Platelet-derived microparticle count and surface molecule expression differ between subjects with and without type 2 diabetes,independently of obesity status

This study investigated the impact of either type 2 diabetes or obesity, separately or in combination, on the absolute amounts of microparticles (MP) and the pathways by which these are associated with either condition. The concentrations of circulating MP derived from platelets (PMP), leukocytes (LMP) and monocytes (MMP), together with their specific activation markers, were compared in 30 subjects who were characterised across 4 cohorts as obese or type 2 diabetes. The subjects with type 2 diabetes had elevated concentrations of total PMP (P = 0.003), and PMP that were fibrinogen-positive (P = 0.04), tissue factor-positive (P < 0.001), P-selectin-positive (P = 0.03). Type 2 diabetes did not alter either total or activated LMP or MMP. Obesity per se did not impact on any MP measurement. Elevated concentrations of plasma PMP occurred in subjects with type 2 diabetes, whether they were obese or non-obese. In contrast, obesity in the absence of type 2 diabetes had no effect. The increased concentrations of specific marker-positive PMP in the subjects with diabetes might reflect potential pathways by which PMP may contribute to the pathogenesis of atherosclerosis and type 2 diabetes.     

Mantle cell lymphoma epidemiology: a population-based study in France

Only limited population-based data are available on mantle cell lymphoma (MCL), a relatively rare and aggressive mature B cell non-Hodgkin lymphoma (NHL) entity. We conducted an epidemiological study based on the three French registries devoted to haematological malignancies over the period 2002–2006. Main clinical features and management characteristics were collected. Incidence and survival rates were estimated, and independent prognostic factors were analysed. MCL was diagnosed in 135 patients between 2002 and 2006. Seventy-four percent of patients were men. Age-standardised incidence rate of MCL (per 100,000) was 1.1 in men and 0.26 in women. Median age at diagnosis was 72 years (range 30–92). Advanced-stage (III or IV) disease was diagnosed in 81.5 % of patients, and 55 % of them were identified as high risk according to MCL International Prognostic Index (MIPI). Median net survival time was 41 months (95 % confidence interval (CI), 38–62). Main independent prognostic factors were age at diagnosis, performance status and use of rituximab in first-line treatment. Median overall survival was 36 months (95 % CI, 27–40) for high MIPI and 60 months (95 % CI, 35–74) for low/intermediate MIPI patients (p?=?0.02). This study confirms that MCL remains an aggressive NHL with a median overall survival less than 4 years and demonstrates that the use of rituximab has modified overall survival duration.     

Treatment practice in the elderly patient with chronic lymphocytic leukemia—analysis of the combined SEER and Medicare database

The median age at diagnosis of chronic lymphocytic leukemia (CLL) is 72, but patients enrolled in randomized trials are often a decade younger. Therapy selection and outcomes in the older, comorbid population are less understood. We evaluated treatment patterns and outcomes among 2,985 first primary CLL patients from the linked Surveillance, Epidemiology, and End Results–Medicare database. There were 151 chlorambucil (CLB), 594 rituximab monotherapy (R-mono), 696 rituximab?+?intravenous chemotherapy (R?+?IV Chemo), and 1,544 IV chemo-only patients. Patients administered CLB and R-mono were the oldest and had the highest comorbidity burden while patients receiving R?+?IV Chemo were the youngest and had the lowest comorbidity burden (p?<?0.0001). In the multivariate survival analysis, receipt of R?+?IV Chemo was associated with significantly lower mortality risk vs. IV Chemo-only (hazard ratio (HR)?=?0.73; 95 % confidence interval (CI) 0.62–0.87) and a non-significant mortality risk reduction with R-mono vs. CLB (HR?=?0.47; 95 % CI: 0.21-1.05). Older age and increasing comorbidity score were significantly associated with higher mortality. These findings suggest that chemoimmunotherapy is more effective than chemotherapy in an elderly population with a high prevalence of comorbidity, and this extends the conclusions from clinical trials in younger, medically fit patients.     

