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Abstract Beneficial effects could be achieved by various agents such as nitroglycerin, botulinum toxin A (BoTA), and clopidogrel to improve skin flap ischaemia and venous congestion injuries. Eighty rats were subjected to either arterial ischaemia or venous congestion and applied to a bipedicled U-shaped superficial inferior epigastric artery (SIEA) flap with the administration of nitroglycerin, BoTA, or clopidogrel treatments. After 7 days, all rats were sacrificed for flap evaluation. Necrotic area percentage was significantly minimized in flaps treated with clopidogrel (24.49%) versus the ischemic flaps (34.78%); while nitroglycerin (19.22%) versus flaps with venous congestion (43.26%). With ischemia, light and electron microscopic assessments revealed that nitroglycerin produced degeneration of keratinocytes and disorganization of collagen fibers. At the same time, with clopidogrel administration, there was an improvement in the integrity of these structures. With venous congestion, nitroglycerin and BoTA treatments mitigated the epidermal and dermal injury; and clopidogrel caused coagulative necrosis. There was a significant increase in tissue gene expression and serum levels of vascular endothelial growth factor (VEGF) in ischemic flaps with BoTA and clopidogrel, nitroglycerin, and BoTA clopidogrel in flaps with venous congestion. With the 3 treatment agents, gene expression levels of tumor necrosis factor-α (TNF-α) were up-regulated in the flaps with ischemia and venous congestion. With all treatment modalities, its serum levels were significantly increased in flaps with venous congestion and significantly decreased in ischemic flaps. Our analyses suggest that the best treatment option for ischemic flaps is clopidogrel, while for flaps with venous congestion are nitroglycerin and BoTA.

Abstract Background A female survival advantage after injury has been observed, and animal models of trauma have suggested either hormonal or genetic mechanisms as component causes. Our aim was to compare age and risk-adjusted sex-related mortality in hospital for the three most common mechanisms of injury in relation to hormonal effects as seen by age. Methods All hospital admissions for injury in Sweden during the period 2001–2011 were retrieved from the National Patient Registry and linked to the Cause of Death Registry. The International Classification of Diseases Injury Severity Score (ICISS) was used to adjust for injury severity, and the Charlson Comorbidity Index to adjust for comorbidity. Age categories (0–14, 15–50, and ≥ 51 years) were used to represent pre-menarche, reproductive and post- menopausal women. Results Women had overall a survival benefit (OR 0.51; 95% CI 0.50 to 0.53) after adjustment for injury severity and comorbidity. A similar pattern was seen across the age categories (0–14 years OR 0.56 (95% CI 0.25 to 1.25), 15–50 years OR 0.70 (95% CI 0.57 to 0.87), and ≥ 51 years OR 0.49 (95% CI 0.48 to 0.51)). Conclusion In this 11-year population-based study we found no support for an oestrogen-related mechanism to explain the survival advantage for females compared to males following hospitalisation for injury.

Abstract Background The interpretation of changes in injury-related mortality over time requires an understanding of changes in the incidence of the various types of injury, and adjustment for their severity. Our aim was to investigate changes over time in incidence of hospital admission for injuries caused by falls, traffic incidents, or assaults, and to assess the risk-adjusted short-term mortality for these patients. Methods All patients admitted to hospital with injuries caused by falls, traffic incidents, or assaults during the years 2001–11 in Sweden were identified from the nationwide population-based Patient Registry. The trend in mortality over time for each cause of injury was adjusted for age, sex, comorbidity and severity of injury as classified from the International Classification of diseases, version 10 Injury Severity Score (ICISS). Results Both the incidence of fall (689 to 636/100000 inhabitants: p = 0.047, coefficient − 4.71) and traffic related injuries (169 to 123/100000 inhabitants: p

PATIENTS AND METHODS:Surgically managed burn patients admitted between 2010-14 were included. Operative stay was defined as the time from admission until the last operation, postoperative stay as the time from the last operation until discharge. The difference in variation was analysed with F-test. A retrospective review of medical records was done to explore reasons for extended postoperative stay. Multivariable regression was used to assess factors associated with operative stay and postoperative stay. RESULTS:Operative stay/TBSA% showed less variation than total duration/TBSA% (F test = 2.38, p

