Performance Measures and Plasma Biomarker Levels in Patients with Multiple Sclerosis after 14 Days of Fampridine Treatment: An Explorative Study.

Peripheral cytokine levels may serve as biomarkers for treatment response and disease monitoring in patients with multiple sclerosis (pwMS). The objectives were to assess changes in plasma biomarkers in PwMS after 14 days of fampridine treatment and to explore correlations between changes in performance measures and plasma biomarkers. We included 27 PwMS, 14 women and 13 men, aged 52.0 ± 11.6 years, with a disease duration of 17 ± 8.5 years, and an Expanded Disability Status Scale of 6 [IQR 5.0/6.5]. Gait and hand function were assessed using performance tests completed prior to fampridine and after 14 days of treatment. Venous blood was obtained, and chemiluminescence analysis conducted to assess plasma cytokines and neurodegenerative markers. All performance measures demonstrated improvements. Biomarkers showed decreased tumor necrosis factor (TNF) receptor-2 levels. Associations were found between change scores in (i) Six Spot Step Test and Interleukin (IL)-2, IL-8, and IL-17 levels; (ii) timed 25-foot walk and interferon-γ, IL-2, IL-8, TNF-α, and neurofilament light levels, and (iii) 12-Item Multiple Sclerosis Walking Scale and IL-17 levels. The associations may reflect increased MS-related inflammatory activity rather than a fampridine-induced response or that a higher level of inflammation induces a better response to fampridine.

Early-stage inflammation changes in supraspinatus muscle after rotator cuff tear.

BACKGROUND: Rotator cuff (RC) tendon tear leads to impaired shoulder function and pain. The supraspinatus (SS) tendon is most often affected, but the biological response of the SS muscle to SS tendon tear is largely unknown. This study aimed to investigate time-dependent muscle inflammation, degeneration, fatty infiltration, and regeneration in experimental SS tear conditions. METHODS: Forty-five C57BL/6 mice were subjected to SS tendon tear and allowed to recover for 1, 3, 5, 7, 14, or 28 days. The extent of muscle damage was examined using histologic, flow cytometric, proteomic, and chemiluminescence analyses. RESULTS: We found that muscle inflammation peaked around day 5 with increased monocyte infiltration and increased cytokine levels in the ipsilateral compared to the contralateral SS muscle. Bioinformatics analysis of proteomics on mice that survived 5 days after RC tendon tear revealed upregulated proteins involved in "neutrophil activation involved in immune response" and "extracellular matrix organization," whereas "skeletal muscle tissue development and contraction" and "respiratory electron transport chain" were among the most downregulated. Histologic analysis of collagen showed increased collagen accumulation and fatty infiltration of the ipsilateral SS over time. Finally, we observed time- and lesion-dependent changes in satellite cell and fibro-adipogenic progenitor populations. CONCLUSION: Altogether, we demonstrate that the SS muscle shows severe signs of acute inflammation, early degeneration, and fatty infiltration, as well as reduced regenerative potential following SS tendon tear.

Merkel cell carcinoma. / Merkelcellekarsinom.

Merkel cell carcinoma is an uncommon but aggressive tumour with a high metastatic potential. A rapidly growing, non-tender cutaneous tumour on sun-exposed areas of the body in older patients should raise suspicion of the condition. It may be necessary to combine the patient history with clinical, radiological and pathological findings in order to make the correct diagnosis. Excision with a 1-2 cm margin, direct closure and simultaneous sentinel-node biopsy should be performed without delay. Adjuvant radiation therapy of the tumour site may be relevant. After the diagnosis is made, assessment and treatment should take place in hospitals with special experience of the condition.

Randomized Study of Wound Drainage on Early Complications After Lymph Node Dissection for Melanoma.

