Relapse in stage I(E) diffuse large B-cell lymphoma.

Despite a general favourable outcome in limited stage diffuse large B-cell lymphoma (DLBCL), relapses occur in about 10 to 20% of patients. Prognostic models only partially identify patients at risk for relapse. Moreover, it is not known whether the outcome after such a relapse is similar to the outcome after relapse in advanced stages. From January 2004 through December 2012, all newly diagnosed patients with stage I(E) DLBCL were retrospectively analysed from 2 clinical databases to investigate the relapse pattern and outcome in relation to initial treatment and clinical characteristics. In 126 patients (median age 64 years), histologically confirmed stage I(E) DLBCL was diagnosed. With a median follow-up of 53 months (range 5-132 months), 1 progressive disease and 18 relapses occurred. The 5-year time to tumour progression and disease-specific survival were 85% (95% CI 79-91%) and 92% (95% CI 87%-97%), respectively. We observed no significant difference in relapse localization, time to tumour progression, and disease-specific survival between patients treated with abbreviated R-CHOP plus involved field radiotherapy or with 6 to 8 cycles of R-CHOP. Analysis of relapses showed relapse >5 years after initial treatment (late relapse) in 5 of 19 patients (26%). Six of 19 patients (32%) had central nervous system relapse. Three of 11 relapsed cases available for analysis (28%) showed an MYC translocation, suggesting an overrepresentation in the relapse group. Outcome of patients with a relapse was poor with a median survival after relapse of 8 months. Only 1 patient (5%) underwent successful autologous stem cell transplantation. To improve outcome in these patients, early identification of new biological factors such as a MYC translocation or a high risk for CNS dissemination might be helpful. Moreover, treatment of any relapse after stage I disease should be taken seriously. Salvage treatment should be similar to relapses after advanced DLBCL.

A 1-day visit in a severe asthma centre: effect on asthma control, quality of life and healthcare use.

Patients with uncontrolled asthma report ongoing symptoms, poor quality-of-life and extensive healthcare use (HCU) and might benefit from management by a specialised severe asthma team. It is unknown whether a one-time evaluation by asthma experts, without long-term supervision by a specialised team, provides favourable outcomes. We evaluated asthma control (Asthma Control Questionnaire; ACQ), quality-of-life (Asthma-related Quality of Life Questionnaire; AQLQ) and HCU before and 1 year after a 1-day visit programme in a severe asthma centre, including a multidisciplinary assessment resulting in a personalised management plan to be implemented by patients own pulmonologists.40 uncontrolled asthma patients completed questionnaires (ACQ, AQLQ, HCU) at baseline, and 6 and 12 months follow-up.ACQ improved from 2.6 (interquartile range 1.7-3.2) to 1.8 (1.2-3.2) (p=0.003) and AQLQ from 4.8 (4.0-5.2) to 5.3 (4.4-6.0) (p<0.001). We found a reduction in patients with ≥2 exacerbations (95% versus 17%; p<0.001), ≥1 emergency room visit (78% versus 37%; p<0.001) and ≥1 hospitalisation (47% versus 10%; p=0.001).Evaluation of uncontrolled asthma patients in a 1-day visit programme in a severe asthma centre resulted in significant improvements in asthma control, quality-of-life and healthcare use after 1 year. This 1-day visit approach seems beneficial for uncontrolled asthma patients and might reduce their dependence on expensive treatment modalities and long-term management in specialised centres.

Vitamin D reduces eosinophilic airway inflammation in nonatopic asthma.

BACKGROUND: Low levels of vitamin D are associated with asthma severity, airway remodeling, and exacerbation rate increase, especially in nonatopic asthma. Reduced steroid responsiveness or impaired antimicrobial defense might be underlying mechanisms. OBJECTIVE: We sought to evaluate the effect of vitamin D supplementation on eosinophilic and neutrophilic airway inflammation in patients with nonatopic asthma. METHODS: In a double-blind, randomized, placebo-controlled trial, we investigated the effect of long-acting vitamin D3 (400,000 IU) on sputum neutrophils and eosinophils in 44 patients with nonatopic asthma with neutrophilic (≥53%) and/or eosinophilic (≥3%) airway inflammation. Sputum induction was performed at baseline and after 9 weeks. Other measurements included questionnaires, blood samples, and pulmonary function. RESULTS: Treatment with vitamin D did not significantly affect sputum neutrophils or eosinophils compared with treatment with placebo in the total group. Regarding sputum eosinophils, the effect of vitamin D appeared to be dependent on baseline sputum eosinophil levels (interaction P = .015). In patients with eosinophil levels of 26.2% or more (median in patients with sputum eosinophilia, >3%), eosinophils decreased from a median of 41.0% to 11.8% after vitamin D treatment as compared with an increase from 51.8% to 63.3% in patients receiving placebo (P = .034). Vitamin D treatment also resulted in slightly better Asthma Control Questionnaire scores (P = .08). CONCLUSIONS: Vitamin D supplementation reduced eosinophilic airway inflammation in patients with nonatopic asthma with severe eosinophilic airway inflammation, but did not affect sputum neutrophils. Also, a small effect on asthma control was observed. These findings suggest that vitamin D might have potential as an add-on treatment option in eosinophilic asthma.

