Morphogenetic Roles of Hydrostatic Pressure in Animal Development.

During organismal development, organs and systems are built following a genetic blueprint that produces structures capable of performing specific physiological functions. Interestingly, we have learned that the physiological activities of developing tissues also contribute to their own morphogenesis. Specifically, physiological activities such as fluid secretion and cell contractility generate hydrostatic pressure that can act as a morphogenetic force. Here, we first review the role of hydrostatic pressure in tube formation during animal development and discuss mathematical models of lumen formation. We then illustrate specific roles of the notochord as a hydrostatic scaffold in anterior-posterior axis development in chordates. Finally, we cover some examples of how fluid flows influence morphogenetic processes in other developmental contexts. Understanding how fluid forces act during development will be key for uncovering the self-organizing principles that control morphogenesis.

GLA-modified RNA treatment lowers GB3 levels in iPSC-derived cardiomyocytes from Fabry-affected individuals.

Recent studies in non-human model systems have shown therapeutic potential of nucleoside-modified messenger RNA (modRNA) treatments for lysosomal storage diseases. Here, we assessed the efficacy of a modRNA treatment to restore the expression of the galactosidase alpha (GLA), which codes for α-Galactosidase A (α-GAL) enzyme, in a human cardiac model generated from induced pluripotent stem cells (iPSCs) derived from two individuals with Fabry disease. Consistent with the clinical phenotype, cardiomyocytes from iPSCs derived from Fabry-affected individuals showed accumulation of the glycosphingolipid Globotriaosylceramide (GB3), which is an α-galactosidase substrate. Furthermore, the Fabry cardiomyocytes displayed significant upregulation of lysosomal-associated proteins. Upon GLA modRNA treatment, a subset of lysosomal proteins were partially restored to wild-type levels, implying the rescue of the molecular phenotype associated with the Fabry genotype. Importantly, a significant reduction of GB3 levels was observed in GLA modRNA-treated cardiomyocytes, demonstrating that α-GAL enzymatic activity was restored. Together, our results validate the utility of iPSC-derived cardiomyocytes from affected individuals as a model to study disease processes in Fabry disease and the therapeutic potential of GLA modRNA treatment to reduce GB3 accumulation in the heart.

Origin and development of primary animal epithelia.

Epithelia are the first organized tissues that appear during development. In many animal embryos, early divisions give rise to a polarized monolayer, the primary epithelium, rather than a random aggregate of cells. Here, we review the mechanisms by which cells organize into primary epithelia in various developmental contexts. We discuss how cells acquire polarity while undergoing early divisions. We describe cases where oriented divisions constrain cell arrangement to monolayers including organization on top of yolk surfaces. We finally discuss how epithelia emerge in embryos from animals that branched early during evolution and provide examples of epithelia-like arrangements encountered in single-celled eukaryotes. Although divergent and context-dependent mechanisms give rise to primary epithelia, here we trace the unifying principles underlying their formation.

Polarized transport of membrane and secreted proteins during lumen morphogenesis.

A ubiquitous feature of animal development is the formation of fluid-filled cavities or lumina, which transport gases and fluids across tissues and organs. Among different species, lumina vary drastically in size, scale, and complexity. However, all lumen formation processes share key morphogenetic principles that underly their development. Fundamentally, a lumen simply consists of epithelial cells that encapsulate a continuous internal space, and a common way of building a lumen is via opening and enlarging by filling it with fluid and/or macromolecules. Here, we discuss how polarized targeting of membrane and secreted proteins regulates lumen formation, mainly focusing on ion transporters in vertebrate model systems. We also discuss mechanistic differences observed among invertebrates and vertebrates and describe how the unique properties of the Na+/K+-ATPase and junctional proteins can promote polarization of immature epithelia to build lumina de novo in developing organs.

Monitoring and modulating the trajectory of eosinophilic esophagitis.

Current treatments of eosinophilic esophagitis (EoE) aim to eliminate esophageal mucosal inflammation and attenuate, stabilize, or reverse stricture formation. However, our ability to study the long-term course of esophageal strictures in patients with EoE is hampered by the short-term existence of this disease. It is unclear to what degree of control of inflammation is needed to prevent stricture formation. Additionally, identified phenotypes of EoE may ultimately dictate different levels of concern and time intervals for developing fibrosis. Currently, multiple methods are used to monitor patients' disease progression to fibrosis, as symptoms alone do not correlate with disease activity. Endoscopic findings and mucosal histology are used to monitor disease activity, but these focus on improvements in inflammation with inconsistent evaluation of underlying fibrosis. The use of functional lumen impedance planimetry, barium esophagraphy, and endoscopic ultrasound continues to expand in EoE. The rapid advancements in EoE have led to an armamentarium of measuring tools and therapies that holistically characterize disease severity and response to therapy. Nevertheless, our ability to evaluate gross esophageal fibrosis and stricture formation from a transmural rather than mucosal view should be a focus of future investigations because it is essential to monitoring and modulating the trajectory of EoE.

