Prospective Multicenter Pilot Study Research Articles

Percutaneous internal fixation with Y-STRUT\xae device to prevent both osteoporotic and pathological hip fractures: a prospective pilot study

BackgroundWe studied Y-STRUT® (Hyprevention, France), a new percutaneous internal fixation device, in combination with bone cementoplasty to prevent hip fracture.MethodsBetween February 2013 and February 2015, a total of 16 femoral necks in 4 osteoporotic and 12 oncologic patients have been considered for prophylactic consolidation in this prospective multicentre pilot study involving 4 different hospitals. These consolidations were performed percutaneously under fluoroscopic guidance using Y-STRUT®, a dedicated internal fixation device. For osteoporotic patients, orthopaedic surgeons performed the prophylactic consolidations immediately after surgical treatment of a hip fracture (same anaesthesia) in the opposite side. For oncologic patients, without current hip fracture but considered at risk (Mirels score ≥8), interventional radiologists performed the procedures. We report the preliminary results of feasibility, safety and tolerance of these preventive consolidations using Y-STRUT®.ResultsFour patients (mean 83 years old) had prophylactic consolidation because of a severe osteoporosis (mean T-score −3.30) resulting in first hip fractures. Ten patients (mean 61 years old) were treated because of impending pathological fractures (mean Mirels score 9) related to femoral neck osteolytic metastases. All the procedures were performed with success. Wound healing was achieved in all cases with no access site complication. Radiographic exams performed at 3 months follow-up revealed that Y-STRUT® was well integrated in the bone. For the osteoporotic cohort, mean pain was 0.9 ± 0.7 at 3 weeks. For the oncologic cohort, it decreases from 3.6 ± 2.9 at baseline to 2.4 ± 0.9 at 2 months.ConclusionsPreliminary results demonstrate the feasibility and safety of Y-STRUT® implantation as well as the tolerance of the device.

Long-term Experience of Magnetic Anal Sphincter Augmentation in Patients With Fecal Incontinence.

Magnetic anal sphincter augmentation is a novel technique for the treatment of patients with fecal incontinence. The current study reports the long-term effectiveness and safety of this new treatment modality. This was a prospective multicenter pilot study. The study was performed at 4 clinical sites in Europe and the United States. The cohort included patients with severe fecal incontinence for ≥6 months who had previously failed conservative therapy and were implanted with a magnetic anal sphincter device between 2008 and 2011. Adverse events, symptom severity, quality of life, and bowel diary data were collected. A total of 35 patients (34 women) underwent magnetic anal sphincter augmentation. The median length of follow-up was 5.0 years (range, 0-5.6 years), with 23 patients completing assessment at 5 years. Eight patients underwent a subsequent operation (7 device explantations) because of device failure or complications, 7 of which occurred in the first year. Therapeutic success rates, with patients who underwent device explantation or stoma creation counted as treatment failures, were 63% at year 1, 66% at year 3 and 53% at year 5. In patients who retained their device, the number of incontinent episodes per week and Cleveland Clinic incontinence scores significantly decreased from baseline, and there were significant improvements in all 4 scales of the Fecal Incontinence Quality of Life instrument. There were 30 adverse events reported in 20 patients, most commonly defecatory dysfunction (20%), pain (14%), erosion (11%), and infection (11%). This study does not allow for comparison between surgical treatments and involves a limited number of patients. Magnetic anal sphincter augmentation provided excellent outcomes in patients who retained a functioning device at long-term follow-up. Protocols to reduce early complications will be important to improve overall results.

Safety and efficacy of daptomycin in outpatient parenteral antimicrobial therapy: a prospective and multicenter cohort study (DAPTODOM trial)

