Minimally invasive catheter-based technologies

A simple incision procedure in a blood vessel makes the entire vascular system accessible. Through contrast injection and X-ray visualization, the vascular tree can be mapped and navigated through manual manipulation of thin tubes and wires. This utilization of the vasculature as internal pathways is commonly referred to as the endovascular technique. This technique can be used to deliver implants and drugs, retrieve problematic lesions or objects from the vasculature, or take tissue samples. Compared to open surgery, the advantage of this technique lies in the reduced invasiveness, ideally only leaving a small incision scar at the point of entry. Some interventions, however, are still associated with certain risks, requiring medication or complicating further interventions. The development of sequencing technologies presents an opportunity to improve and miniaturize devices, reducing invasiveness. This thesis aims to mitigate these risks and capitalize on the potential of next-generation sequencing through microfabrication technologies, producing devices that are less invasive than current methods or that enable a new procedure. Initially, the aspect of endovascular heart biopsy is covered. The first work presents the fabrication and in vivo evaluation of a nitinol-based catheter device designed for extracting myocardial tissue. The device is fabricated through picosecond laser machining of nitinol tubes and wires, producing a device that is substantially smaller than what is currently used. The samples are evaluated and compared to samples extracted with conventional devices through RNA-Sequencing, verifying the proof of concept. The second work further emphasizes the device's functionality by evaluating it in a disease model of endomyocardial infarction. Tissue that is affected by the infarct and surrounding healthy tissue is extracted and compared in terms of its genetic expression. This comparison reveals a genetic discrepancy between the sick and healthy tissue, verifying the potential of using the device with RNA-sequencing for diagnostic purposes. The third work evaluates the safety aspects of the novel device in a head-to-head comparison with a conventional device. The study reveals a clear benefit of using the smaller device in terms of the complication rate during the procedure. The fourth work presents the fabrication and in vivo evaluation of another nitinol-based catheter device designed for endothelial cell sampling. The device is fabricated through two-photon polymerization technologies, producing sub-mm brush structures mounted on a nitinol wire. Currently, there are no devices in clinical use that are capable of exclusively extracting endothelial cells. The novel device presents a solution for selective interaction with the innermost layer of the blood vessel. It represents an important step toward sampling endothelial cells for diagnostic and research purposes. The fifth and sixth works collectively present two different aspects of a third nitinol-based catheter device designed to sample tissue from soft organs anywhere in the body. The device is fabricated using laser micromachining, grinding, and two-photon polymerization. The work is separated in terms of the in vivo evaluation and the technical solution. The technical aspects of the device are examined in terms of force generation in miniaturized catheter systems and the problems that arise in terms of mechanical scaling. These problems are solved by attaching pistons along the wire surface coupled with applied pressure to increase the force generated. The sampling with this device is realized, similar to the fourth work, with sub-mm brushes mounted on the wire. In vivo evaluation of this device reveals successful sampling of minute tissue quantities from the liver and kidney, in the size range of 10-100 cells per sample. The seventh work presents the in vivo and in vitro performance of a nanostructure coating on nitinol-based stents. Patients with a stent implant are prescribed an extensive medication regimen to counteract the metal implant's effects on the blood and surrounding tissue. This issue is being continuously targeted by new stent platforms, either with a drug-eluting polymer layer or by being resorbable by the body or through various other means. These implants all have a transient behavior, resulting in different issues over time. Paper VII presents an alternative approach to this problem by instead applying a nanostructure coating that is designed to interact with the blood to a much lesser degree, as demonstrated by CT-angiography and the measurement of multiple biomarkers

Identifying Challenges of Food Living Labs in Food System Sustainability Transformation in Finland