Comorbidity is an independent prognostic factor in patients with advanced-stage diffuse large B-cell lymphoma treated with R-CHOP: a population-based cohort study.

An observational population-based cohort study was performed to investigate the role of comorbidity on outcome and treatment-related toxicity in patients with newly diagnosed advanced-stage diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Data for the clinical characteristics of 154 patients (median age 69 years), including Charlson Comorbidity Index (CCI), treatment, toxicity and outcome were evaluated. Forty-five percent of the patients had an International Prognistic index ≥3 and 16% had a CCI ≥2. The planned R-CHOP schedule was completed by 84% and 75% reached complete remission (CR). In those with CCI ≥2, 67% completed treatment with 46% CR. In patients with a CCI <2, overall survival (OS) after 1, 2 and 5 years was 84%, 79% and 65% respectively and it was 64%, 48% and 48% for those with CCI ≥2. Grade III/IV toxicity was documented in 53%, most frequently febrile neutropenia (27%) and infections (23%). In multivariate analysis CCI ≥2 and IPI ≥3 were independent risk indicators for OS and grade III/IV toxicity. In conclusion, comorbidity is an independent risk indicator for worse OS in patients with advanced DLBCL treated with R-CHOP by interference with intensive treatment schedules and more grade III/IV toxicity. Future studies are warranted to determine the optimal treatment approach in patients with significant comorbidities.

Real-world data from Europe and Africa suggest that accuracy of systems for self-monitoring of blood glucose is frequently impaired by low hematocrit.

AIMS: Certain systems for self-monitoring of blood glucose (SMBG) demonstrate inaccuracy at low and high hematocrit (HCT). Manufacturers define HCT ranges for accurate performance. Our objective was to assess the frequency of HCT values that can lead to clinically relevant errors. METHODS: In this cross-sectional study, we collected real-world data representing over 360,000 outpatients from the Netherlands (NL), the Czech Republic (CZ), and South Africa (ZA). These were subsequently stratified by sex and age and compared to commonly specified HCT range limits, reference intervals, and data from 1780 healthy Czech subjects. RESULTS: HCT values were comparably distributed in NL and CZ. Outpatients had a higher dispersion of values than healthy subjects. Low HCT values in Europe were common in age groups with a high prevalence of diabetes. All ZA age groups showed a higher prevalence of low HCT than in Europe. CONCLUSIONS: Real-world data indicate that SMBG systems specified to perform only within the frequently used 30-55% HCT range would leave 3% of outpatients in Europe and 18% in South Africa at risk of false SMBG results, with individual age strata being substantially higher. This could affect their diabetes management. Adequate SMBG systems should thus be chosen.

Circulating cerebral S100B protein is associated with depressive symptoms following myocardial infarction.

BACKGROUND: Prevalence of depressive symptoms in the post-myocardial infarction (MI) period varies from 8 to 30%. Cerebral damage after MI, caused by transient ischemia, an inflammatory response or both, may contribute to development of post-MI depression. S100B is an established protein marker of cerebral damage. In a pilot study, the authors assessed whether S100B serum levels are: (1) increased during the week after MI, and (2) related to depressive symptoms during index hospital admission and the year following MI. METHODS: This pilot study is a substudy of the Myocardial Infarction and Depression Intervention Trial (MIND-IT). In 48 patients, serum levels of S100B were available at 1, 2, 3, 4 and 8 days following MI. Subsequently, in 27 patients, depressive symptoms were measured at 0, 3, 6, 9 and 12 months following MI with the Beck Depression Inventory (BDI). In 21 of the initial 48 patients, BDI data were lacking due to refusals to fill out BDI forms or missing data. RESULTS: Significant and transient increases in serum S100B were observed in 81.3% of the 48 patients: 37.5% reached S100B serum levels comparable to serum levels found in acute brain injury (>0.20 microg/l) and 43.8% reached mildly elevated S100B serum levels comparable to serum levels found in depressive disorder (0.10-0.20 microg/l). In 18.7%, no S100B was detected in serum. Using non-parametric Spearman rank correlation tests, a trend towards an association was found between serum S100B and depressive symptoms during the post-MI year (rho values between 0.16 and 0.53) in 27 patients who completed both the S100B serum study and the BDI study. CONCLUSION: Transiently elevated levels of S100B are suggestive of minor acute cerebral damage in the first days following MI and associated with depressive symptoms in the year following MI. Cerebral damage could be an important mechanism in the pathogenesis in a subtype of post-MI depression.

No outcome disparities in patients with diffuse large B-cell lymphoma and a low socioeconomic status.

