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1.	Booij, Ronald, et al. (author) Photon-counting detector computed tomography (PCD-CT) – an emerging technology in hand and wrist imaging 2023 In: Journal of Hand Surgery, European Volume. - : SAGE PUBLICATIONS LTD. - 1753-1934 .- 2043-6289. ; 48:5, s. 489-494 Journal article (other academic/artistic)
2.	Högstedt, Alexandra, et al. (author) Investigation of proteins important for microcirculation using in vivo microdialysis after glucose provocation : a proteomic study 2021 In: Scientific Reports. - : NATURE PORTFOLIO. - 2045-2322. ; 11:1 Journal article (peer-reviewed)abstract Insulin has metabolic and vascular effects in the human body. What mechanisms that orchestrate the effects in the microcirculation, and how the responds differ in different tissues, is however not fully understood. It is therefore of interest to search for markers in microdialysate that may be related to the microcirculation. This study aims to identify proteins related to microvascular changes in different tissue compartments after glucose provocation using in vivo microdialysis. Microdialysis was conducted in three different tissue compartments (intracutaneous, subcutaneous and intravenous) from healthy subjects. Microdialysate was collected during three time periods; recovery after catheter insertion, baseline and glucose provocation, and analyzed using proteomics. Altogether, 126 proteins were detected. Multivariate data analysis showed that the differences in protein expression levels during the three time periods, including comparison before and after glucose provocation, were most pronounced in the intracutaneous and subcutaneous compartments. Four proteins with vascular effects were identified (angiotensinogen, kininogen-1, alpha-2-HS-glycoprotein and hemoglobin subunit beta), all upregulated after glucose provocation compared to baseline in all three compartments. Glucose provocation is known to cause insulin-induced vasodilation through the nitric oxide pathway, and this study indicates that this is facilitated through the interactions of the RAS (angiotensinogen) and kallikrein-kinin (kininogen-1) systems.
3.	Högstedt, Alexandra, 1993- (author) Microvascular effects of insulin in the skin 2021 Doctoral thesis (other academic/artistic)abstract The microcirculation in the skin is essential for skin homeostasis. In instances of altered microvascular function, that may be the result of insulin resistance, tissue morbidity may ensue. The underlying mechanisms are however complex and not fully understood. By studying the physiological effects of insulin in the skin, the understanding of the complex interplay between glucose metabolism and skin microcirculation can be improved. The general aim of this thesis was to develop an experimental in vivo model to study metabolic and microvascular responses to insulin in the skin in healthy subjects. Microdialysis is a suiting technique as it allows for both local delivery of drugs and simultaneous monitoring of the local metabolic and vascular effects in the very same tissue compartment. The effects of local and systemic insulin provocation on skin blood flow and metabolism were investigated using microdialysis urea clearance and laser speckle contrast imaging (paper I). An insulin dependent increase in skin blood flow was observed, presumably induced through the nitric oxide pathway (paper II). Investigating the protein expression during an oral glucose provocation using proteomic approaches however indicates interactions with other pathways, such as the renin-angiotensin system and the kallikrein-kinin system (paper IV). Paper III also investigated methodological concerns regarding the sampling of insulin using microdialysis. This in vivo model can, in the future, be applied to assess the microvascular effects of insulin in the skin in different patient groups, including those with micro-vascular dysfunction due to, for instance, insulin resistance.
4.	Bergkvist, Max, 1976- (author) Studies on Polarised Light Spectroscopy 2019 Doctoral thesis (other academic/artistic)abstract This thesis project focuses on measurements of dermal microcirculation during vascular provocations with polarised light spectroscopy. This is done with a non-invasive method commercially available as Tissue viability imaging (TiVi) which measures concentration and oxygenation of red blood cells in the papillary dermis. Three studies were done with human subjects and one with an animal model, to validate and compare the TiVi technique with laser Doppler flowmetry, which is an established method of measuring dermal microcirculation.The TiVi consists of a digital camera with polarisation filters in front of the flash and lens, with software for analysis of the picture. When taking a picture with the TiVi, the polarised light that is reflected on the skin surface is absorbed by the second filter over the lens (which is perpendicular to the first filter) but a portion of light penetrates the surface of the skin and is scattered when it is reflected on tissue components. This makes the light depolarised, passes the second filter, and produces a picture for analysis. The red blood cell (RBC) has a distinct absorption pattern that differs between red and green colour compared to melanin and other components of tissue. This difference is used by the software that calculates differences in each picture element and produces a measure of output which is proportional to the concentration of red blood cells. The oxygenation of RBC can also be calculated, as there is a difference in absorption depending on oxygen state.The first paper takes up possible sources of error such as ambient light, and the angle and distance of the camera. The main experiment was to investigate how the local heating reaction is detected with TiVi compared to LDF.In the second paper arterial and venous stasis are examined in healthy subjects with TiVi.The Third paper is an animal study where skin flaps were raised on pigs, and the vascular pedicle is isolated to enable control of inflow and outflow of blood.The measurements were made during partial venous, total venous, and total arterial occlusion. The TiVi recorded changes in the concentration of RBC, oxygenation and heterogeneity and the results were compared with those of laser Doppler flowmetry.In the fourth paper oxygenation and deoxygenation of RBC: s was studied. Studies were made on the forearms of healthy subjects who were exposed to arterial and venous occlusion. Simultaneous measurements were made with TiVi and Enhanced perfusion and oxygen saturation or EPOS, which is a new device that combines laser Doppler flowmetry and diffuse reflectance spectroscopy in one probe.With TiVi, one can measure RBC concentration and oxygenation in the area of an entire picture or in one or multiple user defined regions of interest (ROI). Methods such as laser Doppler flowmetry makes single point measurements, which is a potential source of error both because of the heterogeneity of the microcirculation, and that the circulation be insufficient in the margins of the investigated area. TiVi has been able to measure venous stasis more accurately than laser Doppler flowmetry, and venous stasis is the more common reason for flaps to fail.The TiVi is an accurate way to measure the concentration of RBC and trends in oxygenation of the dermal microcirculation. It has interesting possible applications for microvascular and dermatological research, monitoring of flaps, and diagnosis of peripheral vascular disease. Future clinical studies are needed as well as development of the user interface.
