Utilisation of cardiac pacemakers over a 20-year period: Results from a nationwide pacemaker registry

The implantation of cardiac pacemakers has become a well-established therapy for conduction disorders and sinus node dysfunction. In many countries pacemaker registries have been initiated in order to collect information on patient characteristics, trends in numbers and the types of pacemakers used, to identify problematic devices, and for safety monitoring. For this utilisation study the Central Pacemaker Patients Registration (CPPR) from the Netherlands Pacemaker Registry Foundation (CPPR-SPRN) containing data collected for more than 20 years was used. During this period nearly 97,000 first pacemakers were implanted. Analyses show an increase in the rate of implanted devices. The change in pacemaker type from VVI to DDD, followed by biventricular stimulation, is reflected by the number of simultaneously implanted leads, which is partly a consequence of cardiac resynchronisation therapy. Our data demonstrate that indications for implantation and type of pacemaker are comparable with other European countries

Suitability of the Cellient (TM) cell block method for diagnosing soft tissue and bone tumors

BACKGROUNDThe diagnosis of tumors of soft tissue and bone (STB) heavily relies on histological biopsies, whereas cytology is not widely used. Cellient(TM) cell blocks often contain small tissue fragments. In addition to Hematoxylin and Eosin (H&E) interpretation of histological features, immunohistochemistry (IHC) can be applied after optimization of protocols. The objective of this retrospective study was to see whether this cytological technique allowed us to make a precise diagnosis of STB tumors. METHODSOur study cohort consisted of 20 consecutive STB tumors, 9 fine-needle aspiration (FNAC) samples, and 11 endoscopic ultrasonography (EUS) FNACs and included 8 primary tumors and 12 recurrences or metastases of known STB tumors. RESULTSIn all 20 cases, H&E stained sections revealed that diagnostically relevant histological and cytological features could be examined properly. In the group of 8 primary tumors, IHC performed on Cellient(TM) material provided clinically important information in all cases. For instance, gastrointestinal stromal tumor (GIST) was positive for CD117 and DOG-1 and a PEComa showed positive IHC for actin, desmin, and HMB-45. In the group of 12 secondary tumors, SATB2 was visualized in metastatic osteosarcoma, whereas expression of S-100 was present in 2 secondary chondrosarcomas. Metastatic chordoma could be confirmed by brachyury expression. Two metastatic alveolar rhabdomyosarcomas were myf4 positive, a metastasis of a gynecologic leiomyosarcoma was positive for actin and estrogen receptor (ER) and a recurrent dermatofibrosarcoma protuberans expressed CD34. CONCLUSIONIn the proper clinical context, including clinical presentation with imaging studies, the Cellient(TM) cell block technique has great potential for the diagnosis of STB tumors

Identification of a methylation panel as an alternative triage to detect CIN3+ in hrHPV-positive self-samples from the population-based cervical cancer screening programme

Background: The Dutch population-based cervical cancer screening programme (PBS) consists of primary high-risk human papilloma virus (hrHPV) testing with cytology as triage test. In addition to cervical scraping by a general practitioner (GP), women are offered self-sampling to increase participation. Because cytological examination on self-sampled material is not feasible, collection of cervical samples from hrHPV-positive women by a GP is required. This study aims to design a methylation marker panel to detect CIN3 or worse (CIN3+) in hrHPV-positive self-samples from the Dutch PBS as an alternative triage test for cytology.Methods: Fifteen individual host DNA methylation markers with high sensitivity and specificity for CIN3+ were selected from literature and analysed using quantitative methylation-specific PCR (QMSP) on DNA from hrHPV-positive self-samples from 208 women with CIN2 or less (&lt; CIN2) and 96 women with CIN3+. Diagnostic performance was determined by area under the curve (AUC) of receiver operating characteristic (ROC) analysis. Self-samples were divided into a train and test set. Hierarchical clustering analysis to identify input methylation markers, followed by model-based recursive partitioning and robustness analysis to construct a predictive model, was applied to design the best marker panel.Results: QMSP analysis of the 15 individual methylation markers showed discriminative DNA methylation levels between &lt; CIN2 and CIN3+ for all markers (p &lt; 0.05). The diagnostic performance analysis for CIN3+ showed an AUC of ≥ 0.7 (p &lt; 0.001) for nine markers. Hierarchical clustering analysis resulted in seven clusters with methylation markers with similar methylation patterns (Spearman correlation&gt; 0.5). Decision tree modeling revealed the best and most robust panel to contain ANKRD18CP, LHX8 and EPB41L3 with an AUC of 0.83 in the training set and 0.84 in the test set. Sensitivity to detect CIN3+ was 82% in the training set and 84% in the test set, with a specificity of 74% and 71%, respectively. Furthermore, all cancer cases (n = 5) were identified.Conclusion: The combination of ANKRD18CP, LHX8 and EPB41L3 revealed good diagnostic performance in real-life self-sampled material. This panel shows clinical applicability to replace cytology in women using self-sampling in the Dutch PBS programme and avoids the extra GP visit after a hrHPV-positive self-sampling test.</p

