Mre11 dimers coordinate DNA end bridging and nuclease processing in double-strand-break repair.

Mre11 forms the core of the multifunctional Mre11-Rad50-Nbs1 (MRN) complex that detects DNA double-strand breaks (DSBs), activates the ATM checkpoint kinase, and initiates homologous recombination (HR) repair of DSBs. To define the roles of Mre11 in both DNA bridging and nucleolytic processing during initiation of DSB repair, we combined small-angle X-ray scattering (SAXS) and crystal structures of Pyrococcus furiosus Mre11 dimers bound to DNA with mutational analyses of fission yeast Mre11. The Mre11 dimer adopts a four-lobed U-shaped structure that is critical for proper MRN complex assembly and for binding and aligning DNA ends. Further, mutations blocking Mre11 endonuclease activity impair cell survival after DSB induction without compromising MRN complex assembly or Mre11-dependant recruitment of Ctp1, an HR factor, to DSBs. These results show how Mre11 dimerization and nuclease activities initiate repair of DSBs and collapsed replication forks, as well as provide a molecular foundation for understanding cancer-causing Mre11 mutations in ataxia telangiectasia-like disorder (ATLD).

Percutaneous treatment of symptomatic deep vein thrombosis in adolescents using large-bore thrombectomy systems.

BACKGROUND: While large-bore mechanical thrombectomy provides effective venous thrombus removal, often with avoidance of thrombolytics, literature surrounding the application of these devices in pediatric patients is sparse. OBJECTIVE: To report technical success and outcomes following large-bore thrombectomy systems in adolescent patients with deep venous thrombosis. MATERIALS AND METHODS: A retrospective review identified all patients less than 18 years of age undergoing mechanical venous thrombectomy at a single institution between 2018 and 2022. No patients were excluded. Technical success was defined as extraction of thrombus sufficient to restore unimpeded flow in affected segments. Clinical success was defined as resolution of presenting symptoms. RESULTS: Nine consecutive patients (6 females, 3 males; age range 15-17 years) underwent 10 thrombectomy procedures using ClotTriever (n=6; 60%), FlowTriever (n=2; 20%), or both (n=2; 20%). Chronicity of thrombus was categorized as acute (<2 weeks) in 6 (60%), subacute (2-6 weeks) in 1 (10%), and chronic (>6 weeks) in 3 (30%). Distribution of thrombus was lower extremity and/or inferior vena cava (IVC) in 9 (90%) and unilateral axillo-subclavian in 1 (10%). Technical success was achieved in 9 interventions (90%). Clinical success was achieved in 8 patients (88.9%). No patients received thrombolytics. There were no intraprocedural adverse events (AE). Minor complications (Society of Interventional Radiology mild adverse events) were observed in a delayed fashion following 2 interventions (20%). CONCLUSIONS: This preliminary experience demonstrated high rates of technical and clinical success with large-bore deep venous thrombectomy in adolescent patients across a range of thrombus chronicity and locations.

Human XPG nuclease structure, assembly, and activities with insights for neurodegeneration and cancer from pathogenic mutations.

Xeroderma pigmentosum group G (XPG) protein is both a functional partner in multiple DNA damage responses (DDR) and a pathway coordinator and structure-specific endonuclease in nucleotide excision repair (NER). Different mutations in the XPG gene ERCC5 lead to either of two distinct human diseases: Cancer-prone xeroderma pigmentosum (XP-G) or the fatal neurodevelopmental disorder Cockayne syndrome (XP-G/CS). To address the enigmatic structural mechanism for these differing disease phenotypes and for XPG's role in multiple DDRs, here we determined the crystal structure of human XPG catalytic domain (XPGcat), revealing XPG-specific features for its activities and regulation. Furthermore, XPG DNA binding elements conserved with FEN1 superfamily members enable insights on DNA interactions. Notably, all but one of the known pathogenic point mutations map to XPGcat, and both XP-G and XP-G/CS mutations destabilize XPG and reduce its cellular protein levels. Mapping the distinct mutation classes provides structure-based predictions for disease phenotypes: Residues mutated in XP-G are positioned to reduce local stability and NER activity, whereas residues mutated in XP-G/CS have implied long-range structural defects that would likely disrupt stability of the whole protein, and thus interfere with its functional interactions. Combined data from crystallography, biochemistry, small angle X-ray scattering, and electron microscopy unveil an XPG homodimer that binds, unstacks, and sculpts duplex DNA at internal unpaired regions (bubbles) into strongly bent structures, and suggest how XPG complexes may bind both NER bubble junctions and replication forks. Collective results support XPG scaffolding and DNA sculpting functions in multiple DDR processes to maintain genome stability.

