Prospective Randomized Multicenter Clinical Trial Research Articles

A Multicenter Randomized Double-blind Controlled Clinical Trial of Fiber Post Cementation Strategies.

The aim of this prospective randomized multicenter clinical trial was to evaluate the survival rate of glass fiber-reinforced posts cemented with self-adhesive or regular resin cements. The sample was comprised of 152 teeth randomized within two centers and in accordance with the adhesive strategies for RelyX U100/U200 (3M ESPE) or Single Bond and RelyX ARC (3M ESPE). The cementation procedures were standardized and performed by previously trained operators. The primary outcome evaluated was post debonding. A trained evaluator, one for each center, assessed all subjects at intervals of 12 months for up to 6 years. Statistical analysis was performed using the Kaplan-Meier method. There was no statistically significant difference in survival rates between the two strategies assessed ( p=0.991), with a 92.7% survival rate for the self-adhesive cement and 93.8% for the regular cement. Both the self-adhesive and the regular resin cements are good alternatives for glass fiber post cementation.

Aggressive intravenous hydration with lactated Ringer's solution for prevention of post-ERCP pancreatitis: a prospective randomized multicenter clinical trial.

In a prospective randomized multicenter trial, average-to-high risk patients who underwent first-time ERCP were randomly assigned to three groups (1:1:1) who received: aggressive intravenous hydration (3mL/kg/h during ERCP, a 20-mL/kg bolus and 3 mL/kg/h for 8 hours after ERCP) with either lactated Ringer's solution (LRS) or normal saline solution (NSS), or standard intravenous hydration with LRS (1.5 mL/kg/h during and for 8 hours after ERCP). The primary end point was post-ERCP pancreatitis (PEP). 395 patients were enrolled, and 385 completed the protocols. The three groups showed no significant differences in demographic characteristics. There was a significant difference in the intention-to-treat (ITT) PEP rate between the aggressive LRS group (3.0 %, 95 % confidence interval [CI] 0.1 % - 5.9 %; 4 /132), the aggressive NSS group (6.7 %, 95 %CI 2.5 % - 10.9 %; 9 /134) and the standard LRS group (11.6 %, 95 %CI 6.1 % - 17.2 %; 15 /129; P = 0.03). In the two-group comparisons, the ITT PEP rate was significantly lower for the aggressive LRS group than for the standard LRS group (relative risk [RR] 0.26, 95 %CI 0.08 - 0.76; P = 0.008). There was no significant difference in the ITT PEP rate between the aggressive NSS group and the standard LRS group (RR 0.57, 95 %CI 0.26 - 1.27; P = 0.17). Aggressive hydration with LRS is the best approach to intravenous hydration for the prevention of PEP in average-to-high risk patients.

Contemporary Postoperative Radiation Therapy Improves the Survival of Patients with Resected Pathological IIIA-N2 Non–small Cell Lung Cancer Treated With Adjuvant Chemotherapy

For pIIIA–N2 non-small cell lung cancer (NSCLC) after complete resection followed by adjuvant chemotherapy (ACT), the effect of PORT on survival may be counterbalanced by severe toxicities induced by suboptimal RT techniques. Our study is to evaluate the effect of contemporary PORT using 3D-CRT/IMRT techniques on survival of patients with resected pIIIA–N2 NSCLC treated with ACT. Between Jan. 2006 and Mar. 2015, patients with pIIIA–N2 NSCLC after complete resection followed by ACT in our single institution were retrospectively analyzed. Using 3D-CRT/IMRT techniques, PORT was given by 2 Gy per fraction to a total dose of 50 Gy. The effect of PORT on overall survival (OS) and disease free survival (DFS) was evaluated with Kaplan-Meier method and log-rank test. The impact of PORT on loco-regional recurrence free survival (LRFS) and distant metastasis free survival (DMFS) was also analyzed. Statistically significant difference was set as p<0.05. Overall, 545 consecutive patients were enrolled, including 187 (34.3%) in the PORT group and 358 (65.7%) in the non-PORT group. The characteristics were comparable between the two groups except that the patients with less positive lymph nodes were more prevalent in the PORT group. The median follow-up time for survival patients was 37.4 months. The median survival time of whole group was 60.0 months. PORT significantly improved the OS (p=0.003). The median survival time was 56.1 months in the non-PORT group and not reached in the PORT group. The 3- and 5-year OS rates were 76.5%, and 65.7%, respectively in the PORT group and were 67.1%, and 47.8%, respectively in the non-PORT group. The differences of the DFS, LRFS and DMFS between the two groups were all statistically significant (p=0.001, p=0.001, and p=0.006, respectively). The 3-, and 5-year DFS rates were 41.4%, and 33.6% in the PORT group and 33.8%, and 19.5% in the non-PORT group, respectively. The 3-, and 5-year LRFS rates were 68.2%, and 51.9% in the PORT group and 58.1%, and 36.9% in the non-PORT group, respectively. The 3-, and 5-year DMFS rates were 45.7%, and 37.7% in the PORT group and 40.0%, and 23.6% in the non-PORT group, respectively. Multivariate analyses also showed that PORT was significantly associated with longer OS (HR=0.640, 95% CI: 0.432-0.947; p=0.025). The other independent prognostic factors included age≤60 year (HR=0.563, 95% CI: 0.420-0.754; p=0.000) and the number of positive nodes ≤4 (HR=0.564, 95% CI: 0.421-0.756; p=0.000). In the PORT group, IMRT was used in 145 patients (75.9%) and 3D-CRT was used in 46 patients (24.1%). Up to the last follow up, none irradiation toxicity-related deaths were observed. Based on our study, postoperative 3D-CRT/IMRT is safe and can significantly improve the survival of patients with pIIIA–N2 NSCLC treated with surgery followed by ACT. A prospective randomized multicenter clinical trial is ongoing to evaluate the definitive role of PORT using contemporary techniques.