INTRODUCTION: The complication rate after axillary lymph node dissection (ALND) and inguinal lymph node dissection (ILND) in melanoma patients is high. The aim of this randomized non-inferiority study was to evaluate the effect of postoperative wound drainage on early complications after ALND and ILND. MATERIALS AND METHODS: Between 2018 and 2020, 104 stage III melanoma patients operated on with ALND or ILND were randomized to a study group with complete wound drain removal 3 wk after surgery or a control group with progressive drain removal. The primary end point was overall early complications graded according to the modified Clavien-Dindo classification. Secondary endpoints were length of hospital stay and prognostic factors for early complications. RESULTS: Of the 99 patients analyzed, ALND was performed in 58 patients and ILND in 41 patients. Overall, 62 patients (62.6%) developed early complications: 30 in the study group and 32 in the control group (P = 0.53). The confidence interval for the difference in proportions of patients without early complications in the two groups was -0.27 to 0.11 (P = 0.42), hence non-inferiority could be claimed. Length of hospital stay was 5 d in the study group compared to 6 in the control group (P < 0.01). ILND was associated with increased risk of early complications compared to ALND (75.6% versus 53.4%, P = 0.04). CONCLUSIONS: Complete drain removal 3 wk after ALN and ILND in stage III melanoma patients did not increase the risk of early complications compared to progressive drain removal.

Elevation of Inflammatory Cytokines and Proteins after Intra-Articular Ankle Fracture: A Cross-Sectional Study of 47 Ankle Fracture Patients.

INTRODUCTION: Intra-articular fractures are the leading etiology for posttraumatic osteoarthritis (PTOA) in the ankle. Elevation of proinflammatory cytokines following intra-articular fracture may lead to synovial catabolism and cartilage degradation. We aimed to compare cytokine levels in injured and healthy ankle joints, examine the longer-term cytokine levels in fractured ankles, and investigate the association between cytokine levels in fractured ankles and plasma. MATERIALS AND METHODS: In this cross-sectional study, synovial fluid (SF) and plasma of forty-seven patients with acute intra-articular ankle fractures and eight patients undergoing implant removal were collected prior to surgery. We determined concentrations of sixteen inflammatory cytokines, two cartilage degradation proteins, and four metabolic proteins and compared the levels in acutely injured ankles with those of the healthy contralateral side or during metal removal. Cytokine levels in injured ankles were also compared to serum cytokine levels. Nonparametric Wilcoxon rank-sum and Spearman tests were used for statistical analysis, and a p value below 0.05 was considered significant. RESULTS: Compared to the healthy ankles, the synovial fluid in ankles with acute intra-articular fracture had elevated levels of several proinflammatory cytokines and proteases (IL-1ß, IL-2, IL-6, IL-8, IL-12p70, TNF, IFNγ, MMP-1, MMP-3, and MMP-9) and anti-inflammatory cytokines (IL-1RA, IL-4, IL-10, and IL-13). The levels of cartilage degradation products (ACG, CTX-2) and metabolic mediators (TGF-ß1 and TGF-ß2) were also significantly higher. Synovial concentrations of ACG, IL-12-p70, IFNγ, IL-4, and bFGF correlated with serum levels. While most of the examined synovial cytokines were unchanged after implant removal, IL-4 and IL-6 levels were upregulated. CONCLUSIONS: We show that an acute ankle fracture is followed by an inflammatory reaction and cartilage degeneration. These data contribute to the current understanding of the protein regulation behind the development of PTOA and is a further step towards supplementing the current surgical treatment. This cross-sectional study was "retrospectively registered" on the 31th October 2017 at ClinicalTrials.gov (NCT03769909). The registration was carried out after inclusion of the first patient and prior to finalization of patient recruitment and statistical analyses: https://clinicaltrials.gov/ct2/show/NCT03769909?term=NCT03769909&draw=2&rank=1.

The Danish Spinal Cord Injury Shoulder (DanSCIS) cohort: methodology and primary results.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To describe the socio-demographics, injury characteristics, prevalence of shoulder and neck symptoms, weekly participation in leisure time physical activity (LTPA) and quality of life (QoL) of individuals with spinal cord injury in Denmark (SCI). SETTING: Nation-wide community survey, Denmark. METHODS: Individuals with SCI for >2 years were included from three SCI rehabilitation departments. Questionnaire data regarding socio-demographic details, SCI injury characteristics, medical history, shoulder and neck symptoms, LTPA and QoL were collected. RESULTS: Of 2454 potential participants, 1517 (62%) responded to the survey (mean age = 56.2, SD 16.1, 37% female, 42% tetraplegia, 23% complete SCI, mean time since injury = 16.9, SD 13.5). 75% used some form of assistive mobility device. Responders and non-responders showed no sex or injury type/severity differences. Shoulder and neck symptoms within the past 3 months were reported by 63 and 67% respectively, with 51% reporting shoulder symptoms within the past week. Among those with symptoms, 61% had experienced shoulder symptoms and 56% neck symptoms, for more than 30 days during the previous 3 months. Symptoms often prevented participants from performing their usual activities (due to shoulder symptoms 46%, neck symptoms 41%). CONCLUSIONS: A high prevalence of self-reported shoulder and neck symptoms was found, which may limit physical function and social activities. We succeeded in generating the Danish Spinal Cord Injury Shoulder (DanSCIS) dataset, which comprised a substantial proportion of Danish adults with SCI. Future studies using data from this cohort will investigate patterns and associations between shoulder/neck symptoms, use of assistive mobility devices, LTPA and QoL.

