Case report: 'Atypical Richter transformation from CLL-type monoclonal B-cell lymphocytosis into Burkitt lymphoma in a treatment naïve patient'.

Background: Richter transformation refers to the progression of an initially slow-growing small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) into an aggressive lymphoma, typically diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma. Case presentation: The patient presented with a rapid onset of localized cervical swelling, accompanied by monoclonal B-cell lymphocytosis displaying a CLL immunophenotype. The histopathological analysis identified a Burkitt lymphoma (BL) located in the submandibular gland and adjacent lymph node. The patient's bone marrow displayed a minor infiltration of monoclonal B-cells with a CLL immunophenotype (< 10%). Molecular analysis demonstrated the presence of the same monoclonal rearrangement in the framework region (FR3 region) of the immunoglobulin heavy chain (IGH) locus. High-throughput sequencing of the immunoglobulin heavy and light chains also confirmed the presence of the same rearrangement in SLL/CLL and in the Burkitt lymphoma sample, but also highlighted the presence of a second rearrangement in the Burkitt lymphoma cells, not shared with the SLL/CLL cells in the bone marrow. The patient was treated with DA-EPOCH-R, which lead to a complete metabolic response. Conclusion: This report provides an exceptionally rare description of a CLL-type monoclonal B-cell lymphocytosis transforming into a very aggressive Burkitt lymphoma in a treatment naïve patient.

Risk factors for heart failure hospitalizations among patients with atrial fibrillation.

BACKGROUND: Patients with atrial fibrillation (AF) have an increased risk for the development of heart failure (HF). In this study, we aimed to detect predictors of HF hospitalizations in an unselected AF population. METHODS: The Basel Atrial Fibrillation Cohort Study is an ongoing observational multicenter cohort study in Switzerland. For this analysis, 1193 patients with documented AF underwent clinical examination, venous blood sampling and resting 12-lead ECG at baseline. Questionnaires about lifestyle and medical history were obtained in person at baseline and during yearly follow-up phone calls. HF hospitalizations were validated by two independent physicians. Cox regression analyses were performed using a forward selection strategy. RESULTS: Overall, 29.8% of all patients were female and mean age was 69 ±12 years. Mean follow-up time was 3.7 ±1.5 years. Hospitalization for HF occurred in 110 patients, corresponding to an incidence of 2.5 events per 100 person years of follow-up. Independent predictors for HF were body mass index (HR 1.40 [95%CI 1.17; 1.66], p = 0.0002), chronic kidney disease (2.27 [1.49; 3.45], p = 0.0001), diabetes mellitus (2.13 [1.41; 3.24], p = 0.0004), QTc interval (1.25 [1.04; 1.49], p = 0.02), brain natriuretic peptide (2.19 [1.73; 2.77], p<0.0001), diastolic blood pressure (0.79 [0.65; 0.96], p = 0.02), history of pulmonary vein isolation or electrical cardioversion (0.54 [0.36; 0.80], p = 0.003) and serum chloride (0.82 [0.70; 0.96], p = 0.02). CONCLUSIONS: In this unselected AF population, several traditional cardiovascular risk factors and arrhythmia interventions predicted HF hospitalizations, providing potential opportunities for the implementation of strategies to reduce HF among AF patients.

QTc interval, cardiovascular events and mortality in patients with atrial fibrillation.

BACKGROUND: A longer QTc interval has been associated with more adverse cardiovascular events and death in the general population. Little evidence is available on these relationships among patients with atrial fibrillation (AF). METHODS: We performed a prospective observational multicenter cohort study of 1413 patients with AF. A resting 12­lead electrocardiogram (ECG) was performed at baseline. QT interval was corrected for heart rate using the Bazett formula (QTc). Endpoints for this study included hospitalizations for congestive heart failure (CHF), a combination of cardiovascular death, myocardial infarction, stroke, systemic arterial embolism (MACE) and all-cause mortality. RESULTS: Mean age of our population was 68±12years and 420 (30%) participants were female. Median QTc was 432ms (interquartile range 409; 457). The mean follow-up time was 3.6±1.5years. After multivariable adjustment, there was a linear increase in risk with increasing QTc interval for incident CHF (hazard ratio (HR) per 1-SD increase in QTc 1.3 [95% CI 1.1; 1.6], p=0.008), MACE (HR 1.2 [1.0; 1.4], p=0.02) and all-cause mortality (HR 1.3 [1.0; 1.6], p=0.002). Results were consistent whether or not patients were in sinus rhythm on the baseline ECG (HR for CHF 1.7 versus 1.3, p interaction 0.08; HR for MACE 1.3 versus 1.2, p interaction 0.9; HR for all-cause mortality 1.4 versus 1.4, p interaction 0.9). CONCLUSIONS: In this large well-characterized cohort of AF patients, QTc interval was independently associated with adverse outcomes. These results were independent of the rhythm on the baseline ECG.