A multicenter prospective randomized clinical trial assessing implant design modifications after 3 years

A multicenter prospective randomized clinical trial assessing implant design modifications after 3 years

Lateral Extra-articular Tenodesis Does Not Influence Knee Abduction Moment During Drop Vertical Jump Following ACL Reconstruction

Objectives:The combination of anterior cruciate ligament (ACL) reconstruction plus lateral extra-articular tenodesis (LET) has shown promising results during preclinical biomechanical and clinical testing at reducing anterolateral rotatory laxity; however, no studies have examined its effectiveness during a dynamic functional task. Therefore, we used the drop vertical jump (DVJ) to compare in vivo biomechanics of ACL reconstructed patients with and without LET from a subset of patients within the Stability randomized clinical study. We hypothesized that there would be a difference in peak knee abduction moment (KAM) between the two treatment groups at six months following surgery.Methods:This is a subset of patients taken from one center, within a pragmatic, multicenter prospective randomized clinical trial. Thirty patients were randomized to receive ACL reconstruction alone (n=16) or ACL reconstruction plus LET (n=14). At six months postoperative, all patients performed a drop vertical jump test and knee kinetics and kinematics were measured using three-dimensional motion analysis. Biomechanical variables of interest included peak initial contact and stance values for knee abduction moment and angle, knee flexion moment and angle and knee internal rotation moment and angle. Independent groups t-tests were used to assess kinetic and kinematic differences between the injured limbs of both treatment groups.Results:There was no significant difference in peak KAM between those who received ACL reconstruction alone (1.31 %BW×ht) and those who received an ACL reconstruction plus LET (1.14 %BW×ht) (Mean Difference, 0.17; 95% CI, -0.50 to 0.84, p = 0.60). Similarly, there were no differences in peak knee flexion moment or peak knee internal rotation moment between treatment groups (p=0.59 and p=0.37 respectively). There were also no significant differences in knee abduction angle, knee flexion angle or knee internal rotation angle at initial contact (p=0.40, p=0.08, p=0.23 respectively) or peak stance phase (p=0.10, p=0.44, p=0.19 respectively).Conclusion:We found no significant biomechanical differences between treatment groups at six months postoperative. However, these are the preliminary results of a larger continuing study and, at this time, no definitive conclusions can be made.

The REMEDEE-OCT Study: An Evaluation of the Bioengineered COMBO Dual-Therapy CD34 Antibody–Covered Sirolimus-Eluting Coronary Stent Compared With a Cobalt-Chromium Everolimus-Eluting Stent in Patients With Acute Coronary Syndromes: Insights From Optical Coherence Tomography Imaging Analysis

