Effect of Antecolic versus Retrocolic Gastroenteric Reconstruction after Pancreaticoduodenectomy on Delayed Gastric Emptying: A Meta-Analysis of Six Randomized Controlled Trials.

BACKGROUND: One of the most frequent complications of pancreaticoduodenectomy (PD) is delayed gastric emptying (DGE). The study aim was to evaluate the impact of the type of gastro/duodenojejunal reconstruction (antecolic vs. retrocolic) after PD on DGE incidence. METHODS: A systematic review was made according to the PRISMA guidelines. Randomized controlled trials (RCTs) comparing antecolic vs. retrocolic reconstruction were included irrespective of the PD techniques. A meta-analysis was then performed. RESULTS: Six RCTs were included for a total of 588 patients. The overall quality was good. General risk of bias was low. DGE was not statistically significantly different between the antecolic and retrocolic group (OR 0.6, 95% CI 0.31-1.16, p = 0.13). The other main surgery-related complications (pancreatic fistula, hemorrhage, intra-abdominal abscess, bile leak and wound infection) were not dependent on the reconstruction route (OR 0.84, 95% CI 0.41-1.70, p = 0.63). No statistically significant difference in terms of length of hospital stay was found between the 2 groups. There was also no difference of DGE incidence if only pylorus-preserving PD was considered and between the DGE grades A, B or C. CONCLUSION: This meta-analysis shows that antecolic reconstruction after PD is not superior to retrocolic reconstruction in terms of DGE.

PERC rule to exclude the diagnosis of pulmonary embolism in emergency low-risk patients: study protocol for the PROPER randomized controlled study.

BACKGROUND: The diagnosis of Pulmonary Embolism (PE) in the emergency department (ED) is crucial. As emergency physicians fear missing this potential life-threatening condition, PE tends to be over-investigated, exposing patients to unnecessary risks and uncertain benefit in terms of outcome. The Pulmonary Embolism Rule-out Criteria (PERC) is an eight-item block of clinical criteria that can identify patients who can safely be discharged from the ED without further investigation for PE. The endorsement of this rule could markedly reduce the number of irradiative imaging studies, ED length of stay, and rate of adverse events resulting from both diagnostic and therapeutic interventions. Several retrospective and prospective studies have shown the safety and benefits of the PERC rule for PE diagnosis in low-risk patients, but the validity of this rule is still controversial. We hypothesize that in European patients with a low gestalt clinical probability and who are PERC-negative, PE can be safely ruled out and the patient discharged without further testing. METHODS/DESIGN: This is a controlled, cluster randomized trial, in 15 centers in France. Each center will be randomized for the sequence of intervention periods: a 6-month intervention period (PERC-based strategy) followed by a 6-month control period (usual care), or in reverse order, with 2 months of "wash-out" between the 2 periods. Adult patients presenting to the ED with a suspicion of PE and a low pre test probability estimated by clinical gestalt will be eligible. The primary outcome is the percentage of failure resulting from the diagnostic strategy, defined as diagnosed venous thromboembolic events at 3-month follow-up, among patients for whom PE has been initially ruled out. DISCUSSION: The PERC rule has the potential to decrease the number of irradiative imaging studies in the ED, and is reported to be safe. However, no randomized study has ever validated the safety of PERC. Furthermore, some studies have challenged the safety of a PERC-based strategy to rule-out PE, especially in Europe where the prevalence of PE diagnosed in the ED is high. The PROPER study should provide high-quality evidence to settle this issue. If it confirms the safety of the PERC rule, physicians will be able to reduce the number of investigations, associated subsequent adverse events, costs, and ED length of stay for patients with a low clinical probability of PE. TRIAL REGISTRATION: NCT02375919 .

Neoadjuvant chemotherapy and extrapleural pneumonectomy (EPP) of malignant pleural mesothelioma (MPM) with or without hemithoracic radiotherapy: final results of the randomized multicenter phase II trial SAKK17/04.