Intravascular US: Applications in Interventional Radiology.

Interventional radiology applications of intravascular US (IVUS) continue to expand, complementing intraprocedural angiography and providing a unique vantage from which to guide endovascular interventions. Vascular pathologic conditions become sonographically visualized rather than inferred from the planar appearance of the opacified vascular lumen. Perivascular targets become sonographically visualized rather than approximated on the basis of fluoroscopic landmarks. The authors introduce broad categories of IVUS catheters, namely radial and side-firing varieties, as well as prevailing options for each and their technical specifications. Common applications within interventional radiology are covered in a systems approach, including deep venous thrombosis, May-Thurner syndrome, nutcracker syndrome, transjugular intrahepatic portosystemic shunts, aortic interventions, peripheral arterial disease, and endovascular or perivascular biopsy. Discussions are accompanied by technical pearls from the authors, and summarized evidence where IVUS has been shown to reduce procedural time, intravascular contrast agent dose, radiation exposure, and morbidity in each space is presented. Finally, emerging applications and future directions are discussed. ©RSNA, 2022.

Intravascular ultrasound for endovascular precision in pediatrics.

Intravascular ultrasound (IVUS) is used as a diagnostic adjunct to angiography and has become a valuable diagnostic and interventional tool with a well-documented safety profile. The American College of Cardiology and the European Society of Cardiology have published guidelines regarding the use of IVUS in the setting of percutaneous coronary intervention. IVUS has gained popularity in the interventional radiology (IR) community in recent years; however, there are no consensus guidelines for utilization. Furthermore, IVUS remains an infrequently used modality in pediatric IR, likely because of unfamiliarity with the equipment and techniques, as well as concerns over the compatibility of these instruments with pediatric anatomy. IVUS can be safely used as a helpful and sometimes necessary tool for pediatric interventions in appropriately selected patients. The utility of IVUS for reducing both fluoroscopy time and contrast agent volume makes it particularly valuable in pediatric practice. This article presents an overview of both the rotational and phased-array IVUS types and an in-depth discussion on the most common applications of these techniques in the pediatric setting across multiple procedure categories.

Portomesenteric and portosystemic venous reconstructions in children using balloon-expandable endoprostheses.

BACKGROUND: Portomesenteric and portosystemic venous occlusive disease may lead to portomesenteric hypertension, variceal bleeding, ascites and hypersplenism. Data regarding endovascular reconstructive strategies in children, however, are limited. OBJECTIVE: To report technical success, outcome and patency of portomesenteric and portosystemic venous reconstruction using VIABAHN VBX balloon-expandable endoprostheses in pediatric patients. MATERIALS AND METHODS: Five pediatric patients (median age: 15 years, range: 4-18 years), including 3 (60%) boys and 2 (40%) girls, with portomesenteric or portosystemic venous occlusion or recurrent stenosis, underwent balloon-expandable stent graft reconstruction. Presenting symptoms included acute variceal bleeding, without (n = 2, 40%) or with (n = 1, 20%) splenomegaly, and transfusion-dependent chronic melena (n = 1, 20%). One patient was asymptomatic (n = 1, 20%). Preprocedural imaging included Doppler ultrasound and contrast-enhanced computed tomography (CT) in all patients. Initial imaging showed 4 (80%) occlusions and 1 (20%) recurrent stenosis greater than 50%. Technical aspects of the reconstructions, technical successes, clinical outcomes and adverse events were recorded. Technical success was defined as completion of stent graft reconstruction. Adverse events were categorized according to Society of Interventional Radiology criteria. Clinical success was defined as resolution of the presenting symptoms and/or prevention of portal hypertensive sequela. RESULTS: Venous reconstruction was technically successful in all five patients. Stent graft locations included the main portal vein in 2 (40%), the superior mesenteric vein in 1 (20%), autologous Meso-Rex shunt in 1 (20%) and splenocaval shunt in 1 (20%). Six stent grafts were placed (two stent grafts placed in a single patient). Stent grafts had a median diameter of 7 mm (range: 6-10 mm) and a median length of 59 mm (range: 19-79 mm). Median fluoroscopy time was 36.6 min (range: 13.4-95.8 min) and median air kerma was 301.0 mGy (range: 218.0-1,148.2 mGy). No adverse events occurred. Median clinical follow-up was 18 months (range: 6-29 months). Median imaging follow-up was 17 months (range: 2-29 months). Clinical success was achieved in all patients and maintained during the follow-up period. One patient required follow-up intervention with superior mesenteric vein side extension with a self-expanding bare metal stent due to perigraft stenosis detected on CT 3 months after stent placement. There were no stent graft occlusions. CONCLUSION: Portomesenteric and portosystemic venous reconstruction using balloon-expandable stent grafts in pediatric patients was feasible and clinically successful in this preliminary experience. Additional studies are warranted.

