Search Results for: L’inibizione di un enzima uccide selettivamente le cellule di melanoma

To the Editor We read with great interest the comments by Donia and Prasad suggesting that for patients with tumors exhibiting positive staining (≥1%) for programmed cell death ligand 1 (PD-L1), nivolumab monotherapy offers maximal benefit while cautioning against the necessity of the combination therapy due to toxic effects and cost. However, we wish to address certain points and express our reservations regarding this stance.

In this issue of JAMA Dermatology, Zhang et al report an analysis to estimate differences in risk of second primary melanomas between American Indian or Alaska Native, Asian or Pacific Islander, Black, Hispanic, and White patients using the Surveillance, Epidemiology, and End Results registries. White patients had the highest absolute risk of first and second primary melanomas, whereas Asian or Pacific Islander and Black patients had the highest relative risk of second primary melanomas compared to the general population. The authors also estimated the excess risk of a second primary melanoma by testing 2 hypotheses—one testing independence and one testing dependence of primary and second melanomas. The first hypothesis assumed that the risk of a second primary melanoma is unrelated to the first primary melanoma and that the risk of each is equal. Alternately, the second hypothesis estimated the risk of a second melanoma specifically in patients with a primary melanoma. The difference in these risks yielded the estimated excess risk of developing a second primary melanoma conditional on having a prior melanoma. Here, too, Asian or Pacific Islander and Black individuals—and to some extent also Hispanic individuals—showed lower excess rates of melanoma.

This cohort study assesses the incidence of a second melanoma diagnosis after initial diagnosis among racial and ethnic minority populations.

Università Cattolica, il farmaco ‘spegne’ un enzima nel cervello

Circulation, Volume 150, Issue Suppl_1, Page A4136040-A4136040, November 12, 2024. Background:Cardiovascular diseases (CVD) is the leading cause of non-cancer mortality among cancer survivors. Despite the known benefits of physical activity on cardiovascular health in the general population, evidence regarding post-diagnosis physical activity and CVD risk among cancer survivors is limited.Objectives:To explore the associations of wearable device-measured moderate-to-vigorous intensity physical activity (MVPA) with CVD risk in long-term cancer survivors.Methods:The retrospective analysis involved a prospective cohort of 6109 cancer survivors without CVD from the UK Biobank accelerometry subsample. Cancer diagnoses were obtained from national cancer registries (International Classification of Diseases-10 [ICD-10], C00-C97, except for non-melanoma skin cancer, in situ, and non-well-defined cancers), and participants were followed up through December 31, 2022. A machine-learning algorithm was utilized to categorize MVPA into four groups based on guideline-recommend MVPA duration (0-75 min/week, 75-150 min/week, 150-300 min/week, ≥300 min/week).Results:Over a median follow-up of 7.88 years, there were 539 incident CVD events, including 361 incident CAD events, 155 incident HF events, and 109 incident stroke events. A clear inverse linear dose-response relationship between MVPA volume and the incidence of CVD was observed (P for nonlinear=0.49), with no maximal threshold for the benefits. Adjusted CVD incidence rates (95% confidence intervals [CIs]) across MVPA groups (0-75 min/week, 75-150 min/week, 150-300 min/week, ≥300 min/week) were 15.30 (12.90, 18.10), 13.50 (11.00, 16.40), 12.00 (10.20, 14.10), and 9.86 (8.35, 11.60) per 1000 person-years, respectively. Adjusted hazard ratios (95% CI) for CVD, CAD, HF, and stroke in the highest MVPA group (≥300 min/week) compared with those with the lowest MVPA group (0-75 min/week) were 0.63 (0.49, 0.80), 0.68 (0.51, 0.91), 0.66 (0.42,1.06), 0.72 (0.42, 1.23), respectively.Conclusions:Findings from the UK Biobank study suggest that longer durations of MVPA are associated with reduced incident CVD risk in cancer survivors, particularly in CAD risk reduction, underscoring the potential for physical activity to serve as a key component in cardio-oncology care.