Peer reviewe

Standards for opioid use disorder care : An assessment of Nordic approaches

Aims: Outcomes in opioid use disorder (OUD) in Nordic countries have improved with integrated treatment and harm-reduction programmes. Approaches and the standard of care are different across the region. Evidence of treatment needs and current approaches are defined from evidence to inform development of a common standard. Method: Evidence of population sizes and treatment approach collected. Common standards for care (harm reduction, pharmacotherapy, psychology/social therapy) defined for each country. Results: Evidence defines number in treatment; potential population needing treatment not defined for all countries. Populations sizes, treatment access (ratio in treatment programme compared to total country population) defined: Sweden 4,000 in OUD care (access ratio 40); Finland 3,000 (55); Norway 8,000 (154); Denmark 7,500 (132). Approach to treatment similar: integrated treatment programmes standard. Care provided by specialists in outpatient clinics/primary care; secondary care/inpatient services are available. Harm reduction is limited in Sweden but available and more accessible elsewhere. Treatment entry criteria: access relatively unlimited in Norway and Denmark, more limited in Finland and Sweden. Standards of care defined: easy access to high-quality services, individual planning, care not limited by time, management of relapse, education for patients, continuous engagement, holistic approach including management of comorbidities, needle equipment programmes without limit, treatment in prisons as community. Conclusion: There are opportunities to improve OUD care in the Nordics. Policy makers and clinicians can advance OUD care and share common success factors. Collaborative work across the Nordic countries is valuable. Further research in clinical practice development can yield important results for the benefit of patients with OUD.Peer reviewe

Principles for managing OUD related to chronic pain in the Nordic countries based on a structured assessment of current practice

Background: Long-term use of opioid analgesics (OA) for chronic pain may result in opioid use disorder (OUD). This is associated with adverse outcomes for individuals, families and society. Treatment needs of people with OUD related to chronic pain are different compared to dependence related to use, and also injection, of illicit opioids. In Nordic countries, day-to-day practical advice to assist clinical decision-making is insufficient. Aim: To develop principles based on expert clinical insights for treatment of OUD related to the long-term use of OA in the context of chronic pain. Methods: Current status including an assessment of barriers to effective treatment in Finland, Denmark, Iceland, Norway, Sweden was defined using a patient pathway model. Evidence to describe best practice was identified from published literature, clinical guidelines and expert recommendations from practice experience. Results: Availability of national treatment guidelines for OUD related to chronic pain is limited across the Nordics. Important barriers to effective care identified: patients unlikely to present for help, healthcare system set up limits success, diagnosis tools not used, referral pathways unclear and treatment choices not elucidated. Principles include the development of a specific treatment pathway, awareness/education programs for teams in primary care, guidance on use of diagnostic tools and a flexible treatment plan to encourage best practice in referral, treatment assessment, choice and ongoing management via an integrated care pathway. Healthcare systems and registries in Nordic countries offer an opportunity to further research and identify population risks and solutions. Conclusions: There is an opportunity to improve outcomes for patients with OUD related to chronic pain by developing and introducing care pathways tailored to specific needs of the population.Peer reviewe

Prospective comparison of F-18-PSMA-1007 PET/CT, whole-body MRI and CT in primary nodal staging of unfavourable intermediate- and high-risk prostate cancer

Purpose To prospectively compare F-18-prostate-specific membrane antigen (PSMA)-1007 positron emission tomography (PET)/CT, whole-body magnetic resonance imaging (WBMRI) including diffusion-weighted imaging (DWI) and standard computed tomography (CT), in primary nodal staging of prostate cancer (PCa). Methods Men with newly diagnosed unfavourable intermediate- or high-risk PCa prospectively underwent F-18-PSMA-1007 PET/CT, WBMRI with DWI and contrast-enhanced CT within a median of 8 days. Six readers (two for each modality) independently reported pelvic lymph nodes as malignant, equivocal or benign while blinded to the other imaging modalities. Sensitivity, specificity and accuracy were reported according to optimistic (equivocal lesions interpreted as benign) and pessimistic (equivocal lesions interpreted as malignant) analyses. The reference standard diagnosis was based on multidisciplinary consensus meetings where available histopathology, clinical and follow-up data were used. Results Seventy-nine patients completed all the imaging modalities, except for one case of interrupted WBMRI. Thirty-one (39%) patients had pelvic lymph node metastases, which were detected in 27/31 (87%), 14/31 (45%) and 8/31 (26%) patients by F-18-PSMA-1007 PET/CT, WBMRI with DWI and CT, respectively (optimistic analysis). In 8/31 (26%) patients, only F-18-PSMA-1007 PET/CT detected malignant lymph nodes, while the other two imaging modalities were reported as negative. At the patient level, sensitivity and specificity values for F-18-PSMA-1007 PET/CT, WBMRI with DWI and CT in optimistic analysis were 0.87 (95%CI 0.71-0.95) and 0.98 (95%CI 0.89-1.00), 0.37 (95%CI 0.22-0.55) and 0.98 (95%CI 0.89-1.00) and 0.26 (95%CI 0.14-0.43) and 1.00 (95%CI 0.93-1.00), respectively. Conclusion F-18-PSMA-1007 PET/CT showed significantly greater sensitivity in nodal staging of primary PCa than did WBMRI with DWI or CT, while maintaining high specificity.Peer reviewe

