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Objective: To assess the prevalence and clinical significance of incidental findings identified during computed tomography imaging of coronary artery bypass grafts. Results: This prospective study includes 144 patients undergoing coronary graft patency assessment using computed tomography. Incidental findings were classified as significant if they were considered to need an immediate action or treatment, short-term work-up or follow-up, or minor. A total of 211 incidental findings were present in 109 (75.7%) patients. Seventy-one incidental findings (33.6%) were cardiac and 140 (66.4%) were extracardiac. Most common cardiac incidental findings were atrial dilatation [39 patients, 48 incidental findings (67.6%)] and aortic valve calcifications (7 patients, 9.9%). Among the 140 extracardiac incidental findings, the most common were lung nodules (51 patients, 54 nodules, 38.6%), and emphysema (21 patients, 15%). Thirty-six (25.7%) extracardiac incidental findings were significant and notably, 23 (63.9%) were lung nodules. Follow-up was recommended in 37 cases, among which all patients with significant lung nodules (23 patients, 62.2%). In conclusion, most common computed tomography incidental findings in patients with coronary grafts were lung nodules and emphysema. [ABSTRACT FROM AUTHOR]

Background: Many clinical trials focus on the comparison of the treatment effect between two or more groups concerning a rarely occurring event. In this situation, showing a relevant effect with an acceptable power requires the observation of a large number of patients over a long period of time. For feasibility issues, it is therefore often considered to include several event types of interest, non-fatal or fatal, and to combine them within a composite endpoint. Commonly, a composite endpoint is analyzed with standard survival analysis techniques by assessing the time to the first occurring event. This approach neglects that an individual may experience more than one event which leads to a loss of information. As an alternative, composite endpoints could be analyzed by models for recurrent events. There exists a number of such models, e.g. regression models based on count data or Cox-based models such as the approaches of Andersen and Gill, Prentice, Williams and Peterson or, Wei, Lin and Weissfeld. Although some of the methods were already compared within the literature there exists no systematic investigation for the special requirements regarding composite endpoints.Methods: Within this work a simulation-based comparison of recurrent event models applied to composite endpoints is provided for different realistic clinical trial scenarios.Results: We demonstrate that the Andersen-Gill model and the Prentice- Williams-Petersen models show similar results under various data scenarios whereas the Wei-Lin-Weissfeld model delivers effect estimators which can considerably deviate under commonly met data scenarios.Conclusion: Based on the conducted simulation study, this paper helps to understand the pros and cons of the investigated methods in the context of composite endpoints and provides therefore recommendations for an adequate statistical analysis strategy and a meaningful interpretation of results. [ABSTRACT FROM AUTHOR]

Background: Metastatic pancreatic cancer has a dismal prognosis, with a mean six-month progression-free survival of approximately 50% and a median survival of about 11 months. Despite intensive research, only slight improvements of clinical outcome could be achieved over the last decades. Hence, new and innovative therapeutic strategies are urgently required. ParvOryx is a drug product containing native parvovirus H-1 (H-1PV). Since H-1PV was shown to exert pronounced anti-neoplastic effects in pre-clinical models of pancreatic cancer, the drug appears to be a promising candidate for treatment of this malignancy.Methods: ParvOryx02 is a non-controlled, single arm, open label, dose-escalating, single center trial. In total seven patients with pancreatic cancer showing at least one hepatic metastasis are to be treated with escalating doses of ParvOryx according to the following schedule: i) 40% of the total dose infused intravenously in equal fractions on four consecutive days, ii) 60% of the total dose injected on a single occasion directly into the hepatic metastasis at varying intervals after intravenous infusions. The main eligibility criteria are: age ≥ 18 years, disease progression despite first-line chemotherapy, and at least one hepatic metastasis. Since it is the second trial within the drug development program, the study primarily explores safety and tolerability after further dose escalation of ParvOryx. The secondary objectives are related to the evaluation of certain aspects of anti-tumor activity and clinical efficacy of the drug.Discussion: This trial strongly contributes to the clinical development program of ParvOryx. The individual hazards for patients included in the current study and the environmental risks are addressed and counteracted adequately. Besides information on safety and tolerability of the treatment after further dose escalation, thorough evaluations of pharmacokinetics and intratumoral spread as well as proof-of-concept (PoC) in pancreatic cancer will be gained in the course of the trial.Trial Registration: ClinicalTrials.gov-ID: NCT02653313 , Registration date: Dec. 4th, 2015. [ABSTRACT FROM AUTHOR]

Background: In clinical trials, the opportunity for an early stop during an interim analysis (either for efficacy or for futility) may relevantly save time and financial resources. This is especially important, if the planning assumptions required for power calculation are based on a low level of evidence. For example, when including two primary endpoints in the confirmatory analysis, the power of the trial depends on the effects of both endpoints and on their correlation. Assessing the feasibility of such a trial is therefore difficult, as the number of parameter assumptions to be correctly specified is large. For this reason, so-called 'group sequential designs' are of particular importance in this setting. Whereas the choice of adequate boundaries to stop a trial early for efficacy has been broadly discussed in the literature, the choice of optimal futility boundaries has not been investigated so far, although this may have serious consequences with respect to performance characteristics.Methods: In this work, we propose a general method to construct 'optimal' futility boundaries according to predefined criteria. Further, we present three different group sequential designs for two endpoints applying these futility boundaries. Our methods are illustrated by a real clinical trial example and by Monte-Carlo simulations.Results: By construction, the provided method of choosing futility boundaries maximizes the probability to correctly stop in case of small or opposite effects while limiting the power loss and the probability of stopping the study 'wrongly'. Our results clearly demonstrate the benefit of using such 'optimal' futility boundaries, especially compared to futility boundaries commonly applied in practice.Conclusions: As the properties of futility boundaries are often not considered in practice and unfavorably chosen futility boundaries may imply bad properties of the study design, we recommend assessing the performance of these boundaries according to the criteria proposed in here. [ABSTRACT FROM AUTHOR]

