Comparing Simulation Training of Bronchoscopy-Guided Percutaneous Dilatational Tracheostomy Using Conventional Versus 3D Printed Simulators (TRAC-Sim Study).

Background: Individual implementation rate of bronchoscopy-guided percutaneous dilatational tracheostomy (PDT) varies among intensivists. Simulation training (ST) can increase the safety of medical procedures by reducing stress levels of the performing team. The aim of this study was to evaluate the benefit of ST in PDT regarding procedural time, quality of performance, and percepted feelings of safety of the proceduralist and to compare conventional simulators (CSIM) with simulators generated from 3D printers (3DSIM). Methods: We conducted a prospective, single-center, randomized, blinded cross-over study comparing the benefit of CSIM versus 3DSIM for ST of PDT. Participants underwent a standardized theoretical training and were randomized to ST with CSIM (group A) or 3DSIM (group B). After ST, participants' performance was assessed by two blinded examiners on a porcine trachea regarding time required for successful completion of PDT and correct performance (assessed by a performance score). Percepted feelings of safety were assessed before and after ST. This was followed by a second training and second assessment of the same aspects with crossed groups. Results: 44 participants were included: 24 initially trained with CSIM (group A) and 20 with 3DSIM (group B). Correctness of the PDT performance increased significantly in group B (p < .01) and not significantly in group A (p = .14). Mean procedural time required for performing a PDT after their second ST compared to the first assessment (p < .01) was lower with no difference between group A and group B and irrespective of the participants' previous experience regarding PDT, age, and sex. Moreover, percepted feelings of safety increased after the first ST in both groups (p < .001). Conclusions: ST can improve procedural skills, procedural time, and percepted feelings of safety of the proceduralist in simulated PDT.

Artificial Intelligence-Assisted Sac Diameter Assessment for Complex Endovascular Aortic Repair.

PURPOSE: Artificial intelligence (AI) using an automated, deep learning-based method, Augmented Radiology for Vascular Aneurysm (ARVA), has been verified as a viable aide in aneurysm morphology assessment. The aim of this study was to evaluate the accuracy of ARVA when analyzing preoperative and postoperative computed tomography angiography (CTA) in patients managed with fenestrated endovascular repair (FEVAR) for complex aortic aneurysms (cAAs). MATERIALS AND METHODS: Preoperative and postoperative CTAs from 50 patients (n=100 CTAs) who underwent FEVAR for cAAs were extracted from the picture archiving and communication system (PACS) of a single aortic center equipped with ARVA. All studies underwent automated AI aneurysm morphology assessment by ARVA. Appropriate identification of the outer wall of the aorta was verified by manual review of the AI-generated overlays for each patient. Maximum outer-wall aortic diameters were measured by 2 clinicians using multiplanar reconstruction (MPR) and curved planar reformatting (CPR), and among studies where the aortic wall was appropriately identified by ARVA, they were compared with ARVA automated measurements. RESULTS: Identification of the outer wall of the aorta was accurate in 89% of CTA studies. Among these, diameter measurements by ARVA were comparable to clinician measurements by MPR or CPR, with a median absolute difference of 2.4 mm on the preoperative CTAs and 1.6 mm on the postoperative CTAs. Of note, no significant difference was detected between clinician measurements using MPR or CPR on preoperative and postoperative scans (range 0.5-0.9 mm). CONCLUSION: For patients with cAAs managed with FEVAR, ARVA provides accurate preoperative and postoperative assessment of aortic diameter in 89% of studies. This technology may provide an opportunity to automate cAA morphology assessment in most cases where time-intensive, manual clinician measurements are currently required. CLINICAL IMPACT: In this retrospective analysis of preoperative and postoperative imaging from 50 patients managed with FEVAR, AI provided accurate aortic diameter measurements in 89% of the CTAs reviewed, despite the complexity of the aortic anatomies, and in post-operative CTAs despite metal artifact from stent grafts, markers and embolization materials. Outliers with imprecise automated aortic overlays were easily identified by scrolling through the axial AI-generated segmentation MPR cuts of the entire aorta.This study supports the notion that such emerging AI technologies can improve efficiency of routine clinician workflows while maintaining excellent measurement accuracy when analyzing complex aortic anatomies by CTA.

Surgical Versus Interventional Treatment of Major Access Site Complications During Transfemoral TAVI Procedures at a Large Volume Center.