A Prospective Comparison of F-18-prostate-specific Membrane Antigen-1007 Positron Emission Tomography Computed Tomography, Whole-body 1.5 T Magnetic Resonance Imaging with Diffusion-weighted Imaging, and Single-photon Emission Computed Tomography/Computed Tomography with Traditional Imaging in Primary Distant Metastasis Staging of Prostate Cancer (PROSTAGE)

Background: Computed tomography (CT) and bone scintigraphy (BS) are the imaging modalities currently used for distant metastasis staging of prostate cancer (PCa). Objective: To compare standard staging modalities with newer and potentially more accurate imaging modalities. Design, setting, and participants: This prospective, single-centre trial (NCT03537391) enrolled 80 patients with newly diagnosed high-risk PCa (International Society of Urological Pathology grade group >= 3 and/or prostate-specific antigen [PSA] >= 20 and/or cT >= T3; March 2018-June 2019) to undergo primary metastasis staging with two standard and three advanced imaging modalities. Outcome measurements and statistical analysis: The participants underwent the following five imaging examinations within 2 wk of enrolment and without a prespecified sequence: BS, CT, Tc-99m-hydroxymethylene diphosphonate (Tc-99m-HMDP) single-photon emission computed tomography (SPECT)-CT, 1.5 T whole-body magnetic resonance imaging (WBMRI) using diffusion-weighted imaging, and F-18-prostate-specific membrane antigen-1007 (F-18-PSMA-1007) positron emission tomography(PET)-CT. Each modality was reviewed by two independent experts blinded to the results of the prior studies, who classified lesions as benign, equivocal, or malignant. Pessimistic and optimistic analyses were performed to resolve each equivocal diagnosis. The reference standard diagnosis was defined using all available information accrued during at least 12 mo of clinical follow-up. Patients with equivocal reference standard diagnoses underwent MRI and/or CT to search for the development of anatomical correspondence. PSMA PET-avid lesions without histopathological verification were rated to be malignant only if there was a corresponding anatomical finding suspicious for malignancy at the primary or follow-up imaging. Results and limitations: Seventy-nine men underwent all imaging modalities except for one case of interrupted MRI. The median interval per patient between the first and the last imaging study was 8 d (interquartile range [IQR]: 6-9). The mean age was 70 yr (standard deviation: 7) and median PSA 12 ng/mL (IQR:7-23). The median follow-up was 435 d (IQR: 378-557). Metastatic disease was detected in 20 (25%) patients. The imaging modality F-18-PSMA-1007 PET-CT had superior sensitivity and highest inter-reader agreement. The area under the receiver-operating characteristic curve (AUC) values for bone metastasis detection with PSMA PET-CT were 0.90 (95% confidence interval [CI]: 0.85-0.95) and 0.91 (95% CI: 0.87-0.96) for readers 1 and 2, respectively, while the AUC values for BS, CT, SPECT-CT, and WBMRI were 0.71 (95% CI: 0.58-0.84) and 0.8 (95% CI: 0.67-0.92), 0.53 (95% CI: 0.39-0.67) and 0.66 (95% CI: 0.54-0.77), 0.77 (95% CI: 0.65-0.89) and 0.75 (95% CI: 0.62-0.88), and 0.85 (95% CI: 0.74-0.96) and 0.67 (95% CI: 0.54-0.80), respectively, for the other four pairs of readers. The imaging method F-18-PSMA-1007 PET-CT detected metastatic disease in 11/20 patients in whom standard imaging was negative and influenced clinical decision making in 14/79 (18%) patients. In 12/79 cases, false positive bone disease was reported only by PSMA PET-CT. Limitations included a nonrandomised study setting and few histopathologically validated suspicious lesions. Conclusions: Despite the risk of false positive bone lesions, F-18-PSMA-1007 PET-CT outperformed all other imaging methods studied for the detection of primary distant metastasis in high-risk PCa. Patient summary: In this report, we compared the diagnostic performance of conventional and advanced imaging. It was found that F-18-prostate-specific membrane antigen-1007 positron emission tomography/computed tomography (F-18-PSMA-1007 PET-CT) was superior to the other imaging modalities studied for the detection of distant metastasis at the time of initial diagnosis of high-risk prostate cancer. PSMA PET-CT also appears to detect some nonmetastatic bone lesions. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology.Peer reviewe

