Emergent Coronary Thrombectomy for Acute Myocardial Infarction Immediately Following Craniotomy with Tumor Resection.

The management of perioperative acute myocardial infarction (AMI) following oncologic neurosurgery requires balancing competing risks of myocardial ischemia and postoperative bleeding. There are limited human data to establish the safest timing of antiplatelet or anticoagulation therapy following neurosurgical procedures. For patients with malignancy experiencing AMI in the acute postoperative period, staged percutaneous coronary intervention (PCI) with upfront coronary aspiration thrombectomy followed by delayed completion PCI may offer an opportunity for myocardial salvage while minimizing postoperative bleeding risks. CYP2C19 genotyping and platelet aggregation studies can help confirm adequate platelet inhibition once antiplatelet therapy is resumed.

Building a post-myocardial infarction discharge intervention program for Hispanic patients.

Hispanic patients disproportionally suffer from disparities in care delivery in the setting of acute myocardial infarction (AMI). More specifically, Hispanic patients have higher 30-day readmission rates post-AMI and are less likely to be referred to cardiac rehab. Because of the challenges Hispanic patients face with post-AMI care, the Hispanic Acute Myocardial Infarction Discharge Intervention Study (HAMIDI) was launched to provide a culturally sensitive discharge framework to improve readmission and mortality rates in this population. Patients enrolled in this study participate in a comprehensive post-discharge program involving follow-up with a Spanish-speaking cardiologist, a two-part educational virtual group visit program, and access to support throughout the study. During the initial year of the study, 35 patients enrolled and successfully participated in the program. This case study reviews the implementation process, initial outcomes, challenges, and future plans of the program.

Impact of immune checkpoint inhibitors on atherosclerosis progression in patients with lung cancer.

BACKGROUND: Patients with lung cancer face a heightened risk of atherosclerosis-related cardiovascular events. Despite the strong scientific rationale, there is currently a lack of clinical evidence examining the impact of immune checkpoint inhibitors (ICIs) on the advancement of atherosclerosis in patients with lung cancer. The objective of our study was to investigate whether there is a correlation between ICIs and the accelerated progression of atherosclerosis among individuals with lung cancer. METHODS: In this case-control (2:1 matched by age and gender) study, total, non-calcified, and calcified plaque volumes were measured in the thoracic aorta using sequential contrast-enhanced chest CT scans. Univariate and multivariate rank-based estimation regression models were developed to estimate the effect of ICI therapy on plaque progression in 40 cases (ICI) and 20 controls (non-ICI). RESULTS: The patients had a median age of 66 years (IQR: 58-69), with 50% of them being women. At baseline, there were no significant differences in plaque volumes between the groups, and their cardiovascular risk profiles were similar. However, the annual progression rate for non-calcified plaque volume was 7 times higher in the ICI group compared with the controls (11.2% vs 1.6% per year, p=0.001). Conversely, the controls showed a greater progression in calcified plaque volume compared with the ICI group (25% vs 2% per year, p=0.017). In a multivariate model that considered cardiovascular risk factors, the use of an ICI was associated with a more substantial progression of non-calcified plaque volume. Additionally, individuals treated with combination ICI therapy exhibited greater plaque progression. CONCLUSIONS: ICI therapy was associated with more non-calcified plaque progression. These findings underscore the importance of conducting studies aimed at identifying the underlying mechanisms responsible for plaque advancement in patients undergoing ICI treatment. TRIAL REGISTRATION NUMBER: NCT04430712.

Impact of sodium-glucose cotransporter-2 inhibitors on heart failure and mortality in patients with cancer.