5.	Bergkvist, Max, 1976-, et al. (author) Vascular Occlusion in a Porcine Flap Model : Effects on Blood Cell Concentration and Oxygenation. 2017 In: Plastic and Reconstructive Surgery - Global Open. - : Wolters Kluwer. - 2169-7574. ; 5:11 Journal article (peer-reviewed)abstract Background: Venous congestion in skin flaps is difficult to detect. This study evaluated the ability of tissue viability imaging (TiVi) to measure changes in the concentration of red blood cells (CRBC), oxygenation, and heterogeneity during vascular provocations in a porcine fasciocutaneous flap model.Methods: In 5 pigs, cranial gluteal artery perforator flaps were raised (8 flaps in 5 pigs). The arterial and venous blood flow was monitored with ultrasonic flow probes. CRBC, tissue oxygenation, and heterogeneity in the skin were monitored with TiVi during baseline, 50% and 100% venous occlusion, recovery, 100% arterial occlusion and final recovery, thereby simulating venous and arterial occlusion of a free fasciocutaneous flap. A laser Doppler probe was used as a reference for microvascular perfusion in the flap.Results: During partial and complete venous occlusion, increases in CRBC were seen in different regions of the flap. They were more pronounced in the distal part. During complete arterial occlusion, CRBC decreased in all but the most distal parts of the flap. There were also increases in tissue oxygenation and heterogeneity during venous occlusion.Conclusions: TiVi measures regional changes in CRBC in the skin of the flap during arterial and venous occlusion, as well as an increase in oxygenated hemoglobin during venous occlusion that may be the result of reduced metabolism and impaired delivery of oxygen to the tissue. TiVi may provide a promising method for measuring flap viability because it is hand-held, easy to-use, and provides spatial information on venous congestion.
6.	Droog Tesselaar, Erik, 1977-, et al. (author) Changes in skin microcirculation during radiation therapy for breast cancer 2017 In: Acta Oncologica. - Oxfordshire : Taylor & Francis. - 0284-186X .- 1651-226X. ; 56:8, s. 1072-1080 Journal article (peer-reviewed)abstract BACKGROUND: The majority of breast cancer patients who receive radiation treatment are affected by acute radiation-induced skin changes. The assessment of these changes is usually done by subjective methods, which complicates the comparison between different treatments or patient groups. This study investigates the feasibility of new robust methods for monitoring skin microcirculation to objectively assess and quantify acute skin reactions during radiation treatment.MATERIAL AND METHODS: Laser Doppler flowmetry, laser speckle contrast imaging, and polarized light spectroscopy imaging were used to measure radiation-induced changes in microvascular perfusion and red blood cell concentration (RBC) in the skin of 15 patients undergoing adjuvant radiation therapy for breast cancer. Measurements were made before treatment, once a week during treatment, and directly after the last fraction.RESULTS: In the treated breast, perfusion and RBC concentration were increased after 1-5 fractions (2.66-13.3 Gy) compared to baseline. The largest effects were seen in the areola and the medial area. No changes in perfusion and RBC concentration were seen in the untreated breast. In contrast, Radiation Therapy Oncology Group (RTOG) scores were increased only after 2 weeks of treatment, which demonstrates the potential of the proposed methods for early assessment of skin changes. Also, there was a moderate to good correlation between the perfusion (r = 0.52) and RBC concentration (r = 0.59) and the RTOG score given a week later.CONCLUSION: We conclude that radiation-induced microvascular changes in the skin can be objectively measured using novel camera-based techniques before visual changes in the skin are apparent. Objective measurement of microvascular changes in the skin may be valuable in the comparison of skin reactions between different radiation treatments and possibly in predicting acute skin effects at an earlier stage.
7.	Elawa, Sherif, et al. (author) Microcirculatory changes in the skin after postmastectomy radiotherapy in women with breast cancer 2024 In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 14:1 Journal article (peer-reviewed)abstract Postmastectomy radiotherapy (PMRT) increases the risk for complications after breast reconstruction. The pathophysiological mechanism underlying this increased risk is not completely understood. The aim of this study was to examine if there is a relationship between PMRT and microvascular perfusion in the skin directly after, and at 2 and 6 months after PMRT and to assess if there is impaired responsiveness to a topically applied vasodilator (Methyl nicotinate-MN) after PMRT. Skin microvascular responses after PMRT were measured on two sites in the irradiated chest wall of 22 women before, immediately after, and at 2 and 6 months after unilateral PMRT with the contralateral breast as a control. A significant increase in basal skin perfusion was observed in the irradiated chest wall immediately after RT (p < 0.0001). At 2 and 6 months after RT, there was no longer a difference in basal skin perfusion compared to the contralateral breast and compared to baseline. Similarly, the blood flow response in the skin after application of MN was stronger immediately after RT compared to before RT (p < 0.0001), but there was no difference at later time points. These results indicate that the increased risk for complications after surgical procedures are not directly related to changes in skin perfusion and microvascular responsiveness observed after postmastectomy RT.