Introduction: The role of Adipose-derived mesenchymal stem cells (AD-MSCs) in skin wound healing remains to be fully characterized. This study aims to evaluate the regenerative potential of autologous AD-MSCs in a non-healing porcine wound model, in addition to elucidate key miRNA-mediated epigenetic regulations that underlie the regenerative potential of AD-MSCs in wounds.Methods: The regenerative potential of autologous AD-MSCs was evaluated in porcine model using histopathology and spatial frequency domain imaging. Then, the correlations between miRNAs and proteins of AD-MSCs were evaluated using an integration analysis in primary human AD-MSCs in comparison to primary human keratinocytes. Transfection study of AD-MSCs was conducted to validate the bioinformatics data.Results: Autologous porcine AD-MSCs improved wound epithelialization and skin properties in comparison to control wounds. We identified 26 proteins upregulated in human AD-MSCs, including growth and angiogenic factors, chemokines and inflammatory cytokines. Pathway enrichment analysis highlighted cell signalling-associated pathways and immunomodulatory pathways. miRNA-target modelling revealed regulations related to genes encoding for 16 upregulated proteins. miR-155-5p was predicted to regulate Fibroblast growth factor 2 and 7, C-C motif chemokine ligand 2 and Vascular cell adhesion molecule 1. Transfecting human AD-MSCs cell line with anti-miR-155 showed transient gene silencing of the four proteins at 24 h post-transfection.Discussion: This study proposes a positive miR-155-mediated gene regulation of key factors involved in wound healing. The study represents a promising approach for miRNA-based and cell-free regenerative treatment for difficult-to-heal wounds. The therapeutic potential of miR-155 and its identified targets should be further explored in-vivo.

Abstract Buloxibutid (also known as C21) is a potent and selective angiotensin II type 2 receptor (AT2R) agonist, in development for oral treatment of fibrotic lung disease. This phase I, open‐label, pharmacodynamic study investigated vascular effects of buloxibutid in five healthy male volunteers. Subjects were administered intra‐arterial infusions of buloxibutid for 5 min in ascending doses of 3, 10, 30, 100, and 200 μg/min, infused sequentially in the forearm. Infusions of sodium nitroprusside (SNP) solution in doses of 0.8–3.2 μg/min were administered as a positive control. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Safety and tolerability of intra‐arterial administrations of buloxibutid were evaluated. Following infusion of buloxibutid in doses of 3–200 μg/min, the range of increase in FBF was 27.8%, 17.2%, 37.0%, 28.5%, and 60.5%, compared to the respective baseline. The largest increase was observed in the highest dose group. Infusions of SNP as a positive control, increased FBF 230–320% compared to baseline. Three adverse events (AEs) of mild intensity, not related to buloxibutid or SNP, were reported for two subjects. Two of these AEs were related to study procedures. There were no clinically relevant changes in arterial blood pressure during the study period. Intra‐arterial infusion of buloxibutid in low, ascending doses increased FBF, indicating that buloxibutid may be effective in conditions associated with endothelial dysfunction. Venous occlusion plethysmography was found to be a useful method to explore pharmacodynamic vascular effects of novel AT2R agonists, while avoiding systemic adverse effects.

Abstract To investigate if donor and recipient site morbidity (healing time and cosmesis) could be reduced by a novel, modified split-thickness skin grafting (STSG) technique using a dermal component in the STSG procedure (DG). The STSG technique has been used for 150 years in surgery with limited improvements. Its drawbacks are well known and relate to donor site morbidity and recipient site cosmetic shortcomings (especially mesh patterns, wound contracture, and scarring). The Dermal graft technique (DG) has emerged as an interesting alternative, which reduces donor site morbidity, increases graft yield, and has the potential to avoid the mesh procedure in the STSG procedure due to its elastic properties. A prospective, dual-centre, intra-individual controlled comparison study. Twenty-one patients received both an unmeshed dermis graft and a regular 1:1.5 meshed STSG. Aesthetic and scar assessments were done using The Patient and Observer Scar Assessment Scale (POSAS) and a Cutometer Dual MPA 580 on both donor and recipient sites. These were also examined histologically for remodelling and scar formation. Dermal graft donor sites and the STSG donor sites healed in 8 and 14 days, respectively (p

