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Objective: Patients undergoing graft repair of thoracoabdominal aortic aneurysms (TAAAs) often require concomitant correction of ostial stenoses or dissection involving visceral branches. The purpose of this report is to describe our initial experience with a new strategy for addressing these lesions during open TAAA repair—direct deployment of balloon expandable stents into the renal and mesenteric arteries. Methods: Over a two-year period, 367 patients have undergone TAAA surgery. Balloon expandable stents were used to manage visceral branch lesions during open TAAA repair in 93 (25.3%) of these patients. Fifteen patients (16%) had preoperative renal insufficiency. After opening the aneurysm and exposing the branch artery ostia, premounted balloon expandable stents were deployed in the affected vessels under direct vision. Stents were deployed after an endarterectomy in 40 patients (43%). Eighty patients (86%) had stents placed in one or both renal arteries and 36 (39%) had stents placed in the celiac axis and/or superior mesenteric artery. Postoperative renal function was monitored with daily serum creatinine levels. Results: There were nine early operative deaths (10%). Two patients (2%) had bleeding complications related to stenting, one of which died after developing multiple organ failure. Twelve patients (13%) developed renal failure, eight of which required dialysis. Conclusions: This study demonstrates the feasibility of treating ostial lesions of the visceral branches with balloon expandable stents during open TAAA repair. Despite a high prevalence of preoperative renal insufficiency, the incidence of postoperative renal failure was acceptable. This new strategy may be a valuable adjunct to TAAA repair and warrants further investigation. [Copyright &y& Elsevier]

Neuroinflammation is increasingly recognized as an important mediator of disease progression in patients with amyotrophic lateral sclerosis (ALS). Recent research suggests that pro-inflammatory microglia in ALS mice promote motoneuron cytotoxicity by secreting reactive oxygen species and pro-inflammatory cytokines. Gene expression analyses indicate that peripheral circulating monocytes from ALS patients are skewed towards a pro-inflammatory state that contributes to ALS disease progression. Better understanding of macrophage phenotypes of ALS patients is therefore warranted. In this study, we demonstrate that M1 macrophages differentiated from ALS circulating monocytes produced more pro-inflammatory cytokines, including IL-6 and TNFα, than M1 macrophages derived from healthy control monocytes. More importantly, IL-6 protein levels of ALS M1 macrophages positively correlated with disease burden, and TNFα protein levels of ALS M1 macrophages positively correlate with disease progression rates. Collectively, these data suggest that monocytes from ALS patients are more readily activated and differentiated to a pro-inflammatory M1 phenotype, and represent a potential target for immunomodulatory therapy. [ABSTRACT FROM AUTHOR]

Objective: To determine whether a combination therapy with abatacept (CTLA4-Ig) and interleukin-2 (IL-2) is safe and suppresses markers of oxidative stress, inflammation, and degeneration in ALS., Methods: In this open-label study, four participants with ALS received subcutaneous injections of low dose IL-2 (1 × 10 6 IU/injection/day) for 5 consecutive days every 2 weeks and one subcutaneous injection of CTLA4-Ig (125 mg/mL/injection) every 2 weeks coinciding with the first IL-2 injection of each treatment cycle. Participants received a total of 24 treatment cycles during the first 48 weeks in this 56-week study. They were closely monitored for treatment-emergent adverse events (TEAEs) and disease progression with the ALSFRS-R. Phenotypic changes within T cell populations and serum biological markers of oxidative stress [4-hydroxynonenal (4-HNE) and oxidized-LDL (ox-LDL)], inflammation (IL-18), and structural neuronal degeneration [neurofilament light chain (Nf-L)] were assessed longitudinally., Results: CTLA4-Ig/IL-2 therapy was safe and well-tolerated in all four participants over the 56-week study. During the first 24 weeks, the average rate of change in the ALSFRS-R was +0.04 points/month. Over the 48-week treatment period, the average rate of change was -0.13 points/month with one participant improving by 0.9 points/month while the other three participants experienced an average decrease of -0.47 points/month, which is slower than the average - 1.1 points/month prior to initiation of therapy. Treg suppressive function and numbers increased during treatment. Responses in the biological markers during the first 16 weeks coincided with minimal clinical progression. Mean levels of 4-HNE decreased by 30%, ox-LDL decreased by 19%, IL-18 decreased by 23%, and Nf-L remained the same, on average, in all four participants. Oxidized-LDL levels decreased in all four participants, 4-HNE and IL-18 levels decreased in three out of four participants, and Nf-L decreased in two out of four participants., Conclusion: The combination therapy of CTLA4-Ig and IL-2 in ALS is safe and well-tolerated with promising results of clinical efficacy and suppression of biomarkers of oxidative stress, neuroinflammation and neuronal degeneration. In this open-label study, the efficacy as measured by the ALSFRS-R and corresponding biomarkers suggests the therapeutic potential of this treatment and warrants further study in a phase 2 double-blind, placebo-controlled trial., Clinical Trial Registration: ClinicalTrials.gov, NCT06307301., Competing Interests: The combination therapy of CTLA4-Ig and IL-2 has been licensed from the Houston Methodist Research Institute to Coya Therapeutics, Inc. JT, DB, AF, and SA are listed as inventors in a patent application. SA also serves as scientific consultant for Mitsubishi Tanabe Pharma, Eledon, and UCB Biopharma, and as Chair of the Scientific Advisory Board for Coya Therapeutics, Inc. Coya Therapeutics was not involved in the study concept or design, or acquisition, analysis, and interpretation of data, or drafting of the manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Thonhoff, Beers, Zhao, Faridar, Thome, Wen, Zhang, Wang and Appel.)