Drain Versus No Drain in Open Mesh Repair for Incisional Hernia, Results of a Prospective Randomized Controlled Trial.

Open mesh repair of incisional hernia is associated with different local complications, particularly bleeding and seroma formation. Traditionally, drains have been placed perioperatively to prevent these complications, despite the lack of scientific evidence or expert consensus. We formulated the hypothesis that the absence of drainage would reduce number of patients presenting collections or complications. The present study aimed to compare postoperative complication rates after open mesh repair for incisional hernia with or without prophylactic wound drainage. Prospective randomized study using standardized surgical technique and drain placement. The primary endpoint was the evaluation of residual fluid collection with ultrasound on postoperative day 30. Other complications, subdivided into medical and surgical, were analyzed as secondary endpoints. There were 144 patients randomized (70 with drain, 74 without drain). No difference was identified between both groups for fluid collection at 30 days (60.3% vs. 62%, p = 0.844). However, less surgical complications were identified in the drain group (21.7% vs. 42.7%, p = 0.007), with a lower wound dehiscence rate (1.5% vs. 9.3%, p = 0.041). Prophylactic drainage in open incisional hernia repair does not objectively reduce the rate of postoperative fluid collections. Therefore, our results do not support the use of routine drainage in incisional hernia repair. Trial registration on clinicaltrials.gov (NCT00478348)

Long-term weight loss and metabolic benefit from Roux-en-Y gastric bypass in patients with superobesity.

Although Roux-en-Y gastric bypass (RYGB) is widely performed worldwide, its efficacy in patients with a body mass index (BMI) greater than 50 kg/m2 remains controversial. The aim of the present paper was to assess long-term (10 years or more) weight loss and metabolic results of RYGB in patients with superobesity (SO; BMI > 50 kg/m2), compared with patients with morbid obesity (MO; BMI 35-50 kg/m2). This study involved retrospective analysis of a prospectively followed cohort of adult patients operated on for a primary RYGB between 1999 and 2008. Long-term weight loss and metabolic parameters were compared between SO and MO patients, with a sex-specific subgroup analysis in SO patients. Multiple logistic regression assessed independent predictors of poor long-term weight loss. Among the 957 included patients, 193 (20.2 per cent) were SO (mean BMI 55.3 kg/m2versus 43.3 kg/m2 in MO). Upon 10-year follow-up, which was complete in 86.3 per cent of patients, BMI remained higher in SO patients (mean 39.1 kg/m2versus 30.8 kg/m2, P < 0.001) although total bodyweight loss (per cent TBWL) was similar (28.3 per cent versus 28.8 per cent, P = 0.644). Male SO patients had a trend to higher 10-year per cent TBWL, while initial BMI greater than 50 kg/m2 and low 5-year per cent TBWL were independent predictors of long-term TBWL less than 20 per cent. Diabetes remission was observed in 39 per cent SO and 40.9 per cent MO patients (P = 0.335) at 10 years, and all patients had a significant lipid profile improvement. Substantial improvement in co-morbidities was observed in all patients 10 years after RYGB. Total weight loss was similar in SO and MO patients, leaving SO patients with higher BMI. Suboptimal TBWL 5 years after surgery in SO, especially female patients, may warrant prompt reassessment to improve long-term outcomes

The active metabolite of leflunomide, A77 1726, inhibits the production of prostaglandin E2, matrix metalloproteinase 1 and interleukin 6 in human fibroblast‐like synoviocytes

Objectives. To investigate the effects of the active metabolite of leflunomide, A77 1726, on fibroblast‐like synoviocytes. In rheumatoid arthritis (RA) synoviocytes participate in tissue destruction by producing metalloproteinases (MMP), prostaglandin E2 (PGE2) and interleukin (IL) 6, which are involved in extracellular matrix degradation, resorption of the mineral phase and osteoclast‐mediated bone resorption. Methods. Human synoviocytes were stimulated with IL‐1α or tumour necrosis factor α (TNF‐α) in the presence of A77 1726. Culture supernatants were analysed for production of interstitial collagenase (MMP‐1), tissue‐inhibitor of metalloproteinases 1 (TIMP‐1), PGE2 and IL‐6. Total RNA was isolated and analysed for steady‐state levels of MMP‐1, cyclooxygenase‐2 (COX‐2) and IL‐6 mRNA. Results. A77 1726 inhibited the production of PGE2 in synoviocytes activated by TNF‐α and IL‐1α with median inhibitory concentrations (IC50) of 7 and 3 µm respectively. In contrast, MMP‐1 and IL‐6 production was inhibited at high A77 1726 concentrations (> 10 µm), whereas TIMP‐1 was not affected. The inhibition of MMP‐1 and IL‐6 production was due to the known inhibitory effect of A77 1726 on pyrimidine synthesis, as it was reversed by the addition of uridine. This did not apply to PGE2 production, which was inhibited via direct action of A77 1726 on COX‐2, as shown by the increasing amount of substrate (arachidonic acid) in the culture medium. Conclusion. This study shows that some of the beneficial effect of leflunomide in RA patients may be due to the inhibition of PGE2, IL‐6 and MMP‐1 production in synoviocytes. This effect, coupled with its multiple inhibitory effects on T lymphocyte functions, might account for the significant reduction in the rate of disease progression in RA patients treated with leflunomid

Efficacy and safety of the human anti-IL-1beta monoclonal antibody canakinumab in rheumatoid arthritis: results of a 12-week, phase II, dose-finding study

<p>Abstract</p> <p>Background</p> <p>Canakinumab is a fully human anti-interleukin IL-1beta monoclonal antibody, being investigated for the treatment of rheumatoid arthritis (RA). This multicenter, phase II, randomized, double-blind, placebo-controlled, parallel-group, dose-finding study investigated the efficacy and safety of canakinumab in patients with active RA despite ongoing therapy at stable doses of methotrexate.</p> <p>Methods</p> <p>Patients were randomized to receive one of four regimens, in addition to methotrexate, for 12 weeks: canakinumab 150 mg subcutaneously (SC) every 4 weeks (q4wk), canakinumab 300 mg SC (2 injections of 150 mg SC) every 2 weeks, a 600 mg intravenous loading dose of canakinumab followed by 300 mg SC every 2 weeks', or placebo SC every 2 weeks.</p> <p>Results</p> <p>Among 274 patients with evaluable efficacy data, the percentage of responders according to American College of Rheumatology 50 criteria (the primary endpoint, based on a 28-joint count) was significantly higher with canakinumab 150 mg SC q4wk than with placebo (26.5% vs. 11.4%, respectively; p = 0.028). Compared to placebo, this dosage of canakinumab was also associated with significantly more favorable responses at week 12 with respect to secondary endpoints including the Disease Activity Score 28, scores on the Health Assessment Questionnaire and Functional Assessment of Chronic Illness Therapy-Fatigue, swollen 28-joint count, and patient's and physician's global assessments of disease activity. No safety concerns were raised with canakinumab therapy, particularly with regard to infections. Few injection-site reactions occurred.</p> <p>Conclusion</p> <p>The addition of canakinumab 150 mg SC q4wk improves therapeutic responses among patients who have active RA despite stable treatment with methotrexate.</p> <p>Trial Registration</p> <p>(ClinicalTrials.gov identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00784628">NCT00784628</a>)</p