Epstein-Barr virus-positive, primary cutaneous marginal zone lymphoma, with transformation: Case report and review of the literature.

Epstein-Barr Virus (EBV) positive primary cutaneous marginal zone lymphoma (PCMZL) is uncommon and subsequent transformation is rare. METHODS: We report a patient with EBV positive PCMZL with subsequent transformation to plasmablastic lymphoma and review the literature for transformed PCMZL to assess clinical and pathologic characteristics. In the case we describe, the patient presented with multifocal PCMZL, developed large B cell transformation with plasmacytic differentiation, followed by plasmablastic transformation (PBL), and ultimately died of disease progression despite multiple lines of therapy. Past history was significant for psoriatic arthritis (multiple prior lines of immunomodulatory therapy). The lymphomas and non-involved bone marrow share the same somatic DNMT3A and TET2 mutations, suggesting clonal relatedness and an association with clonal hematopoiesis (CH). RESULTS: Eighteen cases complied the cohort (seventeen cases from the literature and the case reported herein). Nearly half of the eighteen cases of PCMZL with transformation died of progressive disease (44%). Transformed cases were more commonly seen in patients with >2 sites at initial diagnosis. EBV was assessed in 5 patients, 3 were positive (all died of disease). Two patients with NGS studies demonstrated TET2 and DNMT3A mutations. CONCLUSIONS: Transformation of EBV positive PCMZL appears to be a poor prognostic indicator, with our reported case being the first well defined case transformed to PBL, suspected to arise from myeloid-CH.

Chlormethine gel in combination with other therapies for treatment of mycosis fungoides: a review with patient cases.

Topical chlormethine gel has been approved as monotherapy for treatment of adult patients with mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma. In clinical practice, chlormethine gel is often combined with other skin-directed or systemic therapies to optimize response and target recalcitrant lesions. Positive outcomes with combination regimens using chlormethine gel and topical corticosteroids, phototherapy, retinoids, methotrexate, or interferon-α have been reported in literature. However, there are no treatment guidelines on the use of combination regimens with chlormethine gel. To provide real-world evidence and guidance on the use of chlormethine gel combination regimens, several cases of patients treated with chlormethine gel combined with phototherapy (n = 5), retinoids (n = 16), or mogamulizumab (n = 3) are presented. These different combination regimens showed promising results. Most patients had a complete or partial response following treatment and the combinations were well-tolerated over extended treatment periods. Patients receiving chlormethine gel with retinoids had long-term periods of remission, even after treatment discontinuation. Durations of response of up to 3 years were observed in these patients. This long-term disease control may be the result of disease-modifying effects of chlormethine. Previous studies have shown targeted reductions in malignant T-cell clones in patients treated with chlormethine gel as well as improved post-treatment responses. Further research is needed to determine the effectiveness and safety of combination treatment regimens with chlormethine gel and to assess the impact chlormethine gel has on disease control.

Association of cardiovascular health with mortality among COPD patients: National Health and Nutrition Examination Survey III.

BACKGROUND: All-cause and cardiovascular disease (CVD) mortality are higher among patients with chronic obstructive pulmonary disease (COPD). We examined the association between American Heart Association's Life's Simple 7 (LS7) metrics and all-cause as well as CVD mortality in patients with COPD. METHODS: We examined 1513 US adults with COPD aged ≥ 40, without prior CVD, from the National Health and Nutrition Examination Survey III. COPD was defined as FEV1/FVC<0.7 in absence of asthma. Adjusted Cox regression was used to assess the relation of LS7 metrics with all-cause and CVD mortality. RESULTS: Overall, only 74 participants (4.9%) had ideal 5-7 LS7 metrics. Over a mean follow-up of 14.2±7.9 years, 1162 individuals died, of which 315 were due to CVD. Age, sex, and ethnicity-adjusted HRs (95% CI) for all-cause mortality were 0.53 (0.41-0.68), 0.45 (0.34-0.59), 0.66 (0.49-0.87) and 0.75 (0.56-1.00) among those with ideal vs poor control of smoking, diet, physical activity and fasting blood glucose, respectively. However, the ideal and intermediate LS7 metrics were not significantly associated with lower risk of CVD mortality, except for a BMI between 25-29.9 kg/m2. Those with 5-7 vs 0-1 ideal metrics had adjusted HRs 0.50 (0.40-0.87) for all-cause and 0.53 (0.21-1.36) for CVD mortality. CONCLUSION: Ideal levels of multiple behavioral and health factors are associated with substantially lower risks for all-cause mortality, with a trend for lower CVD mortality among US adults with COPD.

Karma of Cardiovascular Disease Risk Factors for Prevention and Management of Major Cardiovascular Events in the Context of Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

There is compelling epidemiological evidence that airway exposure to cigarette smoke, air pollution particles, as well as bacterial and viral pathogens is strongly related to acute ischemic events. Over the years, there have been important animal and human studies that have provided experimental evidence to support a causal link. Studies show that patients with cardiovascular diseases (CVDs) or risk factors for CVD are more likely to have major adverse cardiovascular events (MACEs) after an acute exacerbation of chronic obstructive pulmonary disease (COPD), and patients with more severe COPD have higher cardiovascular mortality and morbidity than those with less severe COPD. The risk of MACEs in acute exacerbation of COPD is determined by the complex interactions between genetics, behavioral, metabolic, infectious, and environmental risk factors. To date, there are no guidelines regarding the prevention, screening, and management of the modifiable risk factors for MACEs in the context of COPD or COPD exacerbations, and there is insufficient CVD risk control in those with COPD. A deeper insight of the modifiable risk factors shared by CVD, COPD, and acute exacerbations of COPD may improve the strategies for reduction of MACEs in patients with COPD through vaccination, tight control of traditional CV risk factors and modifying lifestyle. This review summarizes the most recent studies regarding the pathophysiology and epidemiology of modifiable risk factors shared by CVD, COPD, and COPD exacerbations that could influence overall morbidity and mortality due to MACEs in patients with acute exacerbations of COPD.