Endovascular arch repair of anastomotic aneurysm and pseudoaneurysm in patients after open repair of the ascending aorta and aortic arch: a case series.

OBJECTIVES: The aim of the study was to investigate the outcomes of branched endovascular arch repair (b-TEVAR) with a custom-made double- or triple-branched arch endograft in patients with distal anastomotic aneurysms after open repair of the ascending aorta or proximal arch replacement. METHODS: Retrospective analysis was conducted of all consecutive patients with anastomotic aneurysms after open surgical repair involving the ascending aorta and/or aortic arch treated with b-TEVAR. All patients were treated with a custom-made double or triple inner-branched arch endograft. Study end points were technical success, 30-day and follow-up mortality/morbidity and re-interventions. RESULTS: Between 2018 and 2022, 10 patients were treated with custom-made double- or triple-branched thoracic endovascular aortic repair due to anastomotic aneurysms after open ascending aorta and/or proximal aortic arch replacement. Eight patients received a triple and 2 a double arch-branched endograft. Eight cases were performed electively and 2 urgently for contained rupture. Technical success was achieved in 9 cases (90%). All elective patients survived. Two patients treated due to contained ruptures expired. Within 30 postoperative days, 1 transient ischaemic attack occurred. No early endograft-related re-interventions were necessary. The median follow-up was 20 months. One patient died 2 months after discharge due to sepsis caused by pneumonia. No further deaths or endograft-related re-interventions were observed. CONCLUSIONS: Endovascular aortic arch repair with double or triple inner-branched arch endograft for anastomotic aneurysms after open ascending and/or proximal arch replacement is technically feasible and a promising alternative in a patient cohort unfit for surgery.

Spo13/MEIKIN ensures a Two-Division meiosis by preventing the activation of APC/CAma1 at meiosis I.

Genome haploidization at meiosis depends on two consecutive nuclear divisions, which are controlled by an oscillatory system consisting of Cdk1-cyclin B and the APC/C bound to the Cdc20 activator. How the oscillator generates exactly two divisions has been unclear. We have studied this question in yeast where exit from meiosis involves accumulation of the APC/C activator Ama1 at meiosis II. We show that inactivation of the meiosis I-specific protein Spo13/MEIKIN results in a single-division meiosis due to premature activation of APC/CAma1 . In the wild type, Spo13 bound to the polo-like kinase Cdc5 prevents Ama1 synthesis at meiosis I by stabilizing the translational repressor Rim4. In addition, Cdc5-Spo13 inhibits the activity of Ama1 by converting the B-type cyclin Clb1 from a substrate to an inhibitor of Ama1. Cdc20-dependent degradation of Spo13 at anaphase I unleashes a feedback loop that increases Ama1's synthesis and activity, leading to irreversible exit from meiosis at the second division. Thus, by repressing the exit machinery at meiosis I, Cdc5-Spo13 ensures that cells undergo two divisions to produce haploid gametes.

[Malperfusion after Aortic Dissection - Management and Techniques]. / Malperfusion nach Aortendissektion - Management und Techniken.

Malperfusion is a common complication of aortic dissection and further increases this deadly disease's mortality. An effective treatment strategy requires a timely diagnosis based on the clinical findings and the available instruments, understanding the disease's pathomechanism, recognising the therapy options recommended by the guidelines, and the diagnostic and therapeutic innovations of the area of research. The final treatment decision should be patient- and case-specific. In this work, we have considered malperfusion after aortic dissection, not only as a complication of aortic dissection but as a separate disease and summarise important information that can contribute to efficient therapy decisions in everyday clinical practice.

A prospective survey study on the education and awareness about walking exercise amongst inpatients with symptomatic peripheral arterial disease in Germany.