Elevated tricuspid regurgitant jet velocity in subgroups of thalassemia patients: insight into pathophysiology and the effect of splenectomy

A high tricuspid regurgitant jet velocity (TRV) signifies a risk for or established pulmonary hypertension (PH), which is a serious complication in thalassemia patients. The underlying pathophysiology in thalassemia subgroups and potential biomarkers for early detection and monitoring are not well defined, in particular as they relate to spleen removal. To better understand some of these unresolved aspects, we examined 76 thalassemia patients (35 non-transfused), 25 splenectomized non-thalassemia patients (15 with hereditary spherocytosis), and 12 healthy controls. An elevated TRV (>2.5 m/s) was found in 25/76 (33 %) of the patients, confined to non-transfused or those with a late start of transfusions, including patients with hemoglobin H-constant spring, a finding not previously described. These non or late-transfused patients (76 % splenectomized) had significantly increased platelet activation (sCD40L), high platelet count, endothelial activation (endothelin-1), and hemolysis (LDH, plasma-free Hb), while hypercoagulable and inflammatory markers were not significantly increased. The same markers were increased in the seven patients with confirmed PH on cardiac catheterization, suggesting their possible role for screening patients at risk for PH. A combination of hemolysis and absence of spleen is necessary for developing a high TRV, as neither chronic hemolysis in the non-splenectomized thalassemia patients nor splenectomy without hemolysis, in the non-thalassemia patients, resulted in an increase in TRV.     

Management of initial carious lesions: Iowa survey

BackgroundThe authors explore Iowa dentists’ agreement with the International Caries Classification and Management System (ICCMS) in the nonsurgical management of initial carious lesions in patients at low, moderate, and high caries risk and identify factors related to their agreement.MethodsElectronic surveys were mailed to 916 actively practicing dentists who are alumni of the College of Dentistry at The University of Iowa. Questions included clinical scenarios that used text, clinical photographs, and radiographic images of initial carious lesions. Dentists were asked what type of treatment they would recommend. Treatment options included no treatment, nonsurgical treatment, or surgical treatment. Logistic regression analyses were used to assess associations among agreement with ICCMS, characteristics of the dentist’s practice, and patients’ caries risk level.ResultsA total of 138 Iowa dentists responded to the survey. Agreement with ICCMS regarding nonsurgical management of initial carious lesions for patients at low, moderate, and high risk levels were 73%, 59%, and 51% respectively. Compared with their counterparts, dentists who agreed with the recommendations for nonsurgical treatment were more likely to dry the teeth during caries detection (95% confidence interval [CI], 1.02 to 12.67, P = .0468), use magnification (95% CI, 1.16 to 7.17, P = .0225) for caries detection, have graduated less than 20 years ago (P = .0024), practice in public health settings (P = .0089), and perform a caries risk assessment (95% CI, 1.10 to 4.29, P = .0262).ConclusionsDentists who dry teeth, use magnification for caries detection, graduated in the past 20 years, practice in a public health setting, and perform a caries risk assessment were significantly more likely to make decisions that were consistent with the guidelines of the ICCMS.Practical ImplicationsKnowledge of evidence-based options personalized for a patient’s risk status is essential for applying the best management of initial caries lesions.     

Clinical characteristics and cytokine biomarkers in patients with chronic graft-vs-host disease persisting seven or more years after diagnosis