Background: Daptomycin is an optimal choice for outpatient parenteral antibiotic therapy (OPAT) because of its safety, once-daily administration and its activity against Gram-positive bacteria. Although daptomycin is increasingly being used in OPAT, limited information about its safety in this scenario is available.Methods: We performed a prospective multicentre pilot study to evaluate the safety of daptomycin in outpatients with proved or suspected Gram-positive infections (DAPTODOM). The primary objective was to evaluate the safety and the secondary objective to evaluate the efficacy in OPAT. We also looked at the development of daptomycin resistance in those cases with microbiological failure.Results: We included 54 patients from 12 Spanish hospitals, 67% male with a mean age of 67.1 years. Most patients (87%) had chronic underlying diseases. The main reason for inclusion was skin and soft-tissue infections in 52%, followed by bacteremia or endocarditis in 34%. Staphylococcus aureus accounted for 44% of the isolates (24% were methicillin-resistant), coagulase-negative staphylococci 15% and enterococci 7%. Two patients (4%) had to be readmitted because of complications; only one patient had an adverse effect related to daptomycin (increase in serum creatine kinase levels), which disappeared after discontinuation (2%). At the end of follow-up, 96% of patients had good outcome and only 4% of patients did not have a clinical or microbiological cure. The use of a 2-minute bolus in 18 cases was not associated with adverse effects.Conclusions: Daptomycin was safe and efficacious in outpatients with Gram-positive bacterial infections and can be administered in 2-minute bolus infusion.

Assessment of Synthetic Glue for Mesh Attachment in Laparoscopic Sacrocolpopexy: A Prospective Multicenter Pilot Study

Study ObjectiveTo assess the anatomic efficacy and safety of synthetic glue to fix prosthetic material in laparoscopic sacrocolpopexy. DesignA 1-year follow-up in a prospective multicenter pilot study between November 2013 and November 2014 (Canadian Task Force Classification II-2). SettingAn academic urogynecology research hospital. PatientsSeventy consecutive patients with Pelvic Organ Prolapse Quantification stage ≥3 anterior and/or medial prolapse underwent laparoscopic sacrocolpopexy. InterventionsAll women underwent laparoscopic sacrocolpopexy with the same standardized technique using a synthetic surgical glue to fix anterior and posterior meshes. Measurements and Main ResultsPatients were followed up at 1 month and 1 year, with anatomic and functional assessment (Pelvic Floor Distress Inventory-20, Pelvic Floor Impact Questionnaire-7, and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12). Anatomic success was defined as 1-year Pelvic Organ Prolapse Quantification stage ≤1. Sixty-six patients were included; the mean age was 56.7 ± 1.2 years. The mean operative time was 145 ± 5 minutes. The mean glue fixation time was less than 2 minutes for both anterior and posterior meshes. The 1-year anatomic success rate was 87.5% in the anterior compartment (Ba at −2.3 cm, p < .0001) and 95.3% in the medial compartment (point C at −6.1 cm, p < .0001). There were no intra- or postoperative complications and no cases of mesh exposure; 5 cases of mesh shrinkage (7.8%) were observed at 1 year. The postoperative urinary stress incontinence rate was 29.7% at 1 year. Eight patients (12.1%) underwent revision surgery with transobturator tape. All quality of life scores showed significant improvement (p < .0001) at 1 year. ConclusionSynthetic glue attachment of prosthetic material in laparoscopic sacrocolpopexy proved straightforward, safe, time-saving, and effective at 1 year. Prospective randomized studies will be needed to confirm the long-term benefit.

Impact of an integrated treatment algorithm based on platelet function testing and clinical risk assessment: results of the TRIAGE Patients Undergoing Percutaneous Coronary Interventions To Improve Clinical Outcomes Through Optimal Platelet Inhibition study.

Assessment of platelet reactivity alone for thienopyridine selection with percutaneous coronary intervention (PCI) has not been associated with improved outcomes. In TRIAGE, a prospective multicenter observational pilot study we sought to evaluate the benefit of an integrated algorithm combining clinical risk and platelet function testing to select type of thienopyridine in patients undergoing PCI. Patients on chronic clopidogrel therapy underwent platelet function testing prior to PCI using the VerifyNow assay to determine high on treatment platelet reactivity (HTPR, ≥230 P2Y12 reactivity units or PRU). Based on both PRU and clinical (ischemic and bleeding) risks, patients were switched to prasugrel or continued on clopidogrel per the study algorithm. The primary endpoints were (i) 1-year major adverse cardiovascular events (MACE) composite of death, non-fatal myocardial infarction, or definite or probable stent thrombosis; and (ii) major bleeding, Bleeding Academic Research Consortium type 2, 3 or 5. Out of 318 clopidogrel treated patients with a mean age of 65.9±9.8years, HTPR was noted in 33.3%. Ninety (28.0%) patients overall were switched to prasugrel and 228 (72.0%) continued clopidogrel. The prasugrel group had fewer smokers and more patients with heart failure. At 1-year MACE occurred in 4.4% of majority HTPR patients on prasugrel versus 3.5% of primarily non-HTPR patients on clopidogrel (p=0.7). Major bleeding (5.6 vs 7.9%, p=0.47) was numerically higher with clopidogrel compared with prasugrel. Use of the study clinical risk algorithm for choice and intensity of thienopyridine prescription following PCI resulted in similar ischemic outcomes in HTPR patients receiving prasugrel and primarily non-HTPR patients on clopidogrel without an untoward increase in bleeding with prasugrel. However, the study was prematurely terminated and these findings are therefore hypothesis generating.