8.	Elawa, Sherif, 1988- (author) Microvascular Function Assessment after Mastectomy and Radiation Therapy in Breast Cancer Patients : From Methodology to Clinical Application 2024 Doctoral thesis (other academic/artistic)abstract Post-mastectomy radiotherapy (PMRT) is an important part of the treatment of breast cancer. It reduces the risk of recurrence and improves overall survival. Scaring and fibrotization of the skin and subcutaneous tissue of the chest wall or remaining breast are among its side-effects. These late side-effects of PMRT may in turn affect skin microcirculation and oxygenation, although this connection is not completely established. In patients that later require breast reconstruction, it is difficult as a plastic surgeon to evaluate if the microcirculatory changes have been affected by PMRT, and how such effects should have an impact on the choice of reconstructive method. In the work presented in this thesis, laser speckle contrast imaging (LSCI), laser-doppler flowmetry (LDF) and diffuse reflectance spectroscopy (DRS) have been used with a strong vasodilator, methyl nicotinate (MN) to study the microcirculatory changes after PMRT.In studies I and II, we aimed to find the optimal concentration of MN and its main mechanisms of action. In healthy volunteers, the microvascular response to different concentrations of MN was evaluated on the forearm using LSCI. It was found that a concentration of 20 mmol/l resulted in a quick vasodilatory response with a long plateau phase, minimal tissue edema and no non-responders. In study II, we utilized locally administered drugs to block the three main pathways responsible for skin vasodilation. Subsequently, we provoked the skin with MN and assessed its effect with LSCI. From this study we could conclude that MN’s mechanism of action is largely mediated by prostaglandins and partly by local sensory nerves.In study III, we examined the skin microcirculatory response in breast cancer patients before, immediately after, and at two and six months following unilateral PMRT, using the contralateral breast as a control. A significant increase in basal skin perfusion and perfusion after application of MN was observed on the irradiated chest wall immediately after RT compared to the contralateral breast and compared to before RT. At six months after RT, there was no longer a difference in basal skin perfusion or after application of MN in the irradiated chest wall compared to the contralateral breast and compared to before RT was given. The results from this study concluded that skin perfusion in the irradiated chest wall had returned to normal when measured six months after RT.In study IV, the late effects on skin microvascular function were studied in women who had undergone mastectomy and PMRT several years prior to the study. Skin perfusion and oxygen saturation was measured with white light diffuse reflectance spectroscopy (DRS) combined with Laser Doppler Flowmetry (LDF) before and after application of MN on the irradiated chest wall with the contralateral non-irradiated breast as control. In this study we found that skin perfusion and oxygenation in the breast are affected several years after radiotherapy and that our method could be a valuable clinical tool prior to deciding surgical procedures after PMRT.To conclude, MN can be topically applied to the skin to reliably assess microvascular function and the microvascular capacity. LSCI and LDF have different strengths and drawbacks, with LSCI having the advantage of having a large spatial resolution that allows for measurements of control areas in the same field of view as the provoked areas. LDF in combination with DRS enabled us to further assess perfusion and oxygenation simultaneously which could be an advantage in fibrotic skin where skin perfusion and oxygen saturation may not correlate with each other. Although the study groups differed between the study examining the early effects of PMRT with the late effects of PMRT, we have been able to non-invasively visualize changes in microcirculation in relation to the acute and chronic phase after PMRT. Future studies are needed to investigate the value of pre-operative measurements with MN provocation for predicting surgical outcome.
9.	Elawa, Sherif, et al. (author) Skin perfusion and oxygen saturation after mastectomy and radiation therapy in breast cancer patients 2024 In: Breast. - : Elsevier. - 0960-9776 .- 1532-3080. ; 75 Journal article (peer-reviewed)abstract The pathophysiological mechanism behind complications associated with postmastectomy radiotherapy (PMRT) and subsequent implant-based breast reconstruction are not completely understood. The aim of this study was to examine if there is a relationship between PMRT and microvascular perfusion and saturation in the skin after mastectomy and assess if there is impaired responsiveness to a topically applied vasodilator (Methyl nicotinate - MN). Skin microvascular perfusion and oxygenation >2 years after PMRT were measured using white light diffuse reflectance spectroscopy (DRS) and laser Doppler flowmetry (LDF) in the irradiated chest wall of 31 women with the contralateral breast as a control. In the non-irradiated breast, the perfusion after application of MN (median 0.84, 25th-75th centile 0.59-1.02 % RBC × mm/s) was higher compared to the irradiated chest wall (median 0.51, 25th-75th centile 0.21-0.68 % RBC × mm/s, p < 0.001). The same phenomenon was noted for saturation (median 91 %, 25th-75th centile 89-94 % compared to 89 % 25th-75th centile 77-93 %, p = 0.001). Eight of the women (26%) had a ≥10 % difference in skin oxygenation between the non-irradiated breast and the irradiated chest wall. These results indicate that late microvascular changes caused by radiotherapy of the chest wall significantly affect skin perfusion and oxygenation.
10.	Elmasry, Moustafa, 1981-, et al. (author) Laser speckle contrast imaging in children with scalds : Its influence on timing of intervention, duration of healing and care, and costs 2019 In: Burns. - : Elsevier. - 0305-4179 .- 1879-1409. ; 45:4, s. 798-804 Journal article (peer-reviewed)abstract BackgroundScalds are the most common type of burn injury in children, and the initial evaluation of burn depth is a problem. Early identification of deep dermal areas that need excision and grafting would save unnecessary visits and stays in hospital. Laser speckle contrast imaging (LSCI) shows promise for the evaluation of this type of burn. The aim of this study was to find out whether perfusion measured with LSCI has an influence on the decision for operation, duration of healing and care period, and costs, in children with scalds.MethodsWe studied a group of children with scalds whose wounds were evaluated with LSCI on day 3–4 after injury during the period 2012–2015. Regression (adjustment for percentage total body surface area burned (TBSA%), age, and sex) was used to analyse the significance of associations between degree of perfusion and clinical outcome.ResultsWe studied 33 children with a mean TBSA% of 6.0 (95% CI 4.4–7.7)%. Lower perfusion values were associated with operation (area under the receiver-operating characteristic curve 0.86, 95% CI 0.73–1.00). The perfusion cut-off with 100% specificity for not undergoing an operation was ≥191 PU units (66.7% sensitivity and 72.7% accurately classified). Multivariable analyses showed that perfusion was independently associated with duration of healing and care period.ConclusionLower perfusion values, as measured with LSCI, are associated with longer healing time and longer care period. By earlier identification of burns that will be operated, perfusion measurements may further decrease the duration of care of burns in children with scalds.
11.	Farnebo, Simon, 1972-, et al. (author) Assessment of blood flow changes in human skin by microdialysis urea clearance 2011 In: Microcirculation. - : Wiley. - 1073-9688 .- 1549-8719. ; 18:3, s. 198-204 Research review (peer-reviewed)abstract Objective: The aim of this study was to evaluate the urea clearance technique for the measurement of drug-induced blood flow changes in human skin, and compare it with two non-invasive techniques: polarization light spectroscopy and laser Doppler perfusion imaging. Methods: Fifteen microdialysis catheters were placed intracutaneously on the volar aspect of the forearms of healthy human subjects, and were perfused with nitroglycerine, noradrenaline, and again nitroglycerine, to induce local tissue hyperaemia, hypoperfusion, and hyperaemia, respectively. Results: Urea clearance, but not the other techniques, detected the changes in blood flow during all three periods of altered flow. The last hyperaemic response was detected by all three methods. Conclusion: Urea clearance can be used as a relatively simple method to estimate blood flow changes during microdialysis of vasoactive substances, in particular when the tissue is preconditioned in order to enhance the contrast between baseline and the responses to the provocations. Our results support that, in the model described, urea clearance was superior to the optical methods as it detected both the increases and decrease in blood flow, and the returns to baseline between these periods.
