The intraoperative optical coherence tomography (iOCT) is recently introduced in Descemet membrane endothelial keratoplasty (DMEK) surgery, which aims to increase clinical performance and surgery ...safety. However, the acquisition of this modality is a substantial investment. The objective of this paper is to report on the cost‐effectiveness of an iOCT‐protocol in DMEK surgery with the Advanced Visualization in Corneal Surgery Evaluation (ADVISE) trial. This cost‐effectiveness analysis uses data 6 months postoperatively from the multicentre prospective randomized clinical ADVISE trial. Sixty‐five patients were randomized to usual care (n = 33) or the iOCT‐protocol (n = 32). Quality‐Adjusted Life Years (EQ‐5D‐5L), Vision‐related Quality of Life (NEI‐VFQ‐25) and self‐administered resources questionnaires were administered. Main outcome is the incremental cost‐effectiveness ratio (ICER) and sensitivity analyses. The iOCT protocol reports no statistical difference in ICER. For the usual care group compared with the iOCT protocol, respectively, the mean societal costs are €5027 compared with €4920 (Δ€107). The sensitivity analyses report the highest variability on time variables. This economic evaluation learned that there is no added value in quality of life or cost‐effectiveness in using the iOCT protocol in DMEK surgery. The variability of cost variables depends on the characteristics of an eye clinic. The added value of iOCT could gain incrementally by increasing surgical efficiency, and aiding in surgical decision‐making.
Aims
To illustrate the practical and technical challenges along with the safety aspects when performing MRI‐guided electrophysiological procedures in a pre‐existing diagnostic magnetic resonance ...imaging (MRI) environment.
Methods and Results
A dedicated, well‐trained multidisciplinary interventional cardiac MRI team (iCMR team), consisting of electrophysiologists, imaging cardiologists, radiologists, anaesthesiologists, MRI physicists, electrophysiological (EP) and MRI technicians, biomedical engineers, and medical instrumentation technologists is a prerequisite for a safe and feasible implementation of CMR‐guided electrophysiological procedures (iCMR) in a pre‐existing MRI environment. A formal dry run “mock‐up” to address the entire spectrum of technical, logistic, and safety issues was performed before obtaining final approval of the Board of Directors. With this process we showed feasibility of our workflow, safety protocol, and bailout procedures during iCMR outside the conventional EP lab. The practical aspects of performing iCMR procedures in a pre‐existing MRI environment were addressed and solidified. Finally, the influence on neighbouring MRI scanners was evaluated, showing no interference.
Conclusion
Transforming a pre‐existing diagnostic MRI environment into an iCMR suite is feasible and safe. However, performing iCMR procedures outside the conventional fluoroscopic lab, poses challenges with technical, practical, and safety aspects that need to be addressed by a dedicated multi‐disciplinary iCMR team.
The Earth system model EC-Earth3 for contributions to CMIP6 is documented here, with its flexible coupling framework, major model configurations, a methodology for ensuring the simulations are ...comparable across different high-performance computing (HPC) systems, and with the physical performance of base configurations over the historical period. The variety of possible configurations and sub-models reflects the broad interests in the EC-Earth community. EC-Earth3 key performance metrics demonstrate physical behavior and biases well within the frame known from recent CMIP models. With improved physical and dynamic features, new Earth system model (ESM) components, community tools, and largely improved physical performance compared to the CMIP5 version, EC-Earth3 represents a clear step forward for the only European community ESM. We demonstrate here that EC-Earth3 is suited for a range of tasks in CMIP6 and beyond.
Cone photoreceptor disorders form a clinical spectrum of diseases that include progressive cone dystrophy (CD) and complete and incomplete achromatopsia (ACHM). The underlying disease mechanisms of ...autosomal recessive (ar)CD are largely unknown. Our aim was to identify causative genes for these disorders by genome-wide homozygosity mapping. We investigated 75 ACHM, 97 arCD, and 20 early-onset arCD probands and excluded the involvement of known genes for ACHM and arCD. Subsequently, we performed high-resolution SNP analysis and identified large homozygous regions spanning the PDE6C gene in one sibling pair with early-onset arCD and one sibling pair with incomplete ACHM. The PDE6C gene encodes the cone α subunit of cyclic guanosine monophosphate (cGMP) phosphodiesterase, which converts cGMP to 5′-GMP, and thereby plays an essential role in cone phototransduction. Sequence analysis of the coding region of PDE6C revealed homozygous missense mutations (p.R29W, p.Y323N) in both sibling pairs. Sequence analysis of 104 probands with arCD and 10 probands with ACHM revealed compound heterozygous PDE6C mutations in three complete ACHM patients from two families. One patient had a frameshift mutation and a splice defect; the other two had a splice defect and a missense variant (p.M455V). Cross-sectional retinal imaging via optical coherence tomography revealed a more pronounced absence of cone photoreceptors in patients with ACHM compared to patients with early-onset arCD. Our findings identify PDE6C as a gene for cone photoreceptor disorders and show that arCD and ACHM constitute genetically and clinically overlapping phenotypes.
Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), ...and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options.
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•Invasive lobular carcinoma (ILC) is a clinically and molecularly distinct disease•ILCs show CDH1 and PTEN loss, AKT activation, and mutations in TBX3 and FOXA1•Proliferation and immune-related gene expression signatures define 3 ILC subtypes•Genetic features classify mixed tumors into lobular-like and ductal-like subgroups
A comprehensive analysis of 817 breast tumor samples determines invasive lobular carcinoma as a molecularly distinct disease with characteristic genetic features, providing key information for patient stratification that may allow a more informed clinical follow-up.
The presence of extracranial carotid disease (ECD) is associated with less favorable clinical outcomes in patients with acute ischemic stroke caused by intracranial proximal occlusion. Acute ...intra-arterial treatment (IAT) in the setting of extracranial and intracranial lesions is considered challenging, and whether it yields improved outcomes remains uncertain.
To examine whether the presence of ECD modified the effect of IAT for intracranial proximal anterior circulation occlusion.
Prespecified subgroup analysis of a randomized clinical trial of endovascular treatment for acute ischemic stroke in the Netherlands. (Trial registrations: NTR1804 Netherlands Trial Register and ISRCTN10888758).
16 hospitals in the Netherlands.
Acute ischemic stroke caused by proximal intracranial arterial occlusion of the anterior circulation. Extracranial carotid disease was defined as cervical internal carotid artery stenosis (>50%) or occlusion.
IAT treatment versus no IAT.
The primary outcome was functional outcome, as measured by the modified Rankin Scale at 90 days and reported as adjusted common odds ratio (acOR) for a shift in direction of a better outcome. Multivariable ordinal logistic regression analysis with an interaction term was used to estimate treatment effect modification by ECD.
The overall acOR was 1.67 (95% CI, 1.21 to 2.30) in favor of the intervention. The acOR was 3.1 (CI, 1.7 to 5.8) in the prespecified subgroup of patients with ECD versus 1.3 (CI, 0.9 to 1.9) in patients presenting without ECD. Both acORs are in favor of the intervention (P for interaction = 0.07).
The study was not powered for subgroup analysis.
Intra-arterial treatment may be at least as effective in patients with ECD as in those without ECD, and it should not be withheld in these complex patients with acute ischemic stroke.
Dutch Heart Foundation, AngioCare BV, Medtronic/Covidien/EV3, MEDAC Gmbh/LAMEPRO, Penumbra, Stryker, and Top Medical/Concentric.
Over the last two decades, an increase in office-based procedures under topical anesthesia in laryngology and head and neck oncology has occurred. Adequate anesthesia in the nasal cavity, pharynx, ...and larynx is essential for successful performance of these procedures. Our goal is to provide an objective summary on the available local anesthetics, methods of application, local secondary effects, efficacy, and complications.
A descriptive review of literature on topical anesthesia for office-based procedures in laryngology and head and neck oncology was performed.
Lidocaine is the most applied and investigated topical anesthetic. Topical anesthesia results in decreased sensory function without impairing motor function of the pharynx and larynx. For the nasal cavity, cotton pledgets soaked in anesthetic spray and decongestant, or anesthetic gel, are effective. For the pharynx, anesthetic spray is the most frequently used and effective method. For the larynx, applying local anesthesia through a catheter through the working channel of the endoscope or anesthetic injection through the cricothyroid membrane is effective. Studies comparing the most effective application methods for each anatomical site are lacking. Complications of topical lidocaine administration are rare.
By properly applying topical anesthesia to the upper aerodigestive tract, several surgical procedures in laryngology and head and neck oncology can be performed in the outpatient clinic under topical anesthesia instead of the operating room under general anesthesia. Lidocaine is the most investigated anesthetic, with adequate efficacy and few complications. Studies that determine the most effective application methods are still wanting.
Korruption ist ein weltumspannendes Phänomen, das—wie die jüngsten Fälle bei BMW, Infineon, Siemens und Volkswagen deutlich machen—auch in Deutschland aktuell ist. Wie äußert sich Korruption, welche ...Folgen hat sie für die Volkwirtschaft, und wie lässt sie sich bekämpfen? Robert Vehrkamp behandelt die ökonomischen Konsequenzen der Korruption, Johann Graf Lambsdorff und Mathias Nell die Reformmaßnahmen, die für ihre wirksame Bekämpfung erforderlich sind.
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