ObjectivesThe aim of the present study was to evaluate vascular healing of the bioengineered COMBO Dual Therapy Stent compared with a cobalt-chromium (CoCr) everolimus-eluting stent (EES) as assessed by optical coherence tomography in patients with acute coronary syndromes. BackgroundCD34+ cells promote endothelial repair after vascular injury. The bioengineered COMBO Dual Therapy Stent combines CD34+ cell–capturing technology with abluminal sirolimus release, but more data from clinical studies evaluating the vascular response are needed. MethodsIn a prospective randomized multicenter clinical trial, 60 patients with acute coronary syndromes were randomized 1:1 to COMBO or CoCr EES implantation. The primary endpoint was the percentage of uncovered stent struts per stent. Stent assessment by optical coherence tomography was performed at baseline and at 60 days, followed by independent core laboratory analysis. ResultsThe percentage of uncovered struts per stent was higher with the COMBO than the CoCr EES at 60 days (median 14.7% vs. 7.7%; p = 0.04). However, no significant difference in uncovered stent struts was observed in the strut level–based analysis at 60 days, which also accounted for clustering (COMBO vs. CoCr EES; 13.6% vs. 6.9%; p = 0.09; generalized linear mixed models–adjusted analysis). Neointimal thickness at 60 days was lower with the COMBO compared with the CoCr EES (median 30.17 vs. 50.26 μm; p = 0.02; stent-level analysis). There were no significant differences in the frequency of major adverse cardiac events and each component of major adverse cardiac events within the study population between the 2 groups at 30, 60, 180, 360, and 540 days post-procedure. No target vessel stent thrombosis has been documented within 540 days. ConclusionsThe present multicenter, prospective clinical study for the first time compared the vascular response of the bioengineered COMBO Dual Therapy Stent with a CoCr EES in patients early after acute coronary syndrome by using intracoronary optical coherence tomographic analysis. The percentage of uncovered stent struts per stent was somewhat higher after COMBO versus CoCr EES implantation as detected by optical coherence tomography, associated with reduced neointimal thickness.

Monotherapy versus Combination Therapy against Nonbacteremic Carbapenem-resistant Gram-negative Infections: A Retrospective Observational Study.

Background:Superiority of colistin–carbapenem combination therapy (CCCT) over colistin monotherapy (CMT) against carbapenem-resistant Gram-negative bacterial (CRGNB) infections is not conclusively proven.Aim:The aim of the current study was to analyze the effectiveness of both strategies against CRGNB nonbacteremic infections.Design:This was a retrospective observational cohort study.Subjects and Methods:Case record analysis of patients who had CRGNB nonbacteremic infections identified over a period of 4 years (January 2012–December 2015) was done by medical record review at a tertiary care center in India.Statistical Analysis:P < 0.05 was considered as significant. Multivariate analysis was performed using Cox regression.Results:Out of 153 patients (pneumonia 115, urinary tract infection 17, complicated skin and soft-tissue infection 18, intra-abdominal infection 1, and meningitis 2), 92 patients received CCCT and 61 received CMT. Univariate analysis revealed higher Acute Physiology and Chronic Health Evaluation II (APACHE II) score, pneumonia as the diagnosis, and Klebsiella as the causative organism to be the risk factors for higher 28-day mortality (P = 0.036, 0.006, 0.016, respectively). Combination therapy had no significant impact on mortality (odds ratio [OR] = 0.91, 95% confidence interval [CI] = 0.327–2.535, P = 0.857). Multivariate analysis revealed that higher APACHE II score and infection due to Klebsiella were found to be independent risk factors for higher mortality (OR = 3.16 and 4.9, 95% CI = 1.34–7.4 and 2.19–11.2, P = 0.008 and 0.0001, respectively).Conclusions:In our retrospective single-center series of CRGNB nonbacteremic infections, CCCT was not superior to CMT. Multicenter large observational studies or prospective randomized clinical trials are the need of the hour.

Is Hyaluronic Acid or Corticosteroid Superior to Lactated Ringer Solution in the Short Term for Improving Function and Quality of Life After Arthrocentesis? Part 2