12.	Farnebo, Simon, et al. (author) Differentially Expressed Proteins in Intra Synovial Compared to Extra Synovial Flexor Tendon Grafts in a Rabbit Tendon Transplantation Model 2020 In: Biomedicines. - : MDPI. - 2227-9059. ; 8:10 Journal article (peer-reviewed)abstract Uncomplicated healing of grafts for tendon reconstruction remains an unsolved problem in hand surgery. Results are limited by adhesion formation and decreased strength properties, especially within the tight fibro-osseous sheath of the digits. This is especially problematic when an extra synovial tendon graft is used to replace an intra synovial flexor tendon. Compositional differences are likely to play an important role in these processes. The aim of this study was, therefore, to compare protein expression in pair-matched intra synovial tendon grafts with extra synovial tendon grafts, using a rabbit tendon injury model. We hypothesized that there would be significant differences in proteins critical for response to tensile loading and adhesion formation between the two groups. Using mass spectrometry and multivariate statistical data analysis, we found tissue-specific differences in 22 proteins, where 7 explained 93% (R2) of the variation, with a prediction of 81% (Q2). Among the highest discriminating proteins were Galectin, Histone H2A, and Periostin, which were found in a substantially larger amount in the extra synovial tendons compared to the intra synovial tendons. These findings may contribute to improved understanding of the differences in outcome seen after tendon reconstruction using tendon grafts with intra synovial and extra synovial grafts.
13.	Farnebo, Simon, 1972-, et al. (author) Hand surgery in Sweden 2017 In: Journal of Hand Surgery, European Volume. - : SAGE PUBLICATIONS LTD. - 1753-1934 .- 2043-6289. ; 42:5, s. 537-539 Journal article (other academic/artistic)abstract n/a
14.	Farnebo, Simon, 1972- (author) On microvascular blood flow assessment with the new microdialysis urea clearance technique 2010 Doctoral thesis (other academic/artistic)abstract The aim of this thesis was to develop and evaluate a new way of monitoring blood flow with microdialysis. A thin catheter consisting of a semipermeable membrane is implanted in the tissue being studied. The catheter is perfused by a solution that closely resembles interstitial fluid, and small water-soluble substances are allowed to diffuse passively through the pores of the membrane with the aim at reaching equilibrium with the surrounding tissue. The minimally invasive character of microdialysis, and its ability to sample from the organ being studied, make microdialysis attractive in most research settings as well as for clinical surveillance. It has, however, become increasingly evident that microdialysis under conditions of non-equilibrium - for example, fluctuating regional blood flow, will alter the results gained. We have therefore aimed to explore the possibilities of developing a new marker of blood flow that will yield information about changes in blood flow that occur in the area of the microdialysis catheter itself.We hypothesised that the changes in the diffusion of exogenous urea could be used as markers of changes in tissue blood flow. The theoretical basis for this approach is that the mass transfer of urea will increase across the dialysis membrane secondary to increased blood flow. As removal of urea from the vicinity of the dialysis membrane increases with increased blood flow, the concentration gradient of urea between the perfusate and tissue will also increase. This in turn will result in a greater loss of urea from the perfusate. The changes noted in retrieval of urea from dialysate by the system are therefore thought to be inversely related to changes in blood flow. We tested our hypothesis in two species of animal (rat and pig) and in man, and in three organ systems (muscle, liver, and skin), and present four papers that indicate that the urea clearance technique provides reliable and reproducible results. The technique was evaluated against conventional metabolic markers (lactate and glucose), the ethanol clearance technique (microdialysis), laser Doppler perfusion imaging (LDPI), and polarisation light spectroscopy (TiVi).We present evidence that the urea clearance technique can be used to assess blood flow in the organs studied reliably and reproducibly with microdialysis. The microdialysis technique is minimally invasive and safe for the recipient, and catheters can easily be implanted during operation to monitor organs at risk. Urea is easily analysed as a standard assay among other “basic” metabolic markers (in a standard microdialysis kit) and has favourable characteristics with a standardised measurement system that is routinely used for monitoring metabolites in the clinic. The technique is also effective when used at lower perfusate flow rates (<1 μl/minute), which is advantageous as the recovery of metabolic markers increases at low perfusate flow rates.
15.	Miller, Robert, et al. (author) Insights and trends review: artificial intelligence in hand surgery 2023 In: Journal of Hand Surgery, European Volume. - : SAGE PUBLICATIONS LTD. - 1753-1934 .- 2043-6289. ; 48:5, s. 396-403 Research review (peer-reviewed)abstract Artificial intelligence (AI) in hand surgery is an emerging and evolving field that will likely play a large role in the future care of our patients. However, there remain several challenges to makes this technology meaningful, acceptable and usable at scale. In this review article, we discuss basic concepts in AI, including challenges and key considerations, provide an update on how AI is being used in hand and wrist surgery and propose potential future applications. The aims are to equip clinicians and researchers with the basic knowledge needed to understand and explore the incorporation of AI in hand surgery within their own practice and recommends further reading to develop knowledge in this emerging field.