Blastocoel morphogenesis: A biophysics perspective.

The blastocoel is a fluid-filled cavity characteristic of animal embryos at the blastula stage. Its emergence is commonly described as the result of cleavage patterning, but this historical view conceals a large diversity of mechanisms and overlooks many unsolved questions from a biophysics perspective. In this review, we describe generic mechanisms for blastocoel morphogenesis, rooted in biological literature and simple physical principles. We propose novel directions of study and emphasize the importance to study blastocoel morphogenesis as an evolutionary and physical continuum.

Hydrostatic pressure as a driver of cell and tissue morphogenesis.

Morphogenesis, the process by which tissues develop into functional shapes, requires coordinated mechanical forces. Most current literature ascribes contractile forces derived from actomyosin networks as the major driver of tissue morphogenesis. Recent works from diverse species have shown that pressure derived from fluids can generate deformations necessary for tissue morphogenesis. In this review, we discuss how hydrostatic pressure is generated at the cellular and tissue level and how the pressure can cause deformations. We highlight and review findings demonstrating the mechanical roles of pressures from fluid-filled lumens and viscous gel-like components of the extracellular matrix. We also emphasise the interactions and mechanochemical feedbacks between extracellular pressures and tissue behaviour in driving tissue remodelling. Lastly, we offer perspectives on the open questions in the field that will further our understanding to uncover new principles of tissue organisation during development.

Rap1 regulates lumen continuity via Afadin in renal epithelia.

The continuity of a lumen within an epithelial tubule is critical for its function. We previously found that the F-actin binding protein Afadin is required for timely lumen formation and continuity in renal tubules formed from the nephrogenic mesenchyme in mice. Afadin is a known effector and interactor of the small GTPase Rap1, and in the current study, we examine the role of Rap1 in nephron tubulogenesis. Here, we demonstrate that Rap1 is required for nascent lumen formation and continuity in cultured 3D epithelial spheroids and in vivo in murine renal epithelial tubules derived from the nephrogenic mesenchyme, where its absence ultimately leads to severe morphogenetic defects in the tubules. By contrast, Rap1 is not required for lumen continuity or morphogenesis in renal tubules derived from the ureteric epithelium, which differ in that they form by extension from a pre-existing tubule. We further demonstrate that Rap1 is required for correct localization of Afadin to adherens junctions both in vitro and in vivo. Together, these results suggest a model in which Rap1 localizes Afadin to junctional complexes, which in turn regulates nascent lumen formation and positioning to ensure continuous tubulogenesis.

Rab11 is essential to pancreas morphogenesis, lumen formation and endocrine mass.

The molecular links between tissue-level morphogenesis and the differentiation of cell lineages in the pancreas remain elusive despite a decade of studies. We previously showed that in pancreas both processes depend on proper lumenogenesis. The Rab GTPase Rab11 is essential for epithelial lumen formation in vitro, however few studies have addressed its functions in vivo and none have tested its requirement in pancreas. Here, we show that Rab11 is critical for proper pancreas development. Co-deletion of the Rab11 isoforms Rab11A and Rab11B in the developing pancreatic epithelium (Rab11pancDKO) results in ∼50% neonatal lethality and surviving adult Rab11pancDKO mice exhibit defective endocrine function. Loss of both Rab11A and Rab11B in the embryonic pancreas results in morphogenetic defects of the epithelium, including defective lumen formation and lumen interconnection. In contrast to wildtype cells, Rab11pancDKO cells initiate the formation of multiple ectopic lumens, resulting in a failure to coordinate a single apical membrane initiation site (AMIS) between groups of cells. This results in an inability to form ducts with continuous lumens. Here, we show that these defects are due to failures in vesicle trafficking, as apical and junctional components remain trapped within Rab11pancDKO cells. Together, these observations suggest that Rab11 directly regulates epithelial lumen formation and morphogenesis. Our report links intracellular trafficking to organ morphogenesis in vivo and presents a novel framework for decoding pancreatic development.

