Figure S1. Landscape of somatic mutations and cytogenetics in Moffitt MF cohort. Figure S2. Effects of enforced MYC expression in HSCs in vivo. Figure S3. MYC-induced changes in hematopoietic sub-populations and colony forming potential. Figure S4. The JAK/STAT, PI3K/AKT, MEK/ERK, and alarmin pathways in MYC-driven MF.

Comparison of gene expression profiles of Mx1-Cre+/-;Rosa26LSL-MYC/LSL-MYC vs. Mx1-Cre+/-;Rosa26+/+ mouse.

OBJECTIVE:To investigate associations and characteristics of patients with infective endocarditis (IE) admitted to the cardiac intensive care unit. PATIENTS AND METHODS:Adult patients admitted to the Mayo Clinic cardiac intensive care unit from January 1, 2007, through April 30, 2018, with confirmed acute IE were included. We conducted a retrospective cohort study of data on demographic characteristics, clinical factors, laboratory findings, and outcomes. Patients were categorized by cardiac surgery status: performed, indicated but declined, or not indicated. Primary outcomes were 30-day and 1-year all-cause mortality, analyzed using the Kaplan-Meier method and Cox proportional hazards regression model and adjusted for predictors. RESULTS:A total of 233 patients were included. Native valve IE occurred in 104 patients and prosthetic/device-associated IE in 129 patients. Staphylococcus aureus was the most common organism (99 [42.7%]) and was present in most 30-day deaths (42 [72.4%]). Surgical treatment was indicated in 182 patients (78.1%): 129 underwent a surgical procedure, 53 declined, and 51 had no indication for surgical intervention. The 30-day mortality was 24.9% (58 patients), with older age, higher illness severity and comorbidities, and critical care needs as predictors. The 30-day mortality was higher for those declining surgical treatment (60.4%; adjusted hazard ratio [HR], 2.32; P<.021) and lower for those who underwent surgical intervention vs patients with no indication for such treatment (11.9% vs 23.8%; adjusted HR, 0.40; P=.026). The 1-year mortality was 39.9% (93 patients), with higher mortality in patients who declined surgical intervention (85.1%; adjusted HR, 3.94; P<.001) but similar mortality for those who underwent a surgical procedure vs those with no indication for surgical treatment (31.8% vs 29.3%; adjusted HR, 0.92; P=.80). CONCLUSION:Infective endocarditis in cardiac intensive care unit patients is associated with high mortality. Severity scores, comorbidities, and critical care needs were mortality predictors. Early surgical treatment improved short-term outcomes, but long-term mortality remained high.

Figure S5. Changes in signaling in BM of trisomy 8+ TN-MF patient and MYC MF mice. Figure S6. Effects of silencing S100a9 in MYC-driven MF or overexpression of S100a9. Figure S7. Effects of inhibition of S100a9 or MYC in MYC-driven MF. Figure S8. Synthesis and Characterization of Tasquinimod. Figure S9. Synthesis and Characterization of MYCi975.

Table S1. Demographics of Moffitt Total Cancer Care MF patients. Table S2. Demographic Profile of trisomy 8+ TN-MF patients and HDs used in scRNA-seq analysis and PDX studies. Table S3. List of genes used for PROGENy analysis of human BM cells. Table S4. Demographics of TN-MF patients. Table S5. Clinical parameters of Mx1-Cre+/-;Rosa26LSL-MYC/LSL-MYC studies. Table S6. Clinical parameters of Scl-CreERT+/-;Rosa26LSL-MYC/LSL-MYC in vivo studies. Table S7. Clinical parameters in competitive transplant studies. Table S8. Comparison of gene expression profiles of Mx1-Cre+/-;Rosa26LSL-MYC/LSL-MYC vs. Mx1-Cre+/-;Rosa26+/+ mouse. Table S9. List of genes used for PROGENy analysis of mouse BM cells. Table S10. Cell-cell interaction analyses. Table S11. Clinical parameters of Mx1-Cre+/-;Rosa26LSL-MYC/LSL-MYC;S100a9-/- studies. Table S12. Clinical parameters of S100a9 transgenic mouse studies. Table S13. Clinical parameters of Tasquinimod efficacy studies in MYC-driven MF. Table S14. Clinical parameters of MYCi975 efficacy studies in MYC-driven MF. Table S15: Key Resources Table. Table S16: Sequence Information.

Objective: The purpose of this study was to examine the longitudinal safety and efficacy of hybrid coronary revascularization (HCR) in a large cohort of patients with multivessel coronary artery disease (CAD). Methods: From 2009 to 2020, 561 consecutive patients (median age 64.0 years, predicted risk of mortality 1.3% ± 1.8%, 403 with 2-vessel disease and 158 with 3-vessel disease) underwent a planned HCR procedure with a robot-assisted off-pump left internal mammary artery to left anterior descending (LIMA-LAD) coronary artery bypass graft (CABG) combined with percutaneous coronary intervention (PCI) of non–LAD vessels. Multivariable regression analysis was used to identify risk factors for short-term and longer-term outcomes. Results: Operative mortality and stroke occurred in 4 (0.7%) and 5 patients (0.9%), respectively. Postoperative angiography revealed LIMA patency in 415 of 425 patients (98%). Median follow-up was 4.5 years and was 93% complete. Repeat revascularization occurred in 44 patients (8%) at a median of 2.7 years. Freedom from repeat revascularization and survival at 5 years was similar between patients with 2-vessel and 3-vessel disease ( P = 0.73 and P = 0.19, respectively). Completely revascularized patients had 5-year survival of 91% versus 64% for incompletely revascularized patients (hazard ratio = 3.8, P < 0.001). Age ( P = 0.03), renal failure ( P < 0.001), and history of myocardial infarction ( P = 0.01) were risk factors for late adverse events. Conclusions: HCR is a safe and effective minimally invasive alternative to conventional CABG or multivessel PCI with a low incidence of late repeat revascularization and mortality. HCR can be safely applied to carefully selected patients with either 2-vessel or 3-vessel CAD; however, incomplete revascularization may result in lower long-term survival.