The inflammatory response of the supraspinatus muscle in rotator cuff tear conditions.

BACKGROUND: Rotator cuff (RC) disorders involve a spectrum of shoulder conditions from early tendinopathy to full-thickness tears leading to impaired shoulder function and pain. The pathology of RC disorder is, nonetheless, still largely unknown. Our hypothesis is that a supraspinatus (SS) tendon tear leads to sustained inflammatory changes of the SS muscle along with fatty infiltration and muscle degeneration, which are threshold markers for poor RC muscle function. The aim of this study was to determine the extent of this muscle inflammation in conjunction with lipid accumulation and fibrosis in RC tear conditions. METHODS: We used proteomics, histology, electrochemiluminescence immunoassay, and quantitative polymerase chain reaction analyses to evaluate inflammatory and degenerative markers and fatty infiltration in biopsies from 22 patients undergoing surgery with repair of a full-thickness SS tendon tear. RESULTS: Bioinformatic analysis showed that proteins involved in innate immunity, extracellular matrix organization, and lipid metabolism were among the most upregulated, whereas mitochondrial electronic transport chain along with muscle fiber function was among the most downregulated. Histologic analysis confirmed changes in muscle fiber organization and the presence of inflammation and fatty infiltration. Inflammation appeared to be driven by a high number of infiltrating macrophages, accompanied by elevated matrix metalloprotease levels and changes in transforming growth factor-ß and cytokine levels in the SS compared with the deltoid muscle. CONCLUSIONS: We demonstrated massive SS muscle inflammation after the tendon tear combined with fatty infiltration and degeneration. The regulation of tissue repair is thus extremely complex, and it may have opposite effects at different time points of healing. Inhibition or stimulation of muscle inflammation may be a potential target to enhance the outcome of the repaired torn RC.

Reconstruction of wound defects in the perineum. / Rekonstruksjon av sårdefekter i perineum.

Surgical procedures in the perineum can cause major soft-tissue defects that require reconstruction with plastic surgery. In this article we present plastic surgery principles for the reconstruction of wound defects and common methods used to reconstruct wound defects in the perineum.

Cancer therapy with isolated limb perfusion. / Kreftbehandling med isolert ekstremitetsperfusjon.

For locally advanced soft tissue sarcomas and metastases from melanoma located in the extremities, mutilating surgery or amputation may be necessary to achieve local control. Isolated limb perfusion with high-dose chemotherapy may represent an alternative to amputation for this patient group.

TNF deficiency causes alterations in the spatial organization of neurogenic zones and alters the number of microglia and neurons in the cerebral cortex.