INTRODUCTION: In patients with diffuse large B-cell lymphoma (DLBCL) socioeconomic status (SES) is associated with outcome in several population-based studies. The aim of this study was to further investigate the existence of disparities in treatment and survival. METHODS: A population-based cohort study was performed including 343 consecutive patients with DLBCL, diagnosed between 2005 and 2012, in the North-west of the Netherlands. SES was based on the socioeconomic position within the Netherlands by use of postal code and categorized as low, intermediate or high. With multivariable logistic regression and Cox proportional hazard models the association between SES and respectively treatment and overall survival (OS) was evaluated. RESULTS: Two-third of patients was positioned in low SES. Irrespective of SES an equal proportion of patients received standard immunochemotherapy. SES was not a significant risk indicator for OS (intermediate versus low SES: hazard ratio (HR) 1.31 (95%CI 0.78-2.18); high versus low SES: HR 0.83 (95%CI 0.48-1.46)). The mortality risk remained significantly increased with higher age, advanced performance status, elevated LDH and presence of comorbidity. CONCLUSION: Within the setting of free access to health care, in this cohort of patients with DLBCL no disparities in treatment and survival were seen in those with lower SES.

Clinical profile of patients with adult-onset eosinophilic asthma.

Adult-onset eosinophilic asthma is increasingly recognised as a severe and difficult-to-treat subtype of asthma. In clinical practice, early recognition of patients with this asthma subtype is important because it may have treatment implications. Therefore, physicians need to know the distinct characteristics of this asthma phenotype. The objective of the present study was to determine the characteristic profile of patients with adult-onset eosinophilic asthma. 130 patients with adult-onset (>18 years of age) asthma and high blood eosinophil counts (≥0.3×109 L-1) were compared with 361 adult-onset asthma patients with low (<0.3×109 L-1) blood eosinophils. Measurements included a series of clinical, functional and imaging parameters. Patients with high blood eosinophils were more often male, had less well controlled asthma and higher exacerbation rates, despite the use of higher doses of inhaled corticosteroids. They had higher levels of total IgE without more sensitisation to common inhaled allergens. In addition, these patients had worse lung function, and more often showed fixed airflow limitation, air trapping, nasal polyposis and abnormalities on sinus computed tomography scanning. Chronic rhinosinusitis, air trapping and male sex were three independent factors associated with blood eosinophilia (adjusted OR 3.8 (95% CI 1.7-8.1), 3.0 (95% CI 1.1-8.1) and 2.4 (95% CI 1.3-4.4), respectively). Patients with adult-onset asthma with elevated blood eosinophils exhibit a distinct profile, which can readily be recognised in clinical practice.

Treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone is beneficial but toxic in very elderly patients with diffuse large B-cell lymphoma: a population-based cohort study on treatment, toxicity and outcome.

To assess treatment strategies, toxicity and outcome in very elderly patients (aged ≥ 75 years) diagnosed with diffuse large B-cell lymphoma (DLBCL) in the rituximab era, an observational population-based cohort study was performed. From 103 patients with a median age of 81 years, data of clinical characteristics, treatment, toxicity and outcome were evaluated. Advanced stage DLBCL was documented in 74 patients. In 80 patients chemotherapy was initiated; 70 patients received rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP). In this group, 39 patients completed all cycles and 30 patients achieved a complete remission. Severe chemotherapy-related toxicity occurred in 69%. Two-year overall survival was 70% for elderly patients who completed chemotherapy, 28% for those treated with incomplete or suboptimal chemotherapy and 21% for those receiving palliative radiotherapy or supportive care. In conclusion, the ability to complete R-CHOP was associated with better overall survival compared to other treatment strategies at the expense of severe treatment-related toxicity.

Analyzing DNA from buccal cells is a reliable method for the exclusion of cystic fibrosis. Results of a pilot study.

PURPOSE: In children there is frequently a reason to exclude cystic fibrosis. Sweat testing is used for this. Because sweat testing has some disadvantages we investigated whether analyzing DNA for the local most common CFTR mutations, harvested from buccal cells, is reliable as a method to exclude cystic fibrosis. METHODS: In patients in whom a sweat test had been ordered during the period January 1, 2002 to December 31, 2004, we harvested buccal cell DNA for analysis. When blood was available, DNA from leukocytes was also analyzed. RESULTS: A total of 73 sweat tests were ordered during the two-year study period, mostly because of recurrent pulmonary infections (36; 49%), failure to thrive (20; 27%) and chronic diarrhea (10, 14%). In 70, children the results of the sweat test were normal, in three patients the results were borderline. Sixty buccal smears were analyzed and no patient was homozygous for cystic fibrosis, two were heterozygous for cystic fibrosis. In none of the children the diagnosis of cystic fibrosis was established. CONCLUSION: Analyzing DNA in cells, harvested from the buccal cells, is a reliable alternative to exclude cystic fibrosis. It is safe, simple, and child-friendly.