Postosteonecrotic osteoarthritis-like disorder of the femoral head of rats

The femoral heads of 15 rats were studied histologically 3 months after the induction of ischaemic necrosis by incising the cervical periosteum and cutting the ligamentum teres. The epiphyses consisted of immature disorganized subchondral and trabecular bone. The inter-trabecular spaces contained fibrous or haematopoietic tissue. Residual necrotic bone was rare. There was marked osteoblastic and osteoclastic activity. The articular aspect of the heads showed a spectrum of changes, ranging from cartilaginous degeneration with fibrillation and loss of glycosaminoglycans to an eburnated and polished bony surface. In seven rats, transphyseal bridges connected the epiphyseal and metaphyseal bony trabeculae to each other. It is suggested that the postnecrotic reparative processes, including the resorption of the necrotic debris and its replacement by newly formed, weak bone, led to an osteoarthritis-like disorder. This healing pattern of the necrotic femoral head was reminiscent of the progressive remodelling that occurs in rings in femoral capital osteonecrosis of adult human patients and in Perthes's disease of children.     

Pyogenic granuloma-like reaction in the necrotic, vessels-deprived femoral head of the rat

Osteonecrosis of the femoral head was produced in rats by cutting the ligamentum teres and incising the cervical periosteum. As of the second postoperative week, fibrous tissue pervaded the necrotic epiphyses, macrophages and osteoclasts removed the debris, osteoblasts deposited lamellar-fibred and woven-fibred intramembranous bone, and remodeling began. In 16% of the rats killed during the 2nd postoperative week, the epiphyses contained big fragments of necrotic bone enclosed by densely packed, capillary-sized vessels. Ingrowth of this hypervascularized, pyogenic granuloma-like tissue is presumably due to the presence of excessive growth factors, reflecting an exaggerated pathophysiological reaction within the framework of organization of the necrotic epiphyses.     

Insights from CREDENCE trial indicate an acute drop in estimated glomerular filtration rate during treatment with canagliflozin with implications for clinical practice

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Effects of nutritional status on exercise performance in advanced cystic fibrosis

Initial evaluation of 22 patients with cystic fibrosis (CF) on entry into a trial of home oxygen therapy was used to elucidate the possible effects of poor nutritional status on exercise performance in CF. The patients had advanced lung disease (mean FEV1, 36 percent predicted) and all had a stable resting PaO2 less than or equal to 65 mm Hg. Nutritional status was determined by calculating weight as a percentage of ideal for height (Wt/Ht) for each subject. Exercise testing consisted of a progressive exercise test on a cycle ergometer to measure maximum work capacity (Wmax), and a steady state test at 50 percent of baseline Wmax. During the steady state test, cardiac output (Q) and stroke volume (SV) were computed by the indirect Fick (CO2) method. Wmax, SV, Q and lung function results are expressed as percent predicted. Mean (+/- SD) Wmax was 58 +/- 15 percent predicted. Wmax correlated with both FEV1 and Wt/Ht, but FEV1 and Wt/Ht were not related. During steady state exercise, 12 of 22 patients had a SV less than 80 percent predicted. SV correlated with Wt/Ht, but not with lung function. Thirteen of the 22 patients had a Wt/Ht less than or equal to 90 percent and were considered malnourished. When compared with the well-nourished patients (Wt/Ht greater than 90%), these malnourished subjects had significantly lower mean values for Wmax%, SV% and Q% predicted, but not for lung function parameters. We conclude that: in patients with CF and advanced lung disease, nutritional status plays a significant role in determining exercise capacity; lower exercise tolerance of malnourished patients is an independent effect, as nutritional status and lung function were not related; and malnourished patients with CF have an altered cardiac performance on exercise testing which is due to a reduced SV rather than an impaired heart rate response.     

Neuroanatomical associations of the Edinburgh cognitive and Behavioural ALS screen (ECAS)

Brain Imaging and Behavior - Cognitive impairment is now recognized in a subset of patients with amyotrophic lateral sclerosis (ALS). The objective of the study was to identify group differences...     

Achieving a clinically relevant composite outcome of an HbA1c of <7% without weight gain or hypoglycaemia in type 2 diabetes: a meta-analysis of the liraglutide clinical trial programme

Aim: Effective type 2 diabetes management requires a multifactorial approach extending beyond glycaemic control. Clinical practice guidelines suggest targets for HbA1c, blood pressure and lipids, and emphasize weight reduction and avoiding hypoglycaemia. The phase 3 clinical trial programme for liraglutide, a human glucagon‐like peptide 1 analogue, showed significant improvements in HbA1c and weight with a low risk of hypoglycaemia compared to other diabetes therapies. In this context, we performed a meta‐analysis of data from these trials evaluating the proportion of patients achieving a clinically relevant composite measure of diabetes control consisting of an HbA1c <7% without weight gain or hypoglycaemia. Methods: A prespecified meta‐analysis was performed on 26‐week patient‐level data from seven trials (N = 4625) evaluating liraglutide with commonly used therapies for type 2 diabetes: glimepiride, rosiglitazone, glargine, exenatide, sitagliptin or placebo, adjusting for baseline HbA1c and weight, for a composite outcome of HbA1c <7.0%, no weight gain and no hypoglycaemic events. Results: At 26 weeks, 40% of the liraglutide 1.8 mg group, 32% of the liraglutide 1.2 mg group and 6–25% of comparators (6% rosiglitazone, 8% glimepiride, 15% glargine, 25% exenatide, 11% sitagliptin, 8% placebo) achieved this composite outcome. Odds ratios favoured liraglutide 1.8 mg by 2.0‐ to 10.5‐fold over comparators. Conclusions: As assessed by the composite outcome of HbA1c <7%, no hypoglycaemia and no weight gain, liraglutide was clearly superior to the other commonly used therapies. However, the long‐term clinical impact of this observation remains to be shown.