Prospective comparison of 18F-PSMA-1007 PET/CT, whole-body MRI and CT in primary nodal staging of unfavourable intermediate- and high-risk prostate cancer

Purpose To prospectively compare F-18-prostate-specific membrane antigen (PSMA)-1007 positron emission tomography (PET)/CT, whole-body magnetic resonance imaging (WBMRI) including diffusion-weighted imaging (DWI) and standard computed tomography (CT), in primary nodal staging of prostate cancer (PCa).Methods Men with newly diagnosed unfavourable intermediate- or high-risk PCa prospectively underwent F-18-PSMA-1007 PET/CT, WBMRI with DWI and contrast-enhanced CT within a median of 8 days. Six readers (two for each modality) independently reported pelvic lymph nodes as malignant, equivocal or benign while blinded to the other imaging modalities. Sensitivity, specificity and accuracy were reported according to optimistic (equivocal lesions interpreted as benign) and pessimistic (equivocal lesions interpreted as malignant) analyses. The reference standard diagnosis was based on multidisciplinary consensus meetings where available histopathology, clinical and follow-up data were used.Results Seventy-nine patients completed all the imaging modalities, except for one case of interrupted WBMRI. Thirty-one (39%) patients had pelvic lymph node metastases, which were detected in 27/31 (87%), 14/31 (45%) and 8/31 (26%) patients by F-18-PSMA-1007 PET/CT, WBMRI with DWI and CT, respectively (optimistic analysis). In 8/31 (26%) patients, only F-18-PSMA-1007 PET/CT detected malignant lymph nodes, while the other two imaging modalities were reported as negative. At the patient level, sensitivity and specificity values for F-18-PSMA-1007 PET/CT, WBMRI with DWI and CT in optimistic analysis were 0.87 (95%CI 0.71-0.95) and 0.98 (95%CI 0.89-1.00), 0.37 (95%CI 0.22-0.55) and 0.98 (95%CI 0.89-1.00) and 0.26 (95%CI 0.14-0.43) and 1.00 (95%CI 0.93-1.00), respectively.Conclusion F-18-PSMA-1007 PET/CT showed significantly greater sensitivity in nodal staging of primary PCa than did WBMRI with DWI or CT, while maintaining high specificity.</div

A Prospective Comparison of 18F-prostate-specific Membrane Antigen-1007 Positron Emission Tomography Computed Tomography, Whole-body 1.5 T Magnetic Resonance Imaging with Diffusion-weighted Imaging, and Single-photon Emission Computed Tomography/Computed Tomography with Traditional Imaging in Primary Distant Metastasis Staging of Prostate Cancer (PROSTAGE)