Although arthrocentesis has been used for the management of patients with temporomandibular joint pain, the benefit of hyaluronic acid (HA) or corticosteroid (CS) remains uncertain. The purpose of this study was to assess the efficacy of HA, CS, and lactated Ringer solution (LR; placebo) after arthrocentesis for changes in quality of life (QoL), jaw function (Jaw Function Limitation Scale [JFLS] score), and maximum incisal opening (MIO). This was a prospective multicenter double-blinded randomized clinical trial. Consecutive patients presenting to the oral and maxillofacial departments at Emory University, the University of Pennsylvania, the University of California-Los Angeles, the University of Cincinnati, and the Oregon Health Sciences University were enrolled in the study. Patients were randomized to HA, CS, or LR. All patients underwent arthrocentesis and then instillation of HA, CS, or LR. All patients were evaluated clinically at 1 and 3months. The outcome variables were QoL, JFLS score, and MIO. Univariate, bivariate, and multivariate statistics were computed, with a P value less than .05 considered significant. One hundred two patients were enrolled in the study. Four were lost to follow-up, leaving 98 patients for analysis of data at 1month. An additional 51 were lost to follow-up at 3months, leaving 51 patients for data analysis at this time point. There was no difference among groups for QoL Mental Health Composite score at 1month (P= .70) or 3months (P= .69). There was no difference among groups for JFLS score at 1month (P= .71) or 3months (P= .98). There was no difference among groups for MIO at 1month (P= .47) or 3months (P= .31). All groups showed within-group improvements in JFLS score and MIO at 1 and 3months. Arthrocentesis alone is as efficacious as arthrocentesis with HA or CS in improving jaw function and MIO at 1 and 3months. QoL is not improved with arthrocentesis alone or in combination with CS or HA.

Reduction of the dose of radiotherapy to the elective neck in head and neck squamous cell carcinoma; a randomized clinical trial. Effect on late toxicity and tumor control

Background and purposeA multi-center prospective randomized clinical trial has been performed investigating whether a reduction of the dose to the elective nodal sites in head and neck cancer delivered by intensity modulated radiotherapy (IMRT) would result in a reduction of late side effects without compromising tumor control. Materials and methodsTwo hundred patients were included. The prescription dose to the elective nodal volumes was a normalized iso-effective dose in 2Gy fractions (NID2Gy) of 50Gy in the standard arm and of 40Gy in the experimental arm. Late toxicity was scored at 6, 12, 18 and 24months using the RTOG scoring system. ResultsWe observed a trend toward less dysphagia at 6months in the experimental arm, however this was not confirmed after longitudinal analysis. Regarding moderate salivary gland toxicity we observed lower incidence of salivary gland toxicity ⩾grade 1, at 6 (p=0.01) and 18months (p=0.03).After two years of follow up, we did not observe significant differences in estimated local failure rate (14.1% in the 40Gy arm vs 14.4% in the 50Gy arm), estimated regional failure rate (13.0% vs 5.5% in the 40 and the 50Gy arm respectively), estimated metastatic recurrence (13.4% vs 18.5% in the 40 and the 50Gy arm respectively), estimated disease-free survival (57.9% vs 65.3% in the 40 and the 50Gy arm respectively) nor estimated overall survival (72.0% vs 73.2% in the 40 and the 50Gy arm respectively). ConclusionsIn our study population there was no statistically significant difference regarding survival and estimated recurrence rates between both arms of this study. We found a trend toward less dysphagia at 6months (however not significant after longitudinal analysis) and found a significant reduction of any salivary gland toxicity at 6 and 18months in the 40Gy arm.

Evaluation of Geographic Atrophy from Color Photographs and Fundus Autofluorescence Images: Age-Related Eye Disease Study 2 Report Number 11

To compare measurements of area of geographic atrophy (GA) and change in GA area from color photographs and fundus autofluorescence (FAF) images. The Age-Related Eye Disease Study 2 (AREDS2) was a prospective multicenter randomized clinical trial evaluating progression of dry age-related macular degeneration (AMD) using color photographs at annual visits over a 5-year study period. The FAF images were acquired in a subset of participants who joined the FAF ancillary study at any of the annual visits over the study period. The AREDS2 FAF ancillary study included 8070 corresponding color and FAF visits of 2202 participants with variable follow-up. Corresponding color and FAF images were independently evaluated at a central reading center for GA area measurement, lesion growth, and involvement of the macula center. Presence, area, growth rate of GA, and involvement of center of macula from color and FAF images. Hypoautofluorescence was visible in 2048 visits (25.4%). Agreement for the presence of GA between the 2 modalities had a kappa of 0.79, with 23% of visits with hypoautofluorescence not presenting with GA on color photographs. Percentage agreement for GA presence ranged from 43% at baseline to 81% at year 5 with improving agreement over time. The mean difference in GA area between the 2 modalities was 0.5 mm2, with larger areas on FAF. Growth rate of GA was 1.45 mm2 from color photographs and 1.43 mm2 from FAF images. The center of the macula was involved in 51% of color photographs and 56% with FAF images. Geographic atrophy may be detected earlier by the use of FAF images, but over the course of the study, the 2 modalities become comparable. Progression of GA area is comparable between color photographs and FAF images, but evaluating involvement of the center of the macula may differ, probably because of macular pigmentation blocking autofluorescence.