Abstract Background We investigated whether plasma volume (PV) expansion of 20% albumin is larger when the fluid is administered rapidly compared with a slow infusion. Methods In this open-labeled randomized interventional controlled trial, 12 volunteers (mean age, 28 years) received 3 mL/kg of 20% albumin (approximately 225 mL) over 30 min (fast) and 120 min (slow) in a cross-over fashion. Blood hemoglobin and plasma albumin were measured on 15 occasions during 6 h to estimate the PV expansion and the capillary leakage of albumin and fluid. Results The largest PV expansion was 16.1% ± 6.5% (mean ± SD) for fast infusion and 12.8% ± 4.0% for slow infusion (p = 0.52). The median area under the curve for the PV expansion was 69% larger for the fast infusion during the first 2 h (p = 0.034), but was then similar for both infusions. The half-life of the PV expansion did not differ significantly (median, 5.6 h versus 5.4 h, p = 0.345), whereas the intravascular half-life of the excess albumin was 8.0 h for fast infusion and 6.3 h for slow infusion (p = 0.028). The measured urine output was almost three times larger than the infused volume. The plasma concentration of atrial natriuretic peptide (MR-proANP) accelerated the capillary leakage of albumin and the urine flow. Conclusions The intravascular persistence of albumin was longer, but the fluid kinetics was the same, when 20% albumin was infused over 30 min compared with 120 min. We found no disadvantages of administering the albumin at the higher rate. Trial registration EU Clinical Trials Register, EudraCT2017-003687-12, registered September 22, 2017, https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-003687-12/SE

Abstract Background Pain control following breast surgery is of utmost importance in order to reduce the chance of chronic pain development, and facilitate early rehabilitation. The erector spinae plane block (ESPB) is a recently developed regional anaesthesia procedure successfully used for different types of surgical procedures including thoracic and abdominal surgeries. Methods A double-blind, randomized, controlled trial was conducted on 90 patients who were scheduled for modified radical mastectomy (MRM). Patients were randomly categorized into groups I (women who underwent ESPB), II (women who underwent paravertebral block (PVB), and III (women who underwent general anaesthesia). Results The ESPB (4.9 ± 1.2 mg) and PVB (5.8 ± 1.3 mg) groups had significantly lower total morphine consumption than the control group had (16.4 ± 3.1 mg; p

Abstract Transdermal iontophoresis offers an in vivo alternative to the strain-gauge model for measurement of vascular function but is limited due to lack of technical solutions for outcome assessment. The aims of this study were to, after measurement by polarized reflectance spectroscopy (PRS), use pharmacodynamic dose–response analysis on responses to different concentrations of acetylcholine (ACh); and to examine the effect of three consecutively administered iontophoretic current pulses. The vascular responses in 15 healthy volunteers to iontophorised ACh (5 concentrations, range 0.0001% to 1%, three consecutive pulses of 0.02 mA for 10 min each) were recorded using PRS. Data were fitted to a four-parameter logistic dose response model and compared. Vascular responses were quantifiable by PRS. Similar pharmacodynamic dose response curves could be generated irrespectively of the ACh concentration. Linearly increasing maximum vasodilatory responses were registered with increasing concentration of ACh. A limited linear dose effect of the concentration of ACh was seen between pulses. Polarized reflectance spectroscopy is well suited for measuring vascular responses to iontophoretically administrated ACh. The results of this study support further development of iontophoresis as a method to study vascular function and pharmacological responses in vivo.

Introduction: Regenerative solutions of the skin represent a hope for burn victims with extensive skin loss and chronic wound patients. The development of xeno-free workflow is crucial for clinical application in compliance with the directives of the European Medicines Agency. This study aimed at evaluating the outcome of the xeno-free isolation workflow of keratinocytes from human skin biopsy. Methods: Skin biopsies were obtained from volunteers. The epidermis was digested with TrypLE™ Select, which was deactivated by dilution or with trypsin, deactivated by media with fetal bovine serum. Freshly isolated cells were compared for total cell number, viability, activity of caspase 3, gene expression and the presence of the keratinocyte surface markers cytokeratin 14. The cells were cultured in xeno-free conditions for one week and characterized regarding the number and viability as well as the metalloproteinase secretion. Results: The number of obtained cells was similar in both workflows. The cell viability was less in the TrypLE group, with slight reduction of the cell surface marker cytokeratin 14. Caspase 3 activity was comparable as well as the gene expression of the apoptotic markers BAX, BCL2 and SLUG, as well as the keratinocyte markers cytokeratin 14, stratifin and filaggrin. Upon culture, the number of keratinocytes, their viability and secretion of matrix metalloproteinases 1 and 10 were equal in both groups. Conclusion: This study reports the possibility of isolating functioning and viable keratinocytes through a xeno-free workflow for clinical application.