OBJECTIVES: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce heart failure (HF) in at-risk patients and may possess antitumour effects. We examined the effect of SGLT2i on HF and mortality among patients with cancer and diabetes. METHODS: This was a retrospective propensity score-matched cohort study involving adult patients with type 2 diabetes mellitus diagnosed with cancer between January 2010 and December 2021. The primary outcomes were hospitalisation for incident HF and all-cause mortality. The secondary outcomes were serious adverse events associated with SGLT2i. RESULTS: From a total of 8640 patients, 878 SGLT2i recipients were matched to non-recipients. During a median follow-up of 18.8 months, SGLT2i recipients had a threefold lower rate of hospitalisation for incident HF compared with non-SGLT2i recipients (2.92 vs 8.95 per 1000 patient-years, p=0.018). In Cox regression and competing regression models, SGLT2i were associated with a 72% reduction in the risk of hospitalisation for HF (HR 0.28 (95% CI: 0.11 to 0.77), p=0.013; subdistribution HR 0.32 (95% CI: 0.12 to 0.84), p=0.021). The use of SGLT2i was also associated with a higher overall survival (85.3% vs 63.0% at 2 years, p<0.001). The risk of serious adverse events such as hypoglycaemia and sepsis was similar between the two groups. CONCLUSIONS: The use of SGLT2i was associated with a lower rate of incident HF and prolonged overall survival in patients with cancer with diabetes mellitus.

Global Circumferential and Radial Strain Among Patients With Immune Checkpoint Inhibitor Myocarditis.

BACKGROUND: Global circumferential strain (GCS) and global radial strain (GRS) are reduced with cytotoxic chemotherapy. There are limited data on the effect of immune checkpoint inhibitor (ICI) myocarditis on GCS and GRS. OBJECTIVES: This study aimed to detail the role of GCS and GRS in ICI myocarditis. METHODS: In this retrospective study, GCS and GRS from 75 cases of patients with ICI myocarditis and 50 ICI-treated patients without myocarditis (controls) were compared. Pre-ICI GCS and GRS were available for 12 cases and 50 controls. Measurements were performed in a core laboratory blinded to group and time. Major adverse cardiovascular events (MACEs) were defined as a composite of cardiogenic shock, cardiac arrest, complete heart block, and cardiac death. RESULTS: Cases and controls were similar in age (66 ± 15 years vs 63 ± 12 years; P = 0.20), sex (male: 73% vs 61%; P = 0.20) and cancer type (P = 0.08). Pre-ICI GCS and GRS were also similar (GCS: 22.6% ± 3.4% vs 23.5% ± 3.8%; P = 0.14; GRS: 45.5% ± 6.2% vs 43.6% ± 8.8%; P = 0.24). Overall, 56% (n = 42) of patients with myocarditis presented with preserved left ventricular ejection fraction (LVEF). GCS and GRS were lower in myocarditis compared with on-ICI controls (GCS: 17.5% ± 4.2% vs 23.6% ± 3.0%; P < 0.001; GRS: 28.6% ± 6.7% vs 47.0% ± 7.4%; P < 0.001). Over a median follow-up of 30 days, 28 cardiovascular events occurred. A GCS (HR: 4.9 [95% CI: 1.6-15.0]; P = 0.005) and GRS (HR: 3.9 [95% CI: 1.4-10.8]; P = 0.008) below the median was associated with an increased event rate. In receiver-operating characteristic (ROC) curves, GCS (AUC: 0.80 [95% CI: 0.70-0.91]) and GRS (AUC: 0.76 [95% CI: 0.64-0.88]) showed better performance than cardiac troponin T (cTnT) (AUC: 0.70 [95% CI: 0.58-0.82]), LVEF (AUC: 0.69 [95% CI: 0.56-0.81]), and age (AUC: 0.54 [95% CI: 0.40-0.68]). Net reclassification index and integrated discrimination improvement demonstrated incremental prognostic utility of GRS over LVEF (P = 0.04) and GCS over cTnT (P = 0.002). CONCLUSIONS: GCS and GRS are lower in ICI myocarditis, and the magnitude of reduction has prognostic significance.

The Prediction of Cardiac Events Using Contemporary Risk Prediction Models after Radiation Therapy for Head and Neck Cancer.

