Effects of sporadic inclusion body myositis on skeletal muscle fibre type specific morphology and markers of regeneration and inflammation.

Sporadic inclusion body myositis (sIBM) is a subgroup of idiopathic inflammatory myopathies characterised by progressive muscle weakness and skeletal muscle inflammation. Quantitative data on the myofibre morphology in sIBM remains scarce. Further, no previous study has examined fibre type association of satellite cells (SC), myonuclei number, macrophages, capillaries, and myonuclear domain (MD) in sIBM patients. Muscle biopsies from sIBM patients (n = 18) obtained previously (NCT02317094) were included in the analysis for fibre type-specific myofibre cross-sectional area (mCSA), SCs, myonuclei and macrophages, myonuclear domain, and capillarisation. mCSA (p < 0.001), peripheral myonuclei (p < 0.001) and MD (p = 0.005) were higher in association with type 1 (slow-twitch) than type 2 (fast-twitch) fibres. Conversely, quiescent SCs (p < 0.001), centrally placed myonuclei (p = 0.03), M1 macrophages (p < 0.002), M2 macrophages (p = 0.013) and capillaries (p < 0.001) were higher at type 2 fibres compared to type 1 fibres. In contrast, proliferating (Pax7+/Ki67+) SCs (p = 0.68) were similarly associated with each fibre type. Type 2 myofibres of late-phase sIBM patients showed marked signs of muscle atrophy (i.e. reduced mCSA) accompanied by higher numbers of associated quiescent SCs, centrally placed myonuclei, macrophages and capillaries compared to type 1 fibres. In contrast, type 1 fibres were suffering from pathological enlargement with larger MDs as well as fewer nuclei and capillaries per area when compared with type 2 fibres. More research is needed to examine to which extent different therapeutic interventions including targeted exercise might alleviate these fibre type-specific characteristics and countermeasure their consequences in impaired functional performance.

Lack of muscle stem cell proliferation and myocellular hypertrophy in sIBM patients following blood-flow restricted resistance training.

Sporadic inclusion body myositis (sIBM) is characterised by skeletal muscle inflammation, progressive muscle loss and weakness, which is largely refractory to immunosuppressive treatment. Low-load blood-flow restricted (BFR) training has been shown to evoke gains in myofibre cross sectional area (mCSA) in healthy adults. This could partially be due to the activation and integration of muscle satellite cells (SC) resulting in myonuclei addition. Consequently, this study investigated the effect of 12-weeks lower limb low-load BFR resistance training in sIBM patients on SC and myonuclei content, myofibre size and capillarization. Muscle biopsies from sIBM patients randomised to 12-weeks of low-load BFR resistance training (n = 11) or non-exercising controls (CON) (n = 9) were analysed for SC and myonuclei content, myofibre size and capillarization using three-colour immunofluorescence microscopy and computerised quantification procedures. No between-group differences (time-by-group interactions) or within-groups changes were observed for resident SCs (Pax7+/Six1+), proliferating SCs (Pax7+/ Ki67+), myonuclei (Six1+), type 1 mCSA or capillary number (CD31+). However, a time-by-group interaction for type 2 mCSA was observed (p = 0.04). Satellite cell content, myonuclei number, mCSA and capillary density remained unaffected following 12-weeks low-load BFR resistance training, indicating limited myogenic capacity and satellite cell plasticity in long-term sIBM patients.

[Spinefractures - diagnosis and treatment].

Acute onset back pain is a common reason for referral to primary health care or emergency departments. In this review, the different spine fracture types are highlighted, and a treatment algorithm is proposed. CT is the modality of choice when a spine fracture is suspected. MRI should be performed when disc or ligamentous lesions are suspected or in patients with known ankylosis or diffuse idiopathic skeletal hyperostosis. Treatment is mainly conservative with bracing, but unstable fractures and patients with neurological deficits should be treated surgically.

The immune system in sporadic inclusion body myositis patients is not compromised by blood-flow restricted exercise training.