Abstract Risk adjustment and mortality prediction models are central in optimising care and for benchmarking purposes. In the burn setting, the Baux score and its derivatives have been the mainstay for predictions of mortality from burns. Other well-known measures to predict mortality stem from the ICU setting, where, for example, the Simplified Acute Physiology Score (SAPS 3) models have been found to be instrumental. Other attempts to further improve the prediction of outcome have been based on the following variables at admission: Sequential Organ Failure Assessment (aSOFA) score, determinations of aLactate or Neutrophil to Lymphocyte Ratio (aNLR). The aim of the present study was to examine if estimated mortality rate (EMR, SAPS 3), aSOFA, aLactate, and aNLR can, either alone or in conjunction with the others, improve the mortality prediction beyond that of the effects of age and percentage total body surface area (TBSA%) burned among patients with severe burns who need critical care. This is a retrospective, explorative, single centre, registry study based on prospectively gathered data. The study included 222 patients with median (25th–75th centiles) age of 55.0 (38.0 to 69.0) years, TBSA% burned was 24.5 (13.0 to 37.2) and crude mortality was 17%. As anticipated highest predicting power was obtained with age and TBSA% with an AUC at 0.906 (95% CI 0.857 to 0.955) as compared with EMR, aSOFA, aLactate and aNLR. The largest effect was seen thereafter by adding aLactate to the model, increasing AUC to 0.938 (0.898 to 0.979) (p

Abstract Burn wounds can create significant damage to human skin, compromising one of the key barriers to infection. The leading cause of death among burn wound patients is infection. Even in the patients that survive, infections can be notoriously difficult to treat and can cause lasting damage, with delayed healing and prolonged hospital stays. Biofilm formation in the burn wound site is a major contributing factor to the failure of burn treatment regimens and mortality as a result of burn wound infection. Bacteria forming a biofilm or a bacterial community encased in a polysaccharide matrix are more resistant to disinfection, the rigors of the host immune system, and critically, more tolerant to antibiotics. Burn wound-associated biofilms are also thought to act as a launchpad for bacteria to establish deeper, systemic infection and ultimately bacteremia and sepsis. In this review, we discuss some of the leading burn wound pathogens and outline how they regulate biofilm formation in the burn wound microenvironment. We also discuss the new and emerging models that are available to study burn wound biofilm formation in vivo.

Abstract This article represents the response to the inquiries adopted by Dr. Raghuraman M Sethuraman, M.D., regarding our recently published study which compared the erector spinae plane block (ESPB) versus paravertebral block (PVB) regarding postoperative analgesic consumption following breast surgeries (Elewa et al, BMC Anesthesiol 22: 1-9, 2022). We would like to introduce our appreciation and gratitude to the author for his interest in our work, despite being inaccurate in some of his comments.

Wound healing is regulated by complex crosstalk between keratinocytes and other cell types, including stem cells. In this study, a 7-day direct co-culture model of human keratinocytes and adipose-derived stem cells (ADSCs) was proposed to study the interaction between the two cell types, in order to identify regulators of ADSCs differentiation toward the epidermal lineage. As major mediators of cell communication, miRNome and proteome profiles in cell lysates of cultured human keratinocytes and ADSCs were explored through experimental and computational analyses. GeneChip® miRNA microarray, identified 378 differentially expressed miRNAs; of these, 114 miRNAs were upregulated and 264 miRNAs were downregulated in keratinocytes. According to miRNA target prediction databases and the Expression Atlas database, 109 skin-related genes were obtained. Pathway enrichment analysis revealed 14 pathways including vesicle-mediated transport, signaling by interleukin, and others. Proteome profiling showed a significant upregulation of the epidermal growth factor (EGF) and Interleukin 1-alpha (IL-1α) compared to ADSCs. Integrated analysis through cross-matching the differentially expressed miRNA and proteins suggested two potential pathways for regulations of epidermal differentiation; the first is EGF-based through the downregulation of miR-485-5p and miR-6765-5p and/or the upregulation of miR-4459. The second is mediated by IL-1α overexpression through four isomers of miR-30-5p and miR-181a-5p.

