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Osseointegrated implants is a surgical treatment permitting a direct skeletal attachment of an external prosthesis. It is a treatment for healthy transfemoral amputated patients who cannot tolerate or use a socket prosthesis, thereby alleviating related issues with poor fit, skin problems or discomfort. This review provides a summary of the indications and contraindications for surgery, the most common implants and reported outcomes.

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Fracture-related infections (FRI) is a challenging complication with a high risk of devastation outcomes for the patients. Diagnosing FRI is often difficult, and treatment frequently requires the effort of a multidisciplinary team. Recently, an international consensus group of experts from various scientific and medical organisations has published standardised guidelines of diagnosis and treatment. This review provides a summary of the latest studies and the general principles with respect to diagnosis, treatment and aftercare of patients with FRI.

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Necrotizing soft tissue infections (NSTI) is a serious infection with a mortality of up to 25% at three months. This review gives an overview of the diagnosis and treatment of NSTI. The prognosis is dependent on rapid surgical treatment, aggressive, prompt removal of infected tissue, broad spectrum antibiotic treatment and supportive care. In cases with suspected or verified infection with Streptococcus pyogenes, adjuvant therapy with immunoglobulins can be considered.

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Introduction: Septic arthritis and osteomyelitis of the pubic symphysis (SAS) are rare conditions with nonspecific symptoms leading to diagnostic delay and treatment. Aim: We draw awareness to this condition elucidating the diagnostic procedures, surgical intervention and antibiotic management. Methods: This entail a retrospective follow-up study of 26 consecutive patients, median age of 71 years (range: 48-89) surgically treated for septic arthritis of the pubic symphysis between 2009 and 2020. Patient files, diagnostic imaging and bacterial cultures were evaluated. Results: Before diagnosed with SAS, 21 of the patients had previous pelvic surgery (16 due to malign conditions, 5 due to benign conditions), while 5 of the patients were not previously operated. Median follow-up period after SAS surgery was 18.5 months (range: 8 to 144.5 months). Dominating symptoms were severe suprapubic/pubic pain ( n   =  26), gait difficulties ( n   =  10) and intermittent fever ( n   =  9). Diagnostic delay was between 1 and 12 months. The diagnostic imaging included magnetic resonance imaging (MRI) ( n   =  24), computer tomography (CT) ( n   =  17) and/or PET-CT ( n   =  10), predominantly displaying bone destruction/erosion of the symphysis ( n   =  13), abscess ( n   =  12) and/or fistula ( n   =  5) in the adjacent muscles. All patients underwent surgical debridement with resection of the symphysis and received a minimum of 6 weeks antibiotic treatment. Fourteen patients presented with monocultures and 4 patients with polycultures. Five patients underwent at least one revision surgery. Twenty-three patients experienced postoperative pain relief at 6 weeks follow-up, and 19 patients were ambulant without walking aids. Conclusion: SAS are rare conditions and should be suspected in patients with infection, pubic pain and impaired gait, especially after pelvic surgery. Bone infection, abscess and fistula near the symphysis can be visualized with proper imaging, most frequently with MRI. For most patients in this cohort surgical debridement combined with a minimum of 6 weeks antibiotic treatment resulted in pain relief, improved walking ability and a low recurrence rate.

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Animal models clearly illustrate that the maintenance of skeletal muscle mass depends on the function and interaction of a heterogeneous population of resident and infiltrating mononuclear cells. Several lines of evidence suggest that mononuclear cells also play a role in muscle wasting in humans, and targeting these cells may open new treatment options for intervention or prevention in sarcopenia. Methodological and ethical constraints have perturbed exploration of the cellular characteristics and function of mononuclear cells in human skeletal muscle. Thus, investigations of cellular phenotypes often depend on immunohistochemical analysis of small tissue samples obtained by needle biopsies, which do not match the deep phenotyping of mononuclear cells obtained from animal models. Here, we have developed a protocol for fluorescence-activated cell sorting (FACS), based on single-cell RNA-sequencing data, for quantifying and characterizing mononuclear cell populations in human skeletal muscle. Muscle stem cells, fibro-adipogenic progenitors, and two subsets of macrophages (CD11c+/-) are present in needle biopsies in comparable quantities per milligram tissue to open surgical biopsies. We find that direct cell isolation is preferable due to a substantial shift in transcriptome when using preculture before the FACS procedure. Finally, in vitro validation of the cellular phenotype of muscle stem cells, fibro-adipogenic progenitors, and macrophages confirms population-specific traits. This study demonstrates that mononuclear cell populations can be quantified and subsequently analyzed from needle biopsy material and opens the perspective for future clinical studies of cellular mechanisms in muscle wasting.