Evaluation and management of biliary complications after pediatric liver transplantation: pearls and pitfalls for percutaneous techniques.

In pediatric liver transplantation, bile duct complications occur with a greater incidence than vascular anastomotic dysfunction and represent a major source of morbidity and mortality. While surgical re-anastomosis can reduce the need for retransplantation, interventional radiology offers minimally invasive and graft-saving therapies. The combination of small patient size and prevailing Roux-en-Y biliary enteric anastomotic techniques makes endoscopic retrograde cholangiopancreatography difficult if not impossible. Expertise in percutaneous management is therefore imperative. This article describes post-surgical anatomy, pathophysiology and noninvasive imaging of biliary complications. We review percutaneous techniques, focusing heavily on biliary access and interventions for reduced liver grafts. Subsequently we review the results and adverse events of these procedures and describe conditions that masquerade as biliary obstruction.

Combined ultrasound and fluoroscopy guided tunneled external lumbar drain placement in children.

External lumbar drain placement has been shown to be an efficacious and safe approach to managing various forms of intracranial hypertension in adult patients and children. The use of ultrasound guidance for lumbar punctures in young patients has been described however, but the modality is not routinely used for the placement of tunneled lumbar drains. In this report, two cases are presented that detail experience using ultrasound guidance for tunneled lumbar drains in children.

Yttrium-90 radiation segmentectomy for hepatic metastases: A multi-institutional study of safety and efficacy.

BACKGROUND AND OBJECTIVES: This study assessed the outcomes of Yttrium-90 (90 Y) radiation segmentectomy for hepatic metastases unamenable to resection or ablation. MATERIALS AND METHODS: Over 6 years, 36 patients with 53 tumors underwent segmental radioembolization. Patients were not candidates for surgical resection or thermal ablation. Malignancies included metastases from colorectal cancer (31%), neuroendocrine tumors (28%), sarcoma (19%), and others (22%). Eighty-one percent of patients had undergone prior treatment with systemic chemotherapy. Ongoing systemic chemotherapy was continued. Toxicity, tumor response, tumor progression, and survival were assessed. RESULTS: The median tumor size was 3.6 cm (range 1.2-6.1 cm). Adverse event rates were low, with no hepatic-related Common Terminology Criteria for Adverse Events Grade 3 or 4 toxicity. Target tumor Response Evaluation Criteria in Solid Tumors disease control rate was 92% (28% partial response, 64% stable disease). For patients with enhancing tumors (n = 14), modified Response Evaluation Criteria in Solid Tumors target tumor objective response rate was 100%. During a median follow-up of 12 months, target tumor progression occurred in 28% of treated tumors. Overall survival was 96% and 83% at 6 and 12 months, respectively. CONCLUSIONS: 90 Y radiation segmentectomy for hepatic metastases demonstrates high rates of tumor control and minimal toxicity. Radiation segmentectomy should be considered for patients with metastatic hepatic malignancy who are not candidates for surgical resection.

Confirmatory radiographs have limited utility following ultrasound-guided tunneled femoral central venous catheter placements by interventional radiology.

