DIRECT trial. Diverticulitis recurrences or continuing symptoms: Operative versus conservative treatment. A multicenter randomised clinical trial.

BACKGROUND: Persisting abdominal complaints are common after an episode of diverticulitis treated conservatively. Furthermore, some patients develop frequent recurrences. These two groups of patients suffer greatly from their disease, as shown by impaired health related quality of life and increased costs due to multiple specialist consultations, pain medication and productivity losses.Both conservative and operative management of patients with persisting abdominal complaints after an episode of diverticulitis and/or frequently recurring diverticulitis are applied. However, direct comparison by a randomised controlled trial is necessary to determine which is superior in relieving symptoms, optimising health related quality of life, minimising costs and preventing diverticulitis recurrences against acceptable morbidity and mortality associated with surgery or the occurrence of a complicated recurrence after conservative management.We, therefore, constructed a randomised clinical trial comparing these two treatment strategies. METHODS/DESIGN: The DIRECT trial is a multicenter randomised clinical trial. Patients (18-75 years) presenting themselves with persisting abdominal complaints after an episode of diverticulitis and/or three or more recurrences within 2 years will be included and randomised. Patients randomised for conservative treatment are treated according to the current daily practice (antibiotics, analgetics and/or expectant management). Patients randomised for elective resection will undergo an elective resection of the affected colon segment. Preferably, a laparoscopic approach is used.The primary outcome is health related quality of life measured by the Gastro-intestinal Quality of Life Index, Short-Form 36, EQ-5D and a visual analogue scale for pain quantification. Secondary endpoints are morbidity, mortality and total costs. The total follow-up will be three years. DISCUSSION: Considering the high incidence and the multicenter design of this study, it may be assumed that the number of patients needed for this study (n = 214), may be gathered within one and a half year.Depending on the expertise and available equipment, we prefer to perform a laparoscopic resection on patients randomised for elective surgery. Should this be impossible, an open technique may be used as this also reflects the current situation. TRIAL REGISTRATION: (Trial register number: NTR1478).

A randomized controlled trial comparing oral and intravenous iron supplementation after Roux-en-Y gastric bypass surgery.

BACKGROUND: Iron deficiency (ID) is one of the most common postoperative deficiencies that may develop after Roux-en-Y gastric bypass (RYGB). The optimal mode of treatment is uncertain. AIM: To compare the efficacy of oral ferrous fumarate (FF), oral ferrous gluconate (FG), and a single intravenous infusion of ferric carboxymaltose (FCM) in women with ID after RYGB. METHODS: Multicenter randomized controlled trial including 120 women with a serum ferritin <20 µg/l during follow-up after RYGB. They were randomized into three groups: 41 patients were treated with FF 200 mg three times a day (total daily dose: 195 mg elemental iron), 39 received FG 695 mg twice a day (total daily dose: 160 mg elemental iron) for three months, and 39 patients were treated with a single intravenous dose of FCM (1000 mg elemental iron). Serum ferritin levels were measured at six weeks, and three, six and twelve months after the start of supplementation. RESULTS: At three months, persistence of ID was observed in 29.4% and 42.4% of the patients treated with FF and FG, respectively, but in none of those treated with FCM (p < 0.001). Over the next nine months, recurrence of ID was observed in 56.5% of patients treated with FF, in 52.9% treated with FG, and in 27.8% of those treated with FCM. Adverse effects were most common during oral treatment. CONCLUSION: In women developing ID after RYGB, a single dose of intravenous FCM is more effective and better tolerated than the standard treatment with either FF or FG. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE: The study was registered at clinicaltrials.gov under number NCT02271997.

Hartmann's procedure versus sigmoidectomy with primary anastomosis for perforated diverticulitis with purulent or faecal peritonitis (LADIES): a multicentre, parallel-group, randomised, open-label, superiority trial.

