Effect of statins and testosterone replacement therapy on incident cardiovascular disease among male hormone-related cancer survivors.

Purpose: Statins and testosterone replacement therapy (TTh) have been previously linked with prostate, colorectal and male breast cancer (hereinafter we will refer as hormone related cancers [HRCa]), and cardiovascular disease (CVD). However, there is a poor understanding about the combined association of statins and TTh with incident CVD among HRCa survivors and a matched cancer-free cohort. Methods: We identified 44,330 men of whom 22,165 were previously diagnosed with HRCa, and 22,165 were age-and index-matched cancer-free in SEER-Medicare 2007-2015. Pre-diagnostic prescription of statins and TTh prior to CVD development was ascertained for this analysis in the two matched cohorts. Weighted multivariable-adjusted conditional logistic regression models were used to evaluate the independent and combined associations of statins and TTh with CVD. Results: We found that use of statins (OR = 0.51, 95% CI: 0.46-0.55) and TTh (OR = 0.81, 95% CI: 0.67-0.97) were each independently inversely associated with incident CVD in the overall sample. TTh plus statins was also inversely associated with CVD. Associations were similar in the matched cancer-free cohort. Among HRCa survivors, only statins and combination of TTh plus statins (OR = 0.60, 95% CI: 0.44-0.98) were inversely associated with CVD, but the independent use of TTh was not associated with CVD. Conclusion: In general, pre-diagnostic use of statins and TTh, prior to CVD development, independently or in combination, were inversely associated with CVD in the overall, cancer-free population, and among HRCa survivors (mainly combination). Independent effects and combination of statins and TTh remained to be confirmed with specific CVD outcomes among HRCa survivors.

Testosterone Replacement Therapy in Relation With Cardiovascular Disease in Cisgender Women and Transgender People.

AIMS: This study aimed to investigate the association of testosterone replacement therapy (TTh) with risk of cardiovascular disease (CVD), and CVD-specific outcomes, in cisgender women and transgender population, and to determine whether this association varies by menopausal status. METHODS: In 25 796 cisgender women and 1580 transgender people (≥30 years old) who were enrolled in the Optum's deidentified Clinformatics Data Mart Database (2007-2021), we identified 6288 pre- and postmenopausal cisgender women and 262 transgender people diagnosed with incident composite of CVD (coronary artery disease [CAD], congestive heart failure, stroke, and myocardial infarction). Prediagnostic prescription of TTh was ascertained for this analysis. Multivariable adjusted Cox proportional hazards models were used to examine the independent association of TTh with incident CVD. RESULTS: We found a 24% increased risk of CVD (hazard ratio [HR] = 1.24; 95% CI, 1.15-1.34), 26% risk of CAD (HR = 1.26; 95% CI, 1.14-1.39), and a 29% risk of stroke (HR = 1.29; 95% CI, 1.14-1.45) after comparing cisgender women who used TTh with nonusers. Stratification by age group showed similar effects of TTh on CVD, CAD, and stroke. Among transgender people, TTh did not increase the risk of composite CVD, including by age stratification. CONCLUSION: Use of TTh increased the risk of CVD, CAD, and stroke among cisgender women but not among transgender people. TTh is becoming more widely accepted in women, and it is the main medical treatment for transgender males. Therefore, use of TTh should be further investigated for the prevention of CVD.

Coronary Artery Disease and Aspirin Intolerance: Background and Insights on Current Management.

Aspirin is one of the most widely used medications across the global healthcare system and is the foundation in treating ischemic heart disease, as well as secondary prevention for ischemic and valvular heart disease. Challenges arise in treating patients with cardiovascular disease who have concomitant aspirin intolerance. Through an extensive review of the literature, we provide a comprehensive background on the pharmacology of aspirin, the mechanisms behind aspirin intolerance, the importance of aspirin in cardiovascular disease, and the management of aspirin intolerance in both acute coronary syndrome and stable coronary artery disease. Our review includes a multidisciplinary approach from the internist, allergist/immunologist, and cardiologist when evaluating this important patient population.

The Ability of a Cytomegalovirus ELISPOT Assay to Predict Outcome of Low-Level CMV Reactivation in Hematopoietic Cell Transplant Recipients.

