and physical activity after treatment in patients with a total Achilles tendon rupture. In Study II, 97 patients with an acute Achilles tendon rupture were followed for one year. Surgical and non-surgical treatments were compared; both groups were treated with early mobilisation. The primary end-point was re-rupture. The patients were evaluated using the ATRS, functional tests and clinical examinations. In Study III, 28 patients were evaluated 29 (12-117) months after surgery. A new surgical method to treat a chronic rupture and re-rupture of the Achilles tendon was used and evaluated. The surgical technique involved a single incision, with a free gastrocnemius aponeurosis flap to cover the tendon gap after an end-to-end suture. The patients were evaluated as described in Study II. In Study IV, a new heel-rise work test was evaluated in 78 patients. In Study V, 95 patients from Study II were screened for deep venous thrombosis using Colour Doppler Sonography (CDS). Results: The ATRS was found to be a valid and reliable patient-reported instrument with good responsiveness to measure outcome in terms of symptoms and physical activity in patients with an Achilles tendon rupture. The re-rupture rate was 2 (4%) and 6 (12%) respectively in the surgical and non-surgical group. There were no significant differences when comparing surgically and nonsurgically treated Achilles tendon ruptures, in terms of re-ruptures and patient-reported outcome. Functional tests indicate a difference between the two groups when evaluated 6 months after initial treatment, with better results in the surgically treated group. This was not, however, seen at 12 months, except in the heel-rise work test. The use of a free gastrocnemius aponeurosis flap to treat a chronic rupture and a re-rupture of the Achilles tendon rendered a good overall subjective and objective outcome in the majority of patients. A heel-rise test that measures both the height of each repetition and the number of repetitions had good validity and a greater ability to detect differences between the injured and uninjured sides than a test that measures only the number of heel-rise repetitions. The incidence of asymptomatic and symptomatic deep venous thrombosis was high (34%), however, without any difference between the two groups. 5 Conclusion: We found no strong evidence to suggest that surgical treatment is preferable to non-surgical treatment with regard to re-rupture rate and patient-reported scores in patients with an acute Achilles tendon rupture. However, significant differences in favour of surgery were found in muscle function at 6 months. Both groups improved significantly over time and, at the 12-month evaluation, the results were similar except in the heel-rise work test. The functional tests showed that muscle function deficits remained between the injured and uninjured sides after 12 months, regardless of surgical or non-surgical treatment. The use of a free gastrocnemius aponeurosis flap appears to be a useful alternative when treating a chronic rupture and a re-rupture of the Achilles tendon. The new heel-rise work test has good validity and greater ability to detect differences that measuring the number of heel-rises. There was a high incidence of DVT after Achilles tendon rupture and there is a need to evaluate the benefit of thromboprophylactic treatment in the future. Key words: Achilles tendon rupture, chronic rupture, free flap, augmentation, deep venous thrombosis, movable brace, re-rupture, ATRS, heel-rise work test
Acute Achilles Tendon Rupture. Outcome, Prediction and Optimized treatment
(2013-05-07) Olsson, Nicklas
The optimal treatment for Achilles tendon rupture is the subject of debate and could be either surgical or non-surgical with various alternatives in terms of immobilization and rehabilitation. The purpose of this thesis was to evaluate the short- and long-term outcome of a new surgical treatment protocol, including early tendon loading and ROM training, in comparison with non-surgical treatment using a functional brace. Patients in this randomized, controlled trial were evaluated with regard to symptoms, function and complications at 3, 6 and 12 months. Predictors of outcome were assessed in a multiple linear regression model. The outcome two years after injury was also evaluated in a previous randomized study of Achilles tendon rupture. The studies showed no significant differences between surgical and non-surgical treatment in terms of symptoms, physical activity level or quality of life. There was a trend towards a greater improvement in function in surgically treated patients. No re-ruptures occurred in the group treated with the new surgical technique. The heel-rise test showed that half the patients were unable to perform a single heel rise three months after injury and this ability appears to be an important early achievement, which influences patient-reported outcome and physical activity. Future treatment protocols focusing on regaining strength early after injury appear to be of great importance. Regardless of surgical or non-surgical treatment, there were significant functional deficits on the injured side compared with the contralateral side two years after the tendon rupture and the patients appear to adjust to these changes. Treatment was a moderate predictor, in contrast to age and BMI, which were relatively strong predictors of function and symptoms respectively. This thesis found that an Achilles tendon rupture impacts heavily on a person’s general health and quality of life and has a significant effect on lower leg function but with large inter-individual differences, indicating that the choice of treatment should be based on the best available evidence in combination with individual patient factors.
