Factors associated with discharge destination from acute care after moderate-to-severe traumatic injuries in Norway: a prospective population-based study.

BACKGROUND: Previous studies have demonstrated that the trauma population has needs for rehabilitation services that are best provided in a continuous and coordinated way. The discharge destination after acute care is the second step to ensuring quality of care. There is a lack of knowledge regarding the factors associated with the discharge destination for the overall trauma population. This paper aims to identify sociodemographic, geographical, and injury-related factors associated with discharge destination following acute care at trauma centers for patients with moderate-to-severe traumatic injuries. METHODS: A multicenter, population-based, prospective study was conducted with patients of all ages with traumatic injury [New Injury Severity Score (NISS) > 9] admitted within 72 h after the injury to regional trauma centers in southeastern and northern Norway over a 1-year period (2020). RESULTS: In total, 601 patients were included; a majority (76%) sustained severe injuries, and 22% were discharged directly to specialized rehabilitation. Children were primarily discharged home, and most of the patients ≥ 65 years to their local hospital. Depending on the centrality of their residence [Norwegian Centrality Index (NCI) 1-6, where 1 is most central], we found that patients residing in NCI 3-4 and 5-6 areas sustained more severe injuries than patients residing in NCI 1-2 areas. An increase in the NISS, number of injuries, or a spinal injury with an Abbreviated Injury Scale (AIS) ≥ 3 was associated with discharge to local hospitals and specialized rehabilitation than to home. Patients with an AIS ≥ 3 head injury (RRR 6.1, 95% Confidence interval 2.80-13.38) were significantly more likely to be discharged to specialized rehabilitation than patients with a less severe head injury. Age < 18 years was negatively associated with discharge to a local hospital, while NCI 3-4, preinjury comorbidity, and increased severity of injuries in the lower extremities were positively associated. CONCLUSIONS: Two-thirds of the patients sustained severe traumatic injury, and 22% were discharged directly to specialized rehabilitation. Age, centrality of the residence, preinjury comorbidity, injury severity, length of hospital stay, and the number and specific types of injuries were factors that had the greatest influence on discharge destination.

Lifestyle Factors and Their Influence on Rheumatoid Arthritis: A Narrative Review.

In recent years, a possible association of lifestyle factors with rheumatoid arthritis (RA) has attracted increasing public interest. The aim of this review is to provide an overview of the extent and the limitations of current evidence regarding lifestyle factors and RA. The PubMed medical database was screened for epidemiological and prospective studies investigating the contribution of lifestyle factors to the development and the course of the disease. Large epidemiological studies have identified smoking, unhealthy diet and adiposity, as well as a low educational level and low socioeconomic status, as factors that increase the incidence of RA. In addition, several lifestyle habits influence the response of RA to antirheumatic drugs. Among others, smoking, obesity and poor physical activity are associated with a worse treatment outcome. Methodological problems often impair firm conclusions with respect to the causal role of these factors in the risk and the course of RA. However, current evidence is sufficient to recommend a healthy diet, the prevention of obesity, the cessation of smoking and the maintenance of a high level of physical activity to support the effectivity of modern antirheumatic medication.

A map of metabolic phenotypes in patients with myalgic encephalomyelitis/chronic fatigue syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease usually presenting after infection. Emerging evidence supports that energy metabolism is affected in ME/CFS, but a unifying metabolic phenotype has not been firmly established. We performed global metabolomics, lipidomics, and hormone measurements, and we used exploratory data analyses to compare serum from 83 patients with ME/CFS and 35 healthy controls. Some changes were common in the patient group, and these were compatible with effects of elevated energy strain and altered utilization of fatty acids and amino acids as catabolic fuels. In addition, a set of heterogeneous effects reflected specific changes in 3 subsets of patients, and 2 of these expressed characteristic contexts of deregulated energy metabolism. The biological relevance of these metabolic phenotypes (metabotypes) was supported by clinical data and independent blood analyses. In summary, we report a map of common and context-dependent metabolic changes in ME/CFS, and some of them presented possible associations with clinical patient profiles. We suggest that elevated energy strain may result from exertion-triggered tissue hypoxia and lead to systemic metabolic adaptation and compensation. Through various mechanisms, such metabolic dysfunction represents a likely mediator of key symptoms in ME/CFS and possibly a target for supportive intervention.

Thrombotic microangiopathy and liver toxicity due to a combination therapy of leflunomide and methotrexate: a case report.

BACKGROUND: Treatment of active rheumatoid arthritis may necessitate a methotrexate mono- or combination therapy. As in the present case, novel side effects may occur, when escalating therapy. CASE PRESENTATION: A 63-year-old Caucasian female patient with rheumatoid arthritis on methotrexate for 8 years and on leflunomide for 6 years was admitted for weakness, edema, ascites, and petechiae of the lower legs. Comorbidities included a urinary tract infection, metabolic syndrome with obesity, type-2 diabetes without necessity for insulin or oral antidiabetics, and non-alcoholic fatty liver disease. Laboratory results showed acute liver failure, oliguric acute kidney injury, thrombocytopenia, and schistocyte-positive, Coombs-negative hemolytic anemia. On admission, her ADAMTS13 activity was decreased, and her leflunomide plasma level was elevated (120 µg/l). Due to severe hypoalbuminemia, an intravascular hypovolemia, and severe metabolic alcalosis with hypokalemia were found. For the newly diagnosed thrombotic microangiopathy, leflunomide and methotrexate were discontinued, and 4 units of fresh-frozen plasma were given. Steroid therapy was administered for 5 days, until thrombotic thrombocytopenic purpura was excluded. Intravenous human albumin, oral vitamin K, and cholestyramine were administered for liver failure and leflunomide overdosage, respectively. Liver biopsy revealed a non-alcoholic fatty liver disease transforming into liver cirrhosis. After 2 weeks, our patient was discharged. However, within 3 weeks after discharge, our patient was rehospitalized for a relapse of acute liver failure, urinary tract infection, and influenza. Leflunomide and methotrexate were not reintroduced before or thereafter. Over a period of 11 months after discharge, her thrombotic microangiopathy subsided, and her renal and liver function fully recovered. CONCLUSIONS: Under a combination of leflunomide and methotrexate, liver toxicity and, for the first time, thrombotic microangiopathy occurred as side effects. Non-alcoholic fatty liver disease may have predisposed for the drug-induced liver toxicity.

The effect of gender-specific invitation letters on utilization of colorectal cancer screening.

BACKGROUND AND AIM: Colorectal cancer (CRC) screening can effectively reduce cancer-associated mortality. In Germany, individuals over the age of 50 or 55 have access to CRC screening services. However, utilization rates are persistently low, particular in the male population. This observational study investigates the effect of standard versus gender-specific invitation letters on utilization of CRC screening services. METHODS: We analyzed utilization rates of individuals who were insured by a large health insurance fund in Bavaria, Germany. Persons who became eligible for CRC screening received a standard (2013-2014) or a gender-specific invitation letter (2015-2016). We compared utilization rates within 6 months after receipt of the invitation letter using billing codes of the health insurance fund. RESULTS: Invitation letters were sent to 49 535 individuals, of which 48.8 % were gender-specific. The overall utilization rate did not differ between recipients of the standard versus gender-specific invitation letter (11.6 % vs 11.1 %; RR: 0.97 [0.92-1.02], p = 0.19). However, uptake of screening colonoscopy was significantly higher among recipients of gender-specific invitations (2.9 % vs 3.5 %; RR: 1.21 [1.04-1.39], p = 0.01), whereas utilization of fecal occult blood tests declined (10.4 % vs 9.7 %; RR: 0.93 [0.88-0.99], p = 0.016). CONCLUSIONS: Gender-specific design of invitation letters can modify the patients' preference for specific CRC screening services and increase the acceptance of screening colonoscopy.

Pinning of supracondylar fractures in children - Strategies to avoid complications.

In the pediatric population supracondylar humerus fracture (SHF) is one of the most common injuries. Diagnosis is based on inspection and conventional radiography. SHFs should be classified according to the modified Gartland classification, which guides treatment. Non-displaced or minimally displaced fractures (Gartland type-I) should be treated non-operatively, completely displaced type III fractures require closed reduction and K-wire fixation. In type-II fractures, important landmarks, such as the anterior humeral line (Roger´s line), the shaft-physeal angle (Baumann´s angle) and the shaft condylar angle should be considered to guide treatment. Special attention has to be paid for potential rotational dislocation, which is indicated by a ventral spur. In such cases surgery is necessary. The degree of acceptable extension malpositioning depends on patient´s age. In 10-year-old children fractures with a shaft condylar angle of more than 15° are still suitable for non-operative therapy. Timing for surgery is controversially discussed. Postponing surgery to the next day seems reasonable if absence of pain, intact soft tissue and normal neurovascular status are present. Neurovascular complications are not uncommon, especially in Gartland type-III fractures and in cases with additional forearm injuries. A white hand without palpable pulse needs emergency surgery, the management of the pulseless pink hand is still controversially discussed. Different operative techniques exist for surgical treatment. The golden standard is closed reduction and percutaneous K-wire pinning. Crossed pinning seems to achieve best biomechanical stability. Since ulnar nerve injuries are reported to occur in 6% after medially inserting K-wires, lateral divergent insertion of two K-wires has been compared to crossed pinning fixation in several randomized controlled trials. Meta-analyses demonstrated a higher risk for ulnar nerve injury for the crossed pinning technique while risk for loss of fixation was higher in lateral only pinning. In both cases, K-wires should be removed 3-6 weeks after surgery with consolidation of the fracture. Clinical and radiological follow-up should be carried out at 3 weeks post fracture fixation to rule out loss of reduction. If this should occur, early revision surgery has been demonstrated beneficial.

B-Lymphocyte Depletion in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Previous phase 2 trials indicated benefit from B-lymphocyte depletion in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Objective: To evaluate the effect of the monoclonal anti-CD20 antibody rituximab versus placebo in patients with ME/CFS. Design: Randomized, placebo-controlled, double-blind, multicenter trial. (ClinicalTrials.gov: NCT02229942). Setting: 4 university hospitals and 1 general hospital in Norway. Patients: 151 patients aged 18 to 65 years who had ME/CFS according to Canadian consensus criteria and had had the disease for 2 to 15 years. Intervention: Treatment induction with 2 infusions of rituximab, 500 mg/m2 of body surface area, 2 weeks apart, followed by 4 maintenance infusions with a fixed dose of 500 mg at 3, 6, 9, and 12 months (n = 77), or placebo (n = 74). Measurements: Primary outcomes were overall response rate (fatigue score ≥4.5 for ≥8 consecutive weeks) and repeated measurements of fatigue score over 24 months. Secondary outcomes included repeated measurements of self-reported function over 24 months, components of the Short Form-36 Health Survey and Fatigue Severity Scale over 24 months, and changes from baseline to 18 months in these measures and physical activity level. Between-group differences in outcome measures over time were assessed by general linear models for repeated measures. Results: Overall response rates were 35.1% in the placebo group and 26.0% in the rituximab group (difference, 9.2 percentage points [95% CI, -5.5 to 23.3 percentage points]; P = 0.22). The treatment groups did not differ in fatigue score over 24 months (difference in average score, 0.02 [CI, -0.27 to 0.31]; P = 0.80) or any of the secondary end points. Twenty patients (26.0%) in the rituximab group and 14 (18.9%) in the placebo group had serious adverse events. Limitation: Self-reported primary outcome measures and possible recall bias. Conclusion: B-cell depletion using several infusions of rituximab over 12 months was not associated with clinical improvement in patients with ME/CFS. Primary Funding Source: The Norwegian Research Council, Norwegian Regional Health Trusts, Kavli Trust, MEandYou Foundation, and Norwegian ME Association.

Invitation letters increase participation in colorectal cancer screening - results from an observational study.

Background and Aim Participation rates in the German colorectal cancer screening program are low. Starting in 2013, a large health insurance plan in Bavaria, Germany, is sending an additional invitation letter to insured individuals when they turn 50 or 55 years and become eligible for participation in the program. The letter provides detailed information on colorectal cancer screening. We assessed the impact of the invitation letter on utilization rates. Methods Insurance claims data of a total of 48 343 individuals who had turned 50 or 55 years between 2012 to 2014 were reviewed for utilization rates of screening colonoscopy and fecal blood tests. Utilization rates 1 year prior (2012) and 2 years after introduction of the invitation letter (2013 and 2014) were compared. Furthermore, providers of colorectal cancer screening were determined. Results Within 6 months after turning 50 or 55 years, 8.8 - 10.2 % of all insured individuals participated in colorectal cancer screening, with the majority being females. After the introduction of the invitation letter, a moderate increase in participation rates could be observed (increase to 109 % [RR 101.7 - 117.3 %, p = 0.02] in 2014). The uptake rate of screening colonoscopy was significantly higher in recipients of the letter (increase to 138.4 % [RR 110.4 - 173.8 %, p = 0.0043] in 2013 and to 149 % [RR 119.5 - 186.3 %, p = 0.0003] in 2014). Furthermore, a significantly higher proportion of general practitioners and gastroenterologists provided colorectal cancer screening in individuals receiving the invitation letter. Conclusions Introduction of an invitation letter can improve participation rates for colorectal cancer screening.

Successful treatment of chronic recurrent multifocal osteomyelitis using low-dose radiotherapy : A case report.