Oscillatory contractile forces refine endothelial cell-cell interactions for continuous lumen formation governed by Heg1/Ccm1.

The formation and organization of complex blood vessel networks rely on various biophysical forces, yet the mechanisms governing endothelial cell-cell interactions under different mechanical inputs are not well understood. Using the dorsal longitudinal anastomotic vessel (DLAV) in zebrafish as a model, we studied the roles of multiple biophysical inputs and cerebral cavernous malformation (CCM)-related genes in angiogenesis. Our research identifies heg1 and krit1 (ccm1) as crucial for the formation of endothelial cell-cell interfaces during anastomosis. In mutants of these genes, cell-cell interfaces are entangled with fragmented apical domains. A Heg1 live reporter demonstrated that Heg1 is dynamically involved in the oscillatory constrictions along cell-cell junctions, whilst a Myosin live reporter indicated that heg1 and krit1 mutants lack actomyosin contractility along these junctions. In wild-type embryos, the oscillatory contractile forces at junctions refine endothelial cell-cell interactions by straightening junctions and eliminating excessive cell-cell interfaces. Conversely, in the absence of junctional contractility, the cell-cell interfaces become entangled and prone to collapse in both mutants, preventing the formation of a continuous luminal space. By restoring junctional contractility via optogenetic activation of RhoA, contorted junctions are straightened and disentangled. Additionally, haemodynamic forces complement actomyosin contractile forces in resolving entangled cell-cell interfaces in both wild-type and mutant embryos. Overall, our study reveals that oscillatory contractile forces governed by Heg1 and Krit1 are essential for maintaining proper endothelial cell-cell interfaces and thus for the formation of a continuous luminal space, which is essential to generate a functional vasculature.

EUS-Guided Choledocho-duodenostomy Using Lumen Apposing Stent Versus ERCP With Covered Metallic Stents in Patients With Unresectable Malignant Distal Biliary Obstruction: A Multicenter Randomized Controlled Trial (DRA-MBO Trial).

BACKGROUND & AIMS: Several studies have compared primary endoscopic ultrasound (EUS)-guided biliary drainage to endoscopic retrograde cholangiopancreatography (ERCP) with insertion of metal stents in unresectable malignant distal biliary obstruction (MDBO) and the results were conflicting. The aim of the current study was to compare the outcomes of the procedures in a large-scale study. METHODS: This was a multicenter international randomized controlled study. Consecutive patients admitted for obstructive jaundice due to unresectable MDBO were recruited. Patients were randomly allocated to receive EUS-guided choledocho-duodenostomy (ECDS) or ERCP for drainage. The primary outcome was the 1-year stent patency rate. Other outcomes included technical success, clinical success, adverse events, time to stent dysfunction, reintervention rates, and overall survival. RESULTS: Between January 2017 and February 2021, 155 patients were recruited (ECDS 79, ERCP 76). There were no significant differences in 1-year stent patency rates (ECDS 91.1% vs ERCP 88.1%, P = .52). The ECDS group had significantly higher technical success (ECDS 96.2% vs ERCP 76.3%, P < .001), whereas clinical success was similar (ECDS 93.7% vs ERCP 90.8%, P = .559). The median (interquartile range) procedural time was significantly shorter in the ECDS group (ECDS 10 [5.75-18] vs ERCP 25 [14-40] minutes, P < .001). The rate of 30-day adverse events (P = 1) and 30-day mortality (P = .53) were similar. CONCLUSION: Both procedures could be options for primary biliary drainage in unresectable MDBO. ECDS was associated with higher technical success and shorter procedural time then ERCP. Primary ECDS may be preferred when difficult ERCPs are anticipated. This study was registered to Clinicaltrials.gov NCT03000855.

Shaping epithelial lumina under pressure.

The formation of fluid- or gas-filled lumina surrounded by epithelial cells pervades development and disease. We review the balance between lumen pressure and mechanical forces from the surrounding cells that governs lumen formation. We illustrate the mechanical side of this balance in several examples of increasing complexity, and discuss how recent work is beginning to elucidate how nonlinear and active mechanics and anisotropic biomechanical structures must conspire to overcome the isotropy of pressure to form complex, non-spherical lumina.

Detection of the antibiotic resistance genes content of intestinal Bacteroides, Parabacteroides and Phocaeicola isolates from healthy and carbapenem-treated patients from European countries.