Acute Achilles tendon rupture: The impact of physiological and psychological factors on function and return to activity
(2023-11-17) Jónsdóttir, Unnur
Unfortunately, there is no guarantee of a full return to physical activity after an Achilles tendon rupture. About 20% of those who sustain the injury do not return to their previous level of physical activity. Although the reasons for this have been examined, no definitive conclusion has been reached. The main aim of this thesis was to gain knowledge of what can cause an incomplete recovery, which might negatively influence the return to physical activity. In this thesis, we try to identify interventions to eliminate the causes of incomplete recovery after an Achilles tendon rupture. In Study I foot structure was evaluated. We compared the uninjured and the injured sides 6 years after an Achilles tendon rupture. Two treatment groups (surgical and non-surgical) were also compared. Lower values for navicular drop and drift were found in the foot structure of the injured side in all participants, meaning that the translation of the navicular bone was less on the injured side compared with the uninjured side. The foot structure values (longitudinal arch angle and navicular drop and drift) were lower on the uninjured side in the surgically treated group compared with the non-surgical group, while there were no differences between the groups on the injured side. The effect of fatigue on the kinetics of the lower extremities was evaluated in Study II, two years after an Achilles tendon rupture. The peak power values of the ankle, knee and hip during landing and push-off for a drop countermovement jump were used for evaluation before and after a fatigue protocol. The results showed greater effect on the ankle joint after the fatigue protocol on the uninjured side compared with the injured side. However, there were no differences before and after the fatigue protocol in the knee and hip joints. In Study III, the impact of fear of reinjury on the kinetics in the lower extremities during a drop countermovement jump was evaluated 2 years after an Achilles tendon rupture. The participants were divided into two groups (Fear group and No-Fear group) depending on their answer to the question: “Do you ever refrain from any activity due to fear of reinjuring your Achilles tendon?”. The peak power values of the ankle, knee and hip joints during a drop countermovement jump were compared between the two groups. The results demonstrated increased asymmetry of the lower leg kinetics in the injured side in the Fear group, with less power in the ankle joint and increased compensatory power in the knee joint compared with the injured side in the No-Fear group. A qualitative content analysis was performed in Study IV, aimed at identifying factors that affect return to activity after an Achilles tendon rupture. Twenty participants were interviewed 4-6 years after an Achilles tendon rupture. The interviews were analysed and coded in order to categorize factors that collectively determine the thread/theme of the interviews. The overarching theme of the study was “Help me and then I can fix this”. This theme can be interpreted to the prerequisite that if the support one needs is in order, one can handle the next step. In summary, it is obvious that various physiological and psychological factors affect the return to activity. However, none of the factors examined in this thesis pointed the way towards a clear strategy. The effect of these factors appears to vary between individuals. It can thus be concluded that individualized treatment and rehabilitation are important, with frequent updates and evaluation of progress.