BACKGROUND: Ultrasonography may reliably visualize both appropriately positioned and malpositioned femoral-approach catheter tips. Radiography may be used to confirm catheter tip position after placement, but its utility following intraprocedural ultrasound (US) catheter tip verification is unclear. OBJECTIVES: To report the utility of confirmatory radiographs after US-guided tunneled femoral central venous catheter (CVC) placements by interventional radiology in pediatric patients. MATERIALS AND METHODS: A total of 484 pediatric patients underwent bedside US-guided tunneled femoral CVC placements in an intensive care setting at a single tertiary children's hospital between Jan. 1, 2016, and April 20, 2020. Technical success, adverse events, post-procedure radiographic practices and inter-modality catheter tip concordance were recorded. All radiographs were performed within 12 h of catheter placement. RESULTS: The mean patient age was 175±508 days (range: 1 day to 19 years), including 257 (53.1%) males and 227 (46.9%) females. Of the 484 attempted placements, 472 (97.5%) were primary placements. Four hundred eighty-one (99.4%) placements were technically successful. There were three (0.6%) technical failures due to previously undiagnosed iliofemoral venous occlusive disease. Five (1.0%) adverse events occurred. Radiographs were obtained within 12 h of CVC placement in 171 (35.3%) patients, in 120 (70.2%) of whom the indication was recent catheter placement. All 171 (100%) post-placement radiographs showed catheter tip location concordance with the intra-procedural US. In one (0.2%) patient, in whom there was nonvisualization of a guidewire and clinical concern for malposition during US-guided placement, post-procedure radiographs, coupled with multiplanar venography, demonstrated inadvertent paravertebral venous plexus catheter placement. CONCLUSION: The concordance between intra-procedural US and confirmatory post-procedure radiographs of CVC placements by interventional radiology obviates the need for routine radiographs. Radiographs may be obtained in instances of proceduralist uncertainty or clinical concern.

Transjugular intrahepatic portosystemic shunt creation may be associated with hyperplastic hepatic nodular lesions in the long term: an analysis of 18 pediatric and young adult patients.

BACKGROUND: Retrospective studies have demonstrated the efficacy and safety of pediatric and adolescent transjugular intrahepatic portosystemic shunt (TIPS), but long-term outcomes warrant further investigation. OBJECTIVE: To report on the development of hyperplastic hepatic nodular lesion development in children and young adults (<21 years) with TIPS patency >3 years. MATERIALS AND METHODS: Eighteen children and young adults, including 10 (55.6%) females and 8 (44.4%) males, underwent TIPS creation with >3 years' patency and follow-up evaluation at a tertiary children's hospital. The mean age at the time of TIPS creation was 12.5±5.1 years (range: 1.5-20.0 years). The mean model for end-stage liver disease (MELD) at the time of TIPS creation was 8.1±1.6 (range: 6-11). Indications for TIPS creation included acute variceal bleeding (8/18, 44.4%), primary (1/18, 5.6%) or secondary (7/18, 38.9%) prevention of varices, portal vein thrombosis (1/18, 5.6%), and splenic sequestration (1/18, 5.6%). Technical successes, intra-procedural parameters, hemodynamic and clinical successes, TIPS patencies, adverse events, imaging evaluations, and follow-ups were recorded. RESULTS: All (100%) TIPS placements were successful; however, a direct intrahepatic portosystemic shunt was created in one (5.6%) patient. Mean reduction of the portosystemic shunt gradient was 9.1±3.3 mmHg (range: 4-16 mmHg). Seventeen (94.4%) patients demonstrated clinical success with resolution of their initial clinical indication for TIPS placement. The 3-year TIPS primary, primary-assisted, and secondary patencies were 83.3% (15/18), 94.4% (17/18), and 100% (18/18), respectively. Two (11.1%) patients developed mild, medically controlled hepatic encephalopathy. One (5.6%) patient developed hepatopulmonary syndrome. Nine (50%) patients developed single or multiple hepatic nodules at a mean imaging surveillance time after TIPS of 4.4±3.0 years (range: 1.5-10.2 years). Six (33.3%) patients developed nodules >1 cm with imaging features most consistent with focal nodular hyperplasia or focal nodular hyperplasia-like nodules. The mean follow-up duration was 5.7±2.9 years (range: 3.0-13.1 years). CONCLUSION: Long-term (>3 years) portosystemic shunting via TIPS is associated with the development of hepatic nodular lesions in children. Consequently, children with TIPS may need gray-scale assessment of hepatic parenchyma as part of routine ultrasound exams and extended imaging surveillance until more is understood regarding the natural history of induced nodularity.

Structural Control of Nonnative Ligand Binding in Engineered Mutants of Phosphoenolpyruvate Carboxykinase.