BACKGROUND: Sporadic inclusion body myositis (sIBM) is clinically characterised by progressive proximal and distal muscle weakness and impaired physical function while skeletal muscle tissue displays abnormal cellular infiltration of T cells, macrophages, and dendritic cells. Only limited knowledge exists about the effects of low-load blood flow restriction exercise in sIBM patients, and its effect on the immunological responses at the myocellular level remains unknown. The present study is the first to investigate the longitudinal effects of low-load blood flow restriction exercise on innate and adaptive immune markers in skeletal muscle from sIBM patients. METHODS: Twenty-two biopsy-validated sIBM patients were randomised into either 12 weeks of low-load blood flow restriction exercise (BFRE) or no exercise (CON). Five patients from the control group completed 12 weeks of BFRE immediately following participation in the 12-week control period leading to an intervention group of 16 patients. Muscle biopsies were obtained from either the m. tibialis anterior or the m. vastus lateralis for evaluation of CD3-, CD8-, CD68-, CD206-, CD244- and FOXP3-positive cells by three-colour immunofluorescence microscopy and Visiopharm-based image analysis quantification. A linear mixed model was used for the statistical analysis. RESULTS: Myocellular infiltration of CD3-/CD8+ expressing natural killer cells increased following BFRE (P < 0.05) with no changes in CON. No changes were observed for CD3+/CD8- or CD3+/CD8+ T cells in BFRE or CON. CD3+/CD244+ T cells decreased in CON, while no changes were observed in BFRE. Pronounced infiltration of M1 pro-inflammatory (CD68+/CD206-) and M2 anti-inflammatory (CD68+/CD206+) macrophages were observed at baseline; however, no longitudinal changes in macrophage content were observed for both groups. CONCLUSIONS: Low-load blood flow restriction exercise elicited an upregulation in CD3-/CD8+ expressing natural killer cell content, which suggests that 12 weeks of BFRE training evokes an amplified immune response in sIBM muscle. However, the observation of no changes in macrophage or T cell infiltration in the BFRE-trained patients indicates that patients with sIBM may engage in this type of exercise with no risk of intensified inflammatory activity.

Reproducibility of the stability-based classification for ankle fractures.

BACKGROUND: Classification of ankle fracture is important when deciding for operative or conservative treatment. This study rates the reproducibility of ankle stability assessment and compares it with the classification by Lauge-Hansen and Arbeitsgemeinschaft für Osteosyntesefragen (AO) in adult patients with primary ankle fractures. METHODS: A total of 496 consecutive ankle fractures were included, and the X-ray images were reviewed 2 times by 2 medical students, 2 residents, and 1 consultant in orthopedic traumatology. The raters were blinded to each other and to their own results. Unweighted Kappa statistics were used to assess reproducibility. RESULTS: Overall mean (95% CI) interrater Kappa results were 0.65 (0.64; 0.68) for Lauge-Hansen, 0.62 (0.60; 0.63) for AO and 0.61 (0.57; 0.62) for the stability assessment. The intrarater results ranged from a mean Kappa of 0.64-0.80 for the medical students, 0.65-0.81 for the residents and 0.82-0.84 for the consultant. CONCLUSION: The stability assessment has substantial to almost-perfect agreement which is comparable to the Lauge-Hansen and AO classifications.

Delayed Effect of Blood Flow-restricted Resistance Training on Rapid Force Capacity.

PURPOSE: The aim of the present study was to investigate the effect and time course of high-frequent low-load blood flow-restricted (BFR) resistance training on rapid force capacity (i.e., rate of torque development [RTD]). MATERIALS AND METHODS: Ten male subjects (22.8 ± 2.3 yr) performed four sets of knee extensor exercise (20% one-repetition maximum) to concentric failure during concurrent BFR of the thigh (100 mm Hg), and eight work-matched controls (21.9 ± 3.0 yr) trained without BFR (CON). Twenty-three training sessions were performed within 19 d. Maximal slow and fast knee joint velocity muscle strength and rapid force capacity (e.g., RTD) and evoked twitch contractile parameters were assessed before (Pre) and 5 and 12 d after (Post5 and Post12) training. Muscle biopsies were obtained Pre, after 8 d (Mid8), and 3 and 10 d after (Post3 and Post10) training to examine changes in myofiber area and expression of myocellular proteins known to be modified by cellular stress (CaMKII, annexin A6, SNO-CYS). RESULTS: RTD remained unchanged after BFR training at Post5, while increasing 15%-20% Post12 (P < 0.01). Evoked muscle twitch parameters showed a general decline Post5 (P < 0.01) while returning to baseline levels at Post12. All contractile parameters essentially remained unchanged in CON. Elevated CaMKII was observed with BFR training at Post3 (57%) and Post10 (71%) (P < 0.05), whereas SNO-CYS increased in CON at Mid8 (P < 0.05). CONCLUSION: This study is the first to show that low-load resistance exercise performed with BFR leads to marked increases in rapid force capacity (RTD). However, a general delayed adaptive response was observed for voluntary contractile parameters (including RTD) in parallel with a decline and subsequent recovery in evoked contractile properties, suggesting the delayed gain in rapid force capacity mainly have a peripheral origin.