Abstract Background: The pectoralis major flap, which is usually harvested bilaterally, is considered a workhorse flap in the reconstruction of sternal defects. After a median sternotomy for open heart surgery, 1%-3% of patients develop deep infection and dehiscence of the sternal wound, some of which will eventually require reconstructive surgery. Our aim was to describe the clinical feasibility and associated complications of the unilateral pectoralis major advancement flap in the reconstruction of sternal defects. Methods: A retrospective analysis of all adult patients who were operated on using a unilateral pectoralis major flap for reconstruction of the chest wall at the Linköping University Hospital during 2008–18 was made using data retrieved from medical records. Results: Forty-three patients had reconstructions with unilateral pectoralis major flaps. Three flaps failed completely, and another 10 patients developed complications that required further operation. The factors that were independently associated with loss of the flaps and complications were: older age, male sex, the number of different antibiotics used, and a long duration of treatment with negative wound pressure. Fewer wound revisions before the reconstruction resulted in more complications. The factors that were independently associated with prolonged time to complete healing were emergency reoperation after the initial operation and complications after reconstruction. Conclusion: The unilateral pectoralis major advancement flap has proved to be a useful technique in the reconstruction of most sternal defects after sternal wound infection in older patients. There is, however, need for a follow-up study on a larger number of procedures to evaluate the long-term outcome compared with other methods of sternal reconstruction.

Abstract Background Burn injury is associated with a long-standing inflammatory reaction. The use of albumin solutions for plasma volume support is controversial because of concerns of increased capillary leakage, which could aggravate the commonly seen interstitial oedema. Methods In the present open controlled clinical trial, an intravenous infusion of 20% albumin at 3 mL/kg was given over 30 min to 15 burn patients and 15 healthy volunteers. Blood samples and urine were collected for 5 h. Plasma dilution, plasma albumin and colloid osmotic pressure were compared. Mass balance calculations were used to estimate plasma volume expansion and capillary leakage of fluid and albumin. Results The patients were studied between 4 and 14 (median, 7) days after the burn injury, which spread over 7–48% (median, 15%) of the total body surface area. The albumin solution expanded the plasma volume by almost 15%, equivalent to twice the infused volume, in both groups. The urinary excretion exceeded the infused volume by a factor of 2.5. Capillary leakage of albumin occurred at a rate of 3.4 ± 1.5 g/h in burn patients and 3.7 ± 1.6 g/h in the volunteers (P = 0.61), which corresponded to 2.4 ± 1.0% and 2.5 ± 1.2% per hour of the intravascular pool (P = 0.85). The median half-life of the plasma volume expansion was 5.9 (25th–75th percentiles 2.7–11.7) h in the burn patients and 6.9 (3.4–8.5) h in the volunteers (P = 0.56). Conclusions Albumin 20% was an effective volume expander in patients at 1 week post-burn. No relevant differences were found between burn patients and healthy volunteers. Trial registration EudraCT 2016-000996-26 on May 31, 2016.

Abstract The management of Parkinson's disease (PD) is frequently compromised by complications induced by dopaminergic treatment such as involuntary movements (dyskinesias) and psychosis. Mesdopetam (IRL790) is a novel dopamine D3 receptor antagonist developed for the management of complications of therapy in PD. This study evaluated the safety, tolerability, and pharmacokinetics of escalating single and multiple doses of mesdopetam. We conducted a prospective, single‐center, randomized, double‐blind, placebo‐controlled phase I, and first‐in‐human (FIH) study with mesdopetam administered to healthy male subjects. Overall, mesdopetam was well‐tolerated up to a 120 mg single dose and up to 80 mg upon multiple dosing. Adverse events (AEs) were mainly related to the nervous system and were dose‐dependent. No serious adverse events occurred and no AEs led to withdrawal. The results of the single‐ascending‐dose and multiple‐ascending‐dose parts indicated dose‐ and time‐independent pharmacokinetics with rapid absorption and maximum plasma levels that were generally reached within 2 h after dosing. No accumulation was observed upon multiple dosing. It is concluded that mesdopetam was safe and well‐tolerated in healthy male volunteers. Pharmacokinetic analysis indicated rapid absorption and dose‐linear pharmacokinetics of mesdopetam, with a plasma half‐life of around 7 h, upon single and repeated dosing. The pharmacokinetics of mesdopetam supports twice‐daily use in patients.