BACKGROUND: Although tumor necrosis factor (TNF) inhibitors are used to treat chronic inflammatory diseases, there is little information about how long-term inhibition of TNF affects the homeostatic functions that TNF maintains in the intact CNS. MATERIALS AND METHODS: To assess whether developmental TNF deficiency causes alterations in the naïve CNS, we estimated the number of proliferating cells, microglia, and neurons in the developing neocortex of E13.5, P7 and adult TNF knock out (TNF-/-) mice and wildtype (WT) littermates. We also measured changes in gene and protein expression and monoamine levels in adult WT and TNF-/- mice. To evaluate long-term effects of TNF inhibitors, we treated healthy adult C57BL/6 mice with either saline, the selective soluble TNF inhibitor XPro1595, or the nonselective TNF inhibitor etanercept. We estimated changes in cell number and protein expression after two months of treatment. We assessed the effects of TNF deficiency on cognition by testing adult WT and TNF-/- mice and mice treated with saline, XPro1595, or etanercept with specific behavioral tasks. RESULTS: TNF deficiency decreased the number of proliferating cells and microglia and increased the number of neurons. At the same time, TNF deficiency decreased the expression of WNT signaling-related proteins, specifically Collagen Triple Helix Repeat Containing 1 (CTHRC1) and Frizzled receptor 6 (FZD6). In contrast to XPro1595, long-term inhibition of TNF with etanercept in adult C57BL/6 mice decreased the number of BrdU+ cells in the granule cell layer of the dentate gyrus. Etanercept, but not XPro1595, also impaired spatial learning and memory in the Barnes maze memory test. CONCLUSION: TNF deficiency impacts the organization of neurogenic zones and alters the cell composition in brain. Long-term inhibition of TNF with the nonselective TNF inhibitor etanercept, but not the soluble TNF inhibitor XPro1595, decreases neurogenesis in the adult mouse hippocampus and impairs learning and memory after two months of treatment.

Musculoskeletal application and validation of speckle-tracking ultrasonography.

BACKGROUND: Diseased, injured, or dysfunctional skeletal muscles may demonstrate abnormal function and contractility. Currently, only few in vivo imaging techniques are able to characterize the contractile properties of muscle tissue. This study aimed to test the hypothesis that muscle strain can be tracked in two upper extremity skeletal muscles by speckle-tracking ultrasonography (STU) and correlates with isometric muscle contractions. METHODS: A convenience sample of 10 healthy, adult volunteers with normal shoulder function were tested. The 5 women and 5 men had a mean age of 45 years (range: 39-59 years) and BMI < 30. STU was applied to the supraspinatus (SS) and biceps brachii (BB) muscles using a M11 L-MHz linear transducer (frequency 8-15 MHz) hooked to a Vivid E 9TM ultrasound machine. Strain validation was performed by correlating peak strain against standardized sub-maximal, isometric load conditions of the two muscles (20-80% of maximal voluntary contraction) using a custom-built muscle dynamometer based on strain-gauge technique. Data were analyzed offline using the EchoPac speckle-tracking software and were blinded to the examiner. RESULTS: Intramuscular strain measured by STU in the SS and BB muscles showed moderate to strong correlations with external muscle load (SS: r = - 0.76, p < 0.0001 and BB: r = - 0.60, p < 0.0001). We found strain to vary from approximately 10-20% during increasing submaximal, isometric conditions. CONCLUSIONS: We demonstrate that STU can be applied on healthy skeletal musculature (SS and BB muscles). The observed correlations between strain and isometric contractions suggest a valid technique. However, the concept of measuring muscle strain non-invasively needs further investigation for validity, accuracy, responsiveness, and reliability before its therapeutic and research potential can be realized.

Patients with non-operated traumatic primary or recurrent anterior shoulder dislocation have equally poor self-reported and measured shoulder function: a cross-sectional study.

BACKGROUND: Patients with non-operated traumatic primary anterior shoulder dislocation (PASD) are assumed to have less shoulder impairment than patients with recurrent anterior shoulder dislocations (RASD). This may impact treatment decision strategy. The aim was to study whether patients with non-operated traumatic PASD have less shoulder impairment than those with RASD. METHODS: In a cross-sectional study baseline data from patients with PASD and RASD in a randomised controlled trial of non-operative shoulder exercise treatment were used. Shoulder function was self-reported (Western Ontario Shoulder Instability (WOSI), Tampa Scale of Kinesiophobia (TSK), General Health (EQ-5D-VAS), Numeric Pain Rating Scale (NPRS)), and measured (Constant-Murley shoulder Score (CMS total), CMS - Range of Motion (CMS-ROM, CMS - strength, proprioception, clinical tests). RESULTS: In total, 56 patients (34 (28 men) with PASD and 22 (21 men) with RASD) (mean age 26 years) participated. WOSI total was 1064 and 1048, and TSK above 37 (indicating high re-injury fear) was present in 33 (97%) and 21 (96%) of the groups with PASD and RASD, with no group difference. CMS total (66.4 and 70.4), CMS-ROM (28.7 and 31.5), CMS-strength (injured shoulder: 7.6 kg and 9.1 kg), proprioception and clinical tests were the same. Furthermore, 26 (76%) with PASD and 13 (59%) with RASD reported not to have received non-operative shoulder treatment. CONCLUSIONS: Non-operated patients with PASD and self-reported shoulder trouble three-six weeks after initial injury do not have less shoulder impairment (self-reportedly or objectively measured) than non-operated patients RASD and self-reported shoulder trouble three-six weeks after their latest shoulder dislocation event.