Chronic graft-versus-host disease (cGVHD) is the leading late complication after allogeneic hematopoietic stem cell transplantation (HSCT). Many patients receive multiple lines of systemic therapy until cGVHD resolves, but about 15% remain on systemic treatment for more than 7 years after cGVHD diagnosis. This study describes the clinical and biological factors of patients who present with cGVHD persisting for ≥7 years (persistent cGVHD). Patients with persistent cGVHD (n = 38) and those with cGVHD for <1 year (early cGVHD) (n = 83) were enrolled in a prospective cross-sectional natural history study. Patients in the persistent cGVHD group were a median of 10.2 years from cGVHD diagnosis (range 7-27 years). Fifty-eight percent of persistent cGVHD patients (22/38) were receiving systemic immunosuppression, compared to 88% (73/83) in the early cGVHD group. In multivariable analysis, bone marrow (BM) stem cell source, presence of ENA autoantibodies, higher NIH lung score, higher platelet counts, and higher IgA levels were significantly associated with persistent cGVHD. A high sensitivity panel of serum biomarkers including seven cytokines diagnostic for cGVHD was analyzed and showed significantly lower levels of BAFF and CXCL10 in patients with persistent cGVHD. In conclusion, standardly accepted clinical measures of disease severity may not accurately reflect disease activity in patients with persistent cGVHD. However, many patients with persistent cGVHD are still receiving systemic immunosuppression despite lacking evidence of disease activity. Development of reliable clinical biomarkers of cGVHD activity may help guide future systemic treatments.     

Outcome and determinants of failure to complete primary R-CHOP treatment for reasons other than non-response among patients with diffuse large B-cell lymphoma

Patients with diffuse large B-cell lymphoma (DLBCL) who fail to complete planned treatment with R-CHOP due to toxicity are sparsely described. We investigated the extent of failure to complete treatment (six cycles or more, or three cycles + RT for patients with stage I disease) with R-CHOP for reasons unrelated to non-response, the determinants of such failure and the outcome among these patients. Three thousand one hundred and forty nine adult DLBCL patients who started primary treatment with R-CHOP were identified through the Swedish lymphoma register 2007-2014. Of these, 147 (5%) stopped prematurely after 1-3 cycles of R-CHOP for reasons unrelated to non-response, 168 (5%) after 4-5 cycles and 2639 patients (84%) completed planned treatment. Additionally, 195 (6%) patients did not complete treatment due to non-response or death before treatment end. In a multivariable logistic regression model, age > 75 years, poor performance status, extranodal disease and Charlson Comorbidity Index ≥1 were significantly associated with failure to complete planned R-CHOP treatment for other reasons than non-response. Non-completion of treatment strongly correlated with survival. Five-year overall survival for patients who received 1-3 cycles was 26% (95% CI: 19%-33%), 49% (95% CI: 41%-57%) for 4-5 cycles and 76% (74%-77%) for patients who completed treatment. Failure to complete planned R-CHOP treatment is an important clinical issue associated with inferior survival. Old age and poor performance status most strongly predict such failure. These results indicate a need for improved treatment tailoring for patients with certain baseline demographics to improve tolerability and chance for treatment completion.     

Physical activity behaviour in children and adolescents before,during and after cancer treatment

Purpose

Childhood cancer survivors show reduced physical activity (PA) levels which may considerably impact child development, quality of life, social participation and sequelae such as functional and cardiovascular health. This study aims to evaluate different aspects of PA behaviour in patients with childhood cancer (PaC) before (bT), during (dT) and after (aT) cancer treatment.

Methods

In this cross-sectional, multicentre study, 114 PaC and 37 healthy controls between 4 and 20 years of age were enrolled. PA behaviour was assessed using an adapted questionnaire which included items asking about PA level, PA intensity and domains of PA.

Results

Patients reported lower PA levels and less minutes of PA at moderate-intensity dT than aT and bT (P?≤?0.05). Healthy controls reported higher PA levels than patients aT (P?≤?0.05). At school, 41.7% of PaC did not participate in physical education aT or bT. Lastly, 45.6% of PaC who were engaged in sport club activities bT did no more participate in sport club activities aT.

Conclusion

Patients reported different PA behaviours dT and aT than bT. Therefore, monitoring of PA should be considered to increase PA levels in PaC. Future studies also need to examine how PA behaviour can be influenced in a positive way in PaC.