Background: Struma ovarii is a rare monodermal germ cell tumor where the ovary is comprised of at least half thyroid tissue. This phenomenon may indicate an embryological origin. Case presentation: A 30-year old nulliparous woman presented with acute right lower quadrant pain and underwent laparoscopic right salpingo-oophorectomy. The excised ovarian mass showed evidence of strumaderived papillary thyroid carcinoma. Ultrasound of the thyroid showed mild enlargement with two solid nodules. A fine needle aspirate of a thyroid nodule was positive for malignancy and a total thyroidectomy was performed. Microscopic features of the thyroid were consistent with papillary thyroid carcinoma. The two tumours were considered as synchronous independent primaries based on their histological presentation. Conclusions: We believe that aggressive surgical management followed by radioiodine therapy is best to reduce recurrence risk and optimize survival. The broad scope of interventions needed to treat malignant struma ovarii require a strong interdisciplinary team. [ABSTRACT FROM AUTHOR]

Background: Effective treatment of paroxysmal atrial fibrillation (AF) is essential for reducing the risk of stroke and heart failure. Cryoballoon (CB) ablation has been developed as an alternative to the use of radiofrequency (RF) energy for electrical isolation of the pulmonary veins. Herein, we provide long-term data regarding the efficacy of CB ablation in comparison to RF.Methods: FreezeAF was a randomised non-inferiority study comparing CB ablation with RF ablation for the treatment of patients with drug-refractory paroxysmal AF. Procedural success for the long-term follow-up (30 months) was defined as freedom from AF with an absence of persistent complications.Results: Of the 315 patients that were randomised and received catheter ablation, 292 (92.7%) completed the 30-month follow-up (147 in the RF group and 145 in the CB group). The baseline characteristics of the RF and CB groups were similar. Single-procedure success was achieved by 40% of patients in the RF group and 42% of the CB group (p < 0.001 for non-inferiority). When including re-do procedures in the analysis, the multiple procedure success rate was 72% in the RF group and 76% in the CB group.Conclusion: The data provide long-term evidence that CB ablation is non-inferior to RF ablation, with high proportions of patients reporting freedom from AF 30 months after the index procedure.Trial Registration: ClinicalTrials.gov Identifier: NCT00774566 ; first registered October 16, 2008; first patient included October 20, 2008. [ABSTRACT FROM AUTHOR]

Background: Current literature has shown the mechanism of how indirect fractures occur but has not determined what factors increase the risks of such fractures. The objective of this study is thus to determine the effect of clothing and soft tissue thickness on the risk of indirect fracture formation. Methods: Twenty-five fresh red deer femora embedded in ballistic gelatine were shot with varying distances off their medial cortex with a 5.56 × 45 mm North Atlantic Treaty Organization (NATO) bullet while being filmed with a slow-motion video. We compared the effect of two different gelatine depths and the effect of denim cloth laid onto the impact surface of the moulds. Results: Bullet passage in thinner moulds failed to cause fracture because the bullet exited the mould before a large expanding temporary cavity was produced. Clothing dramatically altered the size and depth of the expanding cavity, as well as increased lateral pressures, resulting in more severe fractures with greater bullet distances from the bone that can cause fracture. Conclusions: Clothing increases the risk of indirect fracture and results in larger, more superficial temporary cavities, with greater lateral pressures than are seen in unclothed specimens, resulting in more comminuted fractures. Greater tissue depth affords the 5.56 × 45 mm NATO a chance to yaw and thus develop an enlarging temporary cavity that is sufficient to cause fracture. [ABSTRACT FROM AUTHOR]

Background: Remote ballistic femoral fractures are rare fractures reported in the literature but still debated as to their existence and, indeed, their treatment. This study aimed to prove their existence, understand how they occur and determine which ammunition provides the greatest threat. In addition, fracture patterns, soft tissue disruption and contamination were assessed to aid in treatment planning. Method: We filmed 42 deer femora embedded in ballistic gelatine and shot with four different military (5.56 × 45 mm, 7.62 × 39 mm) and civilian (9 × 19 mm, .44 in.) bullets, at varying distances off the bone (0-10 cm). Results: Two remote ballistic fractures occurred, both with .44 in. hollow-point bullets shot 3 cm off the bone. These fractures occurred when the leading edge of the expanding temporary cavity impacted the femur's supracondylar region, producing a wedge-shaped fracture with an undisplaced limb, deceivingly giving the appearance of a spiral fracture. No communication was seen between the fracture and permanent cavity, despite the temporary cavity encasing the fracture and stripping periosteum from its base. Conclusion: These fractures occur with civilian ammunition, but cannot prove their existence with military rounds. They result from the expanding temporary cavity affecting the weakest part of the bone, creating a potentially contaminated wedge-shaped fracture, important for surgeons considering operative intervention. [ABSTRACT FROM AUTHOR]