Aim: We have previously documented the feasibility of neoadjuvant chemotherapy and EPP in a multicenter trial of MPM (Weder, Ann Oncol 18: 1196, 2007). The objectives of the trimodality trial SAKK17/04 (NCT00334594) were to evaluate the time to loco-regional relapse with or without high dose hemithoracic radiotherapy in a prospective multicenter randomized phase II trial in patients with R0 and R1 resection after neoadjuvant chemotherapy and EPP. Methods: Eligible patients had pathologically confirmed MPM, surgically resectable TNM stage (T1-3 N0-2 M0), PS0-1, ages 18-70 years. Part 1 had a phase II design, and included neoadjuvant chemotherapy with 3 cycles of cisplatin and pemetrexed, followed by restaging and EPP. The primary endpoint of part 1 was complete macroscopic resection (R0-1). Part 2 randomized consenting patients with R0-1 resection into two parallel phase II arms (control arm A and radiotherapy arm B). The primary endpoint for part 2 was loco-regional relapse-free survival (RFS). To detect a 1 year increase with 80% power and 10% alpha, 37 patients were needed for arm B. Secondary endpoints included operability, tolerability of chemotherapy and radiotherapy, survival, and translational research Results: Because accrual of part 2 was slower than planned, the trial was stopped in 2013. Overall, 153 patients entered the trial, of whom 125 underwent surgery and 99 had a complete macroscopic resection (primary endpoint part 1). Of the later patients, 54 could be randomized 1:1 into each arm. Reasons for non-randomization included patient refusal in 24 and ineligibility or protocol deviations in 21. Of the 27 patients randomized to hemithoracic radiotherapy, 25 completed the treatment as planned. For part 1 the median RFS was 8.8 (95%CI: 7.3-10.7) and median OS was 15.0 (95% CI: 12.1-19.3) months. For part 2 the median local RFS for group A was 7.6 (95%CI: 5.5-10.7) and for group B 9.4 (95%CI: 6.5-11.9) months (primary endpoint part 2), while the overall RFS and OS for group A were 5.7 (95%CI: 3.5-8.8) and 16.9 (95%CI: 10.7-23.6) months and for group B 7.6 (95% CI:5.2-10.6) and 14.9 (95%CI: 7.0-17.6) months. Conclusions: This study did not reach the primary endpoint which was defined as one-year increase in loco-regional relapse-free survival and thus does not support the routine use of hemithoracic RT after neoadjuvant chemotherapy and EPP. Disclosure: All authors have declared no conflicts of interest.

A Randomized, Placebo-controlled Trial of Preemptive Antifungal Therapy for the Prevention of Invasive Candidiasis Following Gastrointestinal Surgery for Intra-abdominal Infections.

BACKGROUND: Patients undergoing emergency gastrointestinal surgery for intra-abdominal infection are at risk of invasive candidiasis (IC) and candidates for preemptive antifungal therapy. METHODS: This exploratory, randomized, double-blind, placebo-controlled trial assessed a preemptive antifungal approach with micafungin (100 mg/d) in intensive care unit patients requiring surgery for intra-abdominal infection. Coprimary efficacy variables were the incidence of IC and the time from baseline to first IC in the full analysis set; an independent data review board confirmed IC. An exploratory biomarker analysis was performed using logistic regression. RESULTS: The full analysis set comprised 124 placebo- and 117 micafungin-treated patients. The incidence of IC was 8.9% for placebo and 11.1% for micafungin (difference, 2.24%; [95% confidence interval, -5.52 to 10.20]). There was no difference between the arms in median time to IC. The estimated odds ratio showed that patients with a positive (1,3)-β-d-glucan (ßDG) result were 3.66 (95% confidence interval, 1.01-13.29) times more likely to have confirmed IC than those with a negative result. CONCLUSIONS: This study was unable to provide evidence that preemptive administration of an echinocandin was effective in preventing IC in high-risk surgical intensive care unit patients with intra-abdominal infections. This may have been because the drug was administered too late to prevent IC coupled with an overall low number of IC events. It does provide some support for using ßDG to identify patients at high risk of IC. CLINICAL TRIALS REGISTRATION: NCT01122368.

Final results of the SAKK 16/00 trial: a randomized phase III trial comparing neoadjuvant chemoradiation to chemotherapy alone in stage IIIA/N2 non-small cell lung cancer (NSCLC).