16.	Mirdell, Robin, 1989- (author) Blood Flow Dynamics in Burns 2019 Doctoral thesis (other academic/artistic)abstract Objectives:Burns of intermediate thickness are hard to evaluate clinically. This often leads to unnecessary delays of up to 14 days before a surgical decision can be made. To counter this, several objective methods have been developed to determine the healing potential of the wound. Over the years, measurement of perfusion has proven to be the most successful method for evaluation of healing potential. Laser Doppler imaging (LDI) is currently the most used method and can determine surgical need 2 days after injury with an accuracy >90%. There are however emerging techniques like laser speckle contrast imaging (LSCI), which also measure perfusion. LSCI have several advantages over LDI and is easier to use. LSCI can also investigate aspects of the microcirculation, previously not possible with LDI. The aim of this thesis was to investigate LSCI’s ability to evaluate surgical need in burns of indeterminate partial-thickness. The first objective was to investigate the dynamics of perfusion the first 14 days after injury. The purpose was to find the optimal time-window for perfusion measurements. The next goal was to determine the accuracy of different perfusion cut-offs. In this second study, the benefit of a subsequent measurement was also investigated. After this, interobserver variation between different profession groups was studied. Both the agreement of perfusion measurements and observer assessments were evaluated. Finally, cardiac vasomotion in combination with perfusion (pulsatility) was investigated as a method to determine surgical need <48 hours after injury. Methods:Perfusion was measured in a total of 77 patients at the Department of Plastic Surgery, Hand Surgery and Burns at Linköping University Hospital, Sweden. Most of these patients were children and the most common type of burn was scalds. A laser speckle contrast imager (PeriCam PSI System, Perimed AB, Järfälla, Sweden) was used to measure perfusion. Results: In the first paper we showed a clear relation between perfusion dynamics and the healing potential of the wound. The changes in perfusion were largest the first 5 days after injury, why this time interval was selected for subsequent papers. Perfusion measurements done day 3-4 after injury could predict surgical need with a sensitivity of 100% (95% CI: 83.9-100%) and a specificity of 90.4% (95% CI: 83.8-94.9%). If two measurements were used, <24 hours and 3-4 days after injury, the accuracy was 100%. Furthermore, we found that different observers could consistently predict perfusion, while there was a large variation in their clinical assessments. This was not improved by extensive burn experience. Finally, pulsatility could be used to predict surgical need the same day as the injury occurred with a sensitivity of 100% (95% CI: 88.1-100%) and a specificity of 98.8% (95% CI: 95.7- 99.9%). Conclusions: LSCI is a promising method for evaluation of burns and provides several benefits over LDI. The surgical need of burns can be determined mere hours after injury when pulsatility is measured. However, the benefits of early scald diagnostics in children with LSCI need to be evaluated in a prospective study before the method is ready for routine clinical use.
17.	Moloney, Maria, et al. (author) Distal ulna fractures in adults - subcapitular, transverse fractures did not benefit from surgical treatment 2023 In: Archives of Orthopaedic and Trauma Surgery. - : Springer. - 0936-8051 .- 1434-3916. ; 143:1, s. 381-387 Journal article (peer-reviewed)abstract Introduction Fractures of the distal ulna, excluding the styloid, are rare. The cause of injury is often a fall on an outstretched hand with an extended wrist, and in most cases there is a concomitant distal radius fracture. The aims of this retrospective study were to investigate the results of the current treatment of distal ulna fractures in adults, with or without a concomitant distal radius fracture, and if a recently presented fracture classification could predict outcome. Materials and methods Patients, 18 years or older, treated for a fracture of the distal third of ulna in our county, were included. Fractures of the styloid tip were excluded. The radiographs of the fractures were independently classified by two specialists in radiology according to the 2018 AO/OTA classification. Follow-up was performed 5-7 years after the injury, through the questionnaire Patient-Rated Wrist Evaluation (PRWE) and new radiographs of both wrists. Results Ninety-six patients with 97 fractures were included and filled out the PRWE. 65 patients also had new radiographs taken. 79 patients were women and the mean age at the time of injury was 63 years (SD 14.5). The most common fracture class was the extra-articular transverse fracture, 2U3A2.3 (42%). We found that 40% of the fractures had been treated by internal fixation and only 2 fractures had not healed, one conservatively treated and one operated. The median PRWE was 15 (IQR 33.5). The PRWE score was significantly worse in the operated ulna fractures (p = 0.01) and this was also true for extra-articular transverse fractures 2U3A2.3 (p = 0.001). Initial displacement was more common in operated transverse fractures, but it could not be proven that this was the reason for the inferior result. Conclusions Distal ulna fractures almost always unite and the result is comparable to that of isolated distal radius fractures when measured by PRWE. Based on the opinions of the radiologists and how often a consensus discussion was needed for classification, we found the updated AO classification system difficult to use, if dependent only on standard radiographic views. In the present study, transverse extra-articular ulna fractures did not benefit from internal fixation regardless if associated with a distal radius fracture or isolated.
18.	Moloney, Maria, et al. (author) Incidence of distal ulna fractures in a Swedish county: 74/100,000 person-years, most of them treated non-operatively 2020 In: Acta Orthopaedica. - : TAYLOR & FRANCIS LTD. - 1745-3674 .- 1745-3682. ; 91:1, s. 104-108 Journal article (peer-reviewed)abstract Background and purpose - Fractures of the distal ulna can occur in isolation or in conjunction with a distal radius fracture. They may result in incongruence and instability of the distal radioulnar joint. We investigated the incidence of distal ulna fractures, whether any fracture types were more common, and the methods of treatment used. Patients and methods - Data were collected from patients 18 years or older, treated for a fracture of the distal ulna in ostergotland, Sweden, during 2010-2012. Patients were identified in the patient registry. The fractures were classified according to the AO comprehensive classification of fractures. Results - The incidence of distal ulna fractures was 74/100,000 person-years. The most common fracture type was that of the ulnar styloid Q1 (79%), followed by the ulnar neck Q2 (11%). Rarest was ulna head fracture, type Q4 (1%). Incidental findings were a mean age of 63 years (SD 18), a concomitant distal radius fracture in 92% of the patients and that 79% were caused by falling from standing height. Internal fixation was performed in 30% of the Q2-Q6 fractures. This indicates that most were considered stable without internal fixation or stable after fixation of a concomitant radius fracture. Interpretation - Our results show that fractures of the distal ulna are not very common, and some fracture types are even rare. There seem to be no consensus on treatment.