Assembly, maturation, and degradation of the supraspinatus enthesis.

The development of the rotator cuff enthesis is still poorly understood. The processes in the early and late developmental steps are gradually elucidated, but it is still unclear how cell activities are coordinated during development and maturation of the structured enthesis. This review summarizes current knowledge about development and age-related degradation of the supraspinatus enthesis. Healing and repair of an injured and degenerated supraspinatus enthesis also remain a challenge, as the original graded transitional tissue of the fibrocartilaginous insertion is not re-created after the tendon is surgically reattached to bone. Instead, mechanically inferior and disorganized tissue forms at the healing site because of scar tissue formation. Consequently, the enthesis never reaches mechanical properties comparable to those of the native enthesis. So far, no novel biologic healing approach has been successful in enhancing healing of the injured enthesis. The results revealed in this review imply the need for further research to pave the way for better treatment of patients with rotator cuff disorder.

Glenoid morphology in obstetrical brachial plexus lesion: a three-dimensional computed tomography study.

BACKGROUND: Obstetric brachial plexus lesion (OBPL) frequently leads to glenohumeral dysplasia, and excessive retroversion of the glenoid is among the best known developmental disturbances. Most analyses of the glenoid are based on 2-dimensional (D) imaging and do not address glenoid inclination or provide information on the glenoid in the sagittal plane. We aim to describe the 3-D deformity of the glenoid in children with OBPL. METHODS: Preoperative computed tomography (CT) scans of the nonaffected and the affected scapula of 24 children (aged 5 to 12 years) with developmental disturbances after OBPL years were analyzed. The dimensions of the scapula and the deformation of the glenoid were visualized in 3-D. RESULTS: The retroversion of the glenoid fossa was greater in all affected shoulders, and 2-D measurements significantly overestimated retroversion compared with angles measured in 3-D. The inclination of the glenoid fossa was altered, and a distal bony edge loss was observed on 3-D reformations in the sagittal plane. The reliability of the measured angles was excellent, and the κ agreement for the description of the glenoid form was substantial. Furthermore, the dimensions of the scapula were significantly smaller on the affected shoulders. CONCLUSION: OBPL is indeed a 3-D disorder. Our measurements revealed excessive retroversion of the glenoid fossa, and the reliability of the 3-D CT measurements was superior to their 2-D counterparts. 3-D CT reformations of the glenoid in the coronal and the sagittal plane added further to 3-D understanding of glenoid morphology in OBPL. These new findings legitimatize a 3-D CT-based description of the glenoid deformities connected with OPBL.

Simultaneous cutaneous melanoma and ipsilateral breast cancer with metastasis to the same axilla. A case report with a focus on a multidisciplinary approach.

INTRODUCTION AND IMPORTANCE: Treatment of simultaneously occurring primary malignancies with separate lymphatic drainage is a surgical and medical challenge. We present a patient in which multidisciplinary management of coexisting melanoma and breast cancer was mandatory for optimal results. CASE PRESENTATION: A 67-year-old female had a primary surgical resection for a skin lesion on the back. Histology revealed melanoma with a Breslow thickness of 4.8 mm. According to guidelines, a wide local excision was scheduled. Prior to the surgery, routine mammography revealed simultaneous ipsilateral breast cancer. A preoperative work-up revealed a pathological lymph node in the left axilla. Biopsies found metastasis from malignant melanoma. She had combined surgery with breast-conserving therapy, wide local excision of the skin on the back, and extended axillary clearance of levels I-III. Final histology revealed axillary metastases both from melanoma and breast cancer. Adjuvant therapy was decided based on a multidisciplinary approach. CLINICAL DISCUSSION: To our knowledge, cases of synchronous primary cutaneous melanoma with biopsy-verified axillary metastases and independent, ipsilateral primary breast carcinoma have not been described. The surgical approach was done according to guidelines. The breast cancer was re-staged based on the histology of the surgical specimen. Adjuvant treatment was a combination of treatment strategies for the two primary malignancies. CONCLUSION: This case highlights the need for a multidisciplinary approach in treating simultaneous breast cancer and melanoma both with axillary metastasis. The optimal treatment approach was based on close collaboration between surgeons, oncologists, radiologists, and pathologists. Multidisciplinary meetings are mandatory for optimal results.

