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Background: The parallel wire technique (PW) is a classic part of the antegrade strategy to open chronic total coronary occlusions (CTO)., Aims: With modern wires and dual-lumen catheters (DLC) the approach has evolved, but this progress had not been evaluated in a contemporary registry of CTO interventions., Method: This analysis is based on 26,589 CTO procedures performed by 36 operators with > 50 procedures annually between 2015 and 2022. The different strategies and techniques were analyzed with respect to clinical and lesion characteristics, procedural resource use and periprocedural complications. Within the antegrade approach, PW was compared to antegrade wire escalation (AWE) and antegrade-dissection re-entry (ADR)., Results: The primary antegrade approach was used in 65.9%, primary retrograde in 16.9% and a strategy change in 17.2% with a wide inter-operator variability. In primary antegrade approach, PW was applied in 10.8% and ADR in 5.3%. Lesion complexity was higher in AWE and PW than with single wire, and highest in ADR procedures, leading to more complex procedures with higher contrast and radiation usage. Complications increased with ADR, while they were similar with PW and AWE. Through the observation period PW adoption increased steadily from 6.7% to 10.7%, as the DLC use facilitating PW increased from 8.3% to 17.0% over the observation period., Conclusion: In this largest database of contemporary CTO PCI from Europe, PW adoption increased over time but remained low at about 10%. While there was a wide individual variety among the operators, it was a safe and successful technique., (© 2024 Wiley Periodicals LLC.)

For over a century, there was a major gap in our understanding of the evolution of the flying Mesozoic reptiles, the pterosaurs, with a major morphological gap between the early forms and the derived pterodactyloids. 1 Recent discoveries have found a cluster of intermediate forms that have the head and neck of the pterodactyloids but the body of the early grade, 2 yet this still leaves fundamental gaps between these intermediates and both earlier and more derived pterosaurs. Here, we describe a new and large Jurassic pterosaur, Skiphosoura bavarica gen. et sp. nov., preserved in three dimensions, that helps bridge the gap between current intermediate pterosaurs and the pterodactyloids. A new phylogeny shows that there is a general progression of key characteristics of increasing head size, increasing length of neck and wing metacarpal, modification to the fifth toe that supports the rear wing membrane, and gradual reduction in tail length and complexity from earlier pterosaurs into the first pterodactyloids. This also shows a clear evolution of the increasing terrestrial competence of derived pterosaurs. Furthermore, this closes gaps between the intermediates and their ancestors and descendants, and it firmly marks the rhamphorhynchines and ctenochasmatid clades as, respectively, being the closest earliest and latest groups to this succession of transitional forms., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) present as a main feature ≤50% stenosis upon angiography despite clinical symptoms and biomarker elevation related to acute coronary syndrome. Due to broad availability of high sensitivity troponin testing as well as invasive and non-invasive imaging, this clinical entity receives increasing clinical awareness., Objective: We aimed to investigate the in-hospital work flow and economic impact of MINOCA vs. MICAD (myocardial infarction with obstructive coronary artery disease) patients and related clinical outcomes in a single-center patient collective of a large university heart center in Germany., Methods: We retrospectively screened and analyzed all patients who were admitted to our hospital under the suspicion of an acute coronary syndrome within a 12-month period (2017-2018) for further diagnostics and treatment. All included patients showed a pathological troponin elevation and received invasive coronary angiography for acute coronary syndrome. Associated in-hospital costs, procedural and various clinical parameters as well as timelines and parameters of work-flow were obtained., Results: After screening of 3,021 patients, we included 660 patients with acute coronary syndrome. Of those, 118 patients were attributed to the MINOCA-group. 542 patients presented with a "classical" myocardial infarction (MICAD group). MINOCA patients were less frail, more likely female, but showed no relevant difference in age or other selected comorbidities except for fewer cases of diabetes. In-hospital mortality (11% vs. 0%; p  < 0.001) and 30-day mortality (17.3% vs. 4.2%; p  < 0.001) after the index event were significantly higher in the "classical" myocardial infarction group (MICAD)- Despite a shorter overall length of hospital stay (9.5 ± 8.7 days vs. 12.3 ± 10.5 days, p  < 0.01) with a significantly shorter duration of high care monitoring (intensive/intermediate care or chest pain units) (2.4 ± 2.1 days vs. 4.7 ± 3.3 days, p  < 0.01) MINOCA patients consumed a relevant contingent of hospital resources. Thus, in a 12-months period a total sum of almost 300 days was attributed to high care monitoring for MINOCA patients with a mean difference of approximately 50% compared to patients with classical myocardial infarction. With average and median costs of 50% less per index, MINOCA treatment costs were lower compared to the MICAD group in the hospital reimbursement system of Germany. Consequently, MINOCA treatment was not associated with a relevant profit for these expanses and a relevant share of nearly 40% of the total costs was generated due to high care monitoring., Conclusion: In light of lower mortality than MICAD and growing scarcity of staff, financial and capacity resources the clinical symptom complex of MINOCA should be put under particular consideration for refining care concepts and resource allocation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Haertel, Montag, Kraeplin, Lauer, Memisevic, Moebius-Winkler, Schulze and Otto.)