BACKGROUND: Cytomegalovirus (CMV) infections in hematopoietic cell transplant (HCT) recipients cause substantial morbidity and mortality. CMV cell-mediated immunity (CMV-CMI) can be determined by levels of interferon gamma (IFN-γ) production using an enzyme-linked immunospot (ELISPOT) CMV assay (T-SPOT.CMV assay). In this study, we evaluated the ability of this assay to predict the outcome of low-level CMV reactivation in HCT recipients. METHODS: We followed 55 HCT recipients with low-level CMV reactivation up to 8 weeks from enrollment. Progression to clinically significant CMV infection (CS-CMVi) was defined as a CMV load >1000 IU/mL or > 500 IU/mL in patients receiving matched related/autologous or matched unrelated transplants, respectively, and initiation of antiviral treatment. RESULTS: Progression to CS-CMVi occurred in 31 (56%) of the HCT recipients. Spot counts of CMV-specific pp65 and IE1 antigens were significantly lower in patients who had CS-CMVi than in patients who did not. On multivariate analysis, the ELISPOT CMV responses and steroids use were the only predictors of progression to CS-CMVi. CONCLUSIONS: A strong association between low CMV-CMI and progression to CS-CMVi was observed in HCT recipients. The implementation of serial monitoring of CMV-CMI may identify patients at risk of progression to CS-CMVi that require antiviral therapy.

Brincidofovir (CMX-001) for refractory and resistant CMV and HSV infections in immunocompromised cancer patients: A single-center experience.

BACKGROUND: The emergence of resistance to available antiviral drugs may cause higher Cytomegalovirus (CMV)-associated morbidity and mortality in hematopoietic cell transplant (HCT) recipients. Few novel antiviral drugs are being developed with potential effect against refractory or resistant CMV infections. Brincidofovir, an oral nucleotide analog and prodrug of cidofovir, has shown in vitro activity against CMV. METHODS: We reviewed data of 4 cancer patients with resistant CMV or herpes simplex virus (HSV) infections and were treated with brincidofovir under emergency IND application. RESULTS: Three out of the 4 patients with resistant CMV or HSV infections responded to brincidofovir. Brincidofovir achieved virological response in 2 patients with confirmed UL97 mutation (ganciclovir-resistant CMV infection), but failed to control CMV when a specific UL54 mutation was present (conferring resistance to foscarnet and cidofovir), as seen with patient 3. Furthermore, brincidofovir was effective for treatment of acyclovir resistant HSV infection, as described in patient 4 which is in alignment with the high in vitro potency of brincidofovir (about 100-fold more than acyclovir) for inhibition of HSV replication. Only one patient had brincidofovir-related diarrhea without any evidence of concurrent gastrointestinal GVHD. CONCLUSION: Without the nephrotoxicity of cidofovir, brincidofovir could be an effective alternative for CMV-resistant and HSV-resistant infections. Combination therapy of brincidofovir with other antiviral agent, at a conventional or a lower dose, could be considered to potentiate efficacy and minimize side effects of the approved antiviral agents.

Outcomes of Cancer Patients Undergoing Percutaneous Pericardiocentesis for Pericardial Effusion.

BACKGROUND: Pericardial effusion (PE) is common in cancer patients, but the optimal therapeutic approach is not well defined. Percutaneous pericardiocentesis is less invasive than surgery, but its long-term effectiveness and safety have not been well documented. OBJECTIVES: The goal of this study was to evaluate outcomes of cancer patients undergoing percutaneous pericardiocentesis for PE and assess the procedure's safety in patients with thrombocytopenia. METHODS: Cancer patients who underwent percutaneous pericardiocentesis for PE between November 2009 and October 2014 at the MD Anderson Cancer Center were included. Procedure-related complications, effusion recurrence rate, and overall survival were analyzed. RESULTS: Of 1,645 cancer patients referred for PE, 212 (13%) underwent percutaneous pericardiocentesis. The procedure was successful in 99% of the cases, and there were no procedure-related deaths. Four patients had major procedure-related bleeding that did not vary by platelet count <50,000/µl or ≥50,000/µl (p = 0.1281). Patients with catheter drainage for 3 to 5 days had the lowest recurrence rate (10%). Median overall survival was 143 days; older age (i.e., >65 years), lung cancer, platelet count <20,000/µl, and malignant pericardial fluid were independently associated with poor prognosis. Lung cancer patients with proven malignant effusions had a significantly shorter median 1-year survival compared with those with nonmalignant effusions (16.2% vs. 49.0%, respectively; log-rank test p = 0.0101). A similar difference in 1-year survival was not observed in patients with breast cancer (40.2% vs. 40.0%; log-rank test p = 0.4170). CONCLUSIONS: Percutaneous pericardiocentesis with extended catheter drainage was safe and effective as the primary treatment for PE in cancer patients, including in those with thrombocytopenia. Malignant PE significantly shortened the survival outcome of patients with lung cancer but not those with breast cancer.