Detection of circulating trophoblast particles in maternal blood using density gradient centrifugation in preeclampsia and in normotensive pregnancies

ABSTRACTObjective: Preeclampsia (PE) is a frequent pregnancy-related disease and a major cause of maternal and fetal morbidity and mortality. Despite that, exact mechanisms of its pathophysiology remain largely unknown. In pregnancies complicated by PE, changes in the regulation of apoptosis seem to result in increased apoptotic shedding of trophoblast particles (TPs) into maternal circulation. Since the number of TP in peripheral blood is low, their detection necessitates pre-analytical enrichment. Methods: In this prospective multicenter pilot study we aimed to analyze TP in peripheral blood of 29 women with PE and of 13 unaffected controls using the OncoQuick®plus system for cell enrichment. Using immunocytochemistry, slides were evaluated microscopically for TP. Statistical analyses were performed using Welch’s t-test or Fisher’s exact test. Results: TP were detected in 10 (34.5%) women with PE and in two (15.4%) of unaffected controls. More than one TP were only found in PE. Comparing the mean counts of TP between groups, we detected significantly more TP in PE (p = 0.046). Conclusions: The OncoQuick®plus system can be applied to detect TP in both women with PE and in normotensive pregnancies. Longitudinal studies investigating the role of TP as a screening method for patients at risk for PE are warranted.

Surgeon’s and Caregivers’ Appraisals of Primary Cleft Lip Treatment with and without Nasoalveolar Molding: A Prospective Multicenter Pilot Study

Surgeon’s and Caregivers’ Appraisals of Primary Cleft Lip Treatment with and without Nasoalveolar Molding: A Prospective Multicenter Pilot Study

Impact of a Serious Videogame Designed for Flexible Insulin Therapy on the Knowledge and Behaviors of Children with Type 1 Diabetes: The LUDIDIAB Pilot Study

Flexible (or functional) insulin therapy method is a self-management education approach for intensive insulin therapy in patients with type 1 diabetes. The serious game (or applied game) "L'Affaire Birman" ("Mr. Birman's File") (available at www.gluciweb.com ) was specifically designed as an educational tool for the flexible insulin therapy method. Its educational impact was evaluated in children with type 1 diabetes. This prospective multicenter pilot study evaluated the effect of this videogame on the therapeutic knowledge and behavior of children with type 1 diabetes. PedCarbQuiz (PCQ) and Diabetes Self-Management Profile (DSMP) questionnaires were used before (T0), immediately after (T1), and 6 months after (T2) the unstructured use of the videogame. The 38 children enrolled in the study were 42% boys and 58% girls; they had a mean age of 13.7 ± 2.1 years old, a diabetes duration of 6.0 ± 3.8 years, and hemoglobin A1c (HbA1c) levels of 8.5 ± 1.4% (69.4 ± 9.4 mmol/mol). The children connected to the game 3.3 ± 2.8 times during this 6-month study. Their PCQ score increased from 31.6 ± 4.9 at T0 to 36.0 ± 4.0 at T2 (P < 0.05). Two PCQ subscores also increased significantly: the insulin titration score at T1 and T2 and the carbohydrate quantification score at T2. Conversely, the DSMP score was not different at T0, T1, and T2 (59.1 ± 9.9, 60.2 ± 9.8, and 60.0 ± 10.0, respectively), and HbA1c levels also remained stable throughout the study (8.4 ± 1.3%, 8.4 ± 1.2%, and 8.5 ± 1.5% at T0, T1, and T2, respectively). Subgroup analysis found a greater impact of the game in children with poor glycemic control and low knowledge at baseline. Adherence to the game was rather low (half of the children played less than 2.5 bouts), but no criterion was found to be predictive of this low attractiveness. Nonsupervised usage of the serious game "L'Affaire Birman" was able to improve insulin titration and carbohydrate quantification in children with type 1 diabetes.