Aim: One standard option in the treatment of stage IIIA/N2 NSCLC is neoadjuvant chemotherapy followed by surgery. We investigated in a randomized trial whether the addition of neoadjuvant radiotherapy would improve the outcome. Here we present the final results of this study. Methods: Patients (pts.) with pathologically proven, resectable stage IIIA/N2 NSCLC, performance status 0-1, and adequate organ function were randomized 1:1 to chemoradiation (CRT) with 3 cycles of neoadjuvant chemotherapy (cisplatin 100 mg/m2 and docetaxel 85 mg/m2 d1, q3weeks) followed by accelerated concomitant boost radiotherapy (RT) with 44 Gy in 22 fractions in 3 weeks, or neoadjuvant chemotherapy alone (CT), with subsequent surgery for all pts. The primary endpoint was event-free survival (EFS). Results: 232 pts. were randomized in 23 centers, the median follow-up was 53 months. Two thirds were men, median age was 60 years (range 37-76). Histology was squamous cell in 33%, adenocarcinoma in 43%. Response rate to CRT was 61% vs. 44% with CT. 85% of all pts. underwent surgery, 30-day postoperative mortality was 1%. The rate of complete resection was 91% (CRT) vs. 81% (CT) and the pathological complete remission (pCR) rate was 16% vs. 12%. The median EFS was 13.1 months (95% CI 9.9 - 23.5) for the CRT group vs. 11.8 months (95% CI 8.4 - 15.2) in the CT arm (p 0.665). The median overall survival (OS) with CRT was 37.1 months (95% CI 22.6 -50), with CT 26.1 months ( 95% CI 26.1 - 52.1, p 0.938). The local failure rate was 23% in both arms. In the CT arm 12 pts. were given postoperative radiotherapy (PORT) for R1 resection, 6 pts. received PORT in violation of the protocol. Pts. with a pCR, mediastinal downstaging to ypN0/1 and complete resection had a better outcome. Toxicity of chemotherapy was substantial, especially febrile neutropenia was common, whereas RT was well tolerated. Conclusions: This is the first completed phase III trial to evaluate the role of induction chemoradiotherapy and surgery, in comparison to neoadjuvant CT alone followed by surgery. RT was active, it increased response, complete resection and pCR rates. However, this failed to translate into an improvement of local control, EFS or OS. Notably, surgery after induction treatment was safe, including pneumonectomy. The overall survival rates of our neoadjuvant regimen are very encouraging, especially for a multicenter setting. Disclosure: M. Pless: Advisory Board for Sanofi; R. Cathomas: Advisory Board Sanofi D.C. Betticher: Advisory Board Sanofi. All other authors have declared no conflicts of interest.

Optimization of Radiation Dose and Image Quality in Musculoskeletal CT: Emphasis on Iterative Reconstruction Techniques (Part 2).

Computed tomography (CT) is a modality of choice for the study of the musculoskeletal system for various indications including the study of bone, calcifications, internal derangements of joints (with CT arthrography), as well as periprosthetic complications. However, CT remains intrinsically limited by the fact that it exposes patients to ionizing radiation. Scanning protocols need to be optimized to achieve diagnostic image quality at the lowest radiation dose possible. In this optimization process, the radiologist needs to be familiar with the parameters used to quantify radiation dose and image quality. CT imaging of the musculoskeletal system has certain specificities including the focus on high-contrast objects (i.e., in CT of bone or CT arthrography). These characteristics need to be taken into account when defining a strategy to optimize dose and when choosing the best combination of scanning parameters. In the first part of this review, we present the parameters used for the evaluation and quantification of radiation dose and image quality. In the second part, we discuss different strategies to optimize radiation dose and image quality of CT, with a focus on the musculoskeletal system and the use of novel iterative reconstruction techniques.

SPIRONOLACTONE FOR NONRESOLVING CENTRAL SEROUS CHORIORETINOPATHY: A Randomized Controlled Crossover Study.