Circulation, Volume 150, Issue Suppl_1, Page A4145712-A4145712, November 12, 2024. Introduction:Immune checkpoint inhibitors (ICI) are increasingly used to treat a wide variety of malignancies. The long-term cardiovascular risk profile of ICI therapy remains incompletely understood.Methods:All patients at a single academic center receiving any ICI therapy between 2015 and 2023 were identified. Using ICD codes, we adjudicated major adverse cardiac events (MACE) after initiation of ICI therapy, defined as a composite endpoint of coronary artery disease (CAD), acute coronary syndrome (ACS), cardiomyopathy and heart failure (HF), arrhythmia, ischemic stroke, cardiac arrest, pericarditis, and myocarditis. Cancer type and baseline cardiometabolic risk factors were identified. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for all variables measured.Results:Of patients receiving ICI therapy (n=5991), 1196 developed MACE, including ACS (n=152), stable CAD (n = 300), HF (n=217), arrhythmia (n=380), ischemic stroke (n=92), cardiac arrest (n=30) and myo- or pericarditis (n=25). Prior to a MACE event, patients received an average of 11.6 ± 12.7 ICI doses over 332.4 ± 448.0 days. Compared to the non-MACE group, those who developed MACE were older (OR 1.18, CI 1.09-1.27) and of male sex (OR 1.17, CI 1.00-1.23). They were more likely to have higher body mass index (BMI) (OR 1.13, CI 1.06-1.21), pre-existing hypertension (OR 1.3, CI 1.21-1.39), be on statin therapy (OR 1.19, CI 1.11-1.28) and have higher B-nauretic peptide (BNP) levels (OR 1.25, CI 1.06-1.47). Regarding cancer type, MACE was more likely to develop in those with melanoma (OR 1.11, CI 1.02-1.20), lung (OR 1.22, CI 1.11-1.34), colon (OR 1.08, CI 1.01-1.15), genitourinary (OR 1.19, CI 1.10-1.29), and prostate cancers (OR 1.08, CI 1.01-1.15). MACE was less likely to develop in breast cancer (OR 0.88, CI 0.80-0.96). All-cause mortality was higher in the MACE group (59.4% vs. 51.9%, p < 0.001).Conclusion:Risk factors for developing MACE with ICI therapy include older age, male sex, cancer type, prior MACE, hypertension, statin use, and higher BMI and BNP. MACE is associated with higher all-cause mortality. These findings can assist in identifying and attenuating cardiovascular risk in patients undergoing ICI therapy.

Circulation, Volume 150, Issue Suppl_1, Page A4140400-A4140400, November 12, 2024. Background:Evidence linking cancer diagnosis to risk of incident atherosclerotic cardiovascular disease (ASCVD) remains inconclusive.Research Questions:Do cancer patients experience a higher risk of ASCVD independent of shared risk factors? How does the risk of ASCVD evolve over time following a cancer diagnosis?Aims:To determine the association between cancer diagnosis and subsequent risk of ASCVD (coronary heart disease and stroke), and its trajectory over time after cancer diagnosis.Methods:We prospectively followed 108,689 women in the Nurses’ Health Study (NHS) (1984-2020), 113,608 women in the NHSII (1991-2019) and 45,327 men from the Health Professionals Follow-up Study (HPFS) (1986-2016) who were free of ASCVD and cancer at baseline. We conducted multivariable-adjusted time-varying Cox proportional hazards models to assess ASCVD risk following individual cancer diagnosis. We conducted restricted cubic spline analyses to assess the varied ASCVD risk over time after cancer diagnosis.Results:During up to 36 years of follow-up, 48,069 incident cancer cases and 32,592 ASCVD cases were documented. After adjusting for shared risk factors, ASCVD risk was significantly elevated after diagnosis of cervical cancer (HR: 1.63; 95%CI: 1.10-2.42) and Hodgkin lymphoma (HR: 2.17; 95%CI: 1.42-3.30) compared with non-cancer participants. Prostate cancer diagnosis was associated with a lower ASCVD risk (HR: 0.91; 95% CI: 0.85-0.97). Breast cancer diagnosis was associated with decreased ASCVD risk during the first 15 years after diagnosis, but this risk gradually increased afterward (P =0.02). Bladder cancer was associated with increased ASCVD risk during the first 10 years and attenuated afterward (P=0.03). The risk of ASCVD increased over time after cancer diagnosis among patients with cancers of colorectum (P=0.003), lung (P=0.007), and endometrium (P=0.05). No significant association with ASCVD risk was observed for cancers of oral cavity and pharynx, sarcoma, melanoma, kidney, thyroid, leukemia, or ovary. Results were consistent across sensitivity analyses.Conclusions:Increased ASCVD risk was observed for patients diagnosed with cervical cancer or Hodgkin lymphoma, independent of shared risk factors. ASCVD risk trajectories varied over time after diagnosis according to different cancer types. These findings support a need for tailored ASCVD screening among cancer survivors based on specific cancer types and post-diagnosis durations.

