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The systemic impairment that accompanies liver cirrhosis is known to carry a significant burden on death and postoperative complications in cardiovascular interventions. This review analyzes the impact of liver cirrhosis on short‐ and long‐term outcomes after cardiac surgery and percutaneous procedures, providing an evidence‐based guidance in the decision‐making process and perioperative management of these patients. Several parameters should be considered by the heart teams when assessing eligibility, indications for intervention, and perioperative management of these patients. Life expectancy, long‐term procedural outcomes, Child–Pugh or the Model for End‐Stage Liver Disease score, presence of gastroesophageal varices and hepatic venous pressure gradient were extrapolated as the main determinants in decision making in patients with cirrhosis. Assessment and treatment of gastroesophageal varices is mandatory. Hepatic venous pressure gradient values >20 mm Hg preclude patients from a surgical approach. Considering the poor prognosis of advanced liver cirrhosis, futile treatments should be avoided. A multidimensional heart team approach involving surgical, cardiologic, anesthesiologic, hepatological, and medical considerations is recommended.

BACKGROUND: Arteriovenous malformation (AVM) recurrence after complete surgical resection is a rare but significant clinical event. The underlying mechanisms and factors that predict recurrence remain incompletely defined. METHODS: We conducted a systematic review and meta-analysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. We included case series reporting on AVM recurrence following an angiographically documented complete resection. Data on initial clinical presentation, patients' demographics, AVM features, and patterns of recurrence were extracted and analyzed. RESULTS: We included 15 studies with a total of 1287 patients in our meta-analysis. The overall estimated recurrence rate was 5.4%. Hemorrhagic presentation appeared as a major predictor: in fact, 94% of recurrences occurred in patients with a prior rupture, corresponding to a 7.3% (95% CI, 0.049–0.098) recurrence rate within this high-risk subgroup. Ruptured AVMs were associated with 4-fold higher odds of recurrence compared with unruptured AVMs (odds ratio, 4.072 [95% CI, 1.492–11.113]). Younger age was also found to be a key factor, with pediatric patients accounting for 89% of all recurrences. Deep venous drainage was associated with a nearly 5-fold increased risk of recurrence (odds ratio, 4.96 [95% CI, 1.801–13.662]), while eloquent brain location was not found as a statistically significant predictor. The mean time to recurrence was 39.6 (95% CI, 27.80–51.41) months, while follow-ups varied among patients. CONCLUSIONS: Hemorrhagic presentation, younger age, and deep venous drainage demonstrated to be significant predictors of AVM recurrence after complete resection, whereas vascular aging appears protective. In older individuals, proangiogenic mediators (VEGF [vascular endothelial growth factor], HIF-1 [hypoxia-inducible factor-1] α, eNOS [endothelial nitric oxide synthase], and MMPs [matrix metalloproteinases]) are downregulated via aging-related pathways, limiting neovascularization and making recurrence biologically less likely. These findings underscore the need for prolonged, risk-adapted surveillance protocols, particularly for high-risk pediatric patients who present with hemorrhage.

Functional analyses of mitochondria have been hampered by few effective approaches to manipulate mitochondrial DNA (mtDNA) and a lack of existing animal models. Recently a TALE-derived base editor was shown to induce C-to-T (or G-to-A) sequence changes in mtDNA. We report here the FusX TALE Base Editor (FusXTBE) to facilitate broad-based access to TALE mitochondrial base editing technology. TALE Writer is a de novo in silico design tool to map potential mtDNA base editing sites. FusXTBE was demonstrated to function with comparable activity to the initial base editor in human cells in vitro . Zebrafish embryos were used as a pioneering in vivo test system, with FusXTBE inducing 90+% editing efficiency in mtDNA loci as an example of near-complete induction of mtDNA heteroplasmy in vivo . Gene editing specificity as precise as a single nucleotide was observed for a protein-coding gene. Nondestructive genotyping enables single-animal mtDNA analyses for downstream biological functional genomic applications. FusXTBE is a new gene editing toolkit for exploring important questions in mitochondrial biology and genetics.

Objective: To examine microsurgical outcomes of medial sporadic vestibular schwannoma (VS), defined as a spherical tumor within the cerebellopontine angle (CPA) without tubular internal auditory canal (IAC) extension, compared with a referent cohort of “typical” VS with IAC extension. Study design: Historical matched cohort study. Setting: Tertiary referral center. Patients: Forty patients with medial sporadic VS who met the inclusion criteria were each matched to 3 referent patients by age, CPA tumor size, preoperative hearing class, and surgical approach. Interventions: Microsurgical resection. Main outcome measures: Extent of resection, immediate and long-term postoperative facial nerve weakness (House-Brackmann grade >I), and long-term hearing preservation were compared between patients with medial VS and the referent cohort using conditional logistic regression. Results: Medial VS and matched patients with IAC extension were not statistically significantly different in nongross total extent of resection (OR: 1.04, 95% CI: 0.47-2.31), immediate (OR: 0.82, 95% CI: 0.40-1.67) or long-term (OR: 0.59, 95% CI: 0.23-1.48) postoperative facial nerve weakness, or long-term nonserviceable hearing (OR: 0.84, 95% CI: 0.17-4.22). Conclusions: In this matched cohort study of medial VS, we found no statistically significant differences in the extent of resection, facial nerve function, or hearing preservation between tumors with and without IAC extension.