Acute kidney injury after cardiac surgery and heart transplantation - monitoring, prevention and treatment
(2022-10-14) Tholén, Maria
Background: Acute kidney injury (AKI) is a common and serious complication after cardiac surgery and heart transplantation, leading to increased morbidity and mortality. To date, there are neither proven clinical real-time kidney monitoring techniques, nor effective preventive measures or treatments of AKI for these patients. Aims and methods: This thesis evaluated whether the non-invasive technique, near-infrared spectroscopy (NIRS), can accurately assess renal tissue oxygenation in patients during cardiac surgery. Renal vein oxygen saturation (SrvO2) was compared to renal tissue oxygenation (rSO2) by NIRS. Furthermore, the effects of the inodilator, levosimendan (0.1 µg/kg/min, n=16), on renal blood flow (RBF) and glomerular filtration rate (GFR) were compared to placebo (n=13) in patients with AKI post cardiac surgery. In addition, the renoprotective effect of the atrial natriuretic peptide (ANP) was studied in patients undergoing heart transplantation. Seventy patients undergoing heart transplantation were randomized to receive either ANP (50 ng/kg/min) (n=33) or placebo (n=37) starting after induction of anaesthesia and continued for 4 days after heart transplantation. The primary end-point was measured GFR (mGFR) at day 4, assessed by plasma clearance of 51Cr-EDTA. Finally, the correlation, accuracy and agreement between estimated GFR (eGFR) and measured GFR (mGFR) were tested after heart transplantation. Results: Renal rSO2, as assessed by NIRS, was correlated to (r=0.61. p<0.001), and in agreement with invasively measured SrvO2 with an acceptable error of 17.6%. In hemodynamically stable patients with AKI after cardiac surgery, levosimendan increased RBF (p=0.011), but had little or no effect on GFR (p=0.079). During ongoing ANP infusion, median (IQR) mGFR at day 4 postoperatively was 60.0 (57.0) and 50.1 (36.3) mL/min/1.73 m2 (p=0.705) and the need for dialysis was 21.6% and 9.1% (p=0.197) for the placebo and ANP groups, respectively. The incidences of AKI for the placebo and the ANP groups were 76.5% and 63.6%, respectively (p=0.616). The accuracy of eGFR to assess mGFR was 51%. The bias was 11.2 ± 17.4 mL/min/1.73 m2, indicating that eGFR underestimated renal function (mGFR). The limits of agreement were -23.0 to 45.4 mL/min/1.73 m2 and the error 58%. The concordance rate between eGFR and mGFR was 72% Conclusions: There is a good correlation and agreement between non-invasively measured renal tissue oxygenation and invasively measured renal vein oxygen saturation during cardiac surgery. In post cardiac surgery AKI, levosimendan induces a vasodilation of both afferent and efferent arterioles increasing renal blood flow with little or no effect on renal function. Prophylactic infusion of ANP during and after heart transplantation does not seem to attenuate postoperative renal dysfunction or decrease the incidence of AKI. eGFR underestimated mGFR and the agreement between eGFR and mGFR was poor. Furthermore, the ability of eGFR to assess changes in mGFR, postoperatively, was low. Thus, eGFR is not a good enough marker to assess renal function after heart transplantation.
The acute osteoporotic vertebral compression fracture. Its natural course and characteristics.
(2009-02-21T14:45:07Z) Suzuki, Nobuyuki
Aim: The overall aim of this thesis was to investigate the natural course and the characteristics of the acute osteoporotic vertebral compression fracture in order to better understand and improve treatment for this type of fracture. Patients and methods: Eligible patients were all patients over 40 years of age who sought medical care at the emergency unit at Sahlgrenska University Hospital (studies I-III) or referred to the X-ray Department at Capio Diagnostic Center (study IV) because of back pain with a radiographically-confirmed acute vertebral body fracture which resulted from a low energy trauma. In studies I-III, a total of 107 patients were followed over one year using postal questionnaires. In study IV, a total of 448 patients were included. The pain, disability, ADL, and QoL were measured after 3 weeks, and 3, 6 and 12 months (studies I-III). The patient and fracture characteristics on the first X-ray visit were evaluated in all the studies. Results: Studies I-III. For all the outcome measures, the largest improvements, 10-15%, occurred between 3 weeks and 3 months. Thereafter, all the outcome measures levelled off or even worsened. One year after the fracture event, the patients’ conditions were poor: 60.5 for the pain intensity score, 53.9 for the disability score, 47.6 for the ADL score, and 0.52 for EQ-5D. These average values are similar to values seen preoperatively in patients with a herniated lumbar disc disease or in patients who are 100% disabled from work due to back or neck problems. The most influential factors were the initial fracture deformation severity and the number of previous fractures, whereas fracture level, fracture type, and gender influenced to a lesser extent. Study IV. The acute fracture characteristics were similar to those found in previous population-based studies of incident and prevalent fractures and in studies I-III. In the prevalent fracture analysis, concave fractures were frequent below L2 whereas wedge fractures were more frequent above L2. Mildly deformed fractures increased in the caudal direction and moderately deformed fractures increased in the cranial direction. Severely deformed fractures were frequent in the mid-thoracic spine and at the thoracolumbar junction. Conclusions: One year after the acute fracture, it was striking to find that 76% of the patients still had a high pain intensity and the mean QoL score was 35% lower than the population value for the same age group. This finding is quite different from the generally believed good prognosis for such a fracture. There is potential for better treatment. The relationship between the poor outcomes and the initial facture deformation severity specifically suggests the indication for invasive treatment, such as vertebroplasty or kyphoplasty.