19.	Moloney, Maria, et al. (author) Poor reliability and reproducibility of 3 different radiographical classification systems for distal ulna fractures 2022 In: Acta Orthopaedica. - : Taylor & Francis. - 1745-3674 .- 1745-3682. ; 93, s. 438-443 Journal article (peer-reviewed)abstract Background and purpose - Classification of fractures can be valuable for research purposes but also in clinical work. Especially with rare fractures, such as distal ulna fractures, a treatment algorithm based on a classification can be helpful. We compared 3 different classification systems of distal ulna fractures and investigated their reliability and reproducibility. Patients and methods - patients with 97 fractures of the distal ulna, excluding the ulnar styloid, were included. All fractures were independently classified by 3 observers according to the classification by Biyani, AO/OTA 2007, and AO/OTA 2018. The classification process was repeated after a minimum of 3 weeks. We used Kappa value analysis to determine inter- and intra-rater agreement.Results - The inter-rater agreement of the AO/OTA 2007 classification was judged as fair,. 0.40, whereas the agreement of AO/OTA 2018 and Biyani was moderate at. 0.42 and 0.43 respectively. The intra-rater agreement was judged as moderate for all classifications. Interpretation - The differences between the classifications were small and the overall impression was that neither of them was good enough to be of substantial clinical value. The Biyani classification, being developed specifically for distal ulna fractures, was the easiest and most fitting for the fracture patterns seen in our material, but lacking options for fractures of the distal diaphysis. Standard radiographs were considered insufficient for an accurate classification. A better radiographic method combined with a revised classification might improve accuracy, reliability, and reproducibility.
20.	Moloney, Maria (author) Ulnar fractures and ligament injuries of the wrist 2022 Doctoral thesis (other academic/artistic)abstract Falling over on an outstretched hand with the wrist extended is a common accident that can cause a multitude of injuries in the wrist. Research has mainly focused on distal radius fractures while injuries of the distal ulna and adjacent ligaments have taken a back seat. If not treated adequately, these injuries may result in ulnar-sided wrist pain, sometimes referred to as the “black box” of hand surgery. The distal radio-ulnar joint (DRUJ) enables forearm rotation where the radio-carpal unit rotates around the fixed ulna, stabilised most importantly by the triangular fibrocartilage complex (TFCC). Painless rotation and stability of the forearm under load is important for upper limb function. If full function is to be restored after wrist injury, it is important to treat not only injury to the radius but also those to the ulna and TFCC.The aims of this thesis were to evaluate the long-term results of TFCC injury repair, and contribute to our knowledge on fractures of the distal ulna, their epidemiology, radiographic classification and results of treatment.The long-term outcome of 47 patients with a foveal TFCC tear was evaluated by patient-rated wrist evaluation (PRWE) and radiography 20 years after open repair. The median PRWE score was 22.6 (7-48.5), and 34 % had had further surgery after the initial repair, half of these due to recurrence of DRUJ instability. Signs of osteoarthritis were seen in the radiocarpal joint in 17.5 % and in the DRUJ in 34 %. Higher PRWE scores were seen in patients with osteoarthritis or those who had undergone further surgery. Radio-carpal osteoarthritis was less frequently seen in patients who had undergone initial arthroscopy. This study highlights the importance of arthroscopy in identifying associated injuries. Twenty years after foveal TFCC tear repair patient reported outcomes were similar to those of distal radius fractures.Apart from fractures of the styloid process, distal ulna fractures are rare. All distal ulna fractures in the county of Östergötland 2010-2012 were identified. A total of 766 fractures were found (incidence 74/100 000 person-years), the majority of which were fractures of the ulnar styloid process(79%) usually caused by a fall from standing height. Most patients were female (76%), mean age at the time of injury was 63 years and 92 % had a concomitant distal radius fracture. Second after styloid fractures were fractures of the ulnar neck. A retrospective study of 96 patients with 97 fractures of the distal ulna (excluding the styloid) showed that 40 % were treated by internal fixation. The median PRWE score was 15, with significantly worse scores in patients with an internally fixed distal ulna fracture compared to patients not operated. When classifying these fractures according to AO/OTA 2018, transverse extra-articular fractures (2U3A2.3) had a significantly better outcome when not treated surgically, and these probably do not require internal fixation if the distal radius provides stability and alignment. All 97 fractures were classified by three independent observers according to three classification systems: Biyani, AO/OTA 2007, and AO/OTA 2018. Classification was repeated after a minimum of 3 weeks. Reliability and reproducibility were calculated. The reliability was judged as fair for AO/OTA 2007, and moderate for Biyani and AO/OTA 2018. The reproducibility was moderate for all three systems. These results together with the observers´ opinion that Biyani is an easier system to use, leads us to conclude that a slightly modified Biyani-system together with improved radiological techniques that provide more information about the fracture pattern, may well improve accuracy, reliability and reproducibility.A better classification of distal ulna fractures could help us in the evaluation of new and existing treatments as well as providing the information necessary for designing treatment algorithm. After careful consideration, internal fixation is probably the treatment of choice for certain types of fracture, but this needs further investigation.
21.	Nilsson, Klara, et al. (author) A Novel Technique to Assess Distal Radioulnar Joint Stability Using Increasing Torque 2019 In: Journal of wrist surgery. - : Thieme Medical Publishers. - 2163-3916 .- 2163-3924. ; 8:4, s. 327-334 Journal article (peer-reviewed)abstract Background Previous studies on computed tomography (CT) in patients with a suspected triangular fibrocartilage complex (TFCC) injury have not been successful in assessing distal radioulnar joint (DRUJ) laxity. The aim of this study was to develop a novel servomotor-driven device for the assessment of DRUJ by applying increasing torque to the DRUJ in pronation and supination.Methods A custom-built device was designed to function during four-dimensional (4D) CT of the wrist. A torque meter, positioned between the incoming hand holder, and a direct current (DC) servomotor were used for angular positioning and for applying rotational force to the patient's arm. A total of 110 healthy participants were recruited to gather reference values for the range of motion (ROM), maximum torque in neutral and supinated/pronated position, and the ability to withstand an increasing, device-generated torque in these positions. The device was also used during 4D DRUJ CT in five patients with suspected TFCC injuries.Results A gender- and age-relevant reference chart for ROM and torque was created. Men showed a tendency (ns) toward having a larger ROM and increasing strength with increasing age, whereas women showed the opposite. Also, the dominant hand showed a tendency toward having a larger ROM and being stronger than the nondominant hand (ns). A smaller cohort of patients (n = 5) with suspected TFCC injuries showed a significantly decreased ability to withstand increasing torque in both supination (2.1 ± 0.3 vs. 3.1 ± 0.2 s; p < 0.005) and pronation (2.3 ± 0.5 vs. 3.1 ± 0.4 s; p < 0.0005) and also showed a clear laxity on real-time 4D CT image sequences. Decreased strength at all positions was also found (average 74% decrease compared to noninjured side).Conclusion Reference values for torque strength and ability to withstand increasing torque can be used clinically in the assessment of patients with symptoms that could represent ligamentous injuries to the TFCC. The ability to use the device during CT enables radiographic evaluation of instability during increasing torque.Level of Evidence This is a Level II study.