Cell regenerative therapy is a modern solution for difficult-to-heal wounds. Keratinocytes, the most common cell type in the skin, are difficult to obtain without the creation of another wound. Stem cell differentiation towards keratinocytes is a challenging process, and it is difficult to reproduce in chemically defined media. Nevertheless, a co-culture of keratinocytes with stem cells usually achieves efficient differentiation. This systematic review aims to identify the secretions of normal human keratinocytes reported in the literature and correlate them with the differentiation process. An online search revealed 338 references, of which 100 met the selection criteria. A total of 80 different keratinocyte secretions were reported, which can be grouped mainly into cytokines, growth factors, and antimicrobial peptides. The growth-factor group mostly affects stem cell differentiation into keratinocytes, especially epidermal growth factor and members of the transforming growth factor family. Nevertheless, the reported secretions reflected the nature of the involved studies, as most of them focused on keratinocyte interaction with inflammation. This review highlights the secretory function of keratinocytes, as well as the need for intense investigation to characterize these secretions and evaluate their regenerative capacities.

The primary reason for skin graft failure and the mortality of burn wound patients, particularly those in burn intensive care centers, is bacterial infection. Several animal models exist to study burn wound pathogens. The most commonly used model is the mouse, which can be used to study virulence determinants and pathogenicity of a wide range of clinically relevant burn wound pathogens. However, animal models of burn wound pathogenicity are governed by strict ethical guidelines and hindered by high levels of animal suffering and the high level of training that is required to achieve consistent reproducible results. In this study, we describe for the first time an invertebrate model of burn trauma and concomitant wound infection. We demonstrate that this model recapitulates many of the hallmarks of burn trauma and wound infection seen in mammalian models and in human patients. We outline how this model can be used to discriminate between high and low pathogenicity strains of two of the most common burn wound colonizers Pseudomonas aeruginosa and Staphylococcus aureus, and multi-drug resistant Acinetobacter baumannii. This model is less ethically challenging than traditional vertebrate burn wound models and has the capacity to enable experiments such as high throughput screening of both anti-infective compounds and genetic mutant libraries.

Background:. Dupuytren’s contracture is common among older people in Sweden. Previous studies comparing the treatment with an injection of collagenase with percutaneous needle fasciotomy found no differences. Methods:. We retrospectively compared the degree of improvement in the deficit in extension of the joints in 2 groups of patients who had been treated with collagenase (71 fingers) or needle fasciotomy (109 fingers) before and 1 year after treatment. We compared the improvement of the extension deficit among the metacarpophalangeal (MCP) and proximal interphalangeal joints before and after the intervention; additionally, the level of improvement was classified into 3 levels (mild = 0° to 29°; moderate = 30° to 60°; considerable = 61° and more). Results:. The degree of improvement of extension in the MCP joints was 11° greater in the collagenase group (P = 0.001). The number of patients who had an improvement of >60° (considerable) in extension was greater in the collagenase group (P = 0.02). Conclusion:. Collagenase was more effective than needle fasciotomy in treating extension deficits of the MCP joints in Dupuytren’s contracture in this retrospective analysis. Further prospective studies are required to confirm the finding.