BACKGROUND: Previous studies have suggested that sigmoidectomy with primary anastomosis is superior to Hartmann's procedure. The likelihood of stoma reversal after primary anastomosis has been reported to be higher and reversal seems to be associated with lower morbidity and mortality. Although promising, results from these previous studies remain uncertain because of potential selection bias. Therefore, this study aimed to assess outcomes after Hartmann's procedure versus sigmoidectomy with primary anastomosis, with or without defunctioning ileostomy, for perforated diverticulitis with purulent or faecal peritonitis (Hinchey III or IV disease) in a randomised trial. METHODS: A multicentre, randomised, open-label, superiority trial was done in eight academic hospitals and 34 teaching hospitals in Belgium, Italy, and the Netherlands. Patients aged between 18 and 85 years who presented with clinical signs of general peritonitis and suspected perforated diverticulitis were eligible for inclusion if plain abdominal radiography or CT scan showed diffuse free air or fluid. Patients with Hinchey I or II diverticulitis were not eligible for inclusion. Patients were allocated (1:1) to Hartmann's procedure or sigmoidectomy with primary anastomosis, with or without defunctioning ileostomy. Patients were enrolled by the surgeon or surgical resident involved, and secure online randomisation software was used in the operating room or by the trial coordinator on the phone. Random and concealed block sizes of two, four, or six were used, and randomisation was stratified by age (<60 and ≥60 years). The primary endpoint was 12-month stoma-free survival. Patients were analysed according to a modified intention-to-treat principle. The trial is registered with the Netherlands Trial Register, number NTR2037, and ClinicalTrials.gov, number NCT01317485. FINDINGS: Between July 1, 2010, and Feb 22, 2013, and June 9, 2013, and trial termination on June 3, 2016, 133 patients (93 with Hinchey III disease and 40 with Hinchey IV disease) were randomly assigned to Hartmann's procedure (68 patients) or primary anastomosis (65 patients). Two patients in the Hartmann's group were excluded, as was one in the primary anastomosis group; the modified intention-to-treat population therefore consisted of 66 patients in the Hartmann's procedure group (46 with Hinchey III disease, 20 with Hinchey IV disease) and 64 in the primary anastomosis group (46 with Hinchey III disease, 18 with Hinchey IV disease). In 17 (27%) of 64 patients assigned to primary anastomosis, no stoma was constructed. 12-month stoma-free survival was significantly better for patients undergoing primary anastomosis compared with Hartmann's procedure (94·6% [95% CI 88·7-100] vs 71·7% [95% CI 60·1-83·3], hazard ratio 2·79 [95% CI 1·86-4·18]; log-rank p<0·0001). There were no significant differences in short-term morbidity and mortality after the index procedure for Hartmann's procedure compared with primary anastomosis (morbidity: 29 [44%] of 66 patients vs 25 [39%] of 64, p=0·60; mortality: two [3%] vs four [6%], p=0·44). INTERPRETATION: In haemodynamically stable, immunocompetent patients younger than 85 years, primary anastomosis is preferable to Hartmann's procedure as a treatment for perforated diverticulitis (Hinchey III or Hinchey IV disease). FUNDING: Netherlands Organisation for Health Research and Development.

Perforation of the ileum after a stab wound of the gluteal region: a case report.

We present a case of a patient with a seemingly insignificant single gluteal stab wound which led to a solitary perforation of the ileum and delayed peritonitis. This case report illustrates that, despite the absence of any signs of bowel perforation on presentation, a patient may deteriorate gradually in the subsequent hours. This demonstrates the role of clinical observation in high risk gluteal stab wound patients.

Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn's disease: a randomised controlled, open-label, multicentre trial.