Embryo selection using the Eeva Test, an automated time-lapse quantitative analysis, in conjunction with standard morphology: a prospective multi-center pilot study

Embryo selection using the Eeva Test, an automated time-lapse quantitative analysis, in conjunction with standard morphology: a prospective multi-center pilot study

Intradiscal Injection of Fibrin Sealant for the Treatment of Symptomatic Lumbar Internal Disc Disruption: Results of a Prospective Multicenter Pilot Study with 24-Month Follow-Up

Assess the safety and efficacy of intradiscal fibrin sealant in adults with chronic discogenic low back pain. Prospective, nonrandomized Food and Drug Administration approved pilot study. Three centers in the United States. Fifteen adults with chronic, single, or contiguous two-level lumbar discogenic pain confirmed through meticulous provocation discography. Volume- and pressure-controlled intradiscal delivery of BIOSTAT BIOLOGX(®) Fibrin Sealant with the Biostat(®) Delivery Device into symptomatic lumbar disc(s). Assessments were performed at baseline, 72 hours, and 1, 4, 13, 26, 52, and 104 weeks following intervention. Potential adverse events were evaluated with serial assessment of neurological status, radiographic, and magnetic resonance imaging (MRI). Efficacy measures included serial assessments of low back pain visual analog scale (VAS) measurements and the Roland-Morris Disability Questionnaire (RMDQ). Safety neurological assessments, X-ray, and MRI showed no significant changes. Adverse events were reported in nine subjects. Two instances of low back muscle spasm and one case of discitis were the only events considered related to the procedure or product. Mean low back pain VAS scores (mm) decreased from 72.4 (95% confidence interval 64.6-80.3) at baseline to 31.7 (17.4-46.1), 35.4 (17.7-53.1), and 33.0 (16.3-49.6); mean RMDQ score improved from 15.2 (12.7-17.7) at baseline to 8.9 (5.3-12.5), 6.2 (3.4-9.1), and 5.6 (2.9-8.4) at 26, 52, and 104 weeks, respectively. Intradiscal injection of BIOSTAT BIOLOGX Fibrin Sealant with the Biostat Delivery Device appears safe and may improve pain and function in selected patients with discogenic pain.

Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot: Multicenter Implementation of the Common Data Elements for Traumatic Brain Injury

Traumatic brain injury (TBI) is among the leading causes of death and disability worldwide, with enormous negative social and economic impacts. The heterogeneity of TBI combined with the lack of precise outcome measures have been central to the discouraging results from clinical trials. Current approaches to the characterization of disease severity and outcome have not changed in more than three decades. This prospective multicenter observational pilot study aimed to validate the feasibility of implementing the TBI Common Data Elements (TBI-CDEs). A total of 650 subjects who underwent computed tomography (CT) scans in the emergency department within 24 h of injury were enrolled at three level I trauma centers and one rehabilitation center. The TBI-CDE components collected included: 1) demographic, social and clinical data; 2) biospecimens from blood drawn for genetic and proteomic biomarker analyses; 3) neuroimaging studies at 2 weeks using 3T magnetic resonance imaging (MRI); and 4) outcome assessments at 3 and 6 months. We describe how the infrastructure was established for building data repositories for clinical data, plasma biomarkers, genetics, neuroimaging, and multidimensional outcome measures to create a high quality and accessible information commons for TBI research. Risk factors for poor follow-up, TBI-CDE limitations, and implementation strategies are described. Having demonstrated the feasibility of implementing the TBI-CDEs through successful recruitment and multidimensional data collection, we aim to expand to additional study sites. Furthermore, interested researchers will be provided early access to the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) data set for collaborative opportunities to more precisely characterize TBI and improve the design of future clinical treatment trials. (ClinicalTrials.gov Identifier NCT01565551.).