Background/Objectives: Mavacamten is a first-in-class cardiac myosin inhibitor approved for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (HCM). Long-term data regarding its real-world safety and effectiveness are limited. We aimed to describe the real-world experience of mavacamten in a large obstructive HCM cohort at a high-volume HCM center in the United States. Methods: Adult patients initiated on mavacamten between 29 April 2022 and 19 January 2025 at a single HCM center (n = 163) were retrospectively identified. Clinical effectiveness and safety data were collected through 108 weeks of treatment. Results: Rapid and sustained reductions in resting (baseline mean 53.0 ± 36.7 mm Hg to 10.0 ± 11.0 mm Hg) and Valsalva left ventricular outflow tract gradients (baseline mean 79.7 ± 33.2 mm Hg to 16.6 ± 15.4 mm Hg) were observed during treatment throughout the study period along with substantial improvements in New York Heart Association (NYHA) class (75% with >1 NYHA class improvement by Week 12). Mean maximal left ventricular wall thickness significantly decreased (β = 0.01 mm per week). Ten patients (6.1%) required temporary drug interruption due to decrement in left ventricular ejection fraction, and mavacamten was discontinued in six patients (3.7%). Doses of background beta blocker and nondihydropyridine calcium channel blocker were significantly reduced during the study period (p < 0.001). Conclusions: In this large single-center real-world experience of mavacamten therapy, mavacamten was highly effective and maintained an acceptable safety profile, comparable to the clinical trial long-term extension experience.

Influenza and SARS-CoV-2 viruses are both responsible for respiratory tract infections that have caused global outbreaks. Due to frequent mutations, the CDC recommends annual COVID-19 vaccination (CDC Staying Up to Date with COVID-19 Vaccines, 2025), and studies confirm the safety of co-administering it with the flu shot (CDC Getting a Flu Vaccine and Other Recommended Vaccines at the Same Time, 2025). A combination vaccine streamlines dual immunization, reducing the need for separate vaccinations. This study evaluates the immune response elicited by an intranasal microparticulate combination multivalent vaccine for Influenza and COVID-19. The intranasal route can generate mucosal antibodies that recognize and inhibit the virus at its point of entry. The nasal mucosa is highly vascularized, consisting of circulating immune cells that drain into lymphatic circulation to generate a systemic immune response. This non-invasive route of administration can also significantly benefit patients with needle phobia and vaccine hesitancy. The inactivated SARS-CoV-2 Omicron and Delta variants, along with the H1N1 and H3N2 variants of Influenza A were encapsulated into separate PLGA (co-polymer of lactic and glycolic acids) microparticle matrices utilizing a double emulsion method. The adjuvanted vaccine microparticles were administered to mice as one primary vaccination followed by one booster dose via the intranasal route. Serum and lung supernatant analysis revealed significantly higher antigen-specific IgA and IgG responses than controls. Isolated lymph nodes and spleens showed increased cytotoxic and helper T-cell activation. The intranasal vaccine effectively elicited a significant immune response which was comparable in relation to the intramuscular control vaccination. This supports the potential of an intranasal microparticulate combination vaccine as an effective, needle-free alternative for simultaneous immunization for Influenza and SARS-CoV-2.

Background: For patients with ST segment elevation myocardial infarction (STEMI), rapid access to primary percutaneous coronary intervention (PPCI) is critical, and guidelines recommend communities create regional systems of care dedicated to reducing time to PPCI. Emergency medical services (EMS) transport of a patient with STEMI who lives near a hospital with a cardiac catheterization lab (CCL) to a hospital without a CCL represents a “system failure,” as it may delay PPCI. Research Questions: The study aimed to (1) assess the frequency and regional variability of EMS transport of patients with STEMI to a hospital without a CCL when a CCL was within a 60-minute drive (“system failure”); (2) compare demographic, socioeconomic, and clinical characteristics between patients with and without system failure; and (3) evaluate the association between system failure and time to PPCI. Methods: We analyzed data from the Get With The Guidelines- Coronary Artery Disease registry from January 1, 2020, to December 31, 2023. Adults with pre-hospital STEMI transported by ground EMS were included if they lived within 60 minutes of a CCL hospital. Patients were categorized as system failure (transport to non-CCL hospital) or no system failure (transport directly to CCL hospital). Baseline characteristics and in-hospital outcomes were compared between patients experiencing and not experiencing system failure, and generalized estimating equations adjusting for clinical, demographic, and hospital factors were used to evaluate associations between system failure status and treatment times. Results: Of 46,741 patients with STEMI meeting inclusion criteria, 16% were transported to a hospital without a CCL. System failure rates varied widely across hospital referral regions (HRRs) (Figure 1). On multivariable analysis, patients experiencing system failure were more likely to be older, female, non-White, and be Medicaid-insured or uninsured (p < 0.01 for all comparisons). After adjustment, system failure was associated with significantly longer EMS First medical contact (FMC)-to-PCI times (+26 minutes; 95% CI, 10-42; p<0.001) and lower odds of achieving FMC-to-PCI time ≤ 90 minutes (OR 0.63; 95% CI 0.51-0.78, p<0.001). Conclusions: More than 1 in 6 STEMI patients living near CCL hospitals are transported to non-CCL hospitals, with resultant delays in timely reperfusion. Targeted efforts to optimize EMS transport protocols could improve timely access to reperfusion therapies.