PURPOSE: Access-related vascular complications in transfemoral transcatheter aortic valve implantation (TAVI) can be treated endovascularly or surgically. The aim of this study was to evaluate the short- and long-term outcomes of endovascular treatment compared with surgical repair for access-related vascular complications. METHODS: This retrospective study was performed from January 1, 2018, to December 31, 2020. All transfemorally treated TAVI patients in whom a surgical or endovascular treatment for an access site complication was needed were included. The primary outcome was the need for any related vascular re-operation. RESULTS: In total, 1219 transfemoral TAVI procedures were conducted during the study period. 19 patients suffered an access complication requiring endovascular treatment, while 54 patients required surgical repair. No differences were seen with regard to re-operations (endovascular 15.8% vs surgical 14.8%; p=0.919), wound infections (endovascular 0% vs surgical. 11.1%; p=0.129), and wound healing disorders (endovascular 15.8% vs surgical 29.6%; p=0.237). Patients undergoing endovascular treatment were discharged earlier (endovascular 11.2 vs surgical 14.9 days; p=0.028). After surgical repair, patients received significantly more blood transfusions than endovascularly treated patients (endovascular 1.00 vs surgical 3.1 red blood cell concentrate bags; p<0.001). No differences were found regarding the new onset of walking pain, rest pain, and ischemic ulcers during follow-up. CONCLUSION: In this retrospective cohort, endovascular treatment of access-related vascular complications of transfemoral TAVI procedures was safe and feasible. During the hospital stay, endovascularly treated patients received fewer blood transfusions and were discharged faster than surgically treated patients. No differences regarding clinical outcomes and re-intervention rates were seen during the follow-up. CLINICAL IMPACT: Given the in this retrospective study demonstrated safety and feasibility of endovascular treatment for major access-related vascular complications, along with the in-hospital benefits and absence of follow-up disadvantages compared to surgical treatment, endovascular treatment should be considered in cases of major access-related vascular complications in transfemoral TAVI patients.

Meta-analysis and meta-regression of the total endovascular aortic repair in aortic arch.

Background: The total endovascular repair of the aortic arch is becoming more and more an acceptable alternative to the open repair in selected patients. The aim of the present study is to perform a meta-analysis of the available data on the outcomes of the various endovascular techniques used to treat the pathologies in this challenging anatomical area. Patients and methods: An extensive electronic search in PubMed/MEDLINE, Science Direct Databases, and the Cochrane Library was conducted. All papers published up to January 2022 on the endovascular techniques in the aortic arch (chimney-thoracic endovascular aortic repair (ChTEVAR), fenestrated/branched grafts as custom made devices (CMD) and surgeon modified TEVAR (SM TEVAR) providing information about at least one of the essential outcomes defined in the inclusion criteria. Results: Out of the 5078 studies found through the search in the databases and registers, 26 studies with a total number of patients of 2327 with 3497 target vessels were included in the analysis. The studies reported a high technical success rate with an estimated proportion of 95.8% (95% CI, 93-97.6%). Moreover, the pooled estimation of the early type Ia/III endoleak was 8.1% (95% CI, 5.4-12.1%). The pooled mortality was 4.6% (95 CI, 3.2-6.6%) with a significant heterogeneity and the stroke had an estimated proportion (major and minor combined) of 4.8% (95% CI, 3.5-6.6%). A meta-regression analysis showed no significant variation between the groups in mortality (P=.324) showed however a significant difference between the therapeutic methods regarding stroke P<.001 (lower rate in ChTEVAR and SM vs. CMD). Conclusions: The present meta-analysis could demonstrate good short- and long-term outcomes of the multiple total endovascular repair methods used in the aortic arch.

Cellular and soluble immune checkpoint signaling forms PD-L1 and PD-1 in renal tumor tissue and in blood.

Immune checkpoint blockade therapy is a treatment option of various metastatic cancer diseases including renal cell carcinoma (RCC). Approved antibody drugs target the co-inhibitory signaling of Programmed Cell Death Ligand-1 (PD-L1) and its receptor Programmed Cell Death-1 (PD-1). The combined evaluation of PD-L1 and PD-1 at the mRNA and protein levels in tumor tissue with differentiation of tumor and immune cells as well as of soluble forms (sPD-L1) and (sPD-1) in blood is of basic interest in assessing biomarker surrogates. Here, we demonstrate that PD-L1 determined as fraction of stained tumor cells (TPS-score) correlates with PD-L1-mRNA in tumor tissue, reflecting the predominant expression of PD-L1 in tumor cells. Conversely, PD-1 in immune cells of tumor tissue (IC-score) correlated with PD-1-mRNA tissue levels reflecting the typical PD-1 expression in immune cells. Of note, sPD-L1 in blood did not correlate with either the TPS-score of PD-L1 or with PD-L1-mRNA in tumor tissue. sPD-L1 released into the supernatant of cultured RCC cells closely followed the cellular PD-L1 expression as tested by interferon γ (IFNG) induction and siRNA knockdown of PD-L1. Further analysis in patients revealed that sPD-L1 significantly increased in blood following renal tumor resection. In addition, sPD-L1 correlated significantly with inflammation marker C-reactive protein (CRP) and with PD-L1 mRNA level in whole blood. These results indicate that the major source of sPD-L1 in blood may be peripheral blood cells and not primarily tumor tissue PD-L1.

Long-Term Outcomes after Thoracic Endovascular Aortic Repair Using Chimney Grafts for Aortic Arch Pathologies: 10 Years of Single-Center Experience.

