In a trial involving critically ill patients with severe acute kidney injury, we found no significant difference with regard to mortality between an early and a delayed strategy for the initiation of renal-replacement therapy. A delayed strategy averted the need for renal-replacement therapy in an appreciable number of patients. (Funded by the French Ministry of Health; ClinicalTrials.gov number, NCT01932190.).

Objective. To clarify the involvement of dendritic cells (DCs), chemokines, and proinflammatory Th1 cytokines in the pathogenesis of the chronic muscle diseases dermatomyositis (DM) and polymyositis (PM).Methods. We characterized by immunohistochemistry the DC subsets and their interaction with cells producing chemokines and the Th1 cytokines interleukin-17 (IL-17) and interferon-␥ (IFN␥). Immature and mature DCs were defined by the expression of CD1a and DC-LAMP/CD83, respectively.Results. Immature DCs were mainly detected in lymphocytic infiltrates in DM and PM muscle tissue samples. Mature DCs were detected in perivascular infiltrates and surrounded muscle fibers. IL-17-positive and IFN␥-positive cells were also observed in perivascular infiltrates in both cases. We then focused on the expression of the CCL20/CCR6 chemokine/receptor complex, which controls immature DC migration, and on the expression of the CCL19/CCR7 and CCL21/ CCR7 chemokine/receptor complexes, which control mature DC migration. CCL20 and CCR6 colocalized in lymphocytic infiltrates in DM and PM samples. CCL21 was rarely observed in DM samples and never observed in PM samples. CCL19-and CCR7-expressing cells were absent in both tissues.Conclusion. The close association between CCL20/CCR6 and immature DCs suggests the contribution of CCL20 to CCR6؉ immature DC homing.Detection of mature DCs in DM and PM muscle tissue samples despite the lack of CCL19 and CCR7 is evidence for a local maturation of DCs in inflammatory muscle tissue without lymphoid organ organization.

Background Delaying renal replacement therapy (RRT) for some time in critically ill patients with severe acute kidney injury and no severe complication is safe and allows optimisation of the use of medical devices. Major uncertainty remains concerning the duration for which RRT can be postponed without risk. Our aim was to test the hypothesis that a more-delayed initiation strategy would result in more RRT-free days, compared with a delayed strategy.Methods This was an unmasked, multicentre, prospective, open-label, randomised, controlled trial done in 39 intensive care units in France. We monitored critically ill patients with severe acute kidney injury (defined as Kidney Disease: Improving Global Outcomes stage 3) until they had oliguria for more than 72 h or a blood urea nitrogen concentration higher than 112 mg/dL. Patients were then randomly assigned (1:1) to either a strategy (delayed strategy) in which RRT was started just after randomisation or to a more-delayed strategy. With the more-delayed strategy, RRT initiation was postponed until mandatory indication (noticeable hyperkalaemia or metabolic acidosis or pulmonary oedema) or until blood urea nitrogen concentration reached 140 mg/dL. The primary outcome was the number of days alive and free of RRT between randomisation and day 28 and was done in the intention-to-treat population. The study is registered with ClinicalTrial.gov, NCT03396757 and is completed.

A 3-year, randomized, double-blind, placebo-controlled trial evaluated the effect of oral alendronate on the BMD of 64 adult patients with osteogenesis imperfecta. The mean increases in the lumbar spine BMD were 10.1 ± 9.8% (p < 0.001) and 0.7 ± 5.7% in the alendronate and placebo groups, respectively. Oral alendronate increases BMD in adult patients with osteogenesis imperfecta.Introduction: This study evaluated the effect of oral alendronate on the BMD of adult patients with osteogenesis imperfecta. Materials and Methods:We carried out a 3-year, randomized, double-blind, placebo-controlled trial of oral alendronate in 64 adult patients with osteogenesis imperfecta. The primary endpoint was the difference between the groups in the mean percent change in lumbar spine BMD at 3 years. Secondary outcomes included changes in BMD of total hip, vertebral and peripheral fracture incidence, pain, hearing loss, and bone turnover biochemical markers. Patients were treated daily with either placebo or 10 mg alendronate. All received 1 g of calcium and 800 IU of vitamin D daily. Results: The mean ± SD increases in the lumbar spine BMD were 10.1 ± 9.8% (p < 0.001) and 0.7 ± 5.7% in the alendronate and placebo groups, respectively. Hip BMD increased in the alendronate group by 3.3 ± 0.5% (p ‫ס‬ 0.001) and decreased in the placebo group by 0.3 ± 0.6%. The sample size was not sufficient to determine an effect of alendronate on fracture rate. A significant increase of the pain score was noted in the alendronate group (p ‫ס‬ 0.04) in the intent-to-treat analysis but not in the per protocol analysis. There was no change in hearing in either group. Bone resorption and formation biochemical markers were significantly decreased in the alendronate group (p < 0.001). There were no differences in severe adverse effects between the groups, but there was an increase in nonsevere upper gastrointestinal effects in the alendronate group (p ‫ס‬ 0.003). Conclusions: Oral alendronate increases BMD and increase nonsevere gastrointestinal adverse effects but does not modify the hearing loss in adult patients with osteogenesis imperfecta. More studies are needed to evaluate an effect on the fracture rate.

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