BACKGROUND: Bacteroides fragilis group (BFG) species are the most significant anaerobic pathogens and are also the most antibiotic-resistant anaerobic species. Therefore, surveying their antimicrobial resistance levels and investigating their antibiotic resistance mechanisms is recommended. Since their infections are endogenous and they are important constituents of the intestinal microbiota, the properties of the intestinal strains are also important to follow. The aim of this study was to investigate the main antibiotic gene content of microbiota isolates from healthy people and compare them with the gene carriage of strains isolated from infections. RESULTS: We detected 13, mainly antibiotic resistance determinants of 184 intestinal BFG strains that were isolated in 5 European countries (Belgium, Germany, Hungary, Slovenia and Turkey) and compared these with values obtained earlier for European clinical strains. Differences were found between the values of this study and an earlier one for antibiotic resistance genes that are considered to be mobile, with higher degrees for cfxA, erm(F) and tet(Q) and with lower degrees for msrSA, erm(B) and erm(G). In addition, a different gene prevalence was found depending on the taxonomical groups, e.g., B. fragilis and NBFB. Some strains with both the cepA and cfiA ß-lactamase genes were also detected, which is thought to be exceptional since until now, the B. fragilis genetic divisions were defined by the mutual exclusion of these two genes. CONCLUSIONS: Our study detected the prevalences of a series of antibiotic resistance genes in intestinal Bacteroides strains which is a novelty. In addition, based on the current and some previous data we hypothesized that prevalence of some antibiotic resistance genes detected in the clinical and intestinal BFG strains were different, which could be accounted with the differential composition of the Bacteroides microbiota and/or the MGE mobilities at the luminal vs. mucosal sites of the intestine.

Redox regulation in chloroplast thylakoid lumen: The pmf changes everything, again.

Photosynthesis is the foundation of life on Earth. However, if not well regulated, it can also generate excessive reactive oxygen species (ROS), which can cause photodamage. Regulation of photosynthesis is highly dynamic, responding to both environmental and metabolic cues, and occurs at many levels, from light capture to energy storage and metabolic processes. One general mechanism of regulation involves the reversible oxidation and reduction of protein thiol groups, which can affect the activity of enzymes and the stability of proteins. Such redox regulation has been well studied in stromal enzymes, but more recently, evidence has emerged of redox control of thylakoid lumenal enzymes. This review/hypothesis paper summarizes the latest research and discusses several open questions and challenges to achieving effective redox control in the lumen, focusing on the distinct environments and regulatory components of the thylakoid lumen, including the need to transport electrons across the thylakoid membrane, the effects of pH changes by the proton motive force (pmf) in the stromal and lumenal compartments, and the observed differences in redox states. These constraints suggest that activated oxygen species are likely to be major regulatory contributors to lumenal thiol redox regulation, with key components and processes yet to be discovered.

Urgent Candy-Plug technique for distal false lumen occlusion in chronic aortic dissection.

OBJECTIVE: This study aimed to assess the impact of urgency on early and midterm outcomes of the Candy-Plug (CP) technique for distal false lumen (FL) occlusion in thoracic endovascular aortic repair for aortic dissection. METHODS: The CP registry was reviewed, and patients were categorized into elective and urgent/emergent groups for analysis. End points included technical success, clinical success, early (30-day) computed tomography angiography findings, early (30-day) mortality, adverse events, and aortic remodeling in patients with available computed tomography angiography follow-up and reintervention. RESULTS: A total of 155 patients received a custom-made CP, of whom 32 patients (44% male, mean age 61 ± 9 years) were treated urgently and 123 patients (63% male, mean age 62 ± 11 years) electively. The primary CP rate was higher in the urgent group (28/32, 88%, in the urgent group vs 96/123, 78%, in the elective group, P = .051). The mean contrast volume was higher in the urgent group (157 ± 56 mL in the urgent group vs 130 ± 71 mL in the elective group, P = .017). Technical success was achieved in all patients in both groups. Clinical success was achieved in 25 of 32 (78%) patients in the urgent group vs 113 and 123 (92%) in the elective group (P = .159). The early mortality rate was 13% (4 of 32 patients) in the urgent group vs 1% (1 of 123 patients) in the elective group (P = .120). There was no statistically significant difference regarding the early adverse events between the urgent and elective CP groups. Early aortic-related reinterventions were required in 6 of 32 (19%) patients in the urgent group vs 6 of 123 (5%) in the elective group (P = .094). Thoracic aortic aneurysm sac regression was lower in the urgent group (5/28, 18%, in the urgent group vs 63/114, 55%, in the elective group, P = .001). Stable thoracic aortic aneurysm sac was higher in the urgent group (22/28, 79%, in the urgent group vs 47/114, 41%, in the elective group, P = .000). An increase in thoracic aortic aneurysm sac occurred in 1 of 28 (4%) patients in the urgent group vs 4 of 114 (4%) patients in the elective group (P = .096). CONCLUSIONS: The urgent use of the CP technique for distal FL occlusion in aortic dissection was feasible and effective. The decrease in aortic FL sac diameter may be affected by the urgent use of CP due to limited sizing availability. However, it achieved a high rate of aortic remodeling.

