ABSTRACT
OBJECTIVES: Type I and III endoleaks following endovascular aneurysm repair (EVAR) can lead to catastrophic events that require major re-interventions. We reviewed our experience with aortic endograft re-interventions for type I and III endoleaks and other serious failures among different devices. METHODS: We retrospectively reviewed patients with a prior EVAR who underwent open conversion (OC) or major endovascular intervention (MEI) (re-lining, cuff/limb extension, parallel graft) for type I/III endoleaks at our institution from 2002 to 2019. Baseline characteristics, procedural details, re-interventions, and outcomes were collected. RESULTS: A total of 229 patients (194 men) underwent re-interventions for type I and III endoleaks after EVAR (90 OC, 139 MEI) for devices implanted between 1997 and 2019. Average age at re-intervention was 78±8.5 years. A total of 135 (59%) were implanted at our institution, whereas 93 (41%) were referred. Median time to re-intervention was 4 years with 25% to 75% interquartile range (IQR) of 2.2-6.6 years. There was no significant difference in baseline demographics or type of re-interventions (OC/MEI) between device types. 42/229 (18%) presented with ruptured aneurysms, 20/229 (9%) were symptomatic, whereas the rest presented with asymptomatic radiographic findings. Type 1A endoleak was present in 146/229 (63.8%-72 with proximal migration), type IB in 46/229 (20.1%), type IIIA in 37/229 (16.6%), type IIIB in 15/229 (6.5%), and persistent aneurysm sac growth with no radiographic evidence of an endoleak in 6/229 (2.6%). Devices included most commercial products: AFX, Excluder, AneuRx, Ancure, Endurant, and Zenith. A smaller number of investigational devices accounted for the rest. Type 1A endoleak was the most common indication for re-intervention among all devices except for AFX and ancure devices, proximal migration was a frequent presentation with AneuRx. AFX devices more frequently presented with a type III and ancure devices more frequently presented with a type IB endoleak. CONCLUSIONS: Serious failure modes after EVAR differ between endografts and occur throughout the follow-up period. This is important to guide targeted interrogation of surveillance studies and follow-up schedules, even for discontinued devices, as well as comparisons between various series and estimation of EVAR failure rates. CLINICAL IMPACT: Surveillance after EVAR is critical for long term success of the repair, understanding of the differential modes of failure of every graft available is important in the longitudinal evaluation of these endografts. Equally important is the understanding of the modes of failure of legacy endografts that are no longer on the market but still being followed, in order to be able to tailor a surveillance regiemn and the evntual repair if needed.
ABSTRACT
Safe and effective pain management is a critical healthcare and societal need. The potential for acute liver injury from paracetamol (ApAP) overdose; nephrotoxicity and gastrointestinal damage from chronic non-steroidal anti-inflammatory drug (NSAID) use; and opioids' addiction are unresolved challenges. We developed SRP-001, a non-opioid and non-hepatotoxic small molecule that, unlike ApAP, does not produce the hepatotoxic metabolite N-acetyl-p-benzoquinone-imine (NAPQI) and preserves hepatic tight junction integrity at high doses. CD-1 mice exposed to SRP-001 showed no mortality, unlike a 70% mortality observed with increasing equimolar doses of ApAP within 72 h. SRP-001 and ApAP have comparable antinociceptive effects, including the complete Freund's adjuvant-induced inflammatory von Frey model. Both induce analgesia via N-arachidonoylphenolamine (AM404) formation in the midbrain periaqueductal grey (PAG) nociception region, with SRP-001 generating higher amounts of AM404 than ApAP. Single-cell transcriptomics of PAG uncovered that SRP-001 and ApAP also share modulation of pain-related gene expression and cell signaling pathways/networks, including endocannabinoid signaling, genes pertaining to mechanical nociception, and fatty acid amide hydrolase (FAAH). Both regulate the expression of key genes encoding FAAH, 2-arachidonoylglycerol (2-AG), cannabinoid receptor 1 (CNR1), CNR2, transient receptor potential vanilloid type 4 (TRPV4), and voltage-gated Ca2+ channel. Phase 1 trial (NCT05484414) (02/08/2022) demonstrates SRP-001's safety, tolerability, and favorable pharmacokinetics, including a half-life from 4.9 to 9.8 h. Given its non-hepatotoxicity and clinically validated analgesic mechanisms, SRP-001 offers a promising alternative to ApAP, NSAIDs, and opioids for safer pain treatment.