Single-operator Ultrasound-guided Intravenous Line Placement by Emergency Nurses Reduces the Need for Physician Intervention in Patients with Difficult-to-establish Intravenous Access

BackgroundEmergency physicians (EPs) have become facile with ultrasound-guided intravenous line (USIV) placement in patients for whom access is difficult to achieve, though the procedure can distract the EP from other patient care activities. ObjectivesWe hypothesize that adequately trained Emergency Nurses (ENs) can effectively perform single-operator USIV placement with less physician intervention than is required with blind techniques. MethodsThis was a prospective multicenter pilot study. Interested ENs received a 2-h tutorial from an experienced EP. Patients were eligible for inclusion if they had either two failed blind peripheral intravenous (i.v.) attempts, or if they reported or had a known history of difficult i.v. placement. Consenting patients were assigned to have either EN USIV placement or standard of care (SOC). ResultsFifty patients were enrolled, of which 29 were assigned to USIV and 21 to SOC. There were no significant differences in age, race, gender, or reason for inclusion. Physicians were called to assist in 11/21 (52.4%) of SOC cases and 7/29 (24.1%) of USIV cases (p = 0.04). Mean time to i.v. placement (USIV 27.6 vs. SOC 26.4 minutes, p = 0.88) and the number of skin punctures (USIV 2.0 vs. SOC 2.1, p = 0.70) were not significantly different. Patient satisfaction was higher in the USIV group, though the difference did not reach statistical significance (USIV 86.2% vs. SOC 63.2%, p = 0.06). Patient perception of pain on a 10-point scale was also similar (USIV 4.9 vs. SOC 5.5, p = 0.50). ConclusionsENs performing single-operator USIV placement in patients with difficult-to-establish i.v. access reduces the need for EP intervention.

Magnetic resonance imaging of abdominal versus vaginal prolapse surgery with mesh

We compared two surgical approaches in patients with symptomatic prolapse of the vaginal apex with normal controls by analyzing pelvic landmark relationships measured using magnetic resonance imaging (MRI) before and after surgery. In this prospective multicenter pilot study involving 16 participants, nulliparous controls (n = 6) were compared with ten parous (3.0 ± 1.0) women with uterine apical prolapse equal to or greater than stage 2. Group A (n = 5) underwent abdominal sacral colpopexy with monofilament polypropylene mesh and group B (n = 5) with vaginal mesh kit repair (Total ProLift). Subtotal hysterectomy was performed in all group A and no group B women. All patients underwent preoperative and 3-month postoperative Pelvic Organ Prolapse Quantification (POP-Q) and dynamic MRI. Comparison of MRI pelvic angles and distances was performed and analyzed by Mann-Whitney rank sum test and chi-square test. Vaginal apical support is similar at 3 months for abdominal sacral colpopexy (ASCP) and ProLift by POP-Q examination and MRI analysis. In both treatment groups, the postoperative POP-Q point C and MRI parameters were similar to nulliparous controls at 3 months. Anatomic outcomes for ASCP compared with ProLift were similar at 3 months in terms of vaginal apical support by POP-Q and MRI analysis. Continued comparative analysis of postoperative support with objective imaging seems warranted.

Early Diagnosis and Treatment of Postoperative Endoscopic Recurrence of Crohn’s Disease: Partial Benefit by Infliximab—A Pilot Study

Current data indicate that infliximab-given immediately after surgery-may be very effective in preventing postsurgical recurrence of Crohn's disease. However, it is unknown whether a similar benefit would result from early diagnosis and treatment, rather than prevention of endoscopic recurrence. The primary outcome of this study was to clarify whether infliximab, given after diagnosis of postoperative endoscopic recurrence of Crohn's diseases (Rutgeerts score≥2) can induce endoscopic remission (score<2) at 54weeks. The secondary outcomes were improvement in the endoscopic score and clinical recurrence at 54weeks. In this prospective open label multicenter pilot study 43 patients with ileocolonic Crohn's disease subjected to curative surgery underwent colonoscopy 6months after surgery. Patients with endoscopic recurrence (Rutgeerts score≥2) were treated with either mesalamine 800mg tid or infliximab 5mg/kgbw on a maintenance basis. Colonoscopy was performed after 54weeks of therapy. A total of 24/43 patients were diagnosed with endoscopic recurrence at 6months. Thirteen were treated with infliximab and 11 with mesalamine. None of the 11 mesalamine-treated patients had endoscopic remission at 54weeks. Two had clinical recurrence at 8 and 9months. Fifty-four percent of patients treated with infliximab had endoscopic remission at 54weeks (P=0.01) while 69% had an improvement in the endoscopic score. None had clinical recurrence. Treatment of postsurgical endoscopic lesions by infliximab appears superior to mesalamine. However, a sizeable proportion of patients did not fully benefit from this strategy.