BACKGROUND: Treatment of patients with ileocaecal Crohn's disease who have not responded to conventional therapy is commonly scaled up to biological agents, but surgery can also offer excellent short-term and long-term results. We compared laparoscopic ileocaecal resection with infliximab to assess how they affect health-related quality of life. METHODS: In this randomised controlled, open-label trial, in 29 teaching hospitals and tertiary care centres in the Netherlands and the UK, adults with non-stricturing, ileocaecal Crohn's disease, in whom conventional therapy has failed were randomly allocated (1:1) by an internet randomisation module with biased-coin minimisation for participating centres and perianal fistula to receive laparoscopic ileocaecal resection or infliximab. Eligible patients were aged 18-80 years, had active Crohn's disease of the terminal ileum, and had not responded to at least 3 months of conventional therapy with glucocorticosteroids, thiopurines, or methotrexate. Patients with diseased terminal ileum longer than 40 cm or abdominal abscesses were excluded. The primary outcome was quality of life on the Inflammatory Bowel Disease Questionnaire (IBDQ) at 12 months. Secondary outcomes were general quality of life, measured by the Short Form-36 (SF-36) health survey and its physical and mental component subscales, days unable to participate in social life, days on sick leave, morbidity (additional procedures and hospital admissions), and body image and cosmesis. Analyses of the primary outcome were done in the intention-to-treat population, and safety analyses were done in the per-protocol population. This trial is registered at the Dutch Trial Registry (NTR1150). FINDINGS: Between May 2, 2008, and October 14, 2015, 73 patients were allocated to have resection and 70 to receive infliximab. Corrected for baseline differences, the mean IBDQ score at 12 months was 178·1 (95% CI 171·1-185·0) in the resection group versus 172·0 (164·3-179·6) in the infliximab group (mean difference 6·1 points, 95% CI -4·2 to 16·4; p=0·25). At 12 months, the mean SF-36 total score was 112·1 (95% CI 108·0-116·2) in the resection group versus 106·5 (102·1-110·9) in the infliximab group (mean difference 5·6, 95% CI -0·4 to 11·6), the mean physical component score was 47·7 (45·7-49·7) versus 44·6 (42·5-46·8; mean difference 3·1, 4·2 to 6·0), and the mean mental component score was 49·5 (47·0-52·1) versus 46·1 (43·3-48·9; mean difference 3·5, -0·3 to 7·3). Mean numbers of days of sick leave were 3·4 days (SD 7·1) in the resection group versus 1·4 days (4·7) in the infliximab group (p<0·0001), days not able to take part in social life were 1·8 days (6·3) versus 1·1 days (4·5; p=0·20), days of scheduled hospital admission were 6·5 days (3·8) versus 6·8 days (3·2; p=0·84), and the number of patients who had unscheduled hospital admissions were 13 (18%) of 73 versus 15 (21%) of 70 (p=0·68). Body-image scale mean scores in the patients who had resection were 16·0 (95% CI 15·2-16·8) at baseline versus 17·8 (17·1-18·4) at 12 months, and cosmetic scale mean scores were 17·6 (16·6-18·6) versus 18·6 (17·6-19·6). Surgical intervention-related complications classified as IIIa or worse on the Clavien-Dindo scale occurred in four patients in the resection group. Treatment-related serious adverse events occurred in two patients in the infliximab group. During a median follow-up of 4 years (IQR 2-6), 26 (37%) of 70 patients in the infliximab group had resection, and 19 (26%) of 73 patients in the resection group received anti-TNF. INTERPRETATION: Laparoscopic resection in patients with limited (diseased terminal ileum <40 cm), non-stricturing, ileocaecal Crohn's disease in whom conventional therapy has failed could be considered a reasonable alternative to infliximab therapy. FUNDING: Netherlands Organisation for Health Research and Development.

[Osteoarthritis of the knee: lose weight first?]. / Artrose van de knie: eerst afvallen?

Being heavy and having knee pain often co-exists. To date, the optimal treatment for patients with osteoarthritis of the knee and obesity remains the subject of debate, since patients with a high BMI (> 30 kg/m2) have a higher risk of complications following total knee arthroplasty (TKA). Kerkhoffs and colleagues suggest that these patients should first be submitted to a weight-loss programme prior to their TKA to reduce the risk of complications. This commentary addresses various questions arising from the Dutch meta-analysis by Kerkhoffs. For instance, should patients who fail to lose weight still undergo TKA or have bariatric surgery, or are there other options? Finally, suggestions are made for future research that might shed light upon this critical issue.