Criterion validity of muscle strain analyses of skeletal muscle function in patients with multiple sclerosis.

BACKGROUND: Despite the wide range of existing performance measures to evaluate functional status of patients with multiple sclerosis, the heterogeneous nature of the disease hinders clinical characterization and monitoring of disease severity. Speckle tracking ultrasonography is a non-invasive technique to assess isolated muscle function by evaluating the contractile properties of muscle tissue, i.e. muscle strain. The aim of this study was to investigate whether muscle strain measured by speckle tracking ultrasonography could be a useful quantitative measure of muscle function in patients with multiple sclerosis. The criterion validity of muscle strain was compared to that of validated performance measures of upper and lower extremity function. METHODS: This cross-sectional study used baseline data from an explorative observational cohort study (the MUST study). Participants recruited from a hospital outpatient MS clinic underwent speckle tracking ultrasonography of the biceps brachii, supraspinatus, and soleus muscles of the dominant side according to pre-defined submaximal isometric contractions. Participants also completed the Timed 25-Foot Walk Test, the Six Spot Step Test, the 2-minute walking test, the Nine-Hole Peg Test, the 12-item Multiple Sclerosis Walking Scale, and the Oxford Shoulder Score. Gaussian distribution was investigated by visual inspection of normal probability plots and the Shapiro-Wilk test. The Timed 25-Foot Walk Test and Nine-Hole Peg Test were selected as gold standards for function of the lower and upper extremities, respectively. Criterion validity was assessed using Spearman's rank-order correlation coefficient ρ (rho), comparing the muscle strain and performance measures against predefined gold standards. Differences in criterion validity were estimated using squared correlations on the Fischer's Z-scale, with non-parametric bootstrapping to obtain bias-corrected, accelerated bootstrap confidence intervals (95% BCa). RESULTS: Criterion validity showed good to excellent correlations between the gold standard for lower extremity function and the 2-minute walking test and Six Spot Step Test, and a fair correlation to the 12-item Multiple Sclerosis Walking Scale. No significant correlation was found between the gold standard for upper extremity function and the performance measure. There were no significant correlations between the gold standards and muscle strain. CONCLUSION: The absence of criterion validity for muscle strain alongside fair to strong criterion validity for the performance measures indicates that speckle tracking ultrasonography assessment of muscle strain is either invalid or evaluates other constructs of multiple sclerosis. Muscle strain assessed by speckle tracking ultrasonography cannot be recommended for the evaluation of treatment effects or disease progression in multiple sclerosis.

Long-term experience with surgical treatment of selected patients with bladder pain syndrome/interstitial cystitis.

OBJECTIVE: The role of major surgery in patients with bladder pain syndrome/interstitial cystitis (BPS/IC) is not fully established. This report presents a single-institution experience with major surgery in patients with disabling BPS/IC where conservative treatment had failed. MATERIAL AND METHODS: Forty-one patients (34 women, seven men) with BPS/IC refractory to conservative treatment underwent major surgery from 1983 to 2004. Surgical approach was determined on a case-by-case basis. Postoperative pain and satisfaction were assessed by a questionnaire. RESULTS: Cystectomy was the primary procedure in five patients. The remaining 36 patients were primarily operated on with subtotal cystectomy and bladder augmentation (n = 16) or supravesical urinary diversion with intact bladder (n = 20). Thirteen of these patients were later operated on with cystectomy due to persisting pain 12 (6-146) months after the primary procedure. The questionnaire was answered by 38 of 41 patients after a median follow-up of 66 (6-238) months. In total, 28 patients (74%) were free of pain, and 26 patients (68%) were satisfied with the end result. There was no difference in reported pain between cystectomized and non-cystectomized patients. When comparing patients who reported pain at follow-up with those who did not report pain, preoperative length of symptoms was significantly increased, with 12.1 compared to 5.4 years (p = 0.02). CONCLUSIONS: Major surgery is associated with good symptom relief in strictly selected patients with disabling BPS/IC, where conservative treatment has failed. Extended preoperative duration of symptoms may be a predictor for persisting pain after major surgery for BPS/IC.