International Live Endoscopic Multichannel Demonstration Using Superfast Broadband Internet Connections

Background/AimsTelemedicine is a convenient and efficient tool for remote education in various fields. The telemedicine system can also be used to educate doctors and medical students. The aim of our study was to establish the effectiveness of the telemedical system for use in a live endoscopic multichannel demonstration conference and to test the effectiveness and usefulness of a multicenter-based live endoscopic demonstration through live, interactive, high resolution video transmission using advanced networks and the digital video transport system (DVTS).MethodsThis study is a prospective multicenter pilot study. A live demonstration of an endoscopic submucosal dissection (ESD) and an endoscopic retrograde cholangiopancreatography (ERCP) using advanced network technology was performed.ResultsThe DVTS successfully transmitted uncompressed, high-resolution, digital lectures with endoscopy video during a multichannel endoscopic live demonstration of ESD and ERCP over multiple advanced networks. The overall satisfaction rating when the endoscopic lecture demonstration was performed by combining DVTS was generally good.ConclusionsWe believe that a multicenter-based live endoscopic demonstration is a very effective conferencing method when using advanced networks and DVTS.

A prospective pilot study comparing combined intravitreal ranibizumab and half-fluence photodynamic therapy with ranibizumab monotherapy in the treatment of neovascular age-related macular degeneration

PurposeThis prospective multi-center pilot study compares the use of half-fluence photodynamic therapy combined with ranibizumab with ranibizumab monotherapy for the treatment of neovascular age-related macular degeneration.MethodsAll patients presenting with untreated subfoveal neovascular age-related macular degeneration were considered for inclusion. Patients were randomized to receive either ranibizumab with half-fluence photodynamic therapy or ranibizumab alone. Patients in the ranibizumab alone group were given three consecutive monthly ranibizumab injections and were followed monthly. They were treated with ranibizumab as needed, based on clinical discretion, using vision and optical coherence tomography. Patients in the combined group were given one same-day combined ranibizumab and half-fluence (25 j/cm2) photodynamic therapy treatment and were treated monthly as needed. Outcomes included changes in standardized visual acuity, optical coherence tomography foveal thickness, and percentage of as-needed injections to maintenance examinations.ResultsFifty-six out of 60 enrolled patients completed the twelve month primary outcome visit; this consisted of 27 patients receiving ranibizumab alone and 29 receiving combined treatment. The average age was 79.1 for the ranibizumab alone group and 79.3 for the combined group. The mean visual acuity in the ranibizumab alone group improved from 52.9 Early Treatment of Diabetic Retinopathy letters initially to 62.8 letters at twelve months. The mean visual acuity in the combined group improved from 49.2 letters to 51.8 letters at twelve months. The differences in visual acuity improvements were not statistically significant based on a two-tailed t-test (P = 0.2). Due to the presence of outliers in each group, a Mann–Whitney U test was performed to confirm the results (U = 325; P = 0.28). The mean optical coherence tomography foveal thickness improved 92.5 microns and 106.7 microns in the ranibizumab alone and the combined group, respectively. The difference was not significant based on a two-tailed t-test (P = 0.6). The ranibizumab alone group received an average of 6.8 injections, while the combined group received an average of three injections. This difference was not significant based on a chi-square test (P = 0.11).ConclusionThe groups appeared similar based on statistical analysis, but larger studies are needed to determine possible small differences between combination therapy and monotherapy.

A career in cardiothoracic surgery

BACKGROUND: High-flow nasal cannula (HFNC) oxygen therapy is used to deliver an FIO2 from 0.21 to 1.0. The double-trunk mask (DTM) is a device designed to increase the FIO2 in patients with a high inspiratory flow demand. The aim of our study was to evaluate the effect of DTM in hypoxemic subjects already receiving HFNC. METHODS: We report a prospective multi-center crossover pilot study including 15 subjects treated with HFNC for acute hypoxemic respiratory failure. Measurements were performed at the end of 30-min periods with HFNC only, with HFNC + DTM, and again with HFNC only. RESULTS: Compared with HFNC alone, HFNC + DTM increased PaO2 from 68 ± 14 mm Hg to 85 ± 22 mm Hg (P CONCLUSIONS: In subjects receiving oxygen via HFNC, the addition of the DTM over the HFNC increased PaO2 without changing the PaCO2.