Coronary Artery Plaque Phenotype and 5-Year Clinical Outcomes in Older Patients with Non-ST Elevation Acute Coronary Syndrome.

Background: Lesions with thin-cap fibroatheroma (TCFA), small luminal area and large plaque burden (PB) have been considered at high risk of cardiovascular events. Older patients were not represented in studies which demonstrated correlation between clinical outcome and plaque characteristics. This study aims to investigate the prognostic role of high-risk plaque characteristics and long-term outcome in older patients presenting with non-ST elevation acute coronary syndrome (NSTEACS). Methods: This study recruited older patients aged ≥ 75 years with NSTEACS undergoing virtual-histology intravascular ultrasound (VH-IVUS) imaging from the Improve Clinical Outcomes in high-risk patieNts with acute coronary syndrome (ICON-1). Primary endpoint was the composite of major adverse cardiovascular events (MACE) consisting of all-cause mortality, myocardial infarction (MI), and any revascularisation. Every component of MACE and target vessel failure (TVF) including MI and any revascularisation were considered as secondary endpoints. Results: Eighty-six patients with 225 vessels undergoing VH-IVUS at baseline completed 5-year clinical follow-up. Patients with minimal lumen area (MLA) ≤ 4 mm 2 demonstrated increased risk of MACE (hazard ratio [HR] 2.37, 95% confidence interval [CI] 1.00-5.59, p = 0.048) with a worse event-free survival (Log Rank 4.17, p = 0.041) than patients with MLA > 4 mm 2 . Patients with combination of TCFA, MLA ≤ 4 mm 2 and PB ≥ 70% showed high risk of MI (HR 5.23, 95% CI 1.05-25.9, p = 0.043). Lesions with MLA ≤ 4 mm 2 had 6-fold risk of TVF (HR 6.16, 95% CI 1.24-30.5, p = 0.026). Conclusions: Small luminal area appears as the major prognostic factor in older patients with NSTEACS at long-term follow-up. Combination of TCFA, MLA ≤ 4 mm 2 and PB ≥ 70% was associated with high risk of MI. Clinical Trial Registration: NCT01933581.

Individualized rotation of left double lumen endobronchial tube to improve placement success rate: a randomized controlled trial.

BACKGROUND: In conventional practice, the left double lumen tube (DLT) is rotated 90° counterclockwise when the endobronchial cuff passes glottis. Success rate upon the first attempt is < 80%, likely owing to varying morphology of the bronchial bifurcation. METHODS: We conducted a randomized controlled trial to compare 90° counterclockwise rotation versus individualized degree of rotation in adult patients undergoing elective thoracic surgery using left DLT. The degree of rotation in the individualized group was based on the angle of the left main bronchi as measured on computed tomography (CT). The primary outcome was the first attempt left DLT placement success rate. RESULTS: A total of 556 patients were enrolled: 276 in the control group and 280 in the individualized group. The average angle of the left main bronchi was 100.6±9.5° (range 72° to 119°). The first attempt left DLT placement success rate was 82.6% (228/276) in the control group versus 91.4% (256/280) in the individualized group (P=0.02, χ2 test). The rate of carina mucosal injury, as measured at 30 min after the start of surgery under fibreoptic bronchoscopy, was significantly lower in individualized group than control group (14.0% versus 19.6%, P=0.041). The individualized group also had lower rate of postoperative sore throat (29.4% versus 44.0%, P<0.001) and hoarseness (16.8% versus 24.7%, P＜0.05). CONCLUSIONS: Individualized rotation of left DLT based on the angle of the left main bronchi on preoperative CT increased first attempt success rate in adult patients undergoing elective thoracic surgery. TRIAL REGISTRATION: The trial is registered at Chinese Clinical Trial Registry (ChiCTR2100053349; principal investigator Xiang Quan, date of registration November 19, 2021).

