High-risk cytogenetics and persistent minimal residual disease by multiparameter flow cytometry predict unsustained complete response after autologous stem cell transplantation in multiple myeloma

The achievement of complete response (CR) after high-dose therapy/autologous stem cell transplantation (HDT/ASCT) is a surrogate for prolonged survival in multiple myeloma; however, patients who lose their CR status within 1 year of HDT/ASCT (unsustained CR) have poor prognosis. Thus, the identification of these patients is highly relevant. Here, we investigate which prognostic markers can predict unsustained CR in a series of 241 patients in CR at day +100 after HDT/ASCT who were enrolled in the Spanish GEM2000 (n = 140) and GEM2005 < 65y (n = 101) trials. Twenty-nine (12%) of the 241 patients showed unsustained CR and a dismal outcome (median overall survival 39 months). The presence of baseline high-risk cytogenetics by FISH (hazard ratio 17.3; P = .002) and persistent minimal residual disease by multiparameter flow cytometry at day +100 after HDT/ASCT (hazard ratio 8.0; P = .005) were the only independent factors that predicted unsustained CR. Thus, these 2 parameters may help to identify patients in CR at risk of early progression after HDT/ASCT in whom novel treatments should be investigated.     

Aging increases mitochondrial DNA damage and oxidative stress in liver of rhesus monkeys

While the mechanisms of cellular aging remain controversial, a leading hypothesis is that mitochondrial oxidative stress and mitochondrial dysfunction play a critical role in this process. Here, we provide data in aging rhesus macaques supporting the hypothesis that increased oxidative stress is a major characteristic of aging and may be responsible for the age-associated increase in mitochondrial dysfunction. We measured mitochondrial DNA (mtDNA) damage by quantitative PCR in liver and peripheral blood mononuclear cells of young, middle age, and old monkeys and show that older monkeys have increases in the number of mtDNA lesions. There was a direct correlation between the amount of mtDNA lesions and age, supporting the role of mtDNA damage in the process of aging. Liver from older monkeys showed significant increases in lipid peroxidation, protein carbonylations and reduced antioxidant enzyme activity. Similarly, peripheral blood mononuclear cells from the middle age group showed increased levels in carbonylated proteins, indicative of high levels of oxidative stress. Together, these results suggest that the aging process is associated with defective mitochondria, where increased production of reactive oxygen species results in extensive damage at the mtDNA and protein levels. This study provides valuable data based on the rhesus macaque model further validating age-related mitochondrial functional decline with increasing age and suggesting that mtDNA damage might be a good biomarker of aging.     

Circulating endothelial cells and their progenitors in systemic lupus erythematosus and early rheumatoid arthritis patients

Objective. The aim of this study was to investigate the endothelial progenitor cell population in SLE and early RA patients and its potential relationships with disease features and cytokine serum levels. Methods. Endothelial progenitor cells (EPCs), mature EPCs (mEPCs) and endothelial cells (ECs) were measured in peripheral blood samples from 83 SLE and 85 early RA patients and 39 healthy controls by flow cytometry on the basis of CD34, VEGF receptor 2 and CD133 expression. Serum levels of IL-1β, IL-6, IL-8, IL-17, VEGF-A, IFN-α, TGF-β and GM-CSF were quantified by immunoassays. Clinical and immunological data were obtained by reviewing clinical histories. Results. Circulating EPCs were increased in SLE but not in early RA patients associated with an enhanced CD34(+) bone marrow-progenitor cell release but unrelated to disease features. The amount of mEPCs, however, was significantly higher in SLE patients presenting anti-SSA/SSB antibodies and/or malar rash, whereas the presence of specific autoantibodies was associated with EC counts in early RA and SLE patients. As expected, most cytokines tested were altered in both diseases but, interestingly, IFN-α levels, and to a lesser extent IL-6 and IL-1β, were associated with CD133 loss and increased mEPC number, whereas VEGF and TGF-β seem to exert an opposite effect. Conclusion. Our results show that high IFN-α levels and/or the presence of disease-specific antibodies may identify a group of SLE patients with increased mEPC and EC counts, and consequently probably defective endothelial repair, thus supporting their use as surrogate biomarkers of endothelial damage and high cardiovascular risk.     

Introduction of a competency based haemodialysis education programme: 5 years experience

The quality of care that patients receive is fundamentally related to the knowledge and skills of the staff providing the care. To ensure that all staff within our dialysis clinic network has the knowledge and competence to provide the care, support and education that patients require, a competency based education programme was developed. Roll-out of the programme commenced in 129 clinics in our dialysis clinic network during 2006-2007. Activity with this programme has continued. It is now translated into 12 languages and fully implemented in 11 countries. At the end of December 2010, 3,099 staff had completed the Basic Dialysis Programme and 3,125 staff had completed the Orientation Programme component of the education programme. Results of quality activities have enabled further programme development and have shown that the investment in staff education has benefited our organisation, staff and patients.     

Relapse rates in chronic hepatitis B naïve patients after discontinