An online, two-day educational seminar had no impact on disease-specific knowledge in patients with systemic sclerosis.

Systemic sclerosis (SSc) is a multifaceted disease, and its diagnosis triggers substantial anxiety and uncertainty for those affected. Currently, there are no valid data describing the impact of disease-specific patient education on the disease knowledge available. We created a two-day, online educational seminar to provide SSc patients with disease-specific information. The primary objective of the study was to observe the change in the disease-specific knowledge of the patients. A total of 118 patients were randomized into an intervention group and a waiting list control group. The change in knowledge was assessed using a multiple-choice test. The intervention group completed the questionnaire before, directly after, and 3 months after the seminar, while the waiting list control group also took the test 3 months before the seminar to rule out nonspecific learning. The primary outcome measure was the score difference between baseline and 3 months after baseline. The study was registered in the German Clinical Trials Register (protocol code DRKS00024915). The educational seminar resulted in a small, but measurable, increase in knowledge. While the two tests in the waiting list control group prior to the seminar did not show a nonspecific increase in disease knowledge, the intervention led to a numerical increase in knowledge (mean ± sd score difference 0.34 ± 1.31, 95% CI (- 0.23; 0.86), p = 0.26) that did not reach statistical significance. Multiple linear regression analysis showed that being a member of a self-help group (ß = 1.12; p = 0.03) is a positive predictor of a higher disease knowledge. Although highly appreciated by participants, a two-day online seminar may not be the most appropriate format to generate measurable disease-specific knowledge. Self-help group membership was a positive predictor of a higher level of disease-specific knowledge prior to the educational seminar and should be recommended to every affected person.

Unmet rehabilitation needs in the first 6 months post-injury in a trauma centre population with moderate-to-severe traumatic injuries.

OBJECTIVE: To describe the needs for subacute inpatient rehabilitation and community-based healthcare services, rehabilitation, and social support in patients with moderate-to-severe traumatic injury in the first 6 months post-injury. Further, to explore associations between sociodemographic and clinical characteristics and unmet needs. DESIGN: Multicentre prospective cohort study. SUBJECTS: Of 601 persons (75% males), mean (standard deviation) age 47 (21) years, admitted to trauma centres in 2020 with moderate-to-severe injury, 501 patients responded at the 6-month follow-up and thus were included in the analyses. METHODS: Sociodemographic and injury-related characteristics were recorded at inclusion. Estimation of needs was assessed with the Rehabilitation Complexity Scale Extended-Trauma and the Needs and Provision Complexity Scale on hospital discharge. Provision of services was recorded 6 months post-injury. Multivariable logistic regressions explored associations between baseline variables and unmet inpatient rehabilitation and community-based service needs. RESULTS: In total, 20% exhibited unmet needs for subacute inpatient rehabilitation, compared with 60% for community-based services. Predictors for unmet community-based service needs included residing in less central areas, profound injury severity, severe head injury, and rehabilitation referral before returning home. CONCLUSION: Inadequate provision of healthcare and rehabilitation services, particularly in the municipalities, resulted in substantial unmet needs in the first 6 months following injury.

Needs for community-based rehabilitation services and support 12 months after moderate and severe physical traumatic injuries: a brief report.

ABSTRACT: Patients with physical traumatic injuries frequently require long-term rehabilitation services. To strengthen rehabilitation services in the post-acute phase, we need to assess characteristics of this population and their healthcare and rehabilitation needs in the community. This brief report summarizes the frequency of unmet rehabilitation needs in community-based rehabilitation during the first year after moderate and severe trauma. Additionally, the associations between sociodemographic, injury severity factors and unmet needs were examined. Data from a prospective multicenter cohort study of patients with moderate and severe trauma (New Injury Severity Score > 9) of all ages discharged alive from two regional trauma centers in 2020 were used. Needs were estimated using the Needs and Provision Complexity Scale. Overall, 46% of patients had unmet needs at 12 months post-injury, particularly related to the provision of rehabilitation services, specialist follow-ups, and social and family support. The probability of unmet needs was associated with age, pre-injury comorbidities, and impaired functioning. Our findings support strategies targeting younger patients, those with pre-injury comorbidities, and those with higher levels of disability and provide a starting point for the development of standardized rehabilitation needs assessment and guidelines following injury.

Functional Outcomes at 6 and 12 Months Post-Injury in a Trauma Centre Population with Moderate-to-Severe Traumatic Injuries.

This study aims to evaluate the global functional outcomes after moderate-to-severe traumatic injury at 6 and 12 months and to examine the sociodemographic and injury-related factors that predict these outcomes. A prospective cohort study was conducted in which trauma patients of all ages with a New Injury Severity Score > 9 who were discharged alive from two regional trauma centres in Norway over a one-year period (2020) were included. The Glasgow Outcome Scale Extended (GOSE) score was used to analyse the functional outcomes. Regression analyses were performed to investigate the predictors of the GOSE score. Follow-up assessments were obtained from approximately 85% of the 601 included patients at both time points. The mean (SD) GOSE score was 6.1 (1.6) at 6 months and 6.4 (1.6) at 12 months, which corresponds to an upper-moderate disability. One-half of the patients had a persistent disability at 12 months post-injury. The statistically significant predictors of a low GOSE score at both time points were more pre-injury comorbidity, a higher number of injuries, and higher estimated rehabilitation needs, whereas a thorax injury with an Abbreviated Injury Scale ≥ 3 predicted higher GOSE scores. A high Glasgow Coma Scale score at admission predicted a higher GOSE score at 6 months. This study strengthens the evidence base for the functional outcomes and predictors in this population.

Adherence to Guidelines for Acute Rehabilitation in the Norwegian Trauma Plan.

OBJECTIVE: To evaluate adherence to 3 central operational recommendations for acute rehabilitation in the Norwegian trauma plan. METHODS: A prospective multi-centre study of 538 adults with moderate and severe trauma with New Injury Severity Score > 9. RESULTS: Adherence to the first recommendation, assessment by a physical medicine and rehabilitation physician within 72 h following admission to the intensive care unit (ICU) at the trauma centre, was documented for 18% of patients. Adherence to the second recommendation, early rehabilitation in the intensive care unit, was documented for 72% of those with severe trauma and ≥ 2 days ICU stay. Predictors for early rehabilitation were ICU length of stay and spinal cord injury. Adherence to the third recommendation, direct transfer of patients from acute ward to a specialized rehabilitation unit, was documented in 22% of patients, and occurred more often in those with severe trauma (26%), spinal cord injury (54%) and traumatic brain injury (39%). Being employed, having head or spinal chord injury and longer ICU stay were predictors for direct transfer to a specialized rehabilitation unit. CONCLUSION: Adherence to acute rehabilitation guidelines after trauma is poor. This applies to documented early assessment by a physical medicine and rehabilitation physician, and direct transfer from acute care to rehabilitation after head and extremity injuries. These findings indicate a need for more systematic integration of rehabilitation in the acute treatment phase after trauma.

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.

Correction: Rehabilitation Needs, Service Provision, and Costs in the First Year Following Traumatic Injuries: Protocol for a Prospective Cohort Study.

[This corrects the article DOI: 10.2196/25980.].

Pyroptosis: A Common Feature of Immune Cells of Haemodialysis Patients.

NLRP-3 inflammasome activation can result in interleukin-1ß (IL-1ß) release and inflammatory cell death (pyroptosis). Caspase-1 is able to trigger both processes. However, other caspases, caspase-4, -5 and -8, are believed to initiate pyroptosis without affecting IL-1 secretion. In this study, we evaluated two cardiovascular risk groups, haemodialysis patients (HD) and patients with intact kidney function but high blood pressure (BP), to analyse the mechanisms driving pyroptosis. Twenty HD were age-, gender- and diabetes-matched to BP. We found a common pyroptotic pattern in both patient groups, at which pyroptosis rates but not IL-1 ß levels were significantly higher in monocytes (HD vs. BP: p < 0.05), granulocytes (p < 0.01) and lymphocytes (p < 0.01) of HD patients. As uremic toxins are drivers of inflammation and regulated cell death, we applied a monocyte- and macrophage-like THP-1 model system to demonstrate that the protein-bound uremic toxin indoxyl sulfate (IS) is an inducer of pyroptotic cell death, particularly engaging caspase-4/caspase-5 and to a lesser extent caspase-8 and caspase-1. These data suggest that the uremic toxin IS can mediate pyroptosis in HD patients and the inflammatory caspase-4 and/or caspase-5 contribute to pyroptosis rates to a higher extent in comparison to caspase-1.

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.

Rehabilitation Needs, Service Provision, and Costs in the First Year Following Traumatic Injuries: Protocol for a Prospective Cohort Study.

BACKGROUND: Traumatic injuries, defined as physical injuries with sudden onset, are a major public health problem worldwide. There is a paucity of knowledge regarding rehabilitation needs and service provision for patients with moderate and major trauma, even if rehabilitation research on a spectrum of specific injuries is available. OBJECTIVE: This study aims to describe the prevalence of rehabilitation needs, the provided services, and functional outcomes across all age groups, levels of injury severity, and geographical regions in the first year after trauma. Direct and indirect costs of rehabilitation provision will also be assessed. The overarching aim is to better understand where to target future efforts. METHODS: This is a population-based prospective follow-up study. It encompasses patients of all ages with moderate and severe acute traumatic injury (New Injury Severity Score >9) admitted to the regional trauma centers in southeastern and northern Norway over a 1-year period (2020). Sociodemographic and injury data will be collected. Upon hospital discharge, rehabilitation physicians estimate rehabilitation needs. Rehabilitation needs are assessed by the Rehabilitation Complexity Scale Extended-Trauma (RCS E-Trauma; specialized inpatient rehabilitation), Needs and Provision Complexity Scale (NPCS; community-based rehabilitation and health care service delivery), and Family Needs Questionnaire-Pediatric Version (FNQ-P). Patients, family caregivers, or both will complete questionnaires at 6- and 12-month follow-ups, which are supplemented by telephone interviews. Data on functioning and disability, mental health, health-related quality of life measured by the EuroQol Questionnaire (EQ-5D), and needs and provision of rehabilitation and health care services are collected by validated outcome measures. Unmet needs are represented by the discrepancies between the estimates of the RCS E-Trauma and NPCS at the time of a patient's discharge and the rehabilitation services the patient has actually received. Formal service provision (including admission to inpatient- or outpatient-based rehabilitation), informal care, and associated costs will be collected. RESULTS: The project was funded in December 2018 and approved by the Regional Committee for Medical and Health Research Ethics in October 2019. Inclusion of patients began at Oslo University Hospital on January 1, 2020, and at the University Hospital of North Norway on February 1, 2020. As of February 2021, we have enrolled 612 patients, and for 286 patients the 6-month follow-up has been completed. Papers will be drafted for publication throughout 2021 and 2022. CONCLUSIONS: This study will improve our understanding of existing service provision, the gaps between needs and services, and the associated costs for treating patients with moderate and major trauma. This may guide the improvement of rehabilitation and health care resource planning and allocation. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/25980.

[Current aspects of neurogenic dysfunctions of the lower urinary tract in multiple sclerosis]. / Aktuelles zu neurogenen Dysfunktionen des unteren Harntraktes bei Multipler Sklerose.

BACKGROUND: In the clinical management of patients with multiple sclerosis (MS), the challenge is to make an early diagnosis and initiate adequate treatment of neurogenic disorders of the lower urinary tract (NLUTD). Various national guidelines provide practical recommendations which are sometimes discordant. OBJECTIVE: To develop a simple evidence-based algorithm for detecting NLUTD in patients with MS that could be taken as a principle for deriving therapeutic consequences. MATERIAL AND METHODS: A prospective multicenter study was initiated as a direct result of two multidisciplinary conferences. The aim was to identify statistically and clinically relevant parameters for the routine diagnosis of NLUTD in patients with MS. Urodynamic abnormalities served as the gold standard. At three subsequent consensus conferences, the results of the study were discussed, a diagnostic algorithm was developed and consensus was reached on a first-line treatment. RESULTS AND DISCUSSION: The proposed algorithm enables the detection of NLUTD in patients with MS with the help of four statistically significant predictors: 1) the residual urine volume, 2) the number of urinary tract infections (UTI) within the last 6 months, 3) the standardized micturition frequency and 4) the presence/absence of urinary incontinence. The newly developed algorithm has proved to be efficient with the following results: approximately 75% of the patients do not need a urodynamic examination for a first-line treatment decision. In 25% of cases, urodynamic examinations are essential for an adequate treatment decision. Routine assessments include the patient medical history, residual urine volume measurement, a micturition diary and a uroflowmetry (optional).

NLRP3 Inflammasome Activation in Hemodialysis and Hypertensive Patients with Intact Kidney Function.

Hypertension is not only an integrative characteristic of hemodialysis (HD) patients but is also very common in the general population. There is evidence that the inflammatory cytokine IL-ß, regulated by the NLRP3 inflammasome via caspase-1, contributes to the hypertensive setting. Therefore, we investigated in an observational pilot study whether IL-1ß secretion and inflammatory cell death (pyroptosis) are different in HD and hypertensive patients with intact kidney function. Twenty HD patients were age-, gender-, and diabetes-mellitus-matched to patients with hypertension and intact kidney function. Caspase-1 activity and pyroptosis rates were measured by flow cytometry. IL-1ß was determined by qPCR and the ELISA technique. The inflammatory status (CRP) did not differ between both groups; however, the body mass index, a classical cardiovascular risk factor, was significantly elevated in blood pressure (BP) patients. BP patients had a higher frequency of caspase-1-positive monocytes compared to HD (p < 0.001). IL1-ß protein secretion was significantly enhanced in BP, but ex vivo stimulation of blood cells resulted in higher pyroptosis rates in HD compared to BP patients (p < 0.01). Therefore, HD and BP patients differ in the extent of the NLRP3 inflammasome activation. The consequences of overweight, present in BP patients, may contribute to the significantly higher inflammasomal induction level. Whether low pyroptotic rates are equivalent to a dysfunctional immune response or a high pyroptotic output corresponds to over-activation remains to be clarified.

Author Correction: The wide-binary origin of (2014) MU69-like Kuiper belt contact binaries.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The wide-binary origin of (2014) MU69-like Kuiper belt contact binaries.

Following its flyby and first imaging of the Pluto-Charon binary, the New Horizons spacecraft visited the Kuiper belt object (KBO) 2014 MU69 (also known as (486958) Arrokoth). The imaging showed MU69 to be a contact binary that rotates at a low spin period (15.92 hours), is made of two individual lobes connected by a narrow neck and has a high obliquity (about 98 degrees)1, properties that are similar to those of other KBO contact binaries inferred through photometric observations2. However, all scenarios suggested so far for the origins of such configurations3-5 have failed to reproduce these properties and their probable frequent occurrence in the Kuiper belt. Here we show that semi-secular perturbations6,7 operating on only ultrawide KBO binaries close to their stability limit can robustly lead to gentle, slow binary mergers at arbitrarily high obliquities but low rotational velocities, reproducing the characteristics of MU69 and other similar oblique contact binaries. Using N-body simulations, we find that approximately 15 per cent of all ultrawide binaries with a cosine-uniform inclination distribution5,9 are likely to merge through this process. Moreover, we find that such mergers are sufficiently gentle to deform the shape of the KBO only slightly. The semi-secular contact binary formation channel not only explains the observed properties of MU69, but may also apply to other Kuiper belt or asteroid belt binaries and in the Solar System and extra-solar moon systems.

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.