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Local treatment with gentamicin may be an important tool in the prevention and treatment of surgical site infections in high-risk procedures and patients. The aim of this study was to evaluate the pharmacokinetic profile of gentamicin in bone and surrounding tissue, released from a controlled application of a GentaColl sponge in a porcine model. In eight female pigs, a GentaColl sponge of 10 × 10 cm (1.3 mg gentamicin/cm2 ) was placed in a cancellous bone cavity in the proximal tibia. Microdialysis was used for sampling of gentamicin concentrations over 48 hours from the cavity with the implanted GentaColl sponge, cancellous bone parallel to the cavity over and under the epiphyseal plate, cortical bone, the intramedullary canal, subcutaneous tissue, and the joint cavity of the knee. Venous blood samples were obtained as reference. The main finding was a mean peak drug concentration (95% CI) of gentamicin in the cancellous bone cavity containing the implanted GentaColl sponge of 11 315 (9049-13 581) µg/mL, persisting above 1000 µg/mL until approximately 40 hours after application. Moreover, the concentrations were low (<1 µg/mL) in the surrounding tissues as well as in plasma. The mean peak gentamicin concentration from the cancellous bone cavity after a controlled application of a GentaColl sponge was high and may be adequate for the prevention of biofilm formation. However, high MIC strains and uncontrolled application of the GentaColl sponge may jeopardize this conclusion.

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BACKGROUND: The osseointegrated implant system is a treatment option for people with transfemoral amputation, but implant removal is not uncommon. The association between bone mineral density changes or bone turnover markers and the need for implant removal has not previously been investigated. OBJECTIVES: The aim was to evaluate changes in bone mineral density and bone turnover markers in people with transfemoral amputations treated with osseointegrated implants. STUDY DESIGN: This is a prospective cohort study. METHODS: Nineteen patients were followed up for 30 months or until implant removal. Bone mineral density was measured in the lumbar spine, proximal femur and seven periprosthetic regions. 25-hydroxyvitamin (D2 + D3), parathyroid hormone, N-terminal propeptide of type-I procollagen, C-telopeptide of type-I collagen, bone-specific alkaline phosphatase and osteocalcin were measured in blood samples. RESULTS: Four fixtures and three abutments were removed. Patients with removed implants had a decreased bone mineral density in the seven periprosthetic regions between 27% (95% confidence interval = 6; 43) and 38% (95% confidence interval = 19; 52) at 30-month follow-up compared to baseline (p < 0.02), whereas bone mineral density around non-removed implants normalized to baseline values (p > 0.08). C-telopeptide of type-I collagen was significantly different between the groups at 18- and 24-month follow-up (p < 0.05). None of the measured variables were significant predictors of implant removal (p > 0.07). CONCLUSION: Implant removal was associated with loss of periprosthetic bone mineral density and increase in C-telopeptide of type-I collagen in the years following osseointegrated surgery. CLINICAL RELEVANCE: This study offers new insight into changes in bone mineral density and bone turnover markers that precipitate aseptic or septic osseointegrated implant removal. Results of this study could contribute to clinical guidelines for monitoring rehabilitation progress and implant removal through dual-energy X-ray absorptiometry or surrogate markers like C-telopeptide of type-I collagen.

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BACKGROUND: The osseointegrated (OI) prosthesis is a treatment option for transfemoral amputees with a short residual femur and/or difficulties caused by using the prosthetic socket. Implant removal due to aseptic or septic loosening is not uncommon, but the association between implant migration patterns and the need for removal has not previously been studied. We conducted a prospective model-based radiostereometric analysis study to investigate: if the OI implant migration pattern 1) differs between later removed implants and non-removed implants, (2) predicts later implant removal, and (3) if the precision of the method is acceptable. HYPOTHESIS: Model-based radiostereometric analysis of the OI implant migration pattern can be used to predict later OI implant removal. MATERIAL AND METHODS: A prospective cohort of 17 consecutive transfemoral amputees suitable for surgery (11 males), mean age 50 (range 32-66) were treated with an OI implant (Integrum AB, Sweden). Postoperative stereoradiographs of the OI implant were obtained during 24-month follow-up. X, Y, and Z translations and total translations were evaluated using CAD-implant models. Implant survival was followed for up to 60 months. RESULTS: Six total implant removals (fixture and abutment) and four partial removals (abutment) were conducted (10/17 (59%)), and one patient did not use the OI implant. The removed implants group migrated a mean (±standard deviation) 0.55mm±0.75mm (p=0.009) and the non-removed implants group migrated 0.31mm±0.51mm (p=0.22) in total translations from 3 months to last follow-up. Odds ratio for implant removal was 22.5 (95% CI: 1.6 to 314 (p=0.021)) if the OI implants migrated distally. CONCLUSION: Later removed OI implants migrated from 3 months to last follow-up and more than the non-removed OI implants. Distal implant migration greatly increased the odds of implant removal. Ten out of 17 OI implants were removed within 5 years of follow-up. We advise to use OI implants with caution and close follow-up in consideration of the risk of complications. LEVEL OF EVIDENCE: IV, Prospective study.