Adolescent and young adult cancer survivors - body image and sexual health
(2018-04-25) Olsson, Maria
Background Adolescent and young adult cancer survivors constitute a group in society of which the numbers are increasing. To optimize rehabilitation efforts, we need to understand the possible physical and psychological consequences of cancer treatment for adolescent and young adult cancer survivors. The purpose of this study has been to identify the needs and topics that adolescents and young adults acknowledge as being important to them, and furthermore to explore possible physical and psychological complications post cancer treatment. Methods This thesis uses a combination of qualitative and quantitative methods. Eleven focus group interviews were conducted with adolescent and young adult cancer survivors aged 15-29. Subsequently, a study-specific web-based questionnaire was sent to a population-based cohort of adolescent and young adult cancer survivor and matched controls. 540 out of 721 (74%) eligible participants responded to the questionnaire. The topics covered in the questionnaire were psychosocial health, body image, sexuality, fertility, education, work and leisure. Results Adolescent and young adult cancer survivors reported in focus group interviews that they had unmet needs during and after cancer treatment, including age-appropriate information about sexuality. In the questionnaire study, they reported feeling less attractive than controls due to scars on their bodies, and they reported low satisfaction with their sexual function compared to controls. The participants did not find that questions addressing very personal and emotionally charged issues, like sexual activity, affected them negatively. Conclusions Adolescent and young adult cancer survivors perceived themselves as being unattractive due to scars on their bodies and were less satisfied with their sexual function than matched population-based controls. They also expressed the need for support to reintegrate into normal social life.
Advancements in DSC and BOLD perfusion imaging: Acquisition, analysis and clinical application
(2023-10-31) Arvidsson, Jonathan
This thesis is focused on perfusion MRI techniques and topics related to image acquisition, analysis and clinical applications. The first half of the thesis is focused on dynamic susceptibility contrast (DSC) MRI, a technique which is based on the contrast enhancements caused by an intravenously administered paramagnetic contrast agent. The second half of this thesis is focused on blood oxygen level dependent (BOLD) MRI, which leverages a signal effect caused by paramagnetic properties of venous blood. For application in peripheral muscle, this signal effect can be enhanced by restricting the blood flow of a feeding artery to the studied tissue. In papers I and III, it is shown that the duration of the contrast agent injection and the duration of the flow restriction, indeed affects the measures of perfusion produced with these techniques. The pathophysiology of normal pressure hydrocephalus (iNPH) is not completely understood, but symptoms point toward brain stem regions. In paper II, DSC-MRI and diffusion MRI was applied to patients with iNPH, pre and post shunt-surgery, showing the possible involvement of these regions in iNPH symptoms and disease reversibility. In paper IV peripheral muscle BOLD was applied to patients with peripheral artery disease (PAD) and controls, in an exploratory study. Perfusion related measures derived from acquired BOLD curves were able to separate between PAD patients and controls, in accordance with previous studies. Further data exploration found a number of curve traits that could be indicative of potential disease phenotypes, and these have now been documented. As the technique continues to develop towards individual prognostication, these curve traits may be of value for establishing disease severity. In conclusion, this work has made advancements of the common knowledge base within the field of perfusion imaging, spanning from the well-studied area of DSC-MRI to the comparatively new technique of peripheral muscle BOLD imaging and their application to clinically relevant patient cohorts.