The fossil record of chondrichthyans (chimaeras, sharks, rays and skates) consists largely of isolated teeth, with holomorphic specimens being extraordinary exceptions. However, numerous of these more or less completely preserved specimens are known from several Upper Jurassic deposits of Europe, enabling detailed analysis of their morphology. Batomorphs (rays and skates) resembling modern guitarfishes and wedgefishes (Rhinopristiformes) are among the most common Jurassic chondrichthyans found, but they have been only sporadically studied up to now, resulting in large knowledge gaps concerning their taxonomy and phylogeny. Here, we present the most detailed revision of Late Jurassic holomorphic batomorphs to date, quantitatively analysing body proportions of specimens from Germany (Solnhofen Archipelago), France (Cerin) and the UK (Kimmeridge), using both geometric and traditional morphometrics. Furthermore, we identify qualitative morphological characters for species discrimination, to clarify the taxonomic identity and diversity of Late Jurassic batomorphs based on holomorphic specimens. Our results support the validity of Belemnobatis sismondae, Kimmerobatis etchesi and Spathobatis bugesiacus , as well as that of the previously doubtful Asterodermus platypterus . Moreover, we describe Aellopobatis bavarica , a new taxon, which has hitherto been considered to be a large-sized morphotype of Spathobatis bugesiacus . Our results highlight that the diversity of holomorphic batomorphs during the Late Jurassic was greater than previously thought, and suggest that this group was already well-established and diverse by this time. This study thus provides vital information about the evolutionary history of Late Jurassic batomorphs and has direct implications for batomorph species that are based on isolated teeth only.

Introduction: Despite the prospective randomized controlled JAVELIN Bladder 100 trial, no real-world evidence exists regarding tumor characteristics, adverse events (AEs), and survival of avelumab maintenance (AVM)-treated patients with partial/complete response or stable disease after previous platinum-based chemotherapy for advanced/metastatic urothelial carcinoma (mUC)., Methods: We relied on our institutional database to identify mUC patients who received AVM between January, 2021 and December, 2023. The main outcomes consisted of overall survival (OS) and progression-free survival (PFS) and were computed by Kaplan-Meier estimates. Stratification was performed according to programmed death ligand 1 (PD-L1) status., Results: Overall, 24 AVM patients were identified at a median age of 71 (interquartile range [IQR]: 67-76) years, of which 67% were males. Of these, 63%, 21%, and 17% received AVM therapy for bladder cancer and upper tract urothelial carcinoma or both, respectively. PD-L1 status was positive in 45% of patients. During AVM treatment, AEs were observed in 33% of patients; however, they were limited to ≤2 grade AEs. At a median follow-up of eight (IQR 4-20) months, 71% of patients had progressed under AVM with median PFS of 6.2 months (confidence interval [CI]: 3.2-18.2). Median OS was 13.4 (CI: 6.9 - not reached [NR]) months. One-year OS after AVM was 52%. In PD-L1-positive patients, median PFS and OS were 6.4 (CI: 2.7 - NR) months and 13.4 (CI: 7.7 months - NR), respectively., Conclusion: AVM is associated with moderate AE rates. Despite similarities in baseline characteristics compared to trial-selected JAVELIN Bladder 100 mUC patients, AVM resulted in longer/similar PFS but significantly shorter OS in real-world setting., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Percutaneous coronary intervention (PCI) for chronic total coronary occlusions (CTO) improves clinical symptoms and quality of life. The longer-term safety of PCI compared to optimal medical therapy (OMT) remains uncertain., Aims: We sought to evaluate the long-term safety of PCI for CTO in a randomised trial as compared to OMT., Methods: A total of 396 patients with a symptomatic CTO were enrolled into a randomised, multicentre clinical trial comparing PCI and OMT. Half of the patients had a single CTO; the others had multivessel disease. Non-CTO lesions were treated prior to randomisation (2:1 ratio). During follow-up, crossover from OMT to PCI occurred in 7.3% (1 year) and 17.5% (3 years) of patients., Results: At 3 years, the incidence of cardiovascular death or nonfatal myocardial infarction was not significantly different between the groups (OMT 3.7% vs PCI 6.2%; p=0.29). By per-protocol analysis, the difference remained non-significant (OMT 5.7% vs PCI 4.7%; p=0.67). Overall, major adverse cardiovascular events (MACE) were more frequent with OMT (OMT 21.2% vs PCI 11.2%), largely because of ischaemia-driven revascularisation. The rates of stroke or hospitalisation for bleeding were not different between the groups., Conclusions: At 3 years there was no difference in the rate of cardiovascular death or myocardial infarction between PCI or OMT among patients with a remaining single coronary CTO. The MACE rate was higher in the OMT group due largely to ischaemia-driven revascularisation. CTO PCI appears to be a safe option for patients with a single remaining significant coronary CTO. CinicalTrials.gov: NCT01760083.