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PURPOSE: To investigate what characterizes the process of becoming a user of an osseointegrated prosthesis following transfemoral amputation. METHOD: The study is based on the descriptive phenomenological framework Reflective Lifeworld Research. Data were collected through in-depth interviews with seven participants who had undergone transfemoral implant surgery and currently used their osseointegrated prosthesis. Data were analyzed according to the guidelines given in Reflective Lifeworld Research. RESULTS: The essential meaning of becoming a user of an osseointegrated prosthesis is characterized by determination to achieve rehabilitation results as well as a struggle to get familiar with the new prosthesis. When familiar with the prosthesis, participants begin to experience radical improvements in their everyday life, compared to their life with the socket suspended prosthesis. The essential meaning is elaborated on in four constituents: Determination to achieve rehabilitation results with the short training prosthesis, struggling to get familiar with the osseointegrated prosthesis, experiencing improvements in everyday life and reconnecting with one's prior self-perception. CONCLUSION: All the participants experienced increased action space and a more positive outlook on life. However, it took determination and stamina to become a user of an osseointegrated prosthesis, and participants faced several challenges throughout this process. Consequently, it remains important to raise awareness of the difficulties faced during this process. Implications for Rehabilitation The findings from this study suggest an increased healthcare support to users of an transfemoral osseointegrated prosthesis in the period of rehabilitation and adjustment, as the results of being able to use the osseointegrated prosthesis may outweigh the obstacles of getting there. Implementation of long-term follow-up and psychosocial support initiatives may improve the adjustment process following osseointegration. Support of patients with an osseointegrated prosthesis may be facilitated through formation of specific rehabilitation groups together with increased use of information technology such as social media and relevant online communities which provide forums for interaction and dialog with people in similar situations.

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Visual evaluation of bone changes around an osseointegration (OI) implant in femoral amputees examined on plain radiographs shows that periprosthetic bone resorption takes place during the first years after OI surgery, but the bone mineral density (BMD) change has not been previously quantified by dual-energy X-ray absorptiometry (DXA). Precision is vital when monitoring BMD changes around implants, and thus the aim of this study was to evaluate the precision and feasibility of a scan protocol for BMD measurements in proximity of OI implants. The proximal part of 2 human cadaveric femoral bones (specimens A and B) with OI implants were mounted in a positioning jig and DXA scans were repeated 5 times in increments of 5° from neutral (0°) to 20° flexion and rotation. BMD changes as a result of change in leg position were evaluated. Repeated patient examinations (n = 20) were conducted in a clinical setting and the precision error was calculated for each of 7 periprosthetic custom-made regions of interest (ROIs). The precision of cadaveric BMD measurements in neutral position was <3.3%. Even 5° flexion or rotation in femur position caused significant changes in average BMD (p <0.04). Depending on ROI, the percentage of coefficient of variation (%CV) and average BMD was <6% at 10° flexion and rotation. At 20° flexion, %CV increased up to 12.7% and average BMD increased up to 9.9%. The clinical short-term precision root mean square standard deviation ranged from 0.031 g/cm2 to 0.047 g/cm2 and %CV ranged from 3.12% to 6.57% depending on ROI. Simulated hip flexion or rotation of the femur affected periprosthetic BMD measurements around OI implants in cadaveric femoral bones, which stresses the importance of a reproducible set-up during DXA scans to reduce measurement errors caused by variation in leg position. Adherence to the scan protocol with a relaxed position of the residual limb resulted in an acceptable short-term precision below 6.6%.