Outcomes of Catheter Ablation of Ventricular Tachycardia in the Setting of Structural Heart Disease.

Sustained ventricular tachycardias are common in the setting of structural heart disease, either due to prior myocardial infarction or a variety of non-ischemic etiologies, including idiopathic dilated cardiomyopathy, hypertrophic cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy. Over the past two decades, percutaneous catheter ablation has evolved dramatically and has become an effective tool for the control of ventricular arrhythmias. Single and multicenter observational studies as well as several prospective randomized trials have begun to investigate long-term outcomes after catheter ablation procedures. These studies encompass a wide range of mapping and ablation techniques, including conventional activation mapping/entrainment criteria, substrate modification guided by pacemapping, late potential and abnormal electrogram ablation, scar de-channeling, and core isolation. While large-scale, multicenter prospective randomized clinical trials are somewhat limited, the published data demonstrate favorable outcomes with respect to a reduction in overall ventricular tachycardia (VT) burden, reduction of implantable cardioverter defibrillator (ICD) shocks, and discontinuation of anti-arrhythmic medications across varying disease subtypes and convincingly support the use of catheter ablation as the standard of care for many patients with VT in the setting of structural heart disease.

Randomized clinical trial comparing ten day concomitant and sequential therapies for Helicobacter pylori eradication in a high clarithromycin resistance area

BackgroundCurrently only a few studies compare sequential and concomitant non-bismuth Helicobacter pylori therapies referring to high antibiotic resistance populations. Materials and methodsThis multicenter prospective randomized clinical trial included 353 H. pylori positive, treatment naïve, patients. All patients had positive CLO-test and/or histology and culture. They received sequential (esomeprazole 40mg, amoxicillin 1g/bid for 5days, followed by 5days of esomeprazole 40mg, clarithromycin 500mg and metronidazole 500mg bid), or concomitant treatment (all drugs taken concomitantly bid for 10days). Eradication was confirmed by 13C-urea breath test or histology 4–6weeks after treatment. Adverse events and adherence were evaluated. ResultsAllocated to concomitant were 175 (72F/103M, mean 52.3years, 38.3% smokers, 25.7% ulcer disease) and 178 (87F/91M, mean 52years, 31% smokers, 19.1% ulcer disease) patients to sequential treatment. There were 303/353 (85.8%) positive cultures, with the following resistances: 34% metronidazole, 27.7% clarithromycin, and 7.9% dual. Eradication rates were, respectively, 89.1% (156/175) vs. 78.7% (140/178) by intention to treat (p=0.01, 95% CI=2.7–18) and 93.4%(156/167) vs. 82.8% (140/169) per protocol (p=0.004, 95% CI=3.6–17.6). Overall, adherence was (98.9%, 95% CI=97–100). Eradication rates according to resistance were the following: dual susceptible strains 67/69 (97.1%), 62/67 (92%) (p=0.4), metronidazole single resistant 38/39 (97.4%), 31/39 (79.5%) (p=0.03, 95% CI=3.5–33), clarithromycin single resistant 25/28 (89.3%), 26/31 (83.9%) (p=0.8), and dual resistant 9/12 (75%), 4/11 (36.4%) (p=0.1) for concomitant and sequential regimens, respectively. Side effects were comparable among regimens, except from diarrhea being more frequent among patients treated with concomitant treatment. ConclusionsConcomitant treatment eradication rate overcomes 90% per protocol and has a significant advantage over sequential therapy. This is probably due to its better efficacy on metronidazole resistant strains. Both regimens were well tolerated and safe.

Safety and Efficacy of Subcutaneous Parenteral Nutrition in Older Patients: A Prospective Randomized Multicenter Clinical Trial.

Many patients who cannot tolerate adequate enteral nutrition could benefit from parenteral nutrition support but fail to receive it due to difficult intravenous (IV) access. The objective of this study was to compare the safety and efficacy of subcutaneous (SC) administration of parenteral nutrition with the peripheral IV route. This was a prospective randomized multicenter study of 121 older hospitalized patients. The primary outcome was the composite end point of major local side effects, defined as local edema, blistering, erythema, phlebitis, cellulitis, unbearable pain, or route failure requiring a switch in route. Secondary outcomes were nutrition parameters, biochemical parameters, clinical outcomes, and safety. The SC route (n = 59) was noninferior to the IV route (n = 61) for major local side effects. Major local side effects trended higher in the IV group ( P = .059). Local edema was more common in the SC group ( P < .05), while route failure was more common in the IV group ( P < .001). Nutrition and biochemical parameters, safety, and clinical outcomes were similar between groups. The SC route of nutrient administration was better tolerated than the peripheral IV route. SC administration of parenteral nutrition represents a safe alternative to IV nutrition.

