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Cardiac fibrosis, a hallmark of heart failure and various cardiomyopathies, represents a complex pathological process that has long challenged therapeutic intervention. High-throughput omics technologies have begun revolutionizing our understanding of the molecular mechanisms driving cardiac fibrosis and are providing unprecedented insights into its heterogeneity and progression. This review provides a comprehensive analysis of how techniques—encompassing genomics, epigenomics, transcriptomics, proteomics, and metabolomics—are providing insight into our understanding of cardiac fibrosis. Genomic studies have identified novel genetic variants and regulatory networks associated with fibrosis susceptibility and progression, and single-cell transcriptomics has unveiled distinct cardiac fibroblast subpopulations with unique molecular signatures. Epigenomic profiling has revealed dynamic chromatin modifications controlling fibroblast activation states, and proteomic analyses have identified novel biomarkers and potential therapeutic targets. Metabolomic studies have uncovered important alterations in cardiac energetics and substrate utilization during fibrotic remodeling. The integration of these multi-omic data sets has led to the identification of previously unrecognized pathogenic mechanisms and potential therapeutic targets, including cell-type-specific interventions and metabolic modulators. We discuss how these advances are driving the development of precision medicine approaches for cardiac fibrosis while highlighting current challenges and future directions in translating multi-omic insights into effective therapeutic strategies. This review provides a systems-level perspective on cardiac fibrosis that may inform the development of more effective, personalized therapeutic approaches for heart failure and related cardiovascular diseases.

Importance The use of immune checkpoint inhibitors (ICIs) is increasing. Little is known about the frequency of late-onset immune-related adverse events (irAEs) and the patient-specific risk factors associated with their development. Objectives To assess the incidence of persistent or de novo late-onset irAEs requiring hospitalization and identify patient factors associated with risk of late-onset irAEs. Design, Setting, and Participants This retrospective observational cohort study conducted from January 2011 to October 2022 included patients who received ICIs and were hospitalized with irAEs at an academic medical center. Exclusion criteria included ICI therapy outside of the hospital system and no irAE diagnosis during admission. Data were analyzed from November 15, 2022, to January 8, 2025. Exposure Late-onset irAEs. Main Outcomes and Measures The main study outcomes were (1) incidence of irAE hospitalization at 0 to 6 months (early), more than 6 to 12 months (intermediate), and more than 12 months (late) after ICI initiation and (2) patient factors associated with risk of late-onset irAEs. Results Among the 795 patients hospitalized with irAEs, the median age was 67.3 years (IQR, 58.3-74.8 years); 476 (59.9%) were male. Most patients (n = 517 [65.0%]) received anti–programmed death ligand 1 (PD-L1) and anti–programmed cell death 1 monotherapy, with the most common indications being melanoma (n = 335 [42.1%]) and lung cancer (n = 167 [21.0%]). The median time from start of ICI therapy to hospital admission was 2.7 months (IQR, 1.2-6.1 months), with 14.7% of patients (n = 117 of 795) presenting 6 to 12 months after initial ICI exposure and 10.8% of patients (86 of 795) presenting more than 12 months after initial exposure. The irAEs most likely to present late included those involving the kidney (10 of 32 [31.3%]) and hematologic (5 of 23 [21.7%]) organ systems. In univariate analysis, ICI type was significantly associated with the timing of hospital admission for irAEs; of the 517 patients receiving anti–PD-L1–based therapy, 13.5% (n = 70) presented late compared with 5.4% (9 of 167) receiving dual therapy with anti–cytotoxic T-lymphocyte–associated protein 4 ( P < .001). Patients receiving perioperative ICI therapy were significantly more likely to be admitted at the intermediate interval (16 of 68 [23.5%]) compared with those with metastatic disease (87 of 678 [12.8%]) ( P = .03). Timing of irAE was also significantly associated with active ICI exposure; among the patients presenting late, 7.4% (48 of 651) had received ICI therapy within the last 60 days compared with 26.4% (38 of 144) who had not had recent ICI exposure ( P < .001). Conclusions and Relevance The findings of this retrospective observational cohort study suggest that late irAEs are possible, with a subset of patients presenting years after the start of ICI therapy. Clinicians must remain vigilant for irAEs regardless of elapsed time from ICI therapy, especially as patients live longer and ICIs become more widely used. Future investigations are needed to better understand the risk factors for late-onset irAEs and the distinct immunologic pathways that underlie such events.