Background: Family members are important in the recovery process of persons with severe burns; however, few previous studies have focused on how this group experiences care and rehabilitation. Objective: To explore family members’ experiences and needs, during the time in hospital and after discharge. Methodology: Explorative study with a qualitative descriptive design. Ten semi-structured interviews with family members of injured persons treated at the national burn centres were recorded digitally, transcribed verbatim, and analysed using content analysis. Findings: Five categories were related to experiences during care: Experiencing excellent treatment and support, Experiencing mistrust and a rejecting attitude, Feelings of chaos and shock, Being the hub of the family network, Feeling hope and thankfulness. Three categories were related to experiences during rehabilitation: Ambiguous feelings, Multifaceted support and Handling the situation. Conclusion: The experiences of the time in hospital and during rehabilitation are individual and comprise a mixture of positive and negative experiences and a diversity of needs. The results suggest that healthcare professionals should be proactive and identify specific needs for support as well as provide individualized treatment of family members. Keywords: Burns, Critical care, Family centred care, Family members, Needs, Experiences

Abstract Background Disparity between medical treatment for men and women has been recorded worldwide. However, it is difficult to find out if the disparities in both the use of resources and outcome depend entirely on sex-related discrimination. Our aim was to investigate if there are differences in burn treatments between the sexes. Methods All patients admitted with burns to Linköping University Hospital during the 16-year period 2000–2015 were included. Interventions were prospectively recorded using the validated Burn SCoring system (BSC). Data were analysed using a multivariable panel regression model adjusted for age, percentage total body surface area (%TBSA), and in-hospital mortality. Results A total of 1363 patients were included, who generated a total of 22,301 daily recordings while they were inpatients. Males were 70% (930/1363). Sex was not an independent factor for daily scores after adjustment for age, %TBSA, and mortality in hospital (model R 2=0.60, p

Severe burns are often treated by means of autologous skin grafts, preferably following early excision of the burnt tissue. In the case of, for example, a large surface trauma, autologous skin cells can be expanded in vitro prior to transplantation to facilitate the treatment when insufficient uninjured skin is a limitation. In this study we have analyzed the impact of the enzyme (trypsin or accutase) used for cell dissociation and the incubation time on cell viability and expansion potential, as well as expression of cell surface markers indicative of stemness. Skin was collected from five individuals undergoing abdominal reduction surgery and the epidermal compartment was digested in either trypsin or accutase. Trypsin generally generated more cells than accutase and with higher viability; however, after 7 days of subsequent culture, accutase-digested samples tended to have a higher cell count than trypsin, although the differences were not significant. No significant difference was found between the enzymes in median fluorescence intensity of the analyzed stem cell markers; however, accutase digestion generated significantly higher levels of CD117- and CD49f-positive cells, but only in the 5 h digestion group. In conclusion, digestion time appeared to affect the isolated cells more than the choice of enzyme.

BackgroundHeparin-binding protein (HBP) is released by neutrophils upon activation, and elevated plasma levels are seen in inflammatory states like sepsis, shock, cardiac arrest, and burns. However, little is known about the elimination of HBP. We wanted to study renal clearance of HBP in healthy individuals and in burn patients in intensive care units (ICUs). We also wished to examine the levels of HBP in the effluent of renal replacement circuits in ICU patients undergoing continuous renal replacement therapy (CRRT).MethodsWe measured plasma and urine levels of HBP and urine flow rate in 8 healthy individuals and 20 patients in a burn ICU. In 32 patients on CRRT, we measured levels of HBP in plasma and in the effluent of the CRRT circuit.ResultsRenal clearance of HBP (median (IQR) ml/min) was 0.19 (0.08-0.33) in healthy individuals and 0.30 (0.01-1.04) in burn ICU patients. In ICU patients with cystatin C levels exceeding 1.44 mg/l, clearance was 0.45 (0.15-2.81), and in patients with cystatin C below 1.44 mg/l clearance was lower 0.28 (0.14-0.55) (p = 0.04). Starting CRRT did not significantly alter plasma levels of HBP (p = 0.14), and the median HBP level in the effluent on CRRT was 9.1 ng/ml (IQR 7.8-14.4 ng/ml).ConclusionIn healthy individuals and critically ill burn patients, renal clearance of HBP is low. It is increased when renal function is impaired. Starting CRRT in critically ill patients does not alter plasma levels of HBP significantly, but HBP can be found in the effluent. It seems unlikely that impaired kidney function needs to be considered when interpreting concentrations of HBP in previous studies. Starting CRRT does not appear to be an effective way of reducing HBP concentrations.

