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Postpancreatectomy haemorrhage (PPH) is a rare but potentially fatal complication after pancreatoduodenectomy. Preventive strategies are lacking with scarce data for support. The aim of this study was to investigate whether a prophylactic falciform ligament wrap around the hepatic and gastroduodenal artery can prevent PPH from these vessels.In a randomized, controlled, multicentre trial, patients who were scheduled for elective open partial pancreatoduodenectomy with pancreatojejunostomy between 5 November 2015 and 2 April 2020 were randomly allocated in a 1 : 1 ratio to undergo pancreatoduodenectomy with (intervention) or without (control) a falciform ligament wrap around the hepatic artery. The primary endpoint was the rate of clinically relevant PPH from the hepatic artery or gastroduodenal artery stump within 3 months after pancreatoduodenectomy. Secondary endpoints were the rates of associated postoperative complications, for example postoperative pancreatic fistula (POPF) and PPH.Altogether, 445 patients were randomized with 222 and 223 in each group. Among the patients included in modified intention-to-treat analysis (207 in the intervention group and 210 in the control group), the primary endpoint was observed in six of 207 in the intervention group compared with 15 of 210 in the control group (2.9 versus 7.1 per cent respectively; odds ratio 0.39 (95 per cent c.i. 0.15 to 1.02); P = 0.071). Per protocol analysis showed a significant reduction in the intervention group (odds ratio 0.26 (95 per cent c.i. 0.09 to 0.80); P = 0.017). A soft pancreas texture (43 per cent) and the rate of a clinically relevant POPF were evenly (20 per cent) distributed between the groups. The rate of any clinically relevant PPH including the primary endpoint and other bleeding sites was not significantly different between intervention and control groups (9.7 versus 14.8 per cent respectively).A falciform ligament wrap may reduce PPH from the hepatic artery or gastroduodenal artery stump and should be considered during pancreatoduodenectomy.NCT02588066 (http://www.clinicaltrials.gov).

Background The purpose of this study is to evaluate whether wrapping of the pedicled falciform ligamentum flap around the gastroduodenal artery (GDA) stump/hepatic artery can significantly decrease the incidence of erosion hemorrhage after pancreatoduodenectomy (PD). Methods/design This is a randomized controlled multicenter trial involving 400 patients undergoing PD. Patients will be randomized into two groups. The intervention group consists of 200 patients with a prophylactic wrapping of the GDA stump using the pedicled falciform ligament. The control group consists of 200 patients without the wrap. The primary endpoint is the rate of postoperative erosion hemorrhage of the GDA stump or hepatic artery within 3 months. The secondary endpoints are postpancreatectomy hemorrhage stratified according to the texture of the pancreas, postoperative pancreatic fistula (POPF), postoperative rate of therapeutic interventions, morbidity, and mortality. Discussion Only few retrospective studies investigated the effectiveness of a falciform ligament wrap around the GDA for prevention of erosion hemorrhage. Erosion hemorrhage occurs in up to 6–9% of cases after PD and is most frequently evoked by a POPF. Erosion hemorrhage is associated with a remarkable mortality of over 30%. The rate of hemorrhage after performing the wrap is reported to be low. However, there exist no prospectively controlled data to support its general use. Therefore, the presented randomized controlled trial will provide clinically relevant evidence of the effectiveness of the wrap with statistical significance. Trial registration clinicaltrials.gov, NCT02588066; Registered on 27 October 2015. Electronic supplementary material The online version of this article (10.1186/s13063-018-2580-0) contains supplementary material, which is available to authorized users.

Variability in responsiveness to clopidogrel is a clinical problem in secondary prevention after cerebral ischaemia which has been suggested to be linked to competitive metabolization of clopidogrel and cytochrome P450 (CYP) 3A4-oxidated statins such as simvastatin. We assessed the hypothesis that simvastatin, in contrast to CYP 2C9-metabolized fluvastatin, reduces clopidogrel-mediated platelet inhibition.We performed a randomized, double-blind, double-dummy, two period crossover study in 13 patients with cerebral ischaemia (8F, 5 M), aged 64.1 ± 8.0 years (mean ± SD). After a 14 day period in which all patients received 75 mg clopidogrel day(-1) , patients additionally received either 20 mg simvastatin day(-1) or 80 mg fluvastatin day(-1) for 14 days. Regimens were crossed over after a 14 day wash-out period and switched regimens were continued for another 14 days. Platelet aggregation, clopidogrel active metabolite (CAM) plasma concentrations and routine laboratory parameters including prothrombin time (PT) Quick percent value were assessed at baseline and following each treatment phase.Clopidogrel reduced platelet aggregation in all patients as expected. Platelet aggregation and CAM plasma concentrations were unaltered when simvastatin or fluvastatin was added to clopidogrel. Simvastatin decreased PT Quick percent value (decrease from 109 ± 10.5% to 103 ± 11%, P0.05) when combined with clopidogrel but there was no such change following treatment with fluvastatin and clopidogrel.Our data indicate that treatment with CYP 3A4-metabolized simvastatin does not jeopardize clopidogrel-mediated inhibition of platelet aggregation. After co-administration of simvastatin and clopidogrel we observed a decrease in the PT Quick percent value which could be due to simvastatin-induced reduction of activity of prothrombin fragment 1 + 2.