Background: Pulmonary embolism (PE) is a major cause of morbidity and mortality accounting for 100,000 deaths per year in the United States and 5–10% of in-hospital deaths. There is sparse comparative data on readmission patterns in patients who undergo early versus late catheter directed thrombolysis (CDT) for acute PE. Research Question: Is the procedure day for acute PE associated with a difference in 30-day readmission rates? Study Design and Method: This study was performed by using the Nationwide Readmissions Database between 2016 and 2019. Patients with acute PE who underwent CDT were identified using codes from the International Classification of Diseases, 10th Edition (ICD 10). Results: The 30-day readmission rates were higher for patients who underwent CDT on Day 2 or afterwards compared to Day 1 and Day 0 (7.1% vs. 5.7% vs. 5.2%). Patients who had CDT on Day 2 or later had a higher rate of 30-day readmission mortality compared to those who had CDT on Day 1 or 0 (0.6% vs. 0.3% vs. 0.2%. The 30-day readmission rates for heart failure were higher among patients who had CDT on Day 2 compared to those who had CDT on Day 0 of admission (2% vs. 1.0% vs. 0.9%). Interpretation: Delayed CDT for acute PE was associated with increased rates of 30-day readmission, readmission mortality, and readmission for heart failure. These findings emphasize the need for earlier CDT for the treatment of acute PE.

BACKGROUND: Patients presenting with cervical artery dissection (CAD) are at risk for subsequent ischemic events. We aimed to identify characteristics that are associated with increased risk of ischemic stroke after initial presentation of CAD and to evaluate the differential impact of anticoagulant versus antiplatelet therapy in these high-risk individuals. METHODS: This was a preplanned secondary analysis of the STOP-CAD study (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection), a multicenter international retrospective observational study (63 sites from 16 countries in North America, South America, Europe, Asia, and Africa) that included patients with CAD predominantly between January 2015 and June 2022. The primary outcome was subsequent ischemic stroke by day 180 after diagnosis. Clinical and imaging variables were compared between those with versus without subsequent ischemic stroke. Significant factors associated with subsequent stroke risk were identified using stepwise Cox regression. Associations between subsequent ischemic stroke risk and antithrombotic therapy type (anticoagulation versus antiplatelets) among patients with identified risk factors were explored using adjusted Cox regression. RESULTS: In all, 4023 patients (mean age was 47.4 years; 44.5% were women) were included. By day 180, subsequent ischemic stroke occurred in 5.3% of the cohort. In adjusted Cox regression, factors associated with increased risk of subsequent ischemic stroke were prior history of ischemic stroke (adjusted hazard ratio [aHR], 7.31 [95% CI, 1.61–33.13]; P =0.010), presentation within 7 days from first symptoms (aHR, 3.04 [95% CI, 1.04–8.91]; P =0.043), infarct on baseline imaging (aHR, 9.85 [95% CI, 3.65–26.58]; P <0.001), and occlusive dissection (aHR, 2.34 [95% CI, 1.03–5.34]; P =0.043). Only patients with occlusive dissection demonstrated a reduced risk of subsequent ischemic stroke when treated with anticoagulation versus antiplatelets (aHR, 0.36 [95% CI, 0.16–0.80]; P =0.01). CONCLUSIONS: In this post hoc analysis of the STOP-CAD study, several factors associated with subsequent ischemic stroke were identified among patients with CAD. Furthermore, we identified a potential benefit of anticoagulation in patients with CAD with occlusive dissection. These findings require validation by meta-analyses of prior studies to formulate optimal treatment strategies for specific high-risk CAD subgroups.

Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder marked by progressive motor neuron degeneration in the primary motor cortex (PMC) and spinal cord. Aging is a key factor in ALS onset and progression, with evidence suggesting that biological aging—a process involving cellular decline— far outpaces chronological aging in ALS. This promotes senescent cell accumulation—marked by irreversible cell-cycle arrest, impaired apoptosis, and chronic inflammation—disrupting tissue homeostasis and impairing neuronal support functions. Thus, targeting senescence presents a novel therapeutic strategy for ALS. Here, we investigated the senolytic combination Dasatinib and Quercetin (D&Q) in TDP-43 Q331K ALS mice. D&Q improved neuromuscular function and reduced plasma neurofilament light chain, a biomarker of axonal damage. The most pronounced improvement was the improved cortical excitability, accompanied by reductions in senescence and TDP-43 in the PMC. These findings highlight the potential of senolytics to mitigate ALS-related dysfunction, supporting their viability as a therapeutic strategy. *Jose A. Viteriab, Nathan R. Kerrab, and Charles D. Brennana are co-first authors.

The effectiveness of in-person psychological interventions for chronic pain populations has been widely studied. The current retrospective pilot study evaluates the effectiveness of a 10-week integrative telehealth pain group intervention consisting of cognitive, behavioral, mindfulness, and lifestyle strategies on anxiety, depression, pain catastrophizing, pain interference, and pain intensity. Participants at a large multidisciplinary hospital are referred internally from various medical departments within the hospital. The present study consists of data from 9 group cohorts from October 2020 to June 2022. The study included 86 patients, with 52 completing all 10 weeks of the intervention with post-questionnaire data available. Measures assessing anxiety, depression, pain catastrophizing, pain interference, and pain intensity at baseline and at the completion of the intervention. A series of paired samples t-tests were used to assess change in each outcome measure from baseline to after completion of the program. All the outcome variables including anxiety, depression, pain interference, pain intensity, and pain catastrophizing showed statistically significant reductions after the intervention compared to baseline assessments. There were no significant differences in any of the demographic variables (age, gender, ethnicity, education level) or chronic pain condition between participants who did and did not complete the program. Preliminary data suggest that this 10-week integrative telehealth pain group intervention significantly lowered anxiety, depression, pain catastrophizing, pain interference, and pain intensity from pre- to post-intervention. Larger, randomized controlled studies are needed to validate these results.

Objective: To characterize the relationship between surgeon-staff familiarity and the time required to perform an operation. Summary Background Data: The clinical and operational efficiency of operating rooms is a driver of hospital finances and patient outcomes. Surgeon-staff familiarity is an important focus for quality improvement and process optimization. Methods: A retrospective cohort study was performed analyzing operations performed at 4 academic hospitals between July 1, 2019 and December 31, 2023. Exclusion criteria (urgent operations, 2-specialty cases, low surgeon/specialty volume in data set, scheduled length > 8 hours) were applied to limit heterogeneity. The exposure of interest was familiarity between the surgeon and the allied health staff (scrub technicians and circulating nurses) present during an operation (represented as the median staff experience with the index surgeon in the previous 180 d). The primary outcome was whether the actual case length was (vs. was not) 10% shorter than the scheduled case length (“shorter case length”). A secondary outcome was the quantification of the difference between the observed and expected case length and whether the surgical time (cut-close) was shorter. Results: A total of 257,645 operations performed by 25 different specialties comprised the analyzed cohort. Higher levels of surgeon-staff familiarity were associated with a higher likelihood of a shorter case length (observed:expected ratio = 1.16 [1.14–1.18] for high/high levels of familiarity, compared with 0.90 [0.88–0.91] for low/low levels of familiarity). Greater familiarity was also associated with case lengths that were shorter relative to scheduled case length (high/high levels of familiarity 8.7% shorter than low/low levels, P < 0.001). Within the 4 most common types of cases, those operations performed by teams with higher levels of familiarity had shorter surgical times (cut-to-close). Conclusions: This study found that operations were more efficiently performed when the scrub technician and circulating nurse staff had a greater recent experience with the primary surgeon. Surgical team familiarity should be considered a focus of operational and clinical excellence.