Objective: Diabetes mellitus affects over 25% of adults aged 65+ in the United States and is associated with a heightened risk of developing diabetic foot ulcers. Accumulation of senescent cells within the wound microenvironment can impair cutaneous repair, and senolytic therapies offer a promising approach to accelerate wound healing. Approach: In this study, topical fisetin, a flavonoid that promotes apoptosis of senescent cells, was evaluated for its impact on diabetic wound repair. Full-thickness excisional wounds were created on the dorsal skin of diabetic (db/db) mice. Animals were randomized to receive either topical vehicle ( n = 12) or fisetin ( n = 12) for three consecutive days per week, and wound healing outcomes were longitudinally assessed. Results: Topical fisetin significantly increased the ratio of healthy dermis to granulation by day 7 ( p = 0.04) and reduced dermal fibrosis by day 21 ( p = 0.03). Fisetin decreased p16+ cells ( p = 0.01) but increased p21+ cells ( p = 0.02) at day 7 in the dermis, indicating varied effects on senescent cells. M1 macrophages (CD80+) were decreased in the fisetin-treated group ( p = 0.05) at day 21, accompanied by a decrease in pro-inflammatory senescence-associated secretory phenotype cytokines, tumor necrosis factor alpha ( p = 0.03), and interleukin-1beta ( p = 0.01) at day 7. Innovation: Fisetin is the first topical seno-modulatory agent shown to enhance wound repair when administered after injury onset. Its favorable safety and efficacy in both modulating senescence and inflammation highlight its potential as a novel therapy for diabetic wounds. Conclusion: Topical fisetin enhances diabetic wound healing by reducing fibrosis and promoting healthy dermal regeneration through senescence and inflammation modulation. Saranya Wyles, MD, PhD

Kidney dysfunction after heart transplantation (HT) is associated with significant morbidity and mortality. Recipient and perioperative factors may all influence the risk of kidney injury. Furthermore, data suggest that the incidence of kidney dysfunction, both acute and chronic, is increasing after the implementation of the United States’ 2018 allocation system due to increasing use of temporary mechanical circulatory support and changing recipient characteristics. While data are robust regarding nephroprotective therapies such as renin-angiotensin-aldosterone system inhibition and SGLT2i (sodium-glucose cotransporter 2 inhibitors) to minimize the progression of chronic kidney disease in patients with heart failure, data in HT recipients are beginning to emerge. This state-of-the-art review will critically examine the existing literature regarding the epidemiology of kidney dysfunction after HT, mitigation strategies for acute kidney injury and chronic kidney disease, including pharmacotherapeutics, the need for kidney transplantation after HT, and practical next steps for the larger HT community.

BACKGROUND: Guidelines acknowledge that discordant low-gradient (LG) aortic stenosis (AS) may be severe, but verifying this can be challenging. Right heart catheterization during exercise is considered the gold standard for evaluating ventricular hemodynamics. No invasive studies have compared the hemodynamic response of discordant LG and severe AS during exercise. The aim of this observational study was to describe exercise hemodynamics in patients with asymptomatic discordant AS and left ventricular ejection fraction ≥50%. METHODS: Patients with aortic valve area ≤1.5 cm 2 underwent right heart catheterization at rest and during maximal exercise, measuring pulmonary capillary wedge pressure (PCWP), cardiac output (CO), and the PCWP/CO-slope. Patients were stratified into 3 groups: discordant LG AS (aortic valve area ≤1.0 cm 2 and mean gradient <40 mm Hg); moderate AS (aortic valve area >1.0 cm 2 ); and high-gradient (HG) severe AS (aortic valve area ≤1.0 cm 2 and mean gradient ≥40 mm Hg). RESULTS: Among 86 patients, 17 (20%) had discordant LG, 49 (57%) moderate, and 20 (23%) HG severe AS. The median PCWP/CO-slope was significantly steeper in discordant LG (3.3 [interquartile range, 2.1–4.3] mm Hg/L/min) and HG severe AS (2.7 [1.9–3.4] mm Hg/L per minute) compared with moderate AS (1.9 [0.7–2.8] mm Hg/L per minute), P =0.004. In a regression model adjusted for age, sex, and rest PCWP, systemic arterial compliance and AS severity were significantly associated with the PCWP/CO-slope. Furthermore, patients with discordant LG AS had a leftward-upward shift in the PCWP/CO-curve. CONCLUSIONS: Discordant LG and HG severe AS had similar hemodynamic responses to exercise with steeper PCWP/CO-slope than in moderate AS, suggesting that discordant LG AS is a severe form of AS. In addition, the left upwards shift in PCWP/CO-curve for discordant LG compared with HG severe AS indicates that this group also has heart failure with preserved ejection fraction physiology. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04913870 and NCT02395107.