Objective: To evaluate the effects of levodopa and the dopamine D2 agonist cabergoline on striatal dopamine turnover estimated as the inverse of the effective dopamine distribution volume ratio (EDVR) measured by 18 F-dopa PET in de novo Parkinson disease (PD). Methods: Single-center, parallel-group, randomized, observer-blinded study of cabergoline (3 mg/day) and levodopa (300 mg/day) over 12 weeks in patients with de novo PD. Primary efficacy measure was the change of the side-to-side averaged putaminal EDVR comparing baseline and end-of-maintenance period. Results: Thirty-five out of 39 randomized patients were assigned to the primary efficacy analysis (cabergoline, n = 17; levodopa, n = 18). At the end of treatment period, mean EDVRs were significantly lower compared to baseline solely in the levodopa group (relative change −1.0 ± 13.0% in cabergoline [ p = 0.525 when compared to baseline], −8.3 ± 11.8% in levodopa group [ p = 0.006]) with a nonsignificant trend between groups (mean relative difference: 7.3% (95% confidence interval −1.2% to 15.8%; p = 0.091). There was significant clinical improvement in both groups at 12 weeks compared to baseline, but no significant differences between groups in clinical and PET secondary outcome measures. Both pharmacologic treatments and PET scanning were well-tolerated and safe. Conclusion: Putaminal dopamine turnover is increased by levodopa treatment in de novo PD. The nonsignificant trend toward a larger influence by levodopa compared to cabergoline is supported by ancillary statistical analyses. This augmentation of early compensatory events by levodopa might contribute not only to its symptomatic effects, but also to its induction of motor complications.

The aim of this study was to assess the efficacy, safety and tolerability of the antiepileptic compound levetiracetam (LEV) for the treatment of levodopa-induced dyskinesia (LID) in Parkinson’s disease (PD). We thus performed a randomized, double-blind, placebo-controlled, parallel-group pilot study in PD patients with moderate-to-severe LID on stable dopaminergic therapy. Placebo or LEV was administered twice daily (titrated from 250 to 2,000 mg/day) as add-on therapy. Subjects underwent evaluation of the unified-PD-rating scale (UPDRS) and the modified abnormal involuntary movement scale (AIMS). The primary outcome variable was the change of the AIMS score between baseline and end-of-treatment visit. Secondary variables included total UPDRS score and response to levodopa challenge. Of 32 randomized patients (mean age 65.2 years, 62.5% women), 17 received LEV and 15 placebo. After 11 weeks of treatment, mean changes of the modified AIMS from baseline were −1.5 (−26%) for LEV (p = 0.332) and +0.9 (+13%) for placebo (p = 0.588) without significant differences between groups. Mean changes of the UPDRS item 32/33 sum score from baseline showed significant improvement of dyskinesia in the LEV group [−1.0 (−20%); p = 0.012], but not in the placebo group [−0.4 (−8%); p = 0.306]. Treatment had no effects on UPDRS motor score or levodopa response. Frequency and quality of adverse events were similar in both treatment groups. Together, LEV showed only mild antidyskinetic effects without worsening of Parkinsonian symptoms or compromising levodopa efficacy. LEV was well tolerated in doses up to 2,000 mg/day. Further large controlled studies are warranted to evaluate the impact of LEV on LID in PD patients.

Gastrointestinal graft–versus-host disease (GvHD) is a potentially life-threatening complication after allogeneic stem cell transplantation (SCT). Since therapeutic options are still limited, a prophylactic approach seems to be warranted. In this randomised, double-blind-phase III trial, we evaluated the efficacy of budesonide in the prophylaxis of acute intestinal GvHD after SCT. The trial was registered at https://clinicaltrials.gov , number NCT00180089. Patients were randomly assigned to receive either 3 mg capsule three times daily oral budesonide or placebo. Budesonide was applied as a capsule with pH-modified release in the terminal ileum. Study medication was administered through day 56, follow-up continued until 12 months after transplantation. If any clinical signs of acute intestinal GvHD appeared, an ileocolonoscopy with biopsy specimens was performed. The crude incidence of histological or clinical stage 3–4 acute intestinal GvHD until day 100 observed in 91 (n =48 budesonide, n =43 placebo) evaluable patients was 12.5% (95% CI 3-22%) under treatment with budesonide and 14% (95% CI 4-25%) under placebo (p = 0.888). Histologic and clinical stage 3–4 intestinal GvHD after 12 months occurred in 17% (95% CI 6-28%) of patients in the budesonide group and 19% (CI 7-32%) in the placebo group (p = 0.853). Although budesonide was tolerated well, we observed a trend towards a higher rate of infectious complications in the study group (47.9% versus 30.2%, p = 0.085). The cumulative incidences at 12 months of intestinal GvHD stage >2 with death as a competing event (budesonide 20.8% vs. placebo 32.6%, p = 0.250) and the cumulative incidence of relapse (budesonide 20.8% vs. placebo 16.3%, p = 0.547) and non-relapse mortality (budesonide 28% (95% CI 15-41%) vs. placebo 30% (95% CI 15-44%), showed no significant difference within the two groups (p = 0.911). The trial closed after 94 patients were enrolled because of slow accrual. Within the limits of the final sample size, we were unable to show any benefit for the addition of budesonide to standard GvHD prophylaxis. Budesonide did not decrease the occurrence of intestinal GvHD in this trial. These results imply most likely that prophylactic administration of budenoside with pH-modified release in the terminal ileum is not effective.