This study aims to evaluate the efficacy of the Pooled Cohort Equation (PCE), U.S. Preventative Services Task Force (USPSTF), and Framingham Risk Score (FRS) models in predicting ASCVD events among patients receiving radiation therapy (RT) for head and neck cancer (HNCA). From a large cohort of HNCA patients treated with RT, ASCVD events were adjudicated. Observed vs. predicted ASCVD events were compared. We compared rates by statin eligibility status. Regression models and survival analysis were used to identify the relationship between predicted risk and post-RT outcomes. Among the 723 identified patients, 274 (38%) were statin-eligible based on USPSTF criteria, 359 (49%) based on PCE, and 234 (32%) based on FRS. During follow-up, 17% developed an ASCVD, with an event rate of 27 per 1000 person-years, 68% higher than predicted (RR 1.68 (95% CI: 1.02, 2.12), p < 0.001). In multivariable regression, there was no difference in event rates by statin eligibility status (p > 0.05). Post-RT, the observed event rate was higher than the predicted ASCVD risk across all grades of predicted risk (p < 0.05) and the observed risk of an ASCVD event was high even among patients predicted to have a low risk of ASCVD. In conclusion, current ASCVD risk calculators significantly underestimate the risk for ASCVD among patients receiving RT for HNCA.

Trends in cardiology and oncology artificial intelligence publications.

Study objective: To determine whether there has been growth in publications on the use of artificial intelligence in cardiology and oncology, we assessed historical trends in publications related to artificial intelligence applications in cardiology and oncology, which are the two fields studying the leading causes of death worldwide. Upward trends in publications may indicate increasing interest in the use of artificial intelligence in these crucial fields. Design/setting: To evaluate evidence of increasing publications on the use of artificial intelligence in cardiology and oncology, historical trends in related publications on PubMed (the biomedical repository most frequently used by clinicians and scientists in these fields) were reviewed. Results: Findings indicated that research output related to artificial intelligence (and its subcategories) generally increased over time, particularly in the last five years. With some initial degree of vacillation in publication trends, a slight qualitative inflection was noted in approximately 2015, in general publications and especially for oncology and cardiology, with subsequent consistent exponential growth. Publications predominantly focused on "machine learning" (n = 20,301), which contributed to the majority of the accelerated growth in the field, compared to "artificial intelligence" (n = 4535), "natural language processing" (n = 2608), and "deep learning" (n = 4459). Conclusion: Trends in the general biomedical literature and particularly in cardiology and oncology indicated exponential growth over time. Further exponential growth is expected in future years, as awareness and cross-disciplinary collaboration and education increase. Publications specifically on machine learning will likely continue to lead the way.

Assessment of the Effect of the Go Red for Women Campaign on Search Engine Queries for Cardiovascular Disease in Women.

BACKGROUND: The Go Red for Women (GoRedW) campaign aims to increase awareness of cardiovascular disease (CVD) and stroke in women. However, assessing the effects of social campaigns on information-seeking behaviors may be challenging. The purpose of this study was to ascertain the effect of GoRedW using a large sample of unbiased real-world data from Google Trends (GTr) and evaluate the temporal correlation of online search queries for CVD and stroke in women with GoRedW. METHODS: We conducted a retrospective study using GTr, a public tool from the Google search engine to obtain relative search volumes (RSVs) related to CVD and stroke in women in the period January 2004 to April 2019 in the USA. In addition, trends of GoRedW were compared with those of the well-established Breast Cancer Awareness Month (BCAM) campaign. RESULTS: RSVs increased for queries of GoRedW and all searched terms for CVD but not for stroke in women during February compared to other months of the year without active campaign. The strong pattern with peaks of temporal increase was consistent over the 15-year study period. RSV of "Go Red for Women" in February increased on average 494% (range: 211% to 789%). The highest temporal increase on search queries for CVD was for the term "heart disease (in) women" with an average of 114% (24% to 182%). We found a positive correlation between RSVs of GoRedW and the term "heart disease (in) women" (r = 0.54, P < 0.001). RSVs for "Breast Cancer Awareness Month" had a higher increase during the active campaign month compared to GoRedW and showed a stronger positive correlation (r = 0.78, P < 0.001). CONCLUSIONS: Search engines are a valuable resource to provide insights on information demand and to assess the effectiveness of social campaigns and interventions. Our study showed an increase in the RSVs for queries of GoRedW and all CVD terms which correlated with the active campaign months over a 15-year period.