Protein engineering to alter recognition underlying ligand binding and activity has enormous potential. Here, ligand binding for Escherichia coli phosphoenolpyruvate carboxykinase (PEPCK), which converts oxaloacetate into CO2 and phosphoenolpyruvate as the first committed step in gluconeogenesis, was engineered to accommodate alternative ligands as an exemplary system with structural information. From our identification of bicarbonate binding in the PEPCK active site at the supposed CO2 binding site, we probed binding of nonnative ligands with three oxygen atoms arranged to resemble the bicarbonate geometry. Crystal structures of PEPCK and point mutants with bound nonnative ligands thiosulfate and methanesulfonate along with strained ATP and reoriented oxaloacetate intermediates and unexpected bicarbonate were determined and analyzed. The mutations successfully altered the bound ligand position and orientation and its specificity: mutated PEPCKs bound either thiosulfate or methanesulfonate but never both. Computational calculations predicted a methanesulfonate binding mutant and revealed that release of the active site ordered solvent exerts a strong influence on ligand binding. Besides nonnative ligand binding, one mutant altered the Mn2+ coordination sphere: instead of the canonical octahedral ligand arrangement, the mutant in question had an only five-coordinate arrangement. From this work, critical features of ligand binding, position, and metal ion cofactor geometry required for all downstream events can be engineered with small numbers of mutations to provide insights into fundamental underpinnings of protein-ligand recognition. Through structural and computational knowledge, the combination of designed and random mutations aids in the robust design of predetermined changes to ligand binding and activity to engineer protein function.

Cost-Effectiveness of Transjugular Intrahepatic Portosystemic Shunt versus Large-Volume Paracentesis in Refractory Ascites: Results of a Markov Model Incorporating Individual Patient-Level Meta-Analysis and Nationally Representative Cost Data.

PURPOSE: To compare relative cost-effectiveness of serial large-volume paracentesis (LVP) and transjugular intrahepatic portosystemic shunt (TIPS) creation for treatment of refractory ascites. MATERIALS AND METHODS: A decisional Markov model was developed to estimate payer cost and quality-adjusted life-ears (QALYs) associated with LVP and TIPS treatment strategies for cirrhotic patients with refractory ascites. Survival estimates were derived from an individual patient-level meta-analysis of prospective randomized clinical trials. Health utilities for potential health states were derived from a prospective study of patients with cirrhosis. Cost data were derived from national representative claims databases (MarketScan and Medicare) and included reimbursement amounts for relevant procedures, hospitalizations, and outpatient pharmaceutical costs. One-way and probabilistic sensitivity analyses were performed. RESULTS: LVP resulted in 1.72 QALYs gained at a cost of $41,391, whereas TIPS resulted in 2.76 QALYs gained at a cost of $100,538. Incremental cost-effectiveness ratio of TIPS versus LVP was $57,003/QALY. At a willingness-to-pay ratio of $100,000/QALY, TIPS has a 62% probability of being acceptable compared with LVP. CONCLUSIONS: This study suggests that TIPS should be considered cost-effective in a country that places a relatively high value on health improvements but less so in countries with lower levels of health care resources.

Aggregation propensities of superoxide dismutase G93 hotspot mutants mirror ALS clinical phenotypes.

Protein framework alterations in heritable Cu, Zn superoxide dismutase (SOD) mutants cause misassembly and aggregation in cells affected by the motor neuron disease ALS. However, the mechanistic relationship between superoxide dismutase 1 (SOD1) mutations and human disease is controversial, with many hypotheses postulated for the propensity of specific SOD mutants to cause ALS. Here, we experimentally identify distinguishing attributes of ALS mutant SOD proteins that correlate with clinical severity by applying solution biophysical techniques to six ALS mutants at human SOD hotspot glycine 93. A small-angle X-ray scattering (SAXS) assay and other structural methods assessed aggregation propensity by defining the size and shape of fibrillar SOD aggregates after mild biochemical perturbations. Inductively coupled plasma MS quantified metal ion binding stoichiometry, and pulsed dipolar ESR spectroscopy evaluated the Cu(2+) binding site and defined cross-dimer copper-copper distance distributions. Importantly, we find that copper deficiency in these mutants promotes aggregation in a manner strikingly consistent with their clinical severities. G93 mutants seem to properly incorporate metal ions under physiological conditions when assisted by the copper chaperone but release copper under destabilizing conditions more readily than the WT enzyme. Altered intradimer flexibility in ALS mutants may cause differential metal retention and promote distinct aggregation trends observed for mutant proteins in vitro and in ALS patients. Combined biophysical and structural results test and link copper retention to the framework destabilization hypothesis as a unifying general mechanism for both SOD aggregation and ALS disease progression, with implications for disease severity and therapeutic intervention strategies.