Ultra low-dose chest ct with iterative reconstructions as an alternative to conventional chest x-ray prior to heart surgery (CRICKET study): Rationale and design of a multicenter randomized trial

BackgroundStroke after cardiac surgery is a severe complication with a persistently high incidence of 1.4 – 9.7%. Postoperative strokes are mainly embolic and can be provoked by manipulation and clamping of the aorta during cardiac surgery, resulting in the mobilization of atherothrombotic material and calcifications from the aortic wall. Computed tomography (CT) can offer preoperative visualization of aortic calcifications with low radiation exposure. We hypothesize that preoperative knowledge regarding the location and extent of aortic calcifications can be used to optimize surgical strategy and decrease postoperative stroke rate. Methods/designThe CRICKET study (ultra low-dose chest CT with iterative reconstructions as an alternative to conventional chest x-ray prior to heart surgery) is a prospective multicenter randomized clinical trial to evaluate whether non-contrast chest CT before cardiac surgery can decrease postoperative stroke rate by optimizing surgical strategy. Patients scheduled to undergo cardiac surgery aged 18 years and older are eligible for inclusion. Exclusion criteria are pregnancy, a chest/cardiac CT in the past three months, emergency surgery, concomitant or prior participation in a study with ionizing radiation and unwillingness to be informed about incidental findings. Subjects (n = 1.724) are randomized between routine care, including a chest x-ray, or routine care with an additional low dose chest CT. The primary objective is to investigate whether the postoperative in-hospital stroke rate is reduced in the CT arm compared to the routine care arm of the randomized trial. The secondary outcome measures are altered surgical approach based on CT findings and cost-effectiveness.

Conventional Oral Prednisone Versus High-Dose Dexamethasone for Management of Adult Immune Thrombocytopenia: A Prospective Randomized Multicenter Clinical Trial

Introduction Oral prednisone (PDN) is conventional standard initial management for adult immune thrombocytopenia (ITP). In recent years single arm studies propose that high-dose dexamethasone (HD-DXM) improves response rate and remission duration and reduces adverse effects, though a randomized trial demonstrated no superiority of HD-DXM. It still lacks evidence-based conclusion on which one is better in efficacy and safety. We conducted a prospective randomized multicenter clinical trial to compare the efficacy and safety of HD-DXM and PDN as first-line strategy for adult newly diagnosed ITP.Methods We enrolled adult newly diagnosed ITP patients aging between 18 and 80 years, peripheral PLT count <30x109/L or with bleeding symptoms. Diagnosis of ITP and definition of newly diagnosed ITP followed international working group report and ASH evidence-based guideline. A 1:1 randomization was assigned between HD-DXM and PDN arm. In HD-DXM arm, dexamethasone was administered orally at 40mg/d for 4 consecutive days. If PLT count remained or dropped below 30x109/L by day 10, another four-day course of HD-DXM was given. Patients received prednisone orally at 1.0mg/kg/d for no more than 28 days in PDN arm, and then tapered rapidly to minimized maintenance dosage of <15mg/d in responders or stop in non-responders. Early response was evaluated according to criteria mentioned above. We defined sustained response as PLT count maintaining above 30x109/L for 6 months or more. Responders underwent follow-up for at least 6 months or until relapse. Adverse effects were recorded for analysis of safety. Informed consent was obtained from all enrolled patients in accordance with the Declaration of Helsinki. This study was approved by Ethics Committee of each participating site and registered at http://clinicaltrials.gov/ as NCT01356511.Results From Jan 2011 to May 2014, 182 newly diagnosed adult patients were enrolled from 9 sites over Shandong Province, China, with 92 randomized to HD-DXM arm (62 females and 30 males; age median 43, range 18~73 years) and 90 to PDN arm (68 females and 22 males; age median 44.5, range 18~76 years). Baseline PLT count were 8.93±8.19 (HD-DXM arm) and 10.60±8.67 (PDN arm) x109/L, respectively. Overall response rate in HD-DXM arm was 84.8% (78/92) with 52.2% (48/92) CR, while in PDN arm 74.4% (67/90) and 28.9% (26/90). HD-DXM arm showed similar overall response (P=0.099) but higher CR rate (P=0.002). HD-DXM arm also demonstrated shorter time to response (3.21±1.35 vs. 5.97±4.28 days, P=0.001). 149 patients were available for evaluation of sustained response, 76 in HD-DXM arm and 73 in PDN arm, with follow-up of a median of 10(1-40) and 12(1-39) months, respectively. There was no statistically significant difference between the two arms in sustained response rate (39.5% vs. 49.3%, P=0.251). Generally both treatments were well tolerated. Adverse effects were recorded (HD-DXM/PDN), including hyperglycemia (3/5), hypertension (3/3), peptic ulcer (1/3), gaining weight (0/4), and infection trend (0/2).Conclusion One or two courses of HD-DXM demonstrated higher CR rate and shorter time to response than PDN. HD-DXM could be a better first-line choice for adult ITP.Table 1Characteristics of patients in HD-DXM and PDN armParameterHD-DXMPDNNo. of patients9290Age, median (range)43 (18 - 73)44.5 (18 - 76)Gender, female/male62/3068/22Baseline platelet count, x109/L8.93±8.1910.60±8.67 DisclosuresNo relevant conflicts of interest to declare.