Background and Aims: Currently, less than 20% of patients at very high-risk achieve ESC/EAS dyslipidemia guideline-recommended LDL-C target levels in Europe. "Jena auf Ziel-JaZ" is a prospective cohort study in which early combination therapy with atorvastatin 80 mg and ezetimibe 10 mg was initiated on admission in patients with ST-elevation myocardial infarction (STEMI) and lipid-lowering therapy was escalated during follow-up with bempedoic acid and PCSK9 inhibitors to achieve recommended LDL-C targets in all patients. Moreover, we evaluated side-effects of lipid-lowering therapy., Methods: Patients admitted with STEMI at Jena University Hospital were started on atorvastatin 80 mg and ezetimibe 10 mg on admission. Patients were followed for EAS/ESC LDL-C target achievement during follow-up., Results: A total of 85 consecutive patients were enrolled in the study. On discharge, 32.9% achieved LDL-C targets on atorvastatin 80 mg and ezetimibe 10 mg. After 4-6 weeks, 80% of all patients on atorvastatin 80 mg and ezetimibe started at the index event were on ESC/EAS LDL-C targets. In 20%, combined lipid-lowering therapy was escalated with either bempedoic acid or PCSK9 inhibitors. All patients achieved LDL-C levels of or below 55 mg/dL during follow-up on triple lipid-lowering therapy. Combined lipid-lowering therapy was well-tolerated with rare side effects., Conclusions: Early combination therapy with a high-intensity statin and ezetimibe and escalation of lipid-lowering therapy with either bempedoic acid or PCSK9 inhibitors gets potentially all patients with STEMI on recommended ESC/EAS LDL-C targets without significant side effects., (© 2023. The Author(s).)

Background: The aim of this study was to describe the mechanism of subintimal shift (SIS), standardise diagnostic criteria and sensitise the interventional community to this phenomenon. The treatment of chronic total occlusions (CTO) by means of percutaneous coronary intervention (PCI) is complicated by bifurcation lesions involved in the CTO segment or adjacent to it. Extraplaque expansion of intracoronary devices during CTO PCI may extend the dissection plane over the bifurcation with the consequential side or main branch compression by an intimo-medial flap. This phenomenon is hereby described for the first time and named subintimal shift., Methods: Experienced CTO operators from 3 international high volume centers for CTO PCI retrospectively searched their personal records for paradigmatic cases of SIS, summarising key features and proposing diagnostic criteria., Results: The series comprised 7 demonstrative cases, illustrating SIS by intravascular imaging (2 cases) or indirect angiographic signs during CTO PCI (5 cases). Five cases were triggered by stent expansion, 1 by balloon inflation and 1 case was aborted after angiographic warning signs. In 4 cases, SIS resulted in total occlusion of a branch, refractory to ballooning whenever attempted. Four cases required bailout intervention and in 2 cases the branch was left occluded, resulting in a rise of cardiac markers., Conclusions: Subintimal shift is a noteworthy complication in CTO bifurcations, potentially resulting in occlusion of the relevant side or even the main branch. Intracoronary imaging prior to stenting is recommended to understand the tissue planes. Some counterintuitive peculiarities of this phenomenon, like its refractoriness to ballooning, must be known by CTO operators for its efficient resolution.

Percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) in coronary bifurcation lesions (CBL) is undergoing substantial technical progress and standardization, paralleling the evolution of dedicated devices, tools, and techniques. A standard consensus to classify CTO-CBL might be instrumental to homogenize data collection and description of procedures for scientific and educational purposes. The Medina-CTO classification replicates the classical three digits in Medina classification for bifurcations, representing the proximal main vessel, distal main vessel, and side branch, respectively. Each digit can take a value of 1 if it concerns atherosclerosis and is anatomically stenosed, or 0 if it is not. In addition, the occluded segment(s) of the bifurcation are noted by a subscript, which describes key interventional features of the cap: t (tapered), b (blunt), or a (ambiguous). This approach results in 56 basic categories that can be grouped by means of different elements, depending on the specific needs of each study. Medina-CTO classification, consisting of adding a subscript describing the basic cap characteristics to the totally occluded segment(s) of the standard Medina triplet, might be a useful methodological tool to standardize percutaneous intervention of bifurcational CTO lesions, with interesting scientific and educational applications.

Objective: Chinese-American patients use CIH at high rates but disclosure of CIH use to clinicians is low. Further, the content of CIH talk between patients and their clinicians is not well described. We aimed to characterize CIH talk between Chinese-American patients and their primary care clinicians., Methods: Discourse analysis of 70 audio-recordings of language concordant and discordant-interpreted visits., Results: Nearly half of all visits (48.6%) had some form of CIH communication. 'Simple CIH talk' focused on a single CIH topic resulting in a positive, neutral, or negative response by clinicians. 'CIH-furthering talk' was characterized by clinicians and patients addressing more than one CIH topic or including a combination of orientations to CIH by both clinicians and patients. CIH-furthering talk characterized by clinician humility could enhance rapport, cultural understanding, and open communication. CIH-furthering talk also led to miscommunication and retreat toward biomedicine., Conclusion: CIH communication occurred frequently during language concordant and discordant-interpreted visits with Chinese-American patients. Both patients and clinicians used CIH-furthering talk as a conversational resource for managing care., Innovation: This discourse analysis of visits between Chinese-American patients and their clinicians advances understanding of CIH communication beyond disclosure, illustrating the complexity of linguistic and cultural nuances that affect patient care., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Leah Karliner reports financial support was provided by Patient-Centered Outcomes Research Institute. Leah Karliner reports financial support was provided by National Institutes of Health. Jane Jih reports financial support was provided by National Institutes of Health.

Introduction: Cardiogenic shock due to myocardial infarction or heart failure entails a reduction in end organ perfusion. Patients who cannot be stabilized with inotropes and who experience increasing circulatory failure are in need of an extracorporeal mechanical support system. Today, small, percutaneously implantable cardiac assist devices are available and might be a solution to reduce mortality and complications. A temporary, ventricular, continuous flow propeller pump using magnetic levitation (Impella ® ) has been approved for that purpose., Methods and Study Design: JenaMACS (Jena Mechanical Assist Circulatory Support) is a monocenter, proof-of-concept study to determine whether treatment with an Impella CP ® leads to improvement of hemodynamic parameters in patients with cardiogenic shock requiring extracorporeal, hemodynamic support. The primary outcomes of JenaMACS are changes in hemodynamic parameters measured by pulmonary artery catheterization and changes in echocardiographic parameters of left and right heart function before and after Impella ® implantation at different support levels after 24 h of support. Secondary outcome measures are hemodynamic and echocardiographic changes over time as well as clinical endpoints such as mortality or time to hemodynamic stabilization. Further, laboratory and clinical safety endpoints including severe bleeding, stroke, neurological outcome, peripheral ischemic complications and occurrence of sepsis will be assessed. JenaMACS addresses essential questions of extracorporeal, mechanical, cardiac support with an Impella CP ® device in patients with cardiogenic shock. Knowledge of the acute and subacute hemodynamic and echocardiographic effects may help to optimize therapy and improve the outcome in those patients., Conclusion: The JenaMACS study will address essential questions of extracorporeal, mechanical, cardiac support with an Impella CP ® assist device in patients with cardiogenic shock. Knowledge of the acute and subacute hemodynamic and echocardiographic effects may help to optimize therapy and may improve outcome in those patients., Ethics and Dissemination: The protocol was approved by the institutional review board and ethics committee of the University Hospital of Jena. Written informed consent will be obtained from all participants of the study. The results of this study will be published in a renowned international medical journal, irrespective of the outcomes of the study. Strengths and Limitations: JenaMACS is an innovative approach to characterize the effect of additional left ventricular mechanical unloading during cardiogenic shock via a minimally invasive cardiac assist system (Impella CP ® ) 24 h after onset and will provide valuable data for acute interventional strategies or future prospective trials. However, JenaMACS, due to its proof-of-concept design, is limited by its single center protocol, with a small sample size and without a comparison group.