PURPOSE: To evaluate the effect of spironolactone, a mineralocorticoid receptor antagonist, for nonresolving central serous chorioretinopathy. METHODS: This is a prospective, randomized, double-blinded, placebo-controlled crossover study. Sixteen eyes of 16 patients with central serous chorioretinopathy and persistent subretinal fluid (SRF) for at least 3 months were enrolled. Patients were randomized to receive either spironolactone 50 mg or placebo once a day for 30 days, followed by a washout period of 1 week and then crossed over to either placebo or spironolactone for another 30 days. The primary outcome measure was the changes from baseline in SRF thickness at the apex of the serous retinal detachment. Secondary outcomes included subfoveal choroidal thickness and the ETDRS best-corrected visual acuity. RESULTS: The mean duration of central serous chorioretinopathy before enrollment in study eyes was 10 ± 16.9 months. Crossover data analysis showed a statistically significant reduction in SRF in spironolactone treated eyes as compared with the same eyes under placebo (P = 0.04). Secondary analysis on the first period (Day 0-Day 30) showed a significant reduction in subfoveal choroidal thickness in treated eyes as compared with placebo (P = 0.02). No significant changes were observed in the best-corrected visual acuity. There were no complications related to treatment observed. CONCLUSION: In eyes with persistent SRF due to central serous chorioretinopathy, spironolactone significantly reduced both the SRF and the subfoveal choroidal thickness as compared with placebo.

Sugar-and artificially sweetened beverages and intrahepatic fat : a randomized controlled trial.

OBJECTIVE: To test the hypothesis that substituting artificially sweetened beverages (ASB) for sugar-sweetened beverages (SSB) decreases intrahepatocellular lipid concentrations (IHCL) in overweight subjects with high SSB consumption. METHODS: About 31 healthy subjects with BMI greater than 25 kg/m(2) and a daily consumption of at least 660 ml SSB were randomized to a 12-week intervention in which they replaced SSBs with ASBs. Their IHCL (magnetic resonance spectroscopy), visceral adipose tissue volume (VAT; magnetic resonance imaging), food intake (2-day food records), and fasting blood concentrations of metabolic markers were measured after a 4-week run-in period and after a 12-week period with ASB or control (CTRL). RESULTS: About 27 subjects completed the study. IHCL was reduced to 74% of the initial values with ASB (N = 14; P < 0.05) but did not change with CTRL. The decrease in IHCL attained with ASB was more important in subjects with IHCL greater than 60 mmol/l than in subjects with low IHCL. ALT decreased significantly with SSB only in subjects with IHCL greater than 60 mmol/l. There was otherwise no significant effect of ASB on body weight, VAT, or metabolic markers. CONCLUSIONS: In subjects with overweight or obesity and a high SSB intake, replacing SSB with ASB decreased intrahepatic fat over a 12-week period.

Accelerated Microstructure Imaging via Convex Optimization (AMICO) in crossing fibers

Mapping the microstructure properties of the local tissues in the brain is crucial to understand any pathological condition from a biological perspective. Most of the existing techniques to estimate the microstructure of the white matter assume a single axon orientation whereas numerous regions of the brain actually present a fiber-crossing configuration. The purpose of the present study is to extend a recent convex optimization framework to recover microstructure parameters in regions with multiple fibers.

Effects of oral supplementation of iron on hepcidin blood concentrations among non-anaemic female blood donors: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: Hepcidin is the main hormone that regulates iron balance. Its lowering favours digestive iron absorption in cases of iron deficiency or enhanced erythropoiesis. The careful dosage of this small peptide promises new diagnostic and therapeutic strategies. Its measurement is progressively being validated and now its clinical value must be explored in different physiological situations. Here, we evaluate hepcidin levels among premenopausal female donors with iron deficiency without anaemia. MATERIALS AND METHODS: In a preceding study, a 4-week oral iron treatment (80 mg/day) was administered in a randomized controlled trial (n = 145), in cases of iron deficiency without anaemia after a blood donation. We subsequently measured hepcidin at baseline and after 4 weeks of treatment, using mass spectrometry. RESULTS: Iron supplementation had a significant effect on plasma hepcidin compared to the placebo arm at 4 weeks [+0·29 nm [95% CI: 0·18 to 0·40]). There was a significant correlation between hepcidin and ferritin at baseline (R(2) = 0·121, P < 0·001) and after treatment (R(2) = 0·436, P < 0·001). Hepcidin levels at baseline were not predictive of concentration changes for ferritin or haemoglobin. However, hepcidin levels at 4 weeks were significantly higher (0·79 nm [95% CI: 0·53 to 1·05]) among ferritin responders. CONCLUSIONS: This study shows that a 4-week oral treatment of iron increased hepcidin blood concentrations in female blood donors with an initial ferritin concentration of less than 30 ng/ml. Apparently, hepcidin cannot serve as a predictor of response to iron treatment but might serve as a marker of the iron repletion needed for erythropoiesis.