All-inside suture device is superior to meniscal arrows in meniscal repair: a prospective randomized multicenter clinical trial with 2-year follow-up.

PurposeMultiple techniques and implants are available for all-inside meniscal repair, but the knowledge about their failure rates and functional outcome is still incomplete. The hypothesis was that there might be differences between meniscal arrows and suture devices regarding reoperation rates and functional outcome. Thereby, the aim of this study was to compare clinical results following repair with the Biofix® arrows or the FasT-Fix® suture devices.MethodsIn this RCT, 46 patients were treated either by Biofix® (n = 21) or FasT-Fix® (n = 25). The main outcome was reoperation within 2 years. Knee function and activity level were evaluated by KOOS and Tegner activity scale.ResultsTwelve out of 46 (26 %) patients were reoperated within 2 years, nine out of 21 (43 %) in the Biofix®-group versus three out of 25 (12 %) in the FasT-Fix®-group (p = 0.018). The relative risk of reoperation was 3.6 times higher for Biofix® compared to FasT-Fix® (95 % confidence interval 1.1–11.5). Both treatment groups had significant increase in all KOOS subscales, but there were no major differences between the groups. The subgroup of reoperated patients differed from the other patients with higher Tegner score preoperatively (median 5 vs. 4) (p = 0.037) and at 3-month follow-up (median 4 vs. 3) (p = 0.010).ConclusionsThese results indicate that FasT-Fix® suture is superior to Biofix® arrows with significant lower failure rate. Functional outcome did not depend on repair technique. Higher activity score preoperatively and at 3-month follow-up in the reoperated patients indicates that activity level may influence on the risk of reoperation.Level of evidenceI.

Impact of Vitreomacular Adhesion on Ranibizumab Mono- and Combination Therapy for Neovascular Age-Related Macular Degeneration

To investigate the influence of vitreomacular adhesion on the efficacy of pro re nata (PRN) ranibizumab monotherapy and verteporfin photodynamic therapy (PDT) combination therapy for neovascular age-related macular degeneration. Post hoc analysis of prospective randomized 12-month multicenter clinical trial data. Total of 255 treatment-naïve patients with subfoveal choroidal neovascularization. Assessment of the vitreomacular interface on monthly optical coherence tomography with division of patients into the following categories according to continuous 1-year grading: posterior vitreous detachment (n=154), dynamic release of vitreomacular adhesion (n=32), stable vitreomacular adhesion (n=51). Mean best-corrected visual acuity (BCVA) letter and central retinal thickness changes at month 12 in the vitreomacular interface groups. Mean BCVA changes at month 12 were +3.5 (posterior vitreous detachment), +4.3 (release of vitreomacular adhesion), and +6.3 (vitreomacular adhesion) in patients receiving monotherapy (P=.767), and +0.1 (posterior vitreous detachment), +6.6 (release of vitreomacular adhesion), and +9.2 (vitreomacular adhesion) in patients receiving combination therapy (P=.009). Mean central retinal thickness changes were -113 μm (posterior vitreous detachment), -89 μm (release of vitreomacular adhesion), and -122 μm (vitreomacular adhesion) in monotherapy (P=.725) and -121 μm (posterior vitreous detachment), -113 μm (release of vitreomacular adhesion), and -113 μm (vitreomacular adhesion) in combination therapy (P=.924). Mean ranibizumab retreatments during 12 months were 4.9 (posterior vitreous detachment), 6.6 (release of vitreomacular adhesion), and 5.3 (vitreomacular adhesion) in monotherapy (P=.018) and 4.7 (posterior vitreous detachment), 5.2 (release of vitreomacular adhesion), and 5.8 (vitreomacular adhesion) in combination therapy (P=.942). This study adds evidence that the vitreomacular interface status impacts functional outcomes and retreatment requirements. Patients with posterior vitreous detachment achieve acceptable results with fewer injections in PRN monotherapy, but lose potential vision gain with PDT. Patients with other vitreomacular interface configurations may potentially achieve optimized vision outcomes by combination of antiangiogenic treatment and vaso-occlusive PDT.