Spontaneous tumor lysis syndrome in T-cell malignancy: two case reports.

Tumor lysis syndrome (TLS) refers to a constellation of metabolic abnormalities that result from release of intracellular solutes (potassium, phosphate, and nucleic acid metabolites) from rapidly dying tumor cells. While TLS most commonly occurs following chemotherapy, spontaneous TLS can rarely occur in rapidly dividing liquid or solid malignancies. Here, we report the cases of two patients who presented with non-specific symptoms and were found to have spontaneous TLS. Work-up in both cases led to a diagnosis of T-cell malignancy (i.e., acute lymphoblastic leukemia and angioimmunoblastic lymphoma). Given that spontaneous TLS can be the first manifestation of an underlying malignancy, all physicians should be familiar with this oncologic emergency. Early recognition and prompt management can be lifesaving for patients with an otherwise curable malignancy.

Role of Phosphodiesterase-5 Inhibitors in Acute Right Ventricular Failure Due to Pulmonary Embolism.

BACKGROUND Sildenafil is a pulmonary vasodilator and its efficacy has been well established in patients with group 1 pulmonary hypertension. There are no established guidelines regarding its use in acute right ventricle failure. In our experience, it can be used as an adjunctive therapy in acute right ventricle failure due to pulmonary embolism, to reduce right ventricle afterload and hence improve size and function of the right ventricle. CASE REPORT This is a case report where sildenafil was used as a rescue agent to achieve improvement in the right ventricle size and function in a case of acute onset massive pulmonary embolism with acute right ventricle failure in the scenario where systemic thrombolytic therapy was contraindicated. CONCLUSIONS Improvement of right ventricle size and function was achieved using phosphodiesterase-5 Inhibitors in a case of acute right ventricle failure due to acute massive pulmonary embolism. There are no established guidelines regarding this clinical approach, however, given its efficacy in this case as adjunctive therapy in treatment of acute right ventricle, larger studies are needed to further establish its utility.

A Case of Acute Heart Failure due to Immune Checkpoint Blocker Nivolumab.

Immune checkpoint inhibitors can be potentially cardiotoxic. It has not been frequently reported in the literature. Cardiomyopathy with these agents can have early onset and may start with non-specific symptoms like fatigue, weakness before presenting with obvious features of acute heart failure. Rapid progression and fulminant course of this disease necessitate high index of clinical suspicion and early diagnosis. High-dose steroids should be instituted early to blunt the immune response against myocardium. Further bigger studies are needed to fully understand the pathogenesis of this condition.

Multimodal Genetic Approach for Molecular Imaging of Vasculature in a Mouse Model of Melanoma.

PURPOSE: In this study, we evaluated a genetic approach for in vivo multimodal molecular imaging of vasculature in a mouse model of melanoma. PROCEDURES: We used a novel transgenic mouse, Ts-Biotag, that genetically biotinylates vascular endothelial cells. After inoculating these mice with B16 melanoma cells, we selectively targeted endothelial cells with (strept)avidinated contrast agents to achieve multimodal contrast enhancement of Tie2-expressing blood vessels during tumor progression. RESULTS: This genetic targeting system provided selective labeling of tumor vasculature and showed in vivo binding of avidinated probes with high specificity and sensitivity using microscopy, near infrared, ultrasound, and magnetic resonance imaging. We further demonstrated the feasibility of conducting longitudinal three-dimensional (3D) targeted imaging studies to dynamically assess changes in vascular Tie2 from early to advanced tumor stages. CONCLUSIONS: Our results validated the Ts-Biotag mouse as a multimodal targeted imaging system with the potential to provide spatio-temporal information about dynamic changes in vasculature during tumor progression.

4D MEMRI atlas of neonatal FVB/N mouse brain development.