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After a fall without fracture an 83-year-old man who was treated with warfarin was admitted with severe groin pain on the left hip. A few days later he had reduced strength in hip flexion and knee extension, absent patellar tendon reflex, and decreased sensibility of the anterior thigh and the medial lower leg. A magnetic resonance imaging revealed a large haematoma in the left iliac muscle. Iliac haematoma-induced femoral nerve compression neuropathy is a rare condition but should be considered as a differential diagnosis for L4 root compression in patients, who are receiving anticoagulant therapy.

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Simple subcutaneous abscesses are common, and we have examined the literature concerning the ideal treatment of subcutaneous abscesses. We recommend radical debridement with removal of all pus, the abscess wall and any necrosis. If primary suture is chosen, preoperative antibiotics should be administered, and the cavity should be closed without dead space. Antibiotics should not routinely be given, but always be considered in immunocompromised patients or patients with septicaemia. Routine examination of the microbiology has no influence on the treatment and is not recommended.

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To establish infection, pathogens deploy effectors to modify or remove host proteins. Plant immune receptors with nucleotide-binding, leucine-rich repeat domains (NLRs) detect these modifications and trigger immunity. Plant NLRs thus guard host "guardees." A corollary is that autoimmunity may result from inappropriate NLR activation because mutations in plant guardees could trigger corresponding NLR guards. To explore these hypotheses, we expressed 108 dominant-negative (DN) Arabidopsis NLRs in various lesion mimic mutants, including camta3, which exhibits autoimmunity. CAMTA3 was previously described as a negative regulator of immunity, and we find that autoimmunity in camta3 is fully suppressed by expressing DNs of two NLRs, DSC1 and DSC2. Additionally, expression of either NLR triggers cell death that can be suppressed by CAMTA3 expression. These findings support a model in which DSC1 and DSC2 guard CAMTA3, and they suggest that other negative regulators of immunity may similarly represent guardees.

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BACKGROUND: The traditional system of routine outpatient follow-up of chronic disease in secondary care may involve a waste of resources if patients are well. The use of patient-reported outcomes (PRO) could support more flexible, cost-saving follow-up activities. AmbuFlex is a PRO system used in outpatient follow-up in the Central Denmark Region. PRO questionnaires are sent to patients at fixed intervals. The clinicians use the PRO data to decide whether a patient needs a visit or not (standard telePRO). PRO may make patients become more involved in their own care pathway, which may improve their self-management. Better self-management may also be achieved by letting patients initiate contact. The aim of this study is to obtain data on the effects of patient-initiated follow-up (open access telePRO) on resource utilisation, quality of care, and the patient perspective. METHODS: The study is a pragmatic, randomised, controlled trial in outpatients with epilepsy. Participants are randomly assigned to one of two follow-up activities: a) standard telePRO or b) open access telePRO. Inclusion criteria are age ≥ 15 years and previous referral to standard telePRO follow-up at Aarhus University Hospital, Denmark. Furthermore, patients must have answered the last questionnaire via the Internet. The number of contacts will be used as the primary outcome measure. Secondary outcome measures include well-being (WHO-5 Well-Being Index), general health, number of seizures, treatment side effects, mortality, health literacy (Health Literacy Questionnaire), self-efficacy (General Self-Efficacy scale), patient activation, confidence, safety, and satisfaction. In addition, the patient perspective will be explored by qualitative methods. Data will be collected at baseline and 18 month after randomisation. Inclusion of patients in the study started in January 2016. Statistical analysis will be performed on an intention-to-treat and per-protocol basis. For qualitative data, the interpretive description strategy will be used. DISCUSSION: The benefits and possible drawbacks of the PRO-based open access approach will be evaluated. The present study will provide important knowledge to guide future telePRO interventions in relation to effect on resource utilisation, quality of care, and the patient perspective. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02673580 (Registration date January 28, 2016).

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The incidence and severity of methicillin resistant Staphylococcus aureus (MRSA) infections are increasing and cause high mortality and morbidity. We describe the first pediatric case in Scandinavia with Panton-Valentine leucocidin (PVL) positive MRSA septicemia who developed bilateral pneumonia, arthritis of the knee, and osteomyelitis of the tibia. Radiological investigation and interpretation directed the treatment, especially the surgical debridement, and combined with clinical and biochemical findings lead to close interdisciplinary treatment with frequent surgical interventions and antimicrobial combination therapy. The outcome was a healthy patient without sequelae, a favorable course unlike those previously described in the literature. This case underlines the necessity of a close interdisciplinary cooperation in children with severe MRSA infection encompassing pneumonia, septic arthritis, and osteomyelitis, using different imaging modalities to guide the surgical and antibiotic treatment.