22.	Tesselaar, Erik, 1977-, et al. (author) Acute effects of coffee on skin blood flow and microvascular function 2017 In: Microvascular Research. - : Academic Press. - 0026-2862 .- 1095-9319. ; 114, s. 58-64 Journal article (peer-reviewed)abstract ObjectiveStudies on the acute effects of coffee on the microcirculation have shown contradicting results. This study aimed to investigate if intake of caffeine-containing coffee changes blood flow and microvascular reactivity in the skin.MethodsWe measured acute changes in cutaneous vascular conductance (CVC) in the forearm and the tip of the finger, the microvascular response to transdermaliontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) and post-occlusive reactive hyperemia (PORH) in the skin, after intake of caffeinated or decaffeinated coffee.ResultsVasodilatation during iontophoresis of ACh was significantly stronger after intake of caffeinated coffee compared to after intake of decaffeinated coffee (1.26 ± 0.20 PU/mm Hg vs. 1.13 ± 0.38 PU/mm Hg, P < 0.001). Forearm CVC before and after PORH were not affected by caffeinated and decaffeinated coffee. After intake of caffeinated coffee, a more pronounced decrease in CVC in the fingertip was observed compared to after intake of decaffeinated coffee (− 1.36 PU/mm Hg vs. − 0.52 PU/mm Hg, P = 0.002).ConclusionsCaffeine, as ingested by drinking caffeinated coffee acutely improves endothelium-dependent microvascular responses in the forearm skin, while endothelium-independent responses to PORH and SNP iontophoresis are not affected. Blood flow in the fingertip decreases markedly during the first hour after drinking caffeinated coffee compared to decaffeinated coffee.
23.	Wolff, Aviva L., et al. (author) Dynamic assessment of the upper extremity: a review of available and emerging technologies 2023 In: Journal of Hand Surgery, European Volume. - : SAGE PUBLICATIONS LTD. - 1753-1934 .- 2043-6289. ; 48:5, s. 404-411 Research review (peer-reviewed)abstract The purpose of this review article is to provide an update on the realm of emerging technology available for the assessment of dynamic functional movement of the hand and upper limb. A critical overview of the literature and a conceptual framework for use of such technologies is proposed. The framework explores three broad purpose categories including customization of care, functional surveillance and interventions through biofeedback strategies. State-of-the-art technologies are described, from basic activity monitors to feedback-enabled robotic gloves, along with exemplar trials and clinical applications. The future of technologies innovation in hand pathology is proposed in the context of the current obstacles and opportunities for hand surgeons and therapists.
24.	Zdolsek, Markus, 1989- (author) Volume effects of albumin infusion in humans 2023 Doctoral thesis (other academic/artistic)abstract Background: The use of colloids when treating a patient for hypovolemia has been debated throughout the years. During the last decade, albumin solutions have become the colloids of choice in both operating theatres and intensive care settings when crystalloid fluids are insufficient. The volume effects of albumin infusion are explored in this thesis. Methods: Recruitment of fluid from the interstitial fluid compartment to the plasma was estimated in healthy volunteers who received 3 ml/kg of albumin 20% infusion over 30 min. The same infusion protocol was applied to burn patients to study whether significant inflammation changes the volume effect of an albumin infusion. The influence of the infusion rate of albumin 20% on plasma volume (PV) was evaluated in a crossover fashion in healthy volunteers. Additionally, two concentrations, 5% and 20%, with equivalent amounts of albumin, were given to healthy volunteers in a crossover fashion to determine if a difference in volume effect occurred. The volume effects in terms of PV expansion and capillary leakage of albumin were calculated by mass balance and volume kinetics based on repeated blood samples. Results: There was a 10–20 min delay after completion of the albumin 20% infusion until maximum PV expansion was reached. Extravascular fluid was recruited at a ratio of 3.4 times the infused albumin 20%. Both healthy volunteers and burn patients had a 15% increase in PV. Capillary leakage of albumin occurred at a similar rate in both groups. Rapid infusion resulted in a longer intravascular half-life for albumin and a larger initial PV expansion over time without long-term negative compensation. Albumin 20% increased the PV to twice the infused volume in contrast to albumin 5%, which only increased the PV by two-thirds of the infused volume. Conclusion: Albumin infusions provide long-lasting PV expansion in both burn patients and healthy volunteers. Albumin 20% induces the recruitment of extravascular fluid, amounting to three times the infused fluid volume. A rapid infusion rate is beneficial, as it results in a larger initial PV expansion over time and a longer intravascular persistence of albumin. Further, albumin 20% provides a three times more potent PV expansion than albumin 5%. The infused fluid volume of an albumin solution depends more on the amount of albumin infused than the infused volume; albumin 20% could be preferred over other fluids for its dehydrating effect in the prevention of oedema.