Healthy lifestyle and glucagon-like peptide-1 in young and healthy adults: A population-based study.

A healthy lifestyle is associated with a lower risk of cardiovascular events and mortality, but underlying mechanisms are not fully understood. The aim of our study was to investigate the relationships between a healthy lifestyle and glucagon-like peptide-1 (GLP-1), an incretin hormone with both glycemic and cardiovascular properties. Healthy participants aged 25-41years without cardiovascular disease, diabetes or a body mass index (BMI) >35kg/m2 were enrolled in a population-based study. The following metrics were used to build a lifestyle score ranging from 0 to 7 (a higher score indicating a healthier lifestyle): blood pressure (BP) (<120/80mmHg), plasma levels of glycated hemoglobin (<5.7%), total cholesterol levels (<200mg/dl), BMI (<25kg/m2), not smoking cigarettes, moderate (≥150min/week) or vigorous (≥75min/week) physical activity and a healthy diet. Among 2133 participants median age was 36.7years and 53.3% were female. GLP-1 levels decreased significantly from 39.5 to 30.9ng/l (p<0.0001) across increasing lifestyle score categories. This linear relationship persisted in multivariable adjusted linear regression models (B for GLP-1 per 1-unit increase of the lifestyle score -0.06; 95% confidence intervals -0.07, -0.04; p<0.0001). Individual health metrics that were significantly associated with GLP-1 were a normal BMI (-0.07; -0.12, -0.03; p=0.001), low total cholesterol levels (-0.07; -0.12, -0.03; p=0.001), normal BP (-0.05; -0.10, -0.00; p=0.047) and not smoking (-0.06; -0.10, -0.01; p=0.01). A healthy lifestyle is strongly associated with lower GLP-1 levels in young and healthy adults.

Plasma copeptin levels and ambulatory blood pressure characteristics in healthy adults.

OBJECTIVE: We investigated whether copeptin - a well characterized vasopressin-related stress hormone - is associated with circadian ambulatory blood pressure (BP) variability and/or mean BP levels in young adults. METHOD AND RESULTS: We studied a population-based sample of healthy adults aged 25-41 years. Individuals with diabetes, treated hypertension, and cardiovascular disease were excluded. Ambulatory 24-h BP monitoring was performed using validated devices. To evaluate the relationships of copeptin with mean ambulatory BP levels and BP variability during daytime and night-time, multivariable adjusted regression models were constructed. BP variability was defined as SD of all intraindividual BP values. Of the 2012 individuals included in this study, 53% were women and the median age was 37 years. Median plasma copeptin levels were 3.9 (interquartile range 2.7, 5.8) in men and 2.3 pmol/l (interquartile range 1.6, 3.6) in women (P < 0.0001). In multivariable linear regression models, log-transformed copeptin was significantly associated with systolic and diastolic night-time BP levels among men [ß = 1.9, 95% confidence interval (CI) 0.6, 3.1, P = 0.003; and ß = 1.4, 95% CI 0.6, 2.3, P = 0.001, respectively], but not among women. In addition, copeptin was strongly associated with an increased systolic and diastolic daytime (ß = 0.5, 95% CI 0.2, 0.7, P = 0.001; ß = 0.5, 95% CI 0.3, 0.8, P < 0.0001, respectively) and night-time BP variability (ß = 0.6, 95% CI 0.3, 0.9, P = 0.0002; ß = 0.4, 95% CI 0.2, 0.7, P = 0.002, respectively). CONCLUSION: In this large population-based study of young and healthy adults, plasma levels of copeptin were significantly associated with an increased BP variability in both sexes and an elevated night-time BP among men.