Impact of vessel volume on thermodilution measurements in patients with coronary microvascular dysfunction.

BACKGROUND: Two invasive methods are available to estimate microvascular resistance: bolus and continuous thermodilution. Comparative studies have revealed a lack of concordance between measurements of microvascular resistance obtained through these techniques. AIMS: This study aimed to examine the influence of vessel volume on bolus thermodilution measurements. METHODS: We prospectively included patients with angina with non-obstructive coronary arteries (ANOCA) undergoing bolus and continuous thermodilution assessments. All patients underwent coronary CT angiography to extract vessel volume. Coronary microvascular dysfunction was defined as coronary flow reserve (CFR) < 2.0. Measurements of absolute microvascular resistance (in Woods units) and index of microvascular resistance (IMR) were compared before and after volumetric adjustment. RESULTS: Overall, 94 patients with ANOCA were included in this study. The mean age was 64.7 ± 10.8 years, 48% were female, and 19% had diabetes. The prevalence of CMD was 16% based on bolus thermodilution, while continuous thermodilution yielded a prevalence of 27% (Cohen's Kappa 0.44, 95% CI 0.23-0.65). There was no correlation in microvascular resistance between techniques (r = 0.17, 95% CI -0.04 to 0.36, p = 0.104). The adjustment of IMR by vessel volume significantly increased the agreement with absolute microvascular resistance derived from continuous thermodilution (r = 0.48, 95% CI 0.31-0.63, p < 0.001). CONCLUSIONS: In patients with ANOCA, invasive methods based on coronary thermodilution yielded conflicting results for the assessment of CMD. Adjusting IMR with vessel volume improved the agreement with continuous thermodilution for the assessment of microvascular resistance. These findings strongly suggest the importance of considering vessel volume when interpreting bolus thermodilution assessment.

Use of dual-lumen microcatheter pullback injection in complex percutaneous coronary intervention.

Dual-lumen microcatheters (DLMC) are utilized in challenging wiring scenarios as well as for contrast and medication injections. Nonetheless, lesion characterization remains extremely challenging in many cases. We describe a DLMC-facilitated technique which can assist in locating the distal anastomosis while navigating an occluded bypass graft during retrograde chronic total occlusion recanalization, as well as in the differential diagnosis of abrupt vessel closure. This "DLMC Pullback Injection" technique is performed by injecting contrast through the over-the-wire port of the DLMC, while the latter is quickly pulled back across the region of interest in a dynamic fashion. We believe this technique has the potential to solve challenging scenarios and to enrich the complex percutaneous coronary intervention operator's armamentarium.

Pre-emptive False Lumen Embolization to Prevent Persistent Type II Endoleak in Fenestrated-Branched Endovascular Repair of Post-Dissection Thoracoabdominal Aortic Aneurysms.

PURPOSE: The purpose was to describe a technique to promote false lumen (FL) thrombosis in post-dissection thoracoabdominal aortic aneurysms (PD-TAAAs) managed by fenestrated/branched endografting (F/B-EVAR). TECHNIQUE: A 5/6Fr-90 cm length sheath is advanced from the true lumen (TL) to FL through the most distal entry tear of the infrarenal aorta or iliac arteries. It is parked in the most cranial portion of the FL in the thoracic aorta. Aortic endografts are deployed in the TL excluding all the para-visceral/distal entry tears and target visceral vessels bridging stenting is performed. A selective FL angiography is performed through the 5/6Fr sheath to detect the origin of all segmentary arteries. Embolization of FL is performed from above to below by M-reye pushable coils, obtaining the packaging of FL. After completion angiography, the 5/6Fr sheath is retrieved in external iliac artery and molding ballooning of the distal segment of the aortic/iliac endograft is performed. Between 2019 and 2023, this technique was applied in 11cases with a median number of 73 (interquartile range [IQR=12) coils. Out of 8 (72%) patients with available radiological follow-up at 1 year, 7 exhibited complete FL thrombosis. CONCLUSIONS: The FL coiling in PD-TAAAs managed by F/B-EVAR is feasible, safe, and effective to promote the complete FL thrombosis. CLINICAL IMPACT: Preemptive false lumen embolization is a feasible, safe, and effective technique for preventing persistent type II endoleaks after fenestrated-branched endovascular repair of post-dissection thoracoabdominal aortic aneurysms. This technique may be routinely recommended to promote FL thrombosis and aortic remodeling after FB-EVAR in PD-TAAAs, thereby reducing the incidence of reinterventions during follow-up.