Background: Computed tomography (CT) and bone scintigraphy (BS) are the imaging modalities currently used for distant metastasis staging of prostate cancer (PCa).Objective: To compare standard staging modalities with newer and potentially more accurate imaging modalities.Design, setting, and participants: This prospective, single-centre trial (NCT03537391) enrolled 80 patients with newly diagnosed high-risk PCa (International Society of Urological Pathology grade group ≥3 and/or prostate-specific antigen [PSA] ≥20 and/or cT ≥ T3; March 2018-June 2019) to undergo primary metastasis staging with two standard and three advanced imaging modalities.Outcome measurements and statistical analysis: The participants underwent the following five imaging examinations within 2 wk of enrolment and without a prespecified sequence: BS, CT, 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP) single-photon emission computed tomography (SPECT)-CT, 1.5 T whole-body magnetic resonance imaging (WBMRI) using diffusion-weighted imaging, and 18F-prostate-specific membrane antigen-1007 (18F-PSMA-1007) positron emission tomography(PET)-CT. Each modality was reviewed by two independent experts blinded to the results of the prior studies, who classified lesions as benign, equivocal, or malignant. Pessimistic and optimistic analyses were performed to resolve each equivocal diagnosis. The reference standard diagnosis was defined using all available information accrued during at least 12 mo of clinical follow-up. Patients with equivocal reference standard diagnoses underwent MRI and/or CT to search for the development of anatomical correspondence. PSMA PET-avid lesions without histopathological verification were rated to be malignant only if there was a corresponding anatomical finding suspicious for malignancy at the primary or follow-up imaging.Results and limitations: Seventy-nine men underwent all imaging modalities except for one case of interrupted MRI. The median interval per patient between the first and the last imaging study was 8 d (interquartile range [IQR]: 6-9). The mean age was 70 yr (standard deviation: 7) and median PSA 12 ng/mL (IQR:7-23). The median follow-up was 435 d (IQR: 378-557). Metastatic disease was detected in 20 (25%) patients. The imaging modality 18F-PSMA-1007 PET-CT had superior sensitivity and highest inter-reader agreement. The area under the receiver-operating characteristic curve (AUC) values for bone metastasis detection with PSMA PET-CT were 0.90 (95% confidence interval [CI]: 0.85-0.95) and 0.91 (95% CI: 0.87-0.96) for readers 1 and 2, respectively, while the AUC values for BS, CT, SPECT-CT, and WBMRI were 0.71 (95% CI: 0.58-0.84) and 0.8 (95% CI: 0.67-0.92), 0.53 (95% CI: 0.39-0.67) and 0.66 (95% CI: 0.54-0.77), 0.77 (95% CI: 0.65-0.89) and 0.75 (95% CI: 0.62-0.88), and 0.85 (95% CI: 0.74-0.96) and 0.67 (95% CI: 0.54-0.80), respectively, for the other four pairs of readers. The imaging method 18F-PSMA-1007 PET-CT detected metastatic disease in 11/20 patients in whom standard imaging was negative and influenced clinical decision making in 14/79 (18%) patients. In 12/79 cases, false positive bone disease was reported only by PSMA PET-CT. Limitations included a nonrandomised study setting and few histopathologically validated suspicious lesions.Conclusions: Despite the risk of false positive bone lesions, 18F-PSMA-1007 PET-CT outperformed all other imaging methods studied for the detection of primary distant metastasis in high-risk PCa.Patient summary: In this report, we compared the diagnostic performance of conventional and advanced imaging. It was found that 18F-prostate-specific membrane antigen-1007 positron emission tomography/computed tomography (18F-PSMA-1007 PET-CT) was superior to the other imaging modalities studied for the detection of distant metastasis at the time of initial diagnosis of high-risk prostate cancer. PSMA PET-CT also appears to detect some nonmetastatic bone lesions.</p

Removal of Dissolved Al and Ca in Si by SiO2 Additions and Mechanical Stirring

In the oxidative refining of metallurgical grade silicon the loss of Si to the slag in the form of SiO2 is an economical concern. The purpose of this report is to investigate the possibility of using SiO2 and mechanical stirring to remove Ca and Al as a substitute to the oxidative refining. In the experiments graphite crucibles were used in a vertical resistance furnace and controlled argon atmosphere. The removal rate of Ca and Al are measured by X-ray fluorescence and the slag is examined in a scanning electron microscope. The slag formation kinetics are examined and a calculation of the activities of Ca, Al and their respective oxides in the slag phase is conducted. The driving forces of creating CaO and Al2O3 in this system is calculated to better understand the behavior of the Ca and Al removal. The results show that removal of dissolved Ca and Al by mechanical stirring is possible and in this setup a stirring time of 20 minutes is sufficient since no more refining can be obtained by increasing it