Background: To determine the adherence to supervised exercise training and underlying reasons for non-adherence amongst patients with inpatient treatment of symptomatic lower extremity peripheral arterial disease (PAD). Patients and methods: This was a prospective questionnaire-based survey study of all consecutively treated inpatients with treatment for either intermittent claudication or chronic limb-threatening ischaemia (CLTI) surveyed at sixteen participating centres in Germany. Results: A total of 235 patients (median age 70 years) were included, thereof 29.4% females and 34.6% with CLTI. The median time from first PAD diagnosis was 4 years (IQR: 1-8). Only 11.4% have previously participated in any walking exercise programme before the index treatment, thereby 10.0% in the IC subgroup and 12.0% with CLTI. Amongst all patients, 35.6% responded they were appropriately informed about the necessity and benefits of walking exercise programmes by their hospital physicians (25.8% by general practitioners), and 65.3% agreed that adherence to supervised exercise may improve their pain-free walking distance. A total of 24.5% responded they had access to necessary information concerning local walking exercise programmes. Amongst 127 free text comments on the reasons for non-adherence to supervised exercise training, 64% of the comments contained lack of information or consent on such measures. Conclusions: Less than 12% of the patients enrolled in the current study have ever participated in a walking exercise programme during their life course. Although all practice guidelines contain corresponding class I recommendations, especially for patients suffering from IC, most patients responded that they were not appropriately informed about the necessity of exercise training along with the fact that 65% agreed that exercise may increase the pain-free walking distance. Taken all together, these results emphasise that we miss an important opportunity in the patient-physician communication. Efforts should be made to improve acceptance and application of structured walking-exercise for patients with PAD.

Use of Secondary Iliac Branch Devices after Previous Endovascular Abdominal and Thoraco-Abdominal Aortic Aneurysm Repair.

OBJECTIVE: To assess the safety and effectiveness of iliac branch devices (IBDs), as secondary procedure, for the treatment of type Ib endoleak or evolution of iliac artery disease after prior endovascular aortic repair (EVAR) for thoraco-abdominal (TAAAs) or abdominal aortic aneurysms (AAAs). METHODS: A multicentre observational study of three European centres. The study included 75 patients (age 71 ± 9 years, 96% men) with previous EVAR (n = 64, 85%) or fenestrated or branched (FB) EVAR (n = 11, 15%). Overall, 88 IBDs were implanted to treat aneurysmal iliac artery evolution in 40 (53%) and type Ib endoleak in 35 (47%) cases, respectively. Thirteen (17%) patients received bilateral IBDs. Internal iliac artery (IIA) catheterisation was done through a transaxillary access (n = 82, 93%) or up and over (n = 6, 7%) technique. The primary endpoint was technical success. Secondary endpoints were 30 day major adverse event, early and long term freedom from re-intervention and target vessel instability. RESULTS: All procedures were technically successful (100%). During hospitalisation, there were four (5%) major adverse events and three (4%) early re-interventions, but no death, stroke, or damage to previous endografts. The median follow up was 47 (interquartile range 42) months, and the five year survival rate was 78 ± 6% with no aortic related death. Cox's regression analysis showed pre-operative renal function impairment (hazard ratio [HR] 3.4; 95% confidence interval [CI] 1.1 - 10.1; p = .033), and primary TAAA repair (HR 6.1; 95% CI 1.6-22.3; p = .006) as independent factors for long term mortality. Freedom from re-interventions was 85 ± 4% at five years with 11 (12%) cases (five endoleaks, four IBD thromboses, two stenoses). IIA instability was reported in three (3%) limbs and freedom from IIA instability was 95 ± 3% after 60 months. CONCLUSION: Secondary IBD after EVAR is a safe and effective procedure with high technical success and low complication rates. The technique of choice to revascularise the IIA seems not to affect early and follow up results. Long term durability of IBD repair is acceptable with low rates of IIA re-intervention.

A cross-sectional study on the anatomic feasibility of iliac side branch grafts in a real-world setting.