Structural, Functional, and Immunogenic Insights on Cu,Zn Superoxide Dismutase Pathogenic Virulence Factors from Neisseria meningitidis and Brucella abortus.

UNLABELLED: Bacterial pathogens Neisseria meningitidis and Brucella abortus pose threats to human and animal health worldwide, causing meningococcal disease and brucellosis, respectively. Mortality from acute N. meningitidis infections remains high despite antibiotics, and brucellosis presents alimentary and health consequences. Superoxide dismutases are master regulators of reactive oxygen and general pathogenicity factors and are therefore therapeutic targets. Cu,Zn superoxide dismutases (SODs) localized to the periplasm promote survival by detoxifying superoxide radicals generated by major host antimicrobial immune responses. We discovered that passive immunization with an antibody directed at N. meningitidis SOD (NmSOD) was protective in a mouse infection model. To define the relevant atomic details and solution assembly states of this important virulence factor, we report high-resolution and X-ray scattering analyses of NmSOD and of SOD from B. abortus (BaSOD). The NmSOD structures revealed an auxiliary tetrahedral Cu-binding site bridging the dimer interface; mutational analyses suggested that this metal site contributes to protein stability, with implications for bacterial defense mechanisms. Biochemical and structural analyses informed us about electrostatic substrate guidance, dimer assembly, and an exposed C-terminal epitope in the NmSOD dimer. In contrast, the monomeric BaSOD structure provided insights for extending immunogenic peptide epitopes derived from the protein. These collective results reveal unique contributions of SOD to pathogenic virulence, refine predictive motifs for distinguishing SOD classes, and suggest general targets for antibacterial immune responses. The identified functional contributions, motifs, and targets distinguishing bacterial and eukaryotic SOD assemblies presented here provide a foundation for efforts to develop SOD-specific inhibitors of or vaccines against these harmful pathogens. IMPORTANCE: By protecting microbes against reactive oxygen insults, SODs aid survival of many bacteria within their hosts. Despite the ubiquity and conservation of these key enzymes, notable species-specific differences relevant to pathogenesis remain undefined. To probe mechanisms that govern the functioning of Neisseria meningitidis and Brucella abortus SODs, we used X-ray structures, enzymology, modeling, and murine infection experiments. We identified virulence determinants common to the two homologs, assembly differences, and a unique metal reservoir within meningococcal SOD that stabilizes the enzyme and may provide a safeguard against copper toxicity. The insights reported here provide a rationale and a basis for SOD-specific drug design and an extension of immunogen design to target two important pathogens that continue to pose global health threats.

Intra-Arterial Thrombolysis for Hepatic Artery Thrombosis following Liver Transplantation.

PURPOSE: Hepatic artery thrombosis (HAT) is a major cause of morbidity and death following liver transplantation. The purpose of this study was to evaluate the safety and efficacy of intra-arterial thrombolysis (IAT) in liver transplant recipients with HAT. MATERIALS AND METHODS: Adult liver transplant recipients who underwent attempted IAT for HAT were identified. This included patients with early and late HAT (occurring less than or greater than 30 d after transplantation). Records were reviewed to determine the rates of technical success, complications, surgical revascularization, repeat liver transplantation, and ischemic cholangiopathy. RESULTS: Twenty-six patients underwent attempted thrombolysis, 13 of whom had early HAT. IAT was successfully initiated in 23 patients (88%), with a median IAT duration of 28 hours (range, 12-90 h). Recanalization was achieved in 12 patients (46%). Major complications were observed in 11 patients (42%). The early HAT group showed a trend toward increased major bleeding compared with the late HAT group (50% vs 9%; P = .07). Among 12 patients who had technically successful thrombolysis, five (42%) required surgical revascularization or repeat transplantation within 2 months. At 6 months after thrombolysis, 45% with unsuccessful recanalization avoided surgery or development of ischemic cholangiopathy, similar to the proportion in those who had successful recanalization (42%; P = .88). CONCLUSIONS: Posttransplantation hepatic artery thrombolysis yields suboptimal results with a high complication rate, especially in early HAT. Even with successful restoration of flow, clinical outcomes are poor. Although thrombolysis may still be considered in view of the limited treatment options for HAT, awareness of potential complications and suboptimal success rate is essential.