The Verbal Rating Scale Is Reliable for Assessment of Postoperative Pain in Hip Fracture Patients.

Background. Hip fracture patients represent a challenge to pain rating due to the high prevalence of cognitive impairment. Methods. Patients prospectively rated pain on the VRS. Furthermore, patients described the changes in pain after raising their leg, with one of five descriptors. Agreement between paired measures on the VRS at rest and by passive straight leg raise with a one-minute interval between ratings at rest and three-minute interval for straight leg raise was expressed by kappa coefficients. Reliability of this assessment of pain using the VRS was compared to the validity of assessing possible change in pain from the selected descriptors. Cognitive status was quantified by the short Orientation-Memory-Concentration Test. Results. 110 patients were included. Paired scores with maximum disagreement of one scale point reached 97% at rest and 95% at straight leg raise. Linear weighted kappa coefficients ranged from 0.68 (95% CI = 0.59-0.77) at leg raise to 0.75 (95% CI = 0.65-0.85) at rest. Unweighted kappa coefficients of agreement in recalled pain compared to agreement of paired VRS scores ranged from 0.57 (95% CI = 0.49-0.65) to 0.36 (95% CI = 0.31-0.41). Interpretation. The VRS is reliable for assessment of pain after hip fracture. The validity of intermittent questioning about possible change in pain intensity is poor.

Proliferation of myogenic stem cells in human skeletal muscle in response to low-load resistance training with blood flow restriction.

Low-load resistance training with blood flow restriction has been shown to elicit substantial increases in muscle mass and muscle strength; however, the effect on myogenic stem cells (MSCs) and myonuclei number remains unexplored. Ten male subjects (22.8 ± 2.3 years)performed four sets of knee extensor exercise (20% 1RM) to concentric failure during bloodflow restriction (BFR) of the proximal thigh (100 mmHg), while eight work-matched controls(21.9 ± 3.0 years) trained without BFR (control, CON). Twenty-three training sessions were performed within 19 days. Maximal isometric knee extensor strength (MVC) was examined pre- and post-training, while muscle biopsies were obtained at baseline (Pre), after 8 days intervention(Mid8) and 3 (Post3) and 10 days (Post10) post training to examine changes in myofibre area (MFA), MSC and myonuclei number. MVC increased by 7.1% (Post5) and 10.6% (Post12)(P <0.001) with BFR training, while type I and II MFA increased by 38% (Mid8), 35 ­ 37%(Post3) and 31 ­ 32% (Post10) (P <0.001). MSCs per myofibre increased with BFR training from 0.10 ± 0.01 (Pre) to 0.38 ± 0.02 (Mid8), 0.36 ± 0.04 (Post3) and 0.25 ± 0.02 (Post10) (P <0.001). Likewise, myonuclei per myofibre increased from 2.49 ± 0.07 (Pre) to 3.30 ± 0.22(Mid8), 3.20 ± 0.16 (Post3) and 3.11 ± 0.11 (Post10), (P<0.01). Although MFA increased in CON at Mid8, it returned to baseline at Post3. No changes in MSC or myonuclei number were observed in CON. This study is the first to show that short-term low-load resistance exercise performed with partial blood flow restriction leads to marked proliferation of myogenic stem cells and resulting myonuclei addition in human skeletal muscle, which is accompanied by substantial myofibre hypertrophy.