OBJECTIVE: The aim of this cross-sectional, single-center study was to analyze the feasibility of different commercially available iliac branch devices in Europe in a cohort of patients with aorto-iliac aneurysms. METHODS: All patients with aorto-iliac or iliac aneurysms that required iliac aneurysm repair, between 2017 and 2021, were included. Morphologic data was analyzed using computed tomography angiograms. The main outcome was the feasibility of each endoprosthesis (Cook ZBIS, Gore Iliac Branch Endoprosthesis [IBE], and JOTEC E-Iliac) according to the manufacturer's instructions for use. Secondary outcomes were feasibility in all three devices, in any device, and with adjunctive procedures (liberal criteria). Additionally, a comparative analysis of all three grafts was performed to analyze differences in feasibility. RESULTS: Overall, 119 iliac aneurysms in 101 patients were included. The mean age was 71 ± 11 years, and 91.6% were male. Feasibility was 52.9% for Cook ZBIS, 33.6% for Gore IBE, and 26.9% for the JOTEC E-Iliac device. A total of 65.5% of patients were feasible with at least one device, whereas only 10.1% complied with all three devices. The main reasons for lack of feasibility were a short common iliac artery length (Cook ZBIS), a narrow common iliac artery diameter (Gore IBE), and a >50° angulation between the external and internal iliac arteries (JOTEC E-Iliac). There was a significant difference between the feasibility of the three devices (P < .001). Cook ZBIS was the graft with the higher feasibility, with 3.3 and 4.4 higher odds when compared with Gore IBE and JOTEC E-Iliac devices, respectively. There was no significant difference between the Gore IBE and the JOTEC E-Iliac. By using liberal criteria, the overall feasibility increased to 95.8%. CONCLUSIONS: We found that only 65.5% of patients were feasible with one of the available devices according to the manufacturer's instructions for use. The Cook ZBIS was the device with the overall highest feasibility. Extending the use of these devices with adjunctive measures and a more liberal approach increased feasibility to 95.8%.

The Spo13/Meikin pathway confines the onset of gamete differentiation to meiosis II in yeast.

Sexual reproduction requires genome haploidization by the two divisions of meiosis and a differentiation program to generate gametes. Here, we have investigated how sporulation, the yeast equivalent of gamete differentiation, is coordinated with progression through meiosis. Spore differentiation is initiated at metaphase II when a membrane-nucleating structure, called the meiotic plaque, is assembled at the centrosome. While all components of this structure accumulate already at entry into meiosis I, they cannot assemble because centrosomes are occupied by Spc72, the receptor of the γ-tubulin complex. Spc72 is removed from centrosomes by a pathway that depends on the polo-like kinase Cdc5 and the meiosis-specific kinase Ime2, which is unleashed by the degradation of Spo13/Meikin upon activation of the anaphase-promoting complex at anaphase I. Meiotic plaques are finally assembled upon reactivation of Cdk1 at entry into metaphase II. This unblocking-activation mechanism ensures that only single-copy genomes are packaged into spores and might serve as a paradigm for the regulation of other meiosis II-specific processes.

A Case Report: Is the Lack of Sufficient Radial Force Unfreezing the "Frozen Elephant Trunk"?

The "frozen elephant trunk" is a hybrid technique to treat aortic arch and proximal descending aortic pathologies in a single step. Despite its encouraging early and long-term results, some stent-graft-related adverse events have been reported. Here, we describe a possible treatment option to "re-freeze" the FET in case of loss of landing zone. We report a patient who developed significant kinking of the FET over the course of the first 2 postoperative years. The 1-year follow-up computed tomography angiography (CTA) showed significant kinking and proximal migration of the endograft portion of the FET, resulting in new thrombus formation. Due to kinking and thrombus progression in subsequent CTA follow-ups (2 years and 2½ years) with risk for peripheral embolization, a secondary endovascular repair was indicated. Transfemoral relining of the stent component with a thoracic aortic endovascular repair (Zenith®TX2®30142) stent-graft was performed. In the context of postoperative aneurysm sac shrinkage, the low radial force and lack of longitudinal stiffness of the hybrid graft may lead to proximal migration, thus secondary kinking, emphasizing the importance of an adequate degree of oversizing of the primary graft and an appropriate follow-up. Selection of a suitable graft for a particular pathology concerning the radial force and longitudinal stiffness is furthermore important.