AbstractDespite the pivotal role of communication skills in genetic counseling, communication strategies employed by genetic counselors in their current practice remain largely unexplored. The field of genetic counseling could benefit from updated simulated genetic counseling sessions conducted by genetic counselors illustrating a diversity of skills. This paper outlines the development and evaluation of updated simulations used to develop an online training course to identify genetic counseling skills and to assess how commonly these skills are used. Practicing genetic counselors in the United States were recruited to counsel trained standardized patients across six pretest and posttest simulated sessions in cancer, prenatal, and cardiology genetics settings. Sessions were coded using the novel Genetic Counseling Skills Checklist to identify which communication and counseling skills were utilized. Standardized patients were asked to provide session quality ratings and written feedback, which were analyzed using descriptive statistics and content analysis, respectively. Results from 64 recorded sessions involving 20 counselors from a variety of training programs, racial and ethnic backgrounds, states of residence, and with varying years of clinical experience revealed utilization of a broad array of skills across specialty types and clinical indications. The total number of unique skills used varied widely from 12 to 49, with an average of 35.8 out of 56 possible skills checked per session. Differences in skill usage were observed between pretest and posttest sessions. Standardized patient comments were predominantly positive with a focus on information delivery and empathetic responses. Perceptions of areas of improvement were giving less information, having clearer delivery, and expressing more empathy. This work led to the creation of a training course showcasing various skills used by practicing genetic counselors, which summarizes commonly used skills and other promising but less frequently utilized ones.

Introduction and Objectives: Urethral stricture disease is a challenging urologic problem with a high recurrence rate. Initial management is typically completed endoscopically (e.g., urethral dilation, direct visual internal urethrotomy); however, guidelines recommend against repeated endoscopic management. Currently, surgical urethroplasty or intermittent catheterization remains the only other option. We have demonstrated a minimally invasive approach to urethroplasty. In this video, we aim to demonstrate the techniques and early outcomes of transmeatal urethral surgery for short urethral strictures. Materials and Methods: We demonstrate the procedure in two different individuals with idiopathic bulbar urethral strictures less than 2 cm. The patient is prepped in dorsal lithotomy position. Under direct visualization via cystoscopy, the ventral place of the urethral stricture is first incised to a goal of 26 Fr lumen. Next, mucosal realignment is completed via LSI Solutions’ URTRAC sheath and the RD 180 endoscopic suturing device. Two sutures are placed on either side of the urethrotomy incision site, allowing the proximal and distal ends of the mucosa to be pulled perpendicular to the urethrotomy. After reapproximation, a titanium knot is introduced endoscopically to anchor each suture into place. An indwelling catheter is then left in place. Patients are then seen at four months postoperatively. Results: Out of four total patients, there is a 100% success rate cystoscopically at 4 months postoperatively. There have been no recorded intraoperative or postoperative complications. The average operating room time was 54 minutes, and the average estimated blood loss was 9 mL. Conclusions: Transmeatal urethral surgery for short strictures via incision and urethral reapproximation appears to be a safe and effective repair option for the management of short urethral strictures. All research procedures were carried out in accordance with ethical guidelines and institutional policies, reviewed by the IRB. Authors have received and archived patient consent for video recording/publication in advance of video recording of procedure. The authors declare that there are no commercial associations or financial interests in any product or service discussed in this article that might create a conflict of interest. The authors have not engaged in any activities or relationships with commercial entities that would bias or influence the content of this study. Runtime of video: 5 mins 40 secs.