BACKGROUND: Chronic recurrent multifocal osteomyelitis (CRMO) is a rare autoinflammatory disease, which lacks an infectious genesis and predominantly involves the metaphysis of long bones. Common treatments range from nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids at first onset of disease, to immunosuppressive drugs and bisphosphonates in cases of insufficient remission. The therapeutic use of low-dose radiotherapy for CRMO constitutes a novelty. CASE REPORT: A 67-year-old female patient presented with radiologically proven CRMO affecting the right tibia/talus and no response to immunosuppressive therapy. Two treatment series of radiation therapy were applied with an interval of 6 weeks. Each series contained six fractions (three fractions per week) with single doses of 0.5 Gy, thus the total applied dose was 6 Gy. Ten months later, pain and symptoms of osteomyelitis had completely vanished. CONCLUSION: Radiotherapy seems to be an efficient and feasible complementary treatment option for conventional treatment refractory CRMO in adulthood. The application of low doses per fraction is justified by the inflammatory pathomechanism of disease.

Effects of synthetic neural adhesion molecule mimetic peptides and related proteins on the cardiomyogenic differentiation of mouse embryonic stem cells.

BACKGROUND/AIMS: Pluripotent stem cells differentiating into cardiomyocyte-like cells in an appropriate cellular environment have attracted significant attention, given the potential use of such cells for regenerative medicine. However, the precise mechanisms of lineage specification of pluripotent stem cells are still largely to be explored. Identifying the role of various small synthetic peptides involved in cardiomyogenesis may provide new insights into pathways promoting cardiomyogenesis. METHODS: In the present study, using a transgenic murine embryonic stem (ES) cell lineage expressing enhanced green fluorescent protein (EGFP) under the control of α-myosin heavy chain (α-MHC) promoter (pαMHC-EGFP), we investigated the cardiomyogenic effects of 7 synthetic peptides (Betrofin3, FGLs, FGL(L), hNgf_C2, EnkaminE, Plannexin and C3) on cardiac differentiation. The expression of several cardiac-specific markers was determined by RT-PCR whereas the structural and functional properties of derived cardiomyocytes were examined by immunofluorescence and electrophysiology, respectively. RESULTS: The results revealed that Betrofin3, an agonist of brain derived neurotrophic factor (BDNF) peptide exerted the most striking pro-cardiomyogenic effect on ES cells. We found that BDNF receptor, TrkB expression was up-regulated during differentiation. Treatment of differentiating cells with Betrofin3 between days 3 and 5 enhanced the expression of cardiac-specific markers and improved cardiomyocyte differentiation and functionality as revealed by genes regulation, flow cytometry and patch clamp analysis. Thus Betrofin3 may exert its cardiomyogenic effects on ES cells via TrkB receptor. CONCLUSION: Taken together, the results suggest that Betrofin3 modulates BDNF signaling with positive cardiomyogenic effect in stage and dose-dependent manner providing an effective strategy to increase ES cell-based generation of cardiomyocytes and offer a novel therapeutic approach to cardiac pathologies where BDNF levels are impaired.

Erosive and inflammatory joint changes in hereditary hemochromatosis arthropathy detected by low-field magnetic resonance imaging.

The aim of the article is to describe and characterize the hemochromatosis arthropathy of the hand by low-field MRI in symptomatic and asymptomatic patients. Forty-nine patients with hereditary hemochromatosis (37 with and twelve without arthropathy) were examined clinically and by low-field MRI of the hands. The examination showed heterogeneous degenerative and inflammatory joint changes such as erosions (in 84% of all symptomatic patients), synovitis (77%), bone marrow edema (38%), subchondral cysts (30%), tenosynovitis (30%), joint space narrowing (73%) and osteophytes (59%) including hook-shaped osteophytes at MCP joints (32%). Mild joint changes were also seen in a lower percentage of asymptomatic patients. This is the first larger study addressing the joint changes of the hand in hereditary hemochromatosis using low-field MRI. Our study emphasizes the inflammatory and destructive character of the arthropathy besides the well-known degenerative joint changes described in conventional X-ray. The impact of joint changes in asymptomatic patients deserves further investigation.

Impact of human autoantibodies on ß1-adrenergic receptor conformation, activity, and internalization.

AIMS: Autoantibodies against second extracellular loops of ß(1)-adrenergic receptors frequent in dilated cardiomyopathy confer myocardial dysfunction presumably via cAMP stimulation. Here, we investigate the autoantibody impact on receptor conformation and function. METHODS AND RESULTS: IgG was prepared from patients with dilated cardiomyopathy, matched healthy donors (10 each) or commercial IgG preparations (2). IgG binding to ß(1)-adrenergic receptor peptides was detected in 5 of 10 patients and 2 of 10 controls. IgG colocalization with the native receptor was detected in 8 of 10 patients and 1 of 10 controls (10 of 10 patients and 7 of 10 controls at >30 mg IgG/L). All IgGs exhibiting receptor colocalization triggered changes in receptor conformation (determined with fluorescent sensors) not stringently correlated to cAMP stimulation, suggesting the induction of more or less active receptor conformations. Receptor-activating IgG was detected in 8 of 10 patients but only 1 of 10 controls. In addition, IgG from 8 of 10 patients and 3 of 10 controls attenuated receptor internalization (measured by total internal reflection fluorescence microscopy). IgG-inducing inactive receptor conformations had no effect on subsequent cAMP stimulation by isoproterenol. IgG-inducing active receptor conformations dampened or augmented subsequent cAMP stimulation by isoproterenol, depending on whether receptor internalization was attenuated or not. Corresponding IgG effects on the basal beating rate and chronotropic isoproterenol response of embryonic human cardiomyocytes were observed. CONCLUSIONS: (i) Autoantibodies trigger conformation changes in the ß(1)-adrenergic receptor molecule. (ii) Some also attenuate receptor internalization. (iii) Combinations thereof increase the basal beating rate of cardiomyocytes and optionally entail dampening of their chronotropic catecholamine responses. (iv) The latter effects seem specific for patient autoantibodies, which also have higher levels.

Elastic stable intramedullary nailing in pediatric femur and lower leg shaft fractures: intraoperative radiation load.

BACKGROUND: Elastic stable intramedullary nailing (ESIN) is currently the therapy of choice in unstable, transverse and short oblique femoral and tibial-fibular shaft fractures in childhood and adolescence. As with every intramedullary technique, it requires a greater intraoperative reliance on radiological imaging. Literature concerning intraoperative radiation load in ESIN is rare, results having a wide range from less than 1 minute to more than 15 minutes. METHODS: We performed a retrospective analysis of 53 femoral and 24 tibial shaft fractures. In addition, image intensifier times of several steps of the operative procedure in 10 femoral shaft fractures were evaluated prospectively. RESULTS: The average radiation time in femoral fractures was 70.3 (range, 12-193) seconds, in tibial shaft fractures, 42.4 (range, 16-108) seconds. The prospective analysis of femur shaft fractures was able to show the most intense use of imaging during fracture passage (43.2%) and placement of the nail tips (26.6%). Image intensifier times in educational operations were not significantly higher than in operations performed by experienced surgeons. CONCLUSIONS: The actual intraoperative radiation load is influenced by bone mass and soft tissue coverage. Surgeons are able to reduce it only by decreasing the fluoroscopy time. According to our results, image intensifier time should not exceed 3 minutes in ESIN of femoral shaft fractures and 2 minutes in ESIN of lower-leg fractures. Low intraoperative radiation times are a mark of quality with respect to the interests of patients, surgeons, and operation theater staff.

Subthreshold doses of nebulized prostacyclin and rolipram synergistaically protect against lung ischemia-reperfusion.

BACKGROUND: Pulmonary edema caused by increased microvascular permeability is an important feature of lung ischemia-reperfusion (I/R) injury. METHODS: We investigated the impact of co-aerosolized prostaglandin (PG)I(2) and the 3',5-cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase inhibitor rolipram on microvascular leakage following I/R injury. Buffer-perfused rabbit lungs were exposed to 270 minutes of warm ischemia while anoxic ventilation and a positive intravascular pressure were maintained. RESULTS: On reperfusion, a massive increase of the capillary filtration coefficient and severe edema formation were noted, whereas microvascular pressures displayed only minor changes. Short-time aerosolization of subthreshold doses of either rolipram (33 microg) or PGI(2) (2.6 microg) at the beginning of ischemia did not attenuate the leakage response, whereas the co-aerosolization of both agents largely blocked any permeability increase and edema formation, independent of hemodynamic effects. The same was true when the co-aerosolization was undertaken before onset of ischemia. Similarly, the intravascular administration of rolipram and PGI(2) showed a synergistic reduction of I/R-induced vascular leak but demanded 10-fold higher doses. Intravascular release of cAMP was markedly enhanced on combined PGI(2)-rolipram administration but depended on the mode of delivery of these agents. CONCLUSIONS: Low doses of aerosolized prostacyclin and rolipram synergistically protect against severe lung I/R injury and can be used independently of lung perfusion. This strategy may be suitable for an improvement of organ preservation in lung transplantation including early management of non-heart-beating donors.