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Intraosseous needle insertion and infusion is considered an easy and reliable method of achieving a vascular access in acute circulatory collapse where other methods have not been successful within reasonable time. Complications are considered few but may be serious. We present a case of a newborn girl, where intraosseous cannulation of the tibia was lifesaving. Despite following most standard recommendations, the treatment resulted in transtibial amputation due to necrosis. We suspect that the necrosis was a consequence of extravasation of tissue-toxic calcium infusion.

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OBJECTIVE: In whole genome and single gene analyses, genetic variation at the vascular cell adhesion molecule-1 (VCAM-1) locus has been associated with inflammatory disease and stroke in sickle cell anaemia. In the current work, we investigated the functional impact of VCAM-1 missense variants and their effect on cell-cell adhesion. METHODS AND RESULTS: To determine the functional in vitro relevance of five missense VCAM-1 variants (S318F; T384A; G413A; L555V; I716L), we generated wild type and single variant VCAM-1 forms [318F, 384A, 413A, 555V, 716L] in EA.hy926 endothelial cells. Real-time PCR, western blot and ELISA analyses revealed significant differences in mRNA and protein levels for VCAM-1 variants. Monocytic cell lines THP-1 and U937 showed significantly increased adhesion to endothelial cells overexpressing VCAM-1 forms 318F, 555V and 716L compared to those overexpressing wild type VCAM-1 (p < 0.05). CONCLUSIONS: VCAM-1-dependent cell adhesion to endothelial cells in vitro is significantly increased when expressing VCAM-1 missense mutations 318F, 555V and 716L. The underlying mechanism involves altered VCAM-1 protein levels and function. This observation may be of particular relevance for chronic inflammatory pathophysiologic conditions involving cell-cell adhesion such as atherosclerosis and other proinflammatory conditions.

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This study explores the lived experience of losing a leg as described by the patients themselves post-discharge. Studies have documented that regardless of aetiology patients are faced with severe physical as well as psychosocial challenges post-amputation. However, only few studies explore in-depth the patients' perspective on the various challenges following the loss of a leg. The study uses the phenomenological approach of Reflective Lifeworld Research (RLR). Data were collected from 24 in-depth interviews with 12 Danish patients. Data analysis was performed according to the guidelines given in RLR. The essential meaning of losing a leg is a radical and existential upheaval, which restricts patients' lifestyle and irretrievably alters their lifeworld. Life after the operation is associated with despair, and a painful sense of loss, but also with the hope of regaining personal independence. The consequences of losing a leg gradually materialize as the patients realize how the loss of mobility limits their freedom. Patients experience the professional help as primarily directed towards physical care and rehabilitation. The findings show that the loss of a leg and, subsequently, the restricted mobility carry with them an existential dimension which refers to limitation of action space and loss of freedom experienced as an exclusion from life. Our findings demonstrate a need for complementary care and stress the importance of an increased awareness of the psychosocial and existential consequences of losing a limb.

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BACKGROUND: Septic arthritis in the sternoclavicular (SC) region is rare and may be difficult to diagnose clinically and radiologically. It mainly affects immunocompromised persons, and can clinically be misinterpreted as tumor and rheumatic disorders. Lacking radiological reference standard, a multimodality approach may contribute to a prolonged diagnostic process. PURPOSE: To describe the diagnostics of septic arthritis in the SC region. MATERIAL AND METHODS: Between 2001 and 2011 10 patients with Staphylococcus infection in the SC region were investigated in our institution. Clinical, biochemical, radiological, and microbiological findings were studied retrospectively; all CT and MR examinations were re-evaluated. RESULTS: Initial radiography in nine patients and ultrasonography in six patients were inconclusive resulting in supplementary MRI and/or CT. Five patients examined by MRI were immediately diagnosed with septic arthritis whereas CT in five patients led to the diagnosis in only one. Three were subsequently diagnosed by MRI, but delayed more than 2.5 weeks, and one was diagnosed by surgery. The median time to diagnosis was 1.5 weeks. The delay caused by imaging was 0 days to 11.5 weeks (median 0 days). By re-evaluation overlooked complications included mediastinitis in seven patients (three diffuse, four localized), and abscesses and pleuritis each in four patients. CONCLUSION: Awareness of infection in the SC region is important to avoid diagnostic delay. MRI is proposed as the initial imaging procedure.

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