Circulation, Volume 150, Issue Suppl_1, Page A4146198-A4146198, November 12, 2024. Introduction:Lung cancer is divided broadly into two main types: Small cell lung cancer (SCLC) and non-small cell lung cancer-NSCLC. Approximately 70% of SCLC cases have metastasized to other parts of the body including lymph nodes, bone, liver, adrenal glands, and brain [1]. SCLS metastasis to cardiac tissue is rare. Primary cardiac tumors are as rare with a reported prevalence of 0.028% [2]. Here we present a 59-year-old female (59F) with recurrent SCLC metastasis with evidence of a newly diagnosed primary cardiac tumor.Case Presentation:59F with a past medical history of SCLC status-post chemotherapy and radiation presented for evaluation of worsening left upper extremity pain, paresthesia, motor weakness, and neck pain. During the hospital admission, an echocardiogram demonstrated extensive thrombus from the Superior Vena Cava (SVC) into the right atrium (RA) and an irregular echogenic 37 mm x 26 mm mass partially attached to the posterior leaflet of the tricuspid valve. The RA mass was successfully removed by mechanical thrombectomy. Pathological results of the RA mass revealed significant malignant epithelioid and spindled neoplasm with myxoid stroma– concerning for myoepithelial disease.Discussion:Cardiac tumors, although uncommon, should be included in the list of possible diagnoses when observing any abnormal mass detected through cardiovascular or thoracic imaging techniques. Cardiac tumors are likely due to metastatic origins as metastatic cardiac tumors occur 20 times more frequently than primary cardiac tumors[3].When metastatic cardiac tumors are suspected, malignant melanoma and leukemia are the most frequent origins[4]. Rarely does SCLC metastasize to cardiac tissue. Primary cardiac tumors are typically benign (90%), with primary malignant tumors being very rare[5]. Patients may be asymptomatic, or present with nonspecific symptoms such as exertional dyspnea, fevers, arthralgias, or life-threatening cardiac tamponade[6]. For right atrial tumors, treatment strategies are usually dependent on symptomatology, in which removal via aspiration or surgical resection has demonstrated a favorable prognosis[7].Conclusion:Given the rarity of primary cardiac tumors in the setting of metastatic SCLC, there exist no evidence-based guidelines for optimal management of right atrial tumors. In our patient, mechanical aspiration was performed without complications and prevented potential adverse cardiopulmonary events from occurring.

Circulation, Volume 150, Issue Suppl_1, Page A4117414-A4117414, November 12, 2024. Background:Immune checkpoint inhibitors (ICIs) are highly effective anti-cancer treatments for several cancers. However, treatment with ICIs is associated with metabolic perturbations, accelerated atherosclerosis, and increased risks of adverse cardiovascular events. In this study, we aimed to determine risk factors associated with cardiac hospital admissions in patients treated with ICIs for their cancer.Methods:Retrospective data was collected for all patients treated with ICIs between 1 January 2010 and 1 January 2020 through the Hunter New England Local Health District (HNELHD), Australia. Patient medical history and demographics were collected through electronic medical records. Outcome data was obtained from the HNELHD Institutional Cardiac and Stroke Outcomes Unit database. Cardiac admission was defined as cardiac disease based on hospital administrationICD-10codes. Binary logistic regression was used for multivariate analysis and performed through SPSS version 28.Results:A total of 1,080 patients were included in the final analysis. Mean age of patients was 66.9 ± 11.7 years, with the majority male sex (n=685; 63.4%). Primary cancer diagnosis of patients treated with ICIs included melanoma (n=417; 38.7%), and cancer of the lung (n=327; 30.3%). Nivolumab monotherapy was the most used first-line ICI treatment (n=475; 44.0%) followed by pembrolizumab monotherapy (n=428; 39.6%). A total of 266 (24.6%) patients had at least one cardiac hospital admission. On univariate analysis, pre-existing cardiovascular disease (CVD) (p

Il progetto, vincitore dell’Erc Synergy Grant, ha l’obiettivo di rivoluzionare il campo delle terapie a base di cellule staminali per le malattie neurodegenerative

La ricerca degli atenei Tor Vergata e Ucla apre la strada ad ampie applicazioni in medicina e biotecnologia