APC/C-Cdc20 mediates deprotection of centromeric cohesin at meiosis II in yeast.

Cells undergoing meiosis produce haploid gametes through one round of DNA replication followed by 2 rounds of chromosome segregation. This requires that cohesin complexes, which establish sister chromatid cohesion during S phase, are removed in a stepwise manner. At meiosis I, the separase protease triggers the segregation of homologous chromosomes by cleaving cohesin's Rec8 subunit on chromosome arms. Cohesin persists at centromeres because the PP2A phosphatase, recruited by the shugoshin protein, dephosphorylates Rec8 and thereby protects it from cleavage. While chromatids disjoin upon cleavage of centromeric Rec8 at meiosis II, it was unclear how and when centromeric Rec8 is liberated from its protector PP2A. One proposal is that bipolar spindle forces separate PP2A from Rec8 as cells enter metaphase II. We show here that sister centromere biorientation is not sufficient to "deprotect" Rec8 at meiosis II in yeast. Instead, our data suggest that the ubiquitin-ligase APC/CCdc20 removes PP2A from centromeres by targeting for degradation the shugoshin Sgo1 and the kinase Mps1. This implies that Rec8 remains protected until entry into anaphase II when it is phosphorylated concurrently with the activation of separase. Here, we provide further support for this model and speculate on its relevance to mammalian oocytes.

Casein Kinase 1 Coordinates Cohesin Cleavage, Gametogenesis, and Exit from M Phase in Meiosis II.

Meiosis consists of DNA replication followed by two consecutive nuclear divisions and gametogenesis or spore formation. While meiosis I has been studied extensively, less is known about the regulation of meiosis II. Here we show that Hrr25, the conserved casein kinase 1δ of budding yeast, links three mutually independent key processes of meiosis II. First, Hrr25 induces nuclear division by priming centromeric cohesin for cleavage by separase. Hrr25 simultaneously phosphorylates Rec8, the cleavable subunit of cohesin, and removes from centromeres the cohesin protector composed of shugoshin and the phosphatase PP2A. Second, Hrr25 initiates the sporulation program by inducing the synthesis of membranes that engulf the emerging nuclei at anaphase II. Third, Hrr25 mediates exit from meiosis II by activating pathways that trigger the destruction of M-phase-promoting kinases. Thus, Hrr25 synchronizes formation of the single-copy genome with gamete differentiation and termination of meiosis.

Strength of selection pressure is an important parameter contributing to the complexity of antibiotic resistance evolution.

Revealing the genetic changes responsible for antibiotic resistance can be critical for developing novel antibiotic therapies. However, systematic studies correlating genotype to phenotype in the context of antibiotic resistance have been missing. In order to fill in this gap, we evolved 88 isogenic Escherichia coli populations against 22 antibiotics for 3 weeks. For every drug, two populations were evolved under strong selection and two populations were evolved under mild selection. By quantifying evolved populations' resistances against all 22 drugs, we constructed two separate cross-resistance networks for strongly and mildly selected populations. Subsequently, we sequenced representative colonies isolated from evolved populations for revealing the genetic basis for novel phenotypes. Bacterial populations that evolved resistance against antibiotics under strong selection acquired high levels of cross-resistance against several antibiotics, whereas other bacterial populations evolved under milder selection acquired relatively weaker cross-resistance. In addition, we found that strongly selected strains against aminoglycosides became more susceptible to five other drug classes compared with their wild-type ancestor as a result of a point mutation on TrkH, an ion transporter protein. Our findings suggest that selection strength is an important parameter contributing to the complexity of antibiotic resistance problem and use of high doses of antibiotics to clear infections has the potential to promote increase of cross-resistance in clinics.