Advances in MRI based radiation therapy - Bringing MRl-only and multiparametric methods towards clinical applications
(2023-01-12) Palmér, Emilia
MRI data have the advantage of being excellent in soft tissue contrast, therefore having an increasing imaging role in external radiation therapy (RT). Lately, attention has been directed towards MRI-only workflows, with the approach of completely excluding the original CT data as a pre-treatment imaging modality. Instead, the RT workflow is based solely on MRI data. To access the electron densities needed for calculation of the absorbed dose distribution, synthetic CT data (sCT) are generated utilizing image processing or deep learning (DL) based methods. Besides purely anatomical information for guidance of a RT workflow, many functional and microstructural properties, such as cell density, microvascular structure, perfusion, and oxygenation of the tumor, could be highly relevant for RT treatment guidance and early RT assessment. It has been proven that hypoxia has an essential role in treatment outcome for HN cancer patients receiving radiation therapy. The potential to monitor hypoxia by functional and anatomical MRI (i.e., multiparametric MRI) is sparsely evaluated, and more studies are required to be able to establish robust MRI-derived hypoxia biomarkers. The research within this thesis aimed to validate the MRI-only workflow for head and neck (HN) cancer, by evaluating sCT data generated by a nowadays commercially available DL-based method. The geometric and dosimetric properties were compared to the original CT data (Paper I), and as they were similar it was concluded that sCT can be used for dosimetric purposes. Further, both 2D and 3D patient setup verification based on sCT data was evaluated by comparison of the verification registrations with the registrations obtained when using the original CT data (Paper II). As the registrations for sCT and CT obtained similar patient positions, it was concluded that sCT data can be used for patient setup verification. As the generation of sCT data is based on complex models, a quality assurance (QA) process was developed to assess the quality of sCT data for prostate cancer (Paper III). A comparison between calculated absorbed dose distributions based on sCT and cone beam CT (CBCT) acquired for treatment setup verification, was shown to detect intentionally introduced errors within the sCT data. In addition, the research within this thesis aimed to implement and evaluate the potential of Oxygen-Enhanced (OE) MRI, intravoxel incoherent motion (IVIM), and diffusion kurtosis imaging (DKI) to monitor hypoxia, and their potential as useful tools for early response assessment in HN cancers (Paper IV). Each of these MRI pulse sequences was optimized and successfully implemented within a clinical RT setting. By comparing MRI-derived biomarkers acquired before and during RT for HN cancer patients, changes could be monitored during the course of treatment. The research presented in this thesis contributed to the clinical feasibility of MRI-only radiation therapy for multiple cancer types. In addition, the research showed that it is possible to implement multiparametric MRI for tumor characterization and treatment follow-up in the radiation therapy process for the complex HN region.
Allergic Rhinitis in Childhood and Young Adulthood: Epidemiology, Prevalence and Risk Factors
(2025-05-08) Vasileiadou, Styliana
Background and Aim: Allergic rhinitis (AR) is a common chronic condition among young people. This thesis examines the prevalence, risk, and protective factors of AR in 12-year-olds. It also compares questionnaire-derived AR data with Swedish national registers. It analyses AR trends, exploring AR risk factors in young adults. Finally, it examines the incidence and remission of AR from childhood into young adulthood and identifies associated risk factors. Methods: Data for the first two papers were derived from a longitudinal cohort of children born in 2003 in Western Sweden. Parents completed questionnaires for their children from 6 months to 12 years (76% response rate at 12 years). Personal identification numbers linked 3,634 children to Swedish national registers. Paper III presents a cross-sectional analysis of 16- to 25-year-olds from the West Sweden Asthma Study; 2,143 participants in 2008 and 2,484 in 2016. Paper IV included children in grades 1-2 in Norrbotten, using a questionnaire and skin prick tests (SPTs) in 2006 (8-year-olds) and 2016-2017 (19-year-olds). In total, 2,250 participants (91% participation rate) completed the questionnaire; 1,338 underwent SPTs at 8 and 19 years of age. Results: At age 12 years, 22% reported AR. Risk factors were parental AR, male sex, food allergy, and eczema at the first year of life, while living on a farm and early fish consumption at least once a month were protective factors. Concordance between questionnaires and registers on AR was weak due to insufficient registry data on over-the-counter medication and primary care. From 2008-2016, AR prevalence remained stable (22.5% to 24.4%, p=0.144). Growing up on a farm reduced AR risk in both 2008 and 2016. AR incidence from ages 8 to 19 years was 33.6% and the remission rate 40%. Sensitisation increased the risk of AR incidence and reduced the odds of remission. Conclusion: AR affects >20% of children at the age of 12 years. Genetic predisposition and environmental exposures play an important role in AR development, with protective factors such as farm living and early fish consumption suggesting potential preventive strategies. Sensitisation significantly impacts AR, indicating the need for early identification of individuals at risk. Integrating reliable parental questionnaires and registry data provides invaluable tools for sustained AR research.
