Aortic rupture during STABILISE (stent-assisted balloon-induced intimal disruption and relamination in aortic dissection repair) technique.

The STABILISE (stent-assisted balloon-induced intimal disruption and relamination in aortic dissection repair) technique has shown promising results for treating type B aortic dissections, but the potential exists for fatal adverse effects. We present a case of infrarenal aortic rupture while using a compliant balloon to balloon mold the true lumen inside previously placed bare metal stents during the STABILISE technique. Caution is advised for providers who wish to perform the STABILISE technique, and we recommend using a semi-compliant balloon sized to the smallest total aortic diameter to mitigate the risk of rupture.

PepMLM: Target Sequence-Conditioned Generation of Peptide Binders via Masked Language Modeling.

Target proteins that lack accessible binding pockets and conformational stability have posed increasing challenges for drug development. Induced proximity strategies, such as PROTACs and molecular glues, have thus gained attention as pharmacological alternatives, but still require small molecule docking at binding pockets for targeted protein degradation (TPD). The computational design of protein-based binders presents unique opportunities to access "undruggable" targets, but have often relied on stable 3D structures or predictions for effective binder generation. Recently, we have leveraged the expressive latent spaces of protein language models (pLMs) for the prioritization of peptide binders from sequence alone, which we have then fused to E3 ubiquitin ligase domains, creating a CRISPR-analogous TPD system for target proteins. However, our methods rely on training discriminator models for ranking heuristically or unconditionally-derived "guide" peptides for their target binding capability. In this work, we introduce PepMLM, a purely target sequence-conditioned de novo generator of linear peptide binders. By employing a novel masking strategy that uniquely positions cognate peptide sequences at the terminus of target protein sequences, PepMLM tasks the state-of-the-art ESM-2 pLM to fully reconstruct the binder region, achieving low perplexities matching or improving upon previously-validated peptide-protein sequence pairs. After successful in silico benchmarking with AlphaFold-Multimer, we experimentally verify PepMLM's efficacy via fusion of model-derived peptides to E3 ubiquitin ligase domains, demonstrating endogenous degradation of target substrates in cellular models. In total, PepMLM enables the generative design of candidate binders to any target protein, without the requirement of target structure, empowering downstream programmable proteome editing applications.

Risk Factors for Cerebral Hyperperfusion Syndrome following Carotid Revascularization.

BACKGROUND: Cerebral hyperperfusion syndrome (CHS) is a rare but known complication of carotid revascularization that can result in severe postoperative disability and death. CHS is a well-described sequela of carotid endarterectomy (CEA) and, more recently, of transfemoral carotid artery stenting (TFCAS), but its incidence after transcarotid artery revascularization (TCAR) has not been delineated. The aims of this study were to determine the impact of procedure type (CEA versus TCAR versus TFCAS) on the development of CHS as well as to identify perioperative risk factors associated with CHS. METHODS: The Society for Vascular Surgery Vascular Quality Initiative was queried for patients aged ≥18 years who underwent CEA, TCAR, or TFCAS from 2015-2021. Emergent procedures were excluded. The primary outcome was postoperative development of CHS, defined as the presence of postoperative seizures, intracerebral hemorrhage due to hyperperfusion, or both. Bivariate and multivariable logistic regression analyses were performed to identify factors associated with CHS. RESULTS: 156,003 procedures were included (72.7% CEA, 12.4% TCAR, and 14.9% TFCAS). The incidence of CHS after CEA, TCAR, and TFCAS were 0.15%, 0.18%, and 0.53%, respectively. There was no significant difference in risk of CHS after TFCAS compared to CEA (odds ratio [OR]: 1.21; 95% confidence interval [CI] 0.76-1.92; P = 0.416), nor was there a difference between TCAR and CEA (OR: 0.91; 95% CI 0.57-1.45; P = 0.691). Perioperative risk factors associated with an increased risk of CHS included previous history of transient ischemic attack or stroke (OR: 2.50; 95% CI 1.69-3.68; P < 0.0001), necessity for urgent intervention within 48 hr (OR: 2.03; 95% CI 1.43-2.89; P < 0.0001), treatment of a total occlusion (OR: 3.80; 95% CI 1.16-12.47; P = 0.028), and need for postoperative intravenous blood pressure medication (OR: 5.45; 95% CI 3.97-7.48; P < 0.0001). Age, preoperative hypertension, degree of ipsilateral stenosis less than or equal to 99%, and history of prior carotid procedures were not statistically associated with an increased risk of CHS. Discharging patients on an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker was associated with a decreased risk of developing CHS (OR: 0.47; 95% CI 0.34-0.65; P < 0.0001). CONCLUSIONS: Compared with CEA, TCAR and TFCAS were not statistically associated with an increased risk of postoperative CHS. Patients with a previous history of transient ischemic attack or stroke, who require urgent intervention or postoperative intravenous blood pressure medication, or who are treated for a total occlusion are at a higher risk of developing CHS. Using an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker on discharge appears to be protective against CHS and should be considered for the highest risk patients.

Cost-effectiveness Analysis of Submandibular Gland Preservation With Sialendoscopy for the Management of Sialolithiasis.

OBJECTIVE: To compare the cost-effectiveness of sialendoscopy with gland excision for the management of submandibular gland sialolithiasis. STUDY DESIGN: Cost-effectiveness analysis. SETTING: Outpatient surgery centers. METHODS: A Markov decision model compared the cost-effectiveness of sialendoscopy versus gland excision for managing submandibular gland sialolithiasis. Surgical outcome probabilities were found in the primary literature. The quality of life of patients was represented by health utilities, and costs were estimated from a third-party payer's perspective. The effectiveness of each intervention was measured in quality-adjusted life-years (QALYs). The incremental costs and effectiveness of each intervention were compared, and a willingness-to-pay ratio of $150,000 per QALY was considered cost-effective. One-way, multivariate, and probabilistic sensitivity analyses were performed to challenge model conclusions. RESULTS: Over 10 years, sialendoscopy yielded 9.00 QALYs at an average cost of $8306, while gland excision produced 8.94 QALYs at an average cost of $6103. The ICER for sialendoscopy was $36,717 per QALY gained, making sialendoscopy cost-effective by our best estimates. The model was sensitive to the probability of success and the cost of sialendoscopy. Sialendoscopy must meet a probability-of-success threshold of 0.61 (61%) and cost ≤$11,996 to remain cost-effective. A Monte Carlo simulation revealed sialendoscopy to be cost-effective 60% of the time. CONCLUSION: Sialendoscopy appears to be a cost-effective management strategy for sialolithiasis of the submandibular gland when certain thresholds are maintained. Further studies elucidating the clinical factors that determine successful sialendoscopy may be aided by these thresholds as well as future comparisons of novel technology.

Complete response with talimogene laherparepvec in recurrent melanoma of the ear: A case report.

The current standard of care for cutaneous melanoma of the ear is surgical excision. This approach may result in unfavorable functional and cosmetic outcomes. We report here a case of recurrent melanoma of the ear that achieved complete response with talimogene laherparepvec treatment after the patient declined surgical resection.