BACKGROUND: This study reports the early- and long-term outcomes of the thoracic endovascular aortic repair using the Chimney-Graft technique (ChTEVAR) for the treatment of aortic arch pathologies. METHODS: From January 2010 to December 2019, patients who underwent aortic ChTEVAR technique in our institution were included. Early, mid, and long-term outcomes in this group of patients were evaluated. Patient follow-up data were obtained by imaging follow-up that are routinely performed after 3-6 months following initial surgery and then at yearly intervals. RESULTS: Aortic arch repair with a ChTEVAR was performed in 54 patients. The 30-day mortality was 18.5% (n = 10). All-cause 30-day mortality was higher in the subgroup of patients operated urgently (33% vs. 14%) without a significant difference (P = 0.141). Permanent neurological deficit (PND) was observed in 15% (8/54 patients); stroke in 11% (6/54), and paraplegia 4% (2/54). During follow-up the primary and primary-assisted chimney-graft patency was 96.8% and 97.8%, respectively. The multivariate analysis identified the age >70 years and the aortic diameter as independent risk factors for elevated mortality during the follow-up (P = 0.015 and 0.001, respectively). The PND was an independent predictor for 30-day mortality (P = 0.014, hazard ratio 13.5, 95% confidence interval 1.7-106.6). CONCLUSIONS: The ChTEVAR has noninferior results to other open and endovascular aortic arch repair methods with an acceptable long-term survival especially in elective procedures.

Feasibility of Total Endovascular Repair of the Aorta in Patients with Acute Type A Aortic Dissection: Morphological Analysis of 119 Patients.

(1) Background: This study aimed to morphologically analyze acute type A aortic dissection (aTAAD) patients for potential endovascular treatment candidates. The objective was to specify requirements for aTAAD endovascular devices. (2) Methods: A single-center retrospective analysis included aTAAD patients who underwent open surgical repair between November 2005 and December 2020. Preoperative CTA scans were used for morphological analysis, assessing endovascular repair eligibility. Statistical tests were performed. (3) Results: A total of 129 patients with aTAAD were studied, with 119 included. Entry tear (ET) locations were identified, mainly in the aortic root, 20 mm above the sinotubular junction (STJ) and within the ascending aorta (20 mm above STJ to -20 mm before the brachiocephalic trunk). Endovascular treatment was deemed feasible for 36 patients, with suggested solutions for the aortic arch and descending aorta. Significant differences were observed between eligible and noneligible groups for aortic diameter, false lumen diameter, distance between STJ and entry tear, and more. Dissection extension showed no significant difference. (4) Conclusions: Morphological analysis identified potential aTAAD candidates for endovascular treatment, highlighting differences between eligible and noneligible morphologies. This study offers insights for implementing endovascular approaches in aTAAD treatment and emphasizes the need for research and standardized protocols.

Co-Regulation of Immune Checkpoint PD-L1 with Interferon-Gamma Signaling is Associated with a Survival Benefit in Renal Cell Cancer.

BACKGROUND: Programmed death ligand (PD-L1)-based immune checkpoint blockade therapy for metastatic renal cell carcinoma (RCC) achieves significant response rates in a subgroup of patients. The relevance of PD-L1 gene regulation for disease outcome is not clear. OBJECTIVE: To evaluate PD-L1 expression and its dependence on interferon-γ (IFN-γ) in RCC cell lines and tissues in relation to disease outcome. METHODS AND PATIENTS: Regulation of PD-L1-mRNA and PD-L1 protein was studied in cell lines from clear cell RCC (ccRCC) and papillary RCC (pRCC) by quantitative RT-PCR and Western-blot analysis. PD-L1-mRNA correlation and gene-set enrichment analysis (GSEA) of the IFN-γ pathway were conducted with RNA-Seq from ccRCC, pRCC, and skin cutaneous melanoma (SKCM) tissue. In addition, patient overall survival (OS) and disease-free survival (DFS) (cBioPortal for Cancer Genomics) were considered. RESULTS: In ccRCC-like cell lines, PD-L1 was induced by canonical IFN-γ signaling, whereas in a pRCC-like cell line, PD-L1 was refractory towards IFN-γ signaling. In ccRCC and SKCM tissues, GSEA revealed significant IFN-γ pathway activation in tissue samples with high PD-L1-mRNA levels. This was not observed in pRCC tissue. ccRCC and SKMC patients with low PD-L1-mRNA levels had significantly shorter OS and DFS than those with high PD-L1-mRNA levels. In pRCC patients, no significant difference in OS and DFS with regard to PD-L1-mRNA tissue levels was obvious. CONCLUSIONS: The findings suggest that ccRCC and pRCC differ with respect to PD-L1 regulation by IFN-γ-signaling. High PD-L1-mRNA levels in tumor tissues with a positive IFN-γ signature favorably affect OS and DFS.