Update of EULAR recommendations for the treatment of systemic sclerosis

The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc

A Detailed microscopic examination of alterations in normal anular structure induced by mechanical destabilization in an ovine model of disc degeneration

Study Design: Microstructural investigation of anular structure. Objective: To reveal the effect of mechanical destabilization on the anular architecture both locally and distantly. Summary Of Background Data: Several longitudinal ovine-induced disc degeneration studies have documented degenerative changes in disc components using histologic, biomechanical, and biochemical approaches; however, changes in intervertebral disc (IVD) microstructure have largely remained neglected. In recent years, the use of structurally relevant section planes has improved our understanding of disc microstructure, including the presence of significant bridging structures radially linking the lamellae. It has been suggested that the translamellar cross-bridges offer a mechanism by which the anular wall can adaptively remodel itself in response to a changing biomechanical microenvironment. Methods: IVDs harvested from lesion and sham-operated groups of Merino wethers were subjected to en face oblique and vertical sectioning. The macrostructural effect of the destabilization was examined in the vertically sectioned group with conventional histologic techniques. The second group was serially sectioned into 30-μm slices allowing a global examination of the anular microstructure in its fully hydrated state using a differential interference contrast microscope. Results: The previously described induced disc degeneration in the mid-inner anulus fibrosus (AF) and a spontaneous repair process in the outer AF was confirmed. Increased translamellar bridging was observed contralaterally to the lesion in the mechanically destabilized IVD and development of atypical broad bridging elements in the outer lamellae. Structural alterations in the lamellar anchorages to the cartilaginous endplates in destabilized IVDs, including lamellar branching and discontinuities atypical of normal lamellar attachments were also observed. Conclusion: The present investigation has offered a glimpse of an anular wall apparently capable of remodeling in response to perturbations in its normal mechanical environment. The translamellar cross-bridges undergo adaptations in structure, in response to altered stresses locally at the anular defect site but also distantly in the contralateral AF in the destabilized disc. It is currently not known whether such changes in anular microarchitecture, however, predispose the anulus to further mechanical damage or have a stabilizing role to play in this structure.9 page(s

A comparison between acidic and basic protein fractions from whey or milk for reduction of bone loss in the ovariectomised rat

The ability of whey acidic protein fractions to protect against bone loss due to ovariectomy (OVX) in the mature female rat was investigated. The bone bioactivity of these acidic protein fractions, isolated from both mineral acid whey protein concentrate (WPC) and rennet WPC, was compared with that of basic protein fractions isolated from both milk and rennet WPC. Fifty 6-month old rats that had been ovariectomised at 5.5 months were randomised into five groups of ten each. One group remained the OVX control while four groups were each fed one of the acidic or basic protein fractions as 0.3% (w/w) of the diet, for 4 months. Ten sham-operated rats served as a second control group. Sequential measurements of bone mineral density of the spine and femur indicated that the acidic protein fraction prepared from mineral acid WPC reduced bone loss due to OVX, maintaining bone density above OVX levels at week 16 of feeding. Biomechanical data indicated that both acidic fractions tended to increase bone stiffness, and hence resistance against breaking. © 2005 Elsevier Ltd. All rights reserved

Effects of a multinutrient-fortified milk drink combined with exercise on functional performance, muscle strength, body composition, inflammation, and oxidative stress in middle-aged women: a 4-month, double-blind, placebo-controlled, randomized trial

Background Multinutrient protein-enriched supplements are promoted to augment the effects of exercise on muscle mass and strength, but their effectiveness in middle-aged women, or whether there are any additional benefits to physical function, remains uncertain. Objectives We aimed to evaluate whether a multinutrient-fortified milk drink (MFMD) could enhance the effects of exercise on functional muscle power (stair climbing) in middle-aged women. Secondary aims were to evaluate the intervention effects on physical function, muscle strength, lean mass (LM), fat mass (FM), bone mineral content (BMC), muscle cross-sectional area (CSA), muscle density, balance, flexibility, aerobic fitness, inflammation, oxidative stress, bone and cartilage turnover, blood pressure, and blood lipids. Methods In this 4-mo, double-blind, placebo-controlled, randomized trial, 244 women (45–65 y) participated in a multimodal resistance-type exercise program 3 d/wk, with random allocation to a twice-daily MFMD containing added protein, vitamin D, calcium, milk fat globule membrane (phospholipids and other bioactives), and other micronutrients (Ex + MFMD, n = 123) or an energy-matched placebo (Ex + placebo, n = 121). Results A total of 216 women (89%) completed the study. After 4 mo, both groups experienced similar 3.6%–4.3% improvements in the primary outcomes of fast-pace 5- and 10-step stair ascent power. In contrast, Ex + MFMD experienced greater improvements in 5-step regular-pace stair descent time [net difference (95% CI): −0.09 s (−0.18, 0.00 s), P = 0.045], countermovement jump height [0.5 cm (0.04, 1.0 cm), P = 0.038], total body LM [0.3 kg (0.04, 0.60 kg), P = 0.020], FM [−0.6 kg (−1.0, −0.2 kg), P = 0.004], BMC [0.4% (0.1%, 0.6%), P = 0.020], muscle CSA [thigh: 1.8% (0.6%, 2.9%), P = 0.003; lower leg: 0.9% (0.3%, 1.6%), P = 0.005], balance eyes closed [3.3 s (1.1, 5.4 s), P = 0.005], 2-min step performance [8 steps (3, 12 steps), P = 0.003], and sit-and-reach flexibility [1.4 cm (0.6, 2.2 cm), P = 0.026]. MFMD did not enhance the effects of exercise on any measures of muscle strength, gait speed, dynamic balance, reaction time, or blood lipids, and there was no effect of either intervention on blood pressure, markers of inflammation, or cartilage turnover. Ex + placebo had a greater improvement in the oxidative stress marker protein carbonyls (P < 0.01).Conclusions In middle-aged women, daily consumption of an MFMD did not enhance the effects of a multimodal exercise program on the primary outcome of stair climbing ascent power, but did elicit greater improvements in multiple secondary outcomes including various other measures of functional performance, LM, muscle size, FM, balance, aerobic capacity, flexibility, and bone metabolism.This trial was registered at www.anzctr.org.au as ACTRN12617000383369