Use of risk stratification to target therapies in patients with recent onset arthritis; design of a prospective randomized multicenter controlled trial

Background  

Early and intensive treatment is important to inducing remission and preventing joint damage in patients with rheumatoid arthritis. While intensive combination therapy (Disease Modifying Anti-rheumatic Drugs and/or biologicals) is the most effective, rheumatologists in daily clinical practice prefer to start with monotherapy methotrexate and bridging corticosteroids. Intensive treatment should be started as soon as the first symptoms manifest, but at this early stage, ACR criteria may not be fulfilled, and there is a danger of over-treatment. We will therefore determine which induction therapy is most effective in the very early stage of persistent arthritis. To overcome over-treatment and under-treatment, the intensity of induction therapy will be based on a prediction model that predicts patients' propensity for persistent arthritis.     

Is there a place for pediatric valvotomy in the autograft era?

OBJECTIVE: Valvotomy and the autograft procedure are the most common surgical treatment options for children with valvular aortic stenosis. We evaluated the results of these surgical procedures in our institution. METHODS: Retrospective analysis was done of all patients presenting with aortic stenosis and operated upon before the age of 18. In 11 patients a valvotomy was performed and in 36 an autograft procedure. RESULTS: There was no hospital mortality. Mean follow-up in the valvotomy group was 4.8 years (SD 3.3), in the autograft group 4.5 years (SD 3.3). During follow-up one patient died suddenly 2 months after valvotomy. Two patients in the autograft group died (not valve-related). After valvotomy three patients underwent a balloon valvotomy, in one followed by an autograft procedure and one patient had a repeat valvotomy. In the autograft group one patient was reoperated for severe aortic regurgitation and moderate pulmonary stenosis. At last echocardiography after valvotomy (eight remaining patients) in only two patients (25%) no aortic stenosis or regurgitation was present. In the remaining six patients aortic stenosis is mild in two and moderate in three, including one with moderate aortic regurgitation. In one patient without stenosis, moderate aortic regurgitation was seen. No pulmonary stenosis or regurgitation is present. Echocardiography after autografting (33 remaining patients) showed no aortic stenosis. Aortic regurgitation was mild in seven patients, moderate in two, severe in one. Pulmonary stenosis was present in two patients (16%). Pulmonary regurgitation was mild in three patients and moderate in one. CONCLUSIONS: In selected patients with valvular aortic stenosis who are beyond infancy, valvotomy may be adequate and may postpone further surgery for a significant length of time. After valvotomy the main problem is residual aortic stenosis while after autografting a shift occurs to aortic regurgitation and problems related to the pulmonary valve. Careful clinical and echocardiographic follow-up is therefore warranted in young patients after the autograft procedure.     

Microtubule reassembly in surface-activated platelets

It is generally accepted that a circumferential microtubule supports the discoid shape of resting platelets. The fate of the many-coiled polymer following platelet activation, however, has been a subject of considerable debate. Morphological investigations have suggested that the circumferential coils are constricted into tight rings around centrally concentrated organelles during platelet shape change. Biochemical studies employing colchicine-binding assays, on the other hand, have indicated that the bundle of microtubules dissolves almost completely within seconds after activation and reassembles in a new location one to four minutes later. The present study has accepted the latter hypothesis in order to examine the second part of the disassembly-reassembly theory proposed in biochemical studies. Platelets exposed to low temperatures sufficient to remove all microtubules were placed on glass slides and microscope grids to cause surface activation during rewarming. The combined stimuli of rewarming and surface activation might have been expected to cause more rapid assembly than warming alone or activation alone. This was not the case. Reassembly of microtubules during rewarming and simultaneous surface activation was not accelerated. In contrast to the constriction of microtubule rings observed during activation in control platelets, the diameters of coils that developed in chilled platelets one to two hours after rewarming and surface activation were twice those of control cells.     

Autograft and pulmonary allograft performance in the second post-operative decade after the Ross procedure: insights from the Rotterdam Prospective Cohort Study

Aims The objective of the present study was to report our ongoing prospective cohort of autograft recipients with up to 21 years of follow-up. Methods and results All consecutive patients (n = 161), operated between 1988 and 2010, were analysed. Mixed-effects models were used to assess changes in echocardiographic measurements (n = 1023) over time in both the autograft and the pulmonary allograft. The mean patient age was 20.9 years (range 0.05-52.7)-66.5% were male. Early mortality was 2.5% (n = 4), and eight additional patients died during a mean follow-up of 11.6 ± 5.7 years (range 0-21.5). Patient survival was 90% [95% confidence interval (CI), 78-95] up to 18 years. During the follow-up, 57 patients required a re-intervention related to the Ross operation. Freedom from autograft reoperation and allograft re-intervention was 51% (95% CI 38-63) and 82% (95% CI 71-89) after 18 years, respectively. No major changes were observed over time in autograft gradient, and allograft gradient and regurgitation. An initial increase of sinotubular junction and aortic anulus diameter was observed in the first 5 years after surgery. The only factor associated with an increased autograft reoperation rate was pre-operative pure aortic regurgitation (AR) (hazard ratio 1.88; 95% CI 1.04-3.39; P= 0.037). Conclusion We observed good late survival in patients undergoing autograft procedure without reinforcement techniques. However, over half of the autografts failed prior to the end of the second decade. The reoperation rate and the results of echocardiographic measurements over time underline the importance of careful monitoring especially in the second decade after the initial autograft operation and in particular in patients with pre-operative AR.