Surgeons agree more on treatment recommendations than on classification of proximal humeral fractures.

BACKGROUND: Orthopaedic surgeons disagree considerably when classifying fractures of the proximal humerus. However, the clinical implications of low observer agreement remain unclear. The purpose of the study was to compare the agreement on Neer classification with the agreement on treatment recommendations. METHODS: We conducted a multi-centre observer-study. Five experienced shoulder surgeons independently assessed a consecutive series of 193 radiographs at two occasions three months apart. All pairs of radiographs were classified according to Neer. Subsequently, the observers were asked to recommend one of three treatment modalities for each case: non-operative treatment, locking plate osteosynthesis, or hemiarthroplasty. RESULTS: At both classification rounds mean kappa-values for inter-observer agreement on treatment recommendations (0.48 and 0.52) were significantly higher than the agreement on Neer classification (0.33 and 0.36) (p < 0.001 at both rounds). The highest mean kappa-values were found for inter-observer agreement on non-surgical treatment (0.59 and 0.55). In 36% (345 out of 965) of observations an observer changed Neer category between first and second classification round. However, in only 34% of these cases (116 out of 345) the observers changed their treatment recommendations. CONCLUSIONS: We found a significantly higher agreement on treatment recommendations compared to agreement on fracture classification. The low observer agreement on the Neer classification reported in several observer studies may have less clinical importance than previously assumed. However, inter-observer agreement did not exceed moderate levels.

Evaluation of functional outcome measures after fampridine treatment in patients with multiple sclerosis - An interventional follow-up study.

OBJECTIVE: The purpose of this interventional study on participants with multiple sclerosis (MS) with walking disability was to evaluate changes in functional hand and walking measurements after fampridine treatment, after stratifying by the Expanded Disability Status Scale (EDSS). We furthermore wanted to investigate different functional measurements to evaluate their ability to detect responders to fampridine with a clinically relevant improvement. METHODS: Patients were recruited from the MS Clinic at Odense University Hospital and were classified into two disability groups based on their EDSS score (moderate EDSS (EDSSMod) 4.5-5.5 [n = 19] and severe EDSS (EDSSSev) 6.0-7.0 [n = 14]). At baseline (visit 1) they completed the Timed 25-Foot Walk (T25FW), 2-Minute Walk Test (2MWT), Nine Hold Peg Test (9HPT), 12-item Multiple Sclerosis Walking Scale (MSWS-12), and the Six Spot Step Test (SSST). Participants were given 10 mg twice daily fampridine for 14 days before retested (visit 2). For each measurement, cut-off values were used to define responders with a clinically relevant improvement to treatment. The measurements were evaluated separately and in combination. RESULTS: Of the 33 participants, 25 (75.8%) were identified as having a clinically relevant improvement (CRI). For all patients combined (EDSSAll), all five measurements showed significant functional improvement after treatment. For the individual measurements, the highest participant response rates after 14 days of fampridine treatment were seen on the MSWS-12 (57.6%) and 2MWT (42.4%). The 2MWT also showed the largest performance improvement (18.5%) from visit 1 to visit 2. For patients with severe disability (EDSSSev), no significant improvement was seen after fampridine treatment on the T25FW, and most of the responders to T25FW had moderate disability (EDSSMod, 71.5%). Conversely for the SSST, most responders were EDSSSev (83.3%). No participants had a clinically relevant improvement on the 9HPT. The combination of T25FW, SSST, and MSWS-12 was less sensitive in distinguishing responders from non-responders, whereas the combination of 2MWT and MSWS-12 identified the same responders and could better distinguish fampridine responders from non-responders. CONCLUSION: EDSS level did not influence the effect of fampridine treatment on functional hand and walking measures and the responsiveness of the measurements differed only a little between moderate and severe EDSS levels. The combination of self-reported walking capacity (MSWS-12) and walking endurance (2MWT) was better than T25FW, SSST, and MSWS-12 at detecting clinically meaningful improvement after fampridine treatment, which could prove useful in the clinical monitoring of walking disabilities in MS during fampridine treatment.