The HEP-NET B/C co-infection trial: A prospective multicenter study to investigate the efficacy of pegylated interferon-α2b and ribavirin in patients with HBV/HCV co-infection

The efficacy of pegylated interferon alpha and ribavirin in HBV/HCV co-infected patients is unknown. Nineteen patients with chronic HBV/HCV co-infection (HBsAg and HCV-RNA positive; 10 HCV-genotype 1; 9 HCV-genotype 2 or 3) were included in this prospective multicenter pilot study. Baseline HBV-DNA was negative in 13 individuals. All patients received weight-adjusted PEG-IFN-alpha2b and ribavirin for 48 weeks. In the intent-to-treat analysis, a biochemical and an HCV-RNA response were observed in 12 and 14 patients, respectively (63% and 74%). At the end of the treatment as well as at the end of the follow-up the HCV-RNA response was 93% (14/15) in patients adherent to therapy (86% in genotype 1 and 100% in genotypes 2 and 3 infection). Two of the five initially HBV-DNA positive patients with follow-up available were HBV-DNA negative at follow-up week 24. In contrast, HBV-DNA became detectable after the clearance of HCV in four initially HBV-DNA negative patients. Combination therapy with PEG-IFN-a2b and ribavirin is highly effective in inducing a virological response concerning HCV in patients with HBV/HCV co-infection. However, HBV replication may increase after the clearance of HCV and thus close monitoring for both the viruses is recommended even in patients with initially undetectable HBV-DNA.

ASD and PFO closure with the Solysafe septal occluder—Results of a prospective multicenter pilot study

We report the results of a prospective multicenter pilot study performed in Germany, Sweden, and Switzerland with a new self-centering device for transcatheter closure of an atrial septal defect (ASD) or a patent foramen ovale (PFO) called the Solysafe Septal Occluder. The device was successfully implanted in 44 patients. In 15 patients with a median age of 40 years (range 6-76 years), a Solysafe device was successfully implanted in an ASD. The median size of the stretched defects was 17 mm (range 10-21 mm). Three 15-mm devices, eight 20-mm devices, and four 25-mm devices were used. Procedure time ranged from 40 to 107 min (median 66 min) and fluoroscopic time from 5.3 to 17.5 min (median 12 min). In 29 patients with a median age of 47 years (range 15-78 years), a Solysafe device was implanted in a PFO. The procedure time ranged from 21 to 155 min (median 51 min) and fluoroscopic time from 3.1 to 31.3 min (median 7.6 min). At discharge, 1 of the 29 patients (3%) had a small shunt. No patient in either the ASD or the PFO group had any major complication. Six months after implantation, the overall closure rate with the Solysafe septal occluder in both groups was 100% (44/44). With the self-centering Solysafe Septal Occluder, PFOs, and ASDs with a stretched diameter of up to 21 mm can be effectively closed with very high occlusion rates.

Multicenter study on in vitro characterization of dendritic cells

There is growing interest in the use of in vitro-expanded dendritic cells (DC) in cancer immunotherapy as cellular-based vaccines. However, the methods used for in vitro preparation vary widely between institutions. Therefore, a strong need exists for standardization, characterization and quality control (QC) of such vaccines. A first prospective multicenter pilot study was performed to investigate basic QC parameters of frozen/thawed DC. The study design was focused on comparison of test results for cell counts, immunophenotyping and cell viability. CD14+ monocytes were isolated from three healthy volunteers. The cells were expanded in vitro, matured and cryopreserved using a standardized protocol in one laboratory. The aliquots of cryopreserved DC and a panel of reagents were shipped to eight laboratories worldwide. The objective was to compare the results of non-functional QC assays between sites by testing identical DC vaccines and using a pre-defined test protocol. Measurements of nucleated cell (NC) content of thawed DC vaccines with different types of hematology analyzers (HA) gave similar results for the majority of sites. Immunophenotyping using identical clones of monoclonal antibodies for the detection of surface antigens (i.e. CD1a, CD14, CD16, CD83, CD86 and HLA-DR) provided mostly comparable results between laboratories with an acceptable level of variation. In contrast, highly different results between study sites were generated for measuring the viability of thawed DC by flow cytometry using 7-amino-actinomycin D (7-AAD) dye exclusion. In characterizing frozen/thawed DC vaccines, NC counts generated by HA yielded similar results between different laboratories. Furthermore, immunophenotyping of DC vaccines can be standardized between centers, i.e. by using identical reagents. Because of highly variable results between laboratories, 7-AAD viability testing of thawed DC needs to be studied further to identify potential causes for the observed variability.