The widespread use of the mouse as a model system to study brain development has created the need for noninvasive neuroimaging methods that can be applied to early postnatal mice. The goal of this study was to optimize in vivo three- (3D) and four-dimensional (4D) manganese (Mn)-enhanced MRI (MEMRI) approaches for acquiring and analyzing data from the developing mouse brain. The combination of custom, stage-dependent holders and self-gated (motion-correcting) 3D MRI sequences enabled the acquisition of high-resolution (100-µm isotropic), motion artifact-free brain images with a high level of contrast due to Mn-enhancement of numerous brain regions and nuclei. We acquired high-quality longitudinal brain images from two groups of FVB/N strain mice, six mice per group, each mouse imaged on alternate odd or even days (6 3D MEMRI images at each day) covering the developmental stages between postnatal days 1 to 11. The effects of Mn-exposure, anesthesia and MRI were assessed, showing small but significant transient effects on body weight and brain volume, which recovered with time and did not result in significant morphological differences when compared to controls. Metrics derived from deformation-based morphometry (DBM) were used for quantitative analysis of changes in volume and position of a number of brain regions. The cerebellum, a brain region undergoing significant changes in size and patterning at early postnatal stages, was analyzed in detail to demonstrate the spatiotemporal characterization made possible by this new atlas of mouse brain development. These results show that MEMRI is a powerful tool for quantitative analysis of mouse brain development, with great potential for in vivo phenotype analysis in mouse models of neurodevelopmental diseases.

Engineering an effective Mn-binding MRI reporter protein by subcellular targeting.

PURPOSE: Manganese (Mn) is an effective contrast agent and biologically active metal, which has been widely used for Mn-enhanced MRI (MEMRI). The purpose of this study was to develop and test a Mn binding protein for use as a genetic reporter for MEMRI. METHODS: The bacterial Mn-binding protein, MntR was identified as a candidate reporter protein. MntR was engineered for expression in mammalian cells, and targeted to different subcellular organelles, including the Golgi Apparatus where cellular Mn is enriched. Transfected HEK293 cells and B16 melanoma cells were tested in vitro and in vivo, using immunocytochemistry, MR imaging and relaxometry. RESULTS: Subcellular targeting of MntR to the cytosol, endoplasmic reticulum and Golgi apparatus was verified with immunocytochemistry. After targeting to the Golgi, MntR expression produced robust R1 changes and T1 contrast in cells, in vitro and in vivo. Co-expression with the divalent metal transporter DMT1, a previously described Mn-based reporter, further enhanced contrast in B16 cells in culture, but in the in vivo B16 tumor model tested was not significantly better than MntR alone. CONCLUSION: This second-generation reporter system both expands the capabilities of genetically encoded reporters for imaging with MEMRI and provides important insights into the mechanisms of Mn biology which create endogenous MEMRI contrast.

In vivo Mn-enhanced MRI for early tumor detection and growth rate analysis in a mouse medulloblastoma model.

Mouse models have increased our understanding of the pathogenesis of medulloblastoma (MB), the most common malignant pediatric brain tumor that often forms in the cerebellum. A major goal of ongoing research is to better understand the early stages of tumorigenesis and to establish the genetic and environmental changes that underlie MB initiation and growth. However, studies of MB progression in mouse models are difficult due to the heterogeneity of tumor onset times and growth patterns and the lack of clinical symptoms at early stages. Magnetic resonance imaging (MRI) is critical for noninvasive, longitudinal, three-dimensional (3D) brain tumor imaging in the clinic but is limited in resolution and sensitivity for imaging early MBs in mice. In this study, high-resolution (100 µm in 2 hours) and high-throughput (150 µm in 15 minutes) manganese-enhanced MRI (MEMRI) protocols were optimized for early detection and monitoring of MBs in a Patched-1 (Ptch1) conditional knockout (CKO) model. The high tissue contrast obtained with MEMRI revealed detailed cerebellar morphology and enabled detection of MBs over a wide range of stages including pretumoral lesions as early as 2 to 3 weeks postnatal with volumes close to 0.1 mm(3). Furthermore, longitudinal MEMRI allowed noninvasive monitoring of tumors and demonstrated that lesions within and between individuals have different tumorigenic potentials. 3D volumetric studies allowed quantitative analysis of MB tumor morphology and growth rates in individual Ptch1-CKO mice. These results show that MEMRI provides a powerful method for early in vivo detection and longitudinal imaging of MB progression in the mouse brain.