Mono- versus polyaxial locking plates in distal femur fractures: a prospective randomized multicentre clinical trial

Treatment of complex fractures of the distal femur utilizing monoaxial locking plates (e.g. Less Invasive Stabilisation System, LISS®, Synthes) is considered to be superior to conventional plating systems. Due to the limitation that the thread forces the screw into pre-determined positions, modifications have been made to allow screw positioning within a range of 30° (Non Contact Bridging, NCB®-DF, Zimmer). For the first time, this multicenter prospective randomized clinical trial (RCT) investigates the outcome of LISS® vs. NCB®-DF treatment following complex fractures of the distal femur. Since June 2008, 27 patients with a fracture of the distal femur (AO ASIF 33-A-C and periprosthetic fractures) were enrolled in this study by four university trauma centres in southern Germany. Clinical (e.g. range of motion, Oxford knee score, Tegner score) and radiological (e.g. axis deviation, secondary loss of realignment) follow-ups were conducted one and six weeks, as well as three, six, and 12 months after the operation. This study comprises data of 27 patients (8 male, 19 female; 15 NCB®-DF, 12 LISS®). Polyaxial osteosynthesis using the NCB® system tended to result in better functional knee scores and a higher range of motion. Interestingly, fracture union tended to be more rapid using the polyaxial plating system. We present the analysis of a multicenter prospective RCT to compare the monoaxial LISS® vs. the polyaxial NCB®-DF treatment following complex fractures of the distal femur. NCB®-DF treatment tended to result in better functional and radiological outcomes than LISS® treatment. Level I.

MALDI MS profiling of post‐DRE urine samples highlights the potential of β‐microseminoprotein as a marker for prostatic diseases

To use spectra acquired by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) from pre- and post-digital rectal examination (DRE) urine samples to search for discriminating peaks that can adequately distinguish between benign and malignant prostate conditions, and identify the peaks' underlying biomolecules. Twenty-five participants with prostate cancer (PCa) and 27 participants with a variety of benign prostatic conditions as confirmed by a 10-core tissue biopsy were included. Pre- and post-DRE urine samples were prepared for MALDI MS profiling using an automated clean-up procedure. Following mass spectra collection and processing, peak mass and intensity were extracted and subjected to statistical analysis to identify peaks capable of distinguishing between benign and cancer. Logistic regression was used to combine markers to create a sensitive and specific test. A peak at m/z 10,760 was identified as β-microseminoprotein (β-MSMB) and found to be statistically lower in urine from PCa participants using the peak's average areas. By combining serum prostate-specific antigen (PSA) levels with MALDI MS-measured β-MSMB levels, optimum threshold values obtained from Receiver Operator characteristics curves gave an increased sensitivity of 96% at a specificity of 26%. These results demonstrate that with a simple sample clean-up followed by MALDI MS profiling, significant differences of MSMB abundance were found in post-DRE urine samples. In combination with PSA serum levels, obtained from a classic clinical assay led to high classification accuracy for PCa in the studied sample set. Our results need to be validated in a larger multicenter prospective randomized clinical trial.

Long-Term Evaluation of Dysphasia (Bazaz) with the PCM Cervical Disc Compared to ACDF in a Prospective Randomized Clinical Trial: Five-Year Results from the US IDE Study

The PCM® Cervical Disc is a recently FDA-approved non-constrained cervical disc arthroplasty device with a low-profile design. The investigational device exemption (IDE) clinical trial conducted in the United States is the largest reported multicenter prospective randomized clinical trial explicitly evaluating dysphagia in patients treated with anterior cervical approaches.