25.	Zötterman, Johan, 1975-, et al. (author) Intraoperative Laser Speckle Contrast Imaging in DIEP Breast Reconstruction : A Prospective Case Series Study 2020 In: Plastic and Reconstructive Surgery - Global Open. - : Wolters Kluwer. - 2169-7574. ; 8:1, s. e2529-e2529 Journal article (peer-reviewed)abstract Laser speckle contrast imaging (LSCI) is a laser-based perfusion imaging technique that recently has been shown to predict ischemic necrosis in an experimental flap model and predicting healing time of scald burns. The aims were to investigate perfusion in relation to the selected perforator during deep inferior epigastric artery perforator (DIEP) flap surgery, and to evaluate LSCI in assisting of prediction of postoperative complications. METHODS: Twenty-three patients who underwent DIEP-procedures for breast reconstruction at 2 centers were included. Perfusion was measured in 4 zones at baseline, after raising, after anastomosis, and after shaping the flap. The perfusion in relation to the selected perforator and the accuracy of LSCI in predicting complications were analyzed. RESULTS: After raising the flap, zone I showed the highest perfusion (65 ± 10 perfusion units, PU), followed by zone II (58 ± 12 PU), zone III (53 ± 10 PU), and zone IV (45 ± 10 PU). The perfusion in zone I was higher than zone III (P = 0.002) and zone IV (P < 0.001). After anastomosis, zone IV had lower perfusion than zone I (P < 0.001), zone II (P = 0.01), and zone III (P = 0.02). Flaps with areas <30 PU after surgery had partial necrosis postoperatively (n = 4). CONCLUSIONS: Perfusion is highest in zone I. No perfusion difference was found between zones II and III. Perfusion <30 PU after surgery was correlated with partial necrosis. LSCI is a promising tool for measurement of flap perfusion and assessment of risk of postoperative ischemic complications.
26.	Zötterman, Johan, 1975- (author) Laser Speckle Contrast Imaging in Reconstructive Surgery 2020 Doctoral thesis (other academic/artistic)abstract ObjectivesReconstructive surgery aims to restore function or normal appearance by reconstructing defective organs after trauma or disease. In patients undergoing reconstructive surgery, previous trauma, surgery or radiotherapy can result in compromised blood supply. This will affect the viability of the tissue and increases the risk for postoperative complications, such as ischemia and infection. It is therefore important to assess the tissue viability, both before, during and after the surgery. This can be done using different techniques that monitor the perfusion of the skin covering the affected area. In this thesis, LSCI have been evaluated for tissue monitoring in reconstructive surgery. The technique allows for a fast and noninvasive assessment of superficial tissue perfusion over a wide field. Based on previous work on the technology, we have seen clear advantages with LSCI compared to other methods, for example laser Doppler flowmetry (LDF). We have evaluated laser speckle contrast imaging (LSCI) as a tool for tissue monitoring in reconstructive surgery in four studies.MethodsIn study I we used a bench top model and healthy subjects to address methodological concerns subjected to the LSCI technology. We investigated the effect of motion distance and angle on the assessed perfusion value In study II we used a porcine model to compare LSCI and LDF as tools to detect partial and full venous outflow obstruction. We used both methods to assess a flap based on the cranial gluteal artery perforator with partial and complete occlusion of the vein and artery. In study III we used the same porcine model as in study II to investigate the possibility to use LSCI intraoperatively to identify flap areas with compromised circulation and thereby predict areas with a high risk of postoperative necrosis. In study IV we used LSCI for intraoperative evaluation of tissue viability during deep inferior epigastric perforator (DIEP) free flap surgery and to investigate the perfusion distribution according to the Hartrampf zones, as measured with LSCI, in relation to the selected perforator in the deep inferior epigastric perforator free flap.ResultsIn study I we saw that tissue perfusion as measured with LSCI increases with increasing tissue motion, independent of frame rate, number of images, and tissue perfusion. Measured perfusion will decrease when images are acquired at an angle larger than 45° but distances between 15 and 40 cm do not affect the measured perfusion. In study II we observed significant decreases in perfusion during both partial and complete venous occlusion with both LSCI and LDF. However, higher variability seen with LDF, measured as % coefficient of variation. In study III a decrease in perfusion during the first 30 min after raising the flap and a perfusion value below 25 PU after 30 min was a predictor for tissue morbidity 72h after surgery. In study IV the highest perfusion values were found in zone I and higher perfusion in zone II compared to zone III, directly after the flap was raised. No remaining significant difference between zone I, II and III could be seen after anastomosis of the vessels. All flaps with a minimum perfusion <30 PU, measured after the flap was shaped and inserted, later suffered from partial flap necrosis.ConclusionLSCI is a technology that has the potential to contribute to tissue monitoring in reconstructive surgery. It has many advantages over other techniques, such as the fast acquisition time, the spatial resolution and the fact that it is completely non-invasive. However, the current system is still too bulky to be easily introduced into a clinical setting and the technology is also subject to certain drawbacks which limit its usability. It is sensitive to motion artefacts; only superficial tissue is assessed and cannot offer absolute perfusion data. If these disadvantages could be addressed, LSCI could contribute to a more accurate survey of tissue perfusion and thus better outcome in reconstructive surgery.
27.	Zötterman, Johan, et al. (author) Methodological concerns with laser speckle contrast imaging in clinical evaluation of microcirculation 2017 In: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 12:3 Journal article (peer-reviewed)abstract Background Laser Speckle Contrast Imaging (LSCI) is a non-invasive and fast technique for measuring microvascular blood flow that recently has found clinical use for burn assessment and evaluation of flaps. Tissue motion caused by for example breathing or patient movements may however affect the measurements in these clinical applications, as may distance between the camera and the skin and tissue curvature. Therefore, the aims of this study were to investigate the effect of frame rate, number of frames/image, movement of the tissue, measuring distance and tissue curvature on the measured perfusion. Methods Methyl nicotinate-induced vasodilation in the forearm skin was measured using LSCI during controlled motion at different speeds, using different combinations of frame rate and number of frames/image, and at varying camera angles and distances. Experiments were made on healthy volunteers and on a cloth soaked in a colloidal suspension of polystyrene microspheres. Results Measured perfusion increased with tissue motion speed. The relation was independent of the absolute perfusion in the skin and of frame rate and number of frames/image. The measured perfusion decreased with increasing angles (16% at 60, p = 0.01). Measured perfusion did not vary significantly between measurement distances from 15 to 40 cm (p = 0.77, %CV 0.9%). Conclusion Tissue motion increases and measurement angles beyond 45 decrease the measured perfusion in LSCI. These findings have to be taken into account when LSCI is used to assess moving or curved tissue surfaces, which is common in clinical applications.

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