Alpha-radioimmunotherapy with At-211: Evaluations and imaging on normal tissues and tumors
(2011-04-21) Bäck, Tom
Alpha-radioimmunotherapy (alpha-RIT) is an internal conformal radiotherapy at the cellular level using alpha-particle emitting radionuclides. Alpha-particles have a very short range in tissues (<100 micrometer) and high linear energy transfer (LET), making them highly cytotoxic. Due to these characters alpha- emitters are potentially highly effective in eradication of small tumor cell clusters while at the same time toxicity of the adjacent normal tissue is avoided. Thus, alpha-RIT could be effective in treatment of cancers characterized by micrometastatic and minimal residual disease, e.g. ovarian and prostate cancer. The biological effects of alpha-particles are grossly unknown and demand dedicated methodologies and evaluations for their interpretation. The aim was to evaluate the irradiation effects of the alpha-particle emitter 211At for its use in alpha-RIT, using nude mice. This included studies on tumor efficacy, kidney toxicity and a study describing a novel bioimaging system, the alpha-camera, for assessment of radionuclide tissue distribution. Growth inhibition (GI) after alpha-RIT with 211At on s.c. OVCAR-3-tumors was compared with GI after external irradiation using 60Co. For alpha-RIT, the mice were injected with 211At-MX35-F(Ab’)2 at different activities. The GI was calculated for both irradiations and used to estimate the relative biological effectiveness (RBE) for alpha-RIT on tumors. At GI of 0.37, the RBE was found to be 4.8±0.7. The long-term renal function after alpha-RIT was studied by measuring the glomerular filtration rate (GFR) after injection of 211At-MX35-F(Ab’)2 at different activities. The GFR was measured repeatedly, using plasma clearance of 51Cr-EDTA, up to 67 weeks after treatment. Dose-dependent and time-progressive reductions in GFR were found. For tumor-bearing mice, the kidney doses required for 50% reduction in GFR were 16±3.3 and 7.5±2.4 Gy at 8-30 and 31-67 weeks, respectively. For non-tumor-bearing mice the corresponding doses were 14±4.1 and 11.3±2.3 Gy. The maximum tolerable dose (MTD) to the kidneys (50% reduction in GFR) was 10 Gy. A novel imaging system for ex vivo detection and quantification of alpha-emitters in tissues was developed, using an autoradiographic technique based on a scintillator and CCD for light detection. Initial evaluations of the imaging characteristics showed that the spatial resolution was 35 ±11 micrometer, the uniformity better than 2% and that the image pixel intensity was proportional to radioactivity in the imaged specimens. As examples of applications, the alpha-camera visualized and quantified differences in the tissue activity distributions after alpha-RIT with 211At. For tumors, a very nonuniform distribution of 211At-MX35-F(Ab’)2 was found from 10 mpi to 6 hpi. At 21 hpi the distribution was more uniform. Images of kidney-sections could identify the 211At-distribution in different renal compartments. The ‘cortex-to-whole-kidney-ratio’ varied with time and bioconjugate size. The 211At-MX35-F(Ab’)2 showed a marked retention in the renal cortex, corresponding to a ratio of 1.38±0.3 at 2 hpi. The RBE found (4.8±0.7) gives further support for the use of alpha-particles in targeted radiotherapy. The MTD of 10 Gy suggests that the kidneys will not be the primary dose-limiting organ in alpha-RIT with 211At. The alpha-camera will be an important tool for internal alpha-particle-dosimetry and for the development of alpha-RIT.