Focal Thyroid Incidentalomas on F-18-FDG PET/CT:A Systematic Review and Meta-Analysis on Prevalence, Risk of Malignancy and Inconclusive Fine Needle Aspiration

BackgroundThe rising demand for 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET/CT) has led to an increase of thyroid incidentalomas. Current guidelines are restricted in giving options to tailor diagnostics and to suit the individual patient.ObjectivesWe aimed at exploring the extent of potential overdiagnostics by performing a systematic review and meta-analysis of the literature on the prevalence, the risk of malignancy (ROM) and the risk of inconclusive FNAC (ROIF) of focal thyroid incidentalomas (FTI) on 18F-FDG PET/CT.Data SourcesA literature search in MEDLINE, Embase and Web of Science was performed to identify relevant studies.Study SelectionStudies providing information on the prevalence and/or ROM of FTI on 18F-FDG PET/CT in patients with no prior history of thyroid disease were selected by two authors independently. Sixty-one studies met the inclusion criteria.Data AnalysisA random effects meta-analysis on prevalence, ROM and ROIF with 95% confidence intervals (CIs) was performed. Heterogeneity and publication bias were tested. Risk of bias was assessed using the quality assessment of diagnostic accuracy studies (QUADAS-2) tool.Data SynthesisFifty studies were suitable for prevalence analysis. In total, 12,943 FTI were identified in 640,616 patients. The pooled prevalence was 2.22% (95% CI = 1.90% - 2.54%, I2 = 99%). 5151 FTI had cyto- or histopathology results available. The pooled ROM was 30.8% (95% CI = 28.1% - 33.4%, I2 = 57%). 1308 (83%) of malignant nodules were papillary thyroid carcinoma (PTC). The pooled ROIF was 20.8% (95% CI = 13.7% - 27.9%, I2 = 92%).LimitationsThe main limitations were the low to moderate methodological quality of the studies and the moderate to high heterogeneity of the results.ConclusionFTI are a common finding on 18F-FDG PET/CTs. Nodules are malignant in approximately one third of the cases, with the majority being PTC. Cytology results are non-diagnostic or indeterminate in one fifth of FNACs. These findings reveal the potential risk of overdiagnostics of FTI and emphasize that the workup of FTI should be performed within the context of the patient’s disease and that guidelines should adopt this patient tailored approach

Towards the systematic construction of domain-specific transformation languages

The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-319-09195-2-13Proceedings of 10th European Conference, ECMFA 2014, Held as Part of STAF 2014, York, UK, July 21-25, 2014General-purpose transformation languages, like ATL or QVT, are the basis for model manipulation in Model-Driven Engineering (MDE). However, as MDE moves to more complex scenarios, there is the need for specialized transformation languages for activities like model merging, migration or aspect weaving, or for specific domains of wide use like UML. Such domain-specific transformation languages (DSTLs) encapsulate transformation knowledge within a language, enabling the reuse of recurrent solutions to transformation problems. Nowadays, many DSTLs are built in an ad-hoc manner, which requires a high development cost to achieve a full-featured implementation. Alternatively, they are realised by an embedding into general-purpose transformation or programming languages like ATL or Java. In this paper, we propose a framework for the systematic creation of DSTLs. First, we look into the characteristics of domain-specific transformation tools, deriving a categorization which is the basis of our framework. Then, we propose a domain-specific language to describe DSTLs, from which we derive a ready-to-run workbench which includes the abstract syntax, concrete syntax and translational semantics of the DSTL.This work has been funded by the Spanish Ministry of Economy and Competitivity with project “Go Lite” (TIN2011-24139

Trends in service time of pacemakers in the Netherlands:A long-term nationwide follow-up study

Aims: After decades of experience and strongly improved technology, service time of pacemaker generators is expected to increase. To test this hypothesis, we conducted a retrospective review of a large cohort of patients with a pacemaker. Methods: We reviewed data collected between 1984 and 2006 in the first national Dutch pacemaker registry. This registry covered 96% of all generators implanted. We analysed the time of and reason for explantation of pacemaker generators. A 7-year follow-up interval after first implantation and following replacements was used to analyse changes over time. Results: During 22 years of data collection, nearly 97,000 first pacemaker generators were implanted. A total of 27,937 (22.4%) generators were explanted within a mean of 6.3 (standard deviation 3.3) years. Reasons for approximately 60% of these explantations were ` end of life' of the pacemaker generator or elective system change. Complications or failures such as infections and recalls accounted for approximately 20% of the explantations. For the remaining 20%, the reasons for explantation had not been registered. Conclusion: Despite progress in technology, a substantial proportion of pacemaker generators is explanted before its expected service time, with one in five generators being replaced due to technical failures, infections or other complications. Furthermore, the time interval between pacemaker implantation and explantation due to normal 'end of life' (battery EOL) decreased. Infections continue to rank highly as a cause for pacing system replacement, despite all current preventive measures