Transcranial Direct Current Stimulation for the Treatment of Chronic Tinnitus: A Randomized Controlled Study.

BACKGROUND: Tinnitus is an often disabling condition for which there is no effective therapy. Current research suggests that tinnitus may develop due to maladaptive plastic changes and altered activity in the auditory and prefrontal cortex. Transcranial direct current stimulation (tDCS) modulates brain activity and has been shown to transiently suppress tinnitus in trials. OBJECTIVE: To investigate the efficacy and safety of tDCS in the treatment of chronic subjective tinnitus. METHODS: In a randomized, parallel, double-blind, sham-controlled study, the efficacy and safety of cathodal tDCS to the auditory cortex with anode over the prefrontal cortex was investigated in five sessions over five consecutive days. Tinnitus was assessed after the last session on day 5, and at follow-up visits 1 and 3 months post stimulation using the Tinnitus Handicap Inventory (THI, primary outcome measure), Subjective Tinnitus Severity Scale, Hospital Anxiety and Depression scale, Visual Analogue Scale, and Clinical Global Impression scale. RESULTS: 42 patients were investigated, 21 received tDCS and 21 sham stimulation. There were no beneficial effects of tDCS on tinnitus as assessed by primary and secondary outcome measures. Effect size assessed with Cohen's d amounted to 0.08 (95% CI: -0.52 to 0.69) at 1 month and 0.18 (95% CI: -0.43 to 0.78) at 3 months for the THI. CONCLUSION: tDCS of the auditory and prefrontal cortices is safe, but does not improve tinnitus. Different tDCS protocols might be beneficial.

Internet-Based Brief Intervention to Prevent Unhealthy Alcohol Use among Young Men: A Randomized Controlled Trial.

INTRODUCTION: Alcohol use is one of the leading modifiable morbidity and mortality risk factors among young adults. STUDY DESIGN: 2 parallel-group randomized controlled trial with follow-up at 1 and 6 months. SETTING/PARTICIPANTS: Internet based study in a general population sample of young men with low-risk drinking, recruited between June 2012 and February 2013. INTERVENTION: Internet-based brief alcohol primary prevention intervention (IBI). The IBI aims at preventing an increase in alcohol use: it consists of normative feedback, feedback on consequences, calorific value alcohol, computed blood alcohol concentration, indication that the reported alcohol use is associated with no or limited risks for health. INTERVENTION group participants received the IBI. Control group (CG) participants completed only an assessment. MAIN OUTCOME MEASURES: Alcohol use (number of drinks per week), binge drinking prevalence. Analyses were conducted in 2014-2015. RESULTS: Of 4365 men invited to participate, 1633 did so; 896 reported low-risk drinking and were randomized (IBI: n = 451; CG: n = 445). At baseline, 1 and 6 months, the mean (SD) number of drinks/week was 2.4(2.2), 2.3(2.6), 2.5(3.0) for IBI, and 2.4(2.3), 2.8(3.7), 2.7(3.9) for CG. Binge drinking, absent at baseline, was reported by 14.4% (IBI) and 19.0% (CG) at 1 month and by 13.3% (IBI) and 13.0% (CG) at 6 months. At 1 month, beneficial intervention effects were observed on the number of drinks/week (p = 0.05). No significant differences were observed at 6 months. CONCLUSION: We found protective short term effects of a primary prevention IBI. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN55991918.

Nursing intervention versus usual care to improve delirium among home-dwelling older adults receiving homecare after hospitalization: feasibility and acceptability of a Randomized Controlled Trail.