Analysis of body motions based on optical markers. Accuracy, error analysis and clinical applications.
(2010-11-08) Tranberg, Roy
This thesis aims to evaluate the influence of soft-tissue artefacts on analyses of body motions based on optical markers. A second aim is to apply instrumented gait analysis in clinical situations. Introduction: Instrumented gait analysis has been used since 1960 as a clinical evaluation/investigative tool at orthopaedic clinics. The technique is based on a number of reflective spherical markers attached to the skin. The position of the skin markers is recorded as the subject walks through the measurement volume. Recorded data form the basis when monitoring movements of body segments. The crucial and still not completely explored issue is to what extent these systems are able to reproduce the movement of the body segment that is being studied. Material and methods: In Study I, the skin movement at the foot was studied using skin markers and radiographs. The subjects stood on one foot in three positions, 20° dorsal flexion, a neutral position and 30° plantar flexion, while radiographs were exposed. In Study II, the aim was to study problems with soft-tissue movement along the lower extremity. Skin and underlying structures were provoked partly by anterior-posterior and longitudinal strain and partly by being put into vibration to investigate their stiffness and damping characteristics. The aim of Study III was to examine the accuracy of the optical tracking system used throughout Studies IV-V by simultaneous recording using skeletal markers and radiostereometry (RSA). Nine patients with a total knee arthroplasty (2 males/7 females, median age: 63.1 years; range 59-72) were included in Study III. In Study IV, 20 patients with bilateral spastic cerebral palsy (15 males/5 females median age: 12.9 years, range 9.4-15.3) and 20 controls (13 males/7 females, median age: 13.0 years; range 10.2-15.7) were included. For Study V, nineteen unilateral transfemoral amputee patients (9 males/10 females, median age: 46.5 years; range 19.9-62.3) and fifty-seven matched controls were included. Results: Studies of soft tissue motions on the foot revealed marker movement in relation to the bone up to 4.3 mm at the ankle, which decreased gradually to 1.8 mm at the first inter-phalangeal joint. Soft-tissue movements mainly occurred in the anterior-posterior direction of the leg and pronounced self-oscillations were recorded when markers were placed on wands. The results from comparisons between RSA and OTS showed good agreement regarding extension/flexion motions. For abduction/adduction and in-/external rotation, significant differences between the two systems were observed. The group with cerebral palsy was weaker in all muscle groups in the lower limbs and they walked at a slower speed. A significant relationship between plantar flexing torque and the strength of six of the eight investigated muscle groups could be detected in patients with cerebral palsy. An even stronger relationship (rho=0.58-0.76) was found between generating power and muscle strength in all eight muscle groups. Two years after conversion from a conventional to bony anchored leg prosthesis, femoral amputees improved their hip extension and reduced their anterior pelvic tilt. Conclusion: Instrumented gait analysis is a non-invasive and valuable tool to study body motions. Knee motions in the sagittal plane (flexion/extension) are close to data obtained from RSA based on skeletal markers, whereas the resolution of rotations in the two other planes is poorer, probably due to soft tissue motions and geometrical reasons. Further comparative studies with simultaneous use of skeletal and superficial skin markers are needed to explore this issue further; not least concerning the hip and ankle joint.