Background: A burn is one of the most traumatic and painful injuries a child can experience and it is also a very stressful experience for the parents. Given the great psychological distress and perceived lack of multi-professional support experienced by the parents, there is a need for support during in-hospital treatment as well as during recovery. The aim of the study is to develop and evaluate an internet-based information and self-help program for parents of children who have been hospitalized for burn injury. The program aims to decrease parents' symptoms of stress. Methods: Participants will consist of parents of children treated for burns between 2009 and 2013 at either of the two specialized Swedish Burn centers. The study is a two-armed randomized controlled trial with a six-week intervention group and an inactive control group, with a pre- and post-assessment, as well as a 3- and 12-month follow-up. The main outcome is stress (post-traumatic stress, general perceived stress and parental stress). The data will be analyzed with the intention-to-treat principle. The intervention is based on Cognitive-Behavior Therapy (CBT) and is inspired by Acceptance and Commitment Therapy (ACT). It is psycho-educational and provides basic skills training in communication and stress management. Conclusion: We believe that this program will offer parents of children with burns information and support, decrease symptoms of stress, and that parents will perceive the program as useful. If the program is found to be beneficial, it could be implemented in burn care as it is accessible and cost-effective.

Heparin-binding protein (HBP) is released by granulocytes and has been shown to increase vascular permeability in experimental investigations. Increased vascular permeability in the lungs can lead to fluid accumulation in alveoli and respiratory failure. A generalized increase in vascular permeability leads to loss of circulating blood volume and circulatory failure. We hypothesized that plasma concentrations of HBP on admission to the intensive care unit (ICU) would be associated with decreased oxygenation or circulatory failure.This is a prospective, observational study in a mixed 8-bed ICU. We investigated concentrations of HBP in plasma at admission to the ICU from 278 patients. Simplified acute physiology score (SAPS) 3 was recorded on admission. Sequential organ failure assessment (SOFA) scores were recorded daily for three days.Median SAPS 3 was 58.8 (48-70) and 30-day mortality 64/278 (23%). There was an association between high plasma concentrations of HBP on admission with decreased oxygenation (p

Ventilator-induced or ventilator-associated lung injury (VILI/VALI) is common and there is an increasing demand for a tool that can optimize ventilator settings. Electrical impedance tomography (EIT) can detect changes in impedance caused by pulmonary ventilation and perfusion, but the effect of changes in the position of the body and in the placing of the electrode belt on the impedance signal have not to our knowledge been thoroughly evaluated. We therefore studied ventilation-related and perfusion-related changes in impedance during spontaneous breathing in 10 healthy subjects in five different body positions and with the electrode belt placed at three different thoracic positions using a 32-electrode EIT system. We found differences between regions of interest that could be attributed to changes in the position of the body, and differences in impedance amplitudes when the position of the electrode belt was changed. Ventilation-related changes in impedance could therefore be related to changes in the position of both the body and the electrode belt. Perfusion-related changes in impedance were probably related to the interference of major vessels. While these findings give us some insight into the sources of variation in impedance signals as a result of changes in the positions of both the body and the electrode belt, further studies on the origin of the perfusion-related impedance signal are needed to improve EIT further as a tool for the monitoring of pulmonary ventilation and perfusion.

Microvascular changes in the skin due to pharmacological and physiological provocations can be used as a marker for vascular function. While laser Doppler flowmetry (LDF) has been used extensively for measurement of skin microvascular responses, Laser Speckle Contrast Imaging (LSCI) and Tissue Viability Imaging (TiVi) are novel imaging techniques. TiVi measures red blood cell concentration, while LDF and LSCI measure perfusion. Therefore, the aim of this study was to compare responses to provocations in the skin using these different techniques.Changes in skin microcirculation were measured in healthy subjects during (1) iontophoresis of sodium nitroprusside (SNP) and noradrenaline (NA), (2) local heating and (3) post-occlusive reactive hyperemia (PORH) using LDF, LSCI and TiVi.Iontophoresis of SNP increased perfusion (LSCI: baseline 40.9±6.2 PU; 10-min 100±25 PU; p

Outcome after burn injury, as also paralleled by other trauma, has been improving steadily over the years. In this aspect a significant improvement was seen especially in the 1970-ties when the 50% survival chance from a burn injury increased from 45% total body surface area burned (TBSA%) in a 21 year old patient up to almost 80% (TBSA%). Although this improvement may be claimed to have many reasons, a significant one that needs to be stressed is the introduction of more thorough use of protocolized fluid treatment strategies