BACKGROUND: Delirium is an acute cognitive impairment among older hospitalized patients. It can persist until discharge and for months after that. Despite proof that evidence-based nursing interventions are effective in preventing delirium in acute hospitals, interventions among home-dwelling older patients is lacking. The aim was to assess feasibility and acceptability of a nursing intervention designed to detect and reduce delirium in older adults after discharge from hospital. METHODS: Randomized clinical pilot trial with a before/after design was used. One hundred and three older adults were recruited in a home healthcare service in French-speaking Switzerland and randomized into an experimental group (EG, n = 51) and a control group (CG, n = 52). The CG received usual homecare. The EG received usual homecare plus five additional nursing interventions at 48 and 72 h and at 7, 14 and 21 days after discharge. These interventions were tailored for detecting and reducing delirium and were conducted by a geriatric clinical nurse (GCN). All patients were monitored at the start of the study (M1) and throughout the month for symptoms of delirium (M2). This was documented in patients' records after usual homecare using the Confusion Assessment Method (CAM). At one month (M2), symptoms of delirium were measured using the CAM, cognitive status was measured using the Mini-Mental State Examination (MMSE), and functional status was measured using Katz and Lawton Index of activities of daily living (ADL/IADL). At the end of the study, participants in the EG and homecare nurses were interviewed about the acceptability of the nursing interventions and the study itself. RESULTS: Feasibility and acceptability indicators reported excellent results. Recruitment, retention, randomization, and other procedures were efficient, although some potentially issues were identified. Participants and nurses considered organizational procedures, data collection, intervention content, the dose-effect of the interventions, and methodology all to be feasible. Duration, patient adherence and fidelity were judged acceptable. Nurses, participants and informal caregivers were satisfied with the relevance and safety of the interventions. CONCLUSIONS: Nursing interventions to detect/improve delirium at home are feasible and acceptable. These results confirm that developing a large-scale randomized controlled trial would be appropriate. TRIAL REGESTRATION: ISRCTN registry no: 16103589 - 19 February 2016.

Extrafascial injection for interscalene brachial plexus block reduces respiratory complications compared with a conventional intrafascial injection: a randomized, controlled, double-blind trial?.

BACKGROUND: Hemidiaphragmatic paresis after ultrasound-guided interscalene brachial plexus block is reported to occur in up to 100% of patients. We tested the hypothesis that an injection lateral to the brachial plexus sheath reduces the incidence of hemidiaphragmatic paresis compared with a conventional intrafascial injection, while providing similar analgesia. METHODS: Forty ASA I-III patients undergoing elective shoulder and clavicle surgery under general anaesthesia were randomized to receive an ultrasound-guided interscalene brachial plexus block for analgesia, using 20 ml bupivacaine 0.5% with epinephrine 1:200 000 injected either between C5 and C6 within the interscalene groove (conventional intrafascial injection), or 4 mm lateral to the brachial plexus sheath (extrafascial injection). The primary outcome was incidence of hemidiaphragmatic paresis (diaphragmatic excursion reduction >75%), measured by M-mode ultrasonography, before and 30 min after the procedure. Secondary outcomes were forced vital capacity, forced expiratory volume in 1 s, and peak expiratory flow. Additional outcomes included time to first opioid request and pain scores at 24 h postoperatively (numeric rating scale, 0-10). RESULTS: The incidences of hemidiaphragmatic paresis were 90% (95% CI: 68-99%) and 21% (95% CI: 6-46%) in the conventional and extrafascial injection groups, respectively (P<0.0001). Other respiratory outcomes were significantly better preserved in the extrafascial injection group. The mean time to first opioid request was similar between groups (conventional: 802 min [95% CI: 620-984 min]; extrafascial: 973 min [95% CI: 791-1155 min]; P=0.19) as were pain scores at 24 h postoperatively (conventional: 1.6 [95% CI: 0.9-2.2]; extrafascial: 1.6 [95% CI: 0.8-2.4]; P=0.97). CONCLUSIONS: Ultrasound-guided interscalene brachial plexus block with an extrafascial injection reduces the incidence of hemidiaphragmatic paresis and impact on respiratory function while providing similar analgesia, when compared with a conventional injection. CLINICAL TRIAL REGISTRATION: NCT02074397.