Anatomic anterior cruciate ligament reconstruction - aspects of surgical technique
(2016-04-19) Desai, Neel
Anatomic anterior cruciate ligament (ACL) reconstruction is a concept that has gained in interest and it aims to more effectively restore native ACL anatomy and function. Despite extensive research on the topic, the optimal surgical technique to accomplish this is still the subject of debate. Study I is a meta-analysis to determine whether anatomic double-bundle (DB) reconstruction compared with anatomic single-bundle (SB) reconstruction more effectively restores knee laxity, and reduces rates of graft failure. A total of 15 studies were included for analysis. The results revealed significantly less antero-posterior (AP) laxity after anatomic DB reconstruction. No statistically significant differences were seen between anatomic DB and SB techniques in terms of the pivot-shift test, Lachman test, anterior drawer test, total knee rotation or graft failure rates. Study II is a systematic review including the implementation of the Anatomic Anterior Cruciate Ligament Reconstruction Scoring Checklist (AARSC) on studies comparing SB and DB reconstruction in order to evaluate the reporting of surgical details, and the degree to which these clinical studies fulfil the criteria of anatomic ACL reconstruction. Seventy-seven studies were included. Details of the surgical techniques used were more thoroughly reported for DB reconstructions than for SB reconstructions. There was substantial underreporting of surgical data for both the SB and DB groups in clinical studies. Study III is a prospective randomised clinical trial comparing the outcomes of the anatomic DB technique and anatomic SB technique using hamstrings tendon autograft. A total of 105 patients were randomised and underwent ACL reconstruction. At five-year follow-up, no statistically significant differences were found between the groups in terms of subjective or objective outcomes, or in terms of the presence of osteoarthritis (OA). Study IV is a cohort study with data from the Swedish National Knee Ligament Register with the focus on the risk of revision ACL surgery. A total of 17,682 patients were included. Surgical details pertaining to their primary ACL reconstruction were collected via an online questionnaire comprised of items from the AARSC, distributed to the surgeons. Non-anatomic bone tunnel placement via transtibial drilling resulted in the lowest risk of revision surgery. Non-anatomic surgical techniques in general were associated with a lower risk of revision. Anatomic techniques utilising several pertinent items from the AARSC were associated with a lower risk of revision compared with anatomic techniques utilising only some items.
Anatomic anterior cruciate ligament reconstruction - current evidence and future directions
(2012-03-30) Samuelsson, Kristian
Injury to the anterior cruciate ligament (ACL) is one of the most common orthopedic diagnoses. It is also one of the most researched areas in orthopedic surgery, with well over eleven thousand publications. Despite this, the solution for the best reconstructive technique is still not known and patients still suffer from their injury in both the short- and the long-term. An assessment of the outcomes was performed on randomized clinical trials. In terms of rehabilitation, a postoperative knee brace did not affect the clinical outcome and closed kinetic chain exercises produced less anteroposterior laxity and better subjective outcomes than open kinetic chain exercises. In terms of graft type, the patellar tendon graft produced initially more anterior knee pain and kneeling pain than the hamstring tendon graft. Moreover, the harvest site affected muscle strength initially and the hamstring tendon graft produced more tunnel widening. In terms of surgical technique, double-bundle ACL reconstruction produced less rotatory laxity than single-bundle. Finally, bioabsorbable screws and titanium screws produced equal clinical outcome. An analysis and systematic review was performed on studies of primary ACL reconstruction. This analysis revealed that most therapeutic studies were of a low level of evidence and that the most common study type was case series. The three most common represented journals were Arthroscopy, Knee Surgery Sports Traumatology Arthroscopy and The American Journal of Sports Medicine. Furthermore, there was a correlation between the journals’ impact factor and the mean level of evidence and there was a higher mean level of evidence over time. Anatomic ACL reconstruction is currently one of the modern techniques for ACL reconstruction. This shift in paradigm has created confusion about the term “anatomic”. Two systematic reviews assessed surgical data from studies claiming anatomic ACL reconstruction. The reviews revealed substantial under-reporting, making it difficult to do valid interpretations of the outcomes. A current concepts article was therefore published, outlining the concepts of anatomic ACL reconstruction, including principles and a definition: the functional restoration of the ACL to its native dimensions, collagen orientation and insertion sites. Ultimately, a scoring system was developed for the objective grading of surgical methods in studies of anatomic ACL reconstruction. This scoring system was subsequently implemented in studies comparing single- and double-bundle ACL reconstruction, which revealed means of the score well below a proposed minimum. In summary, a thorough analysis and review of what constitutes an anatomic ACL reconstruction was done, and an assessment was performed on studies comparing single- and double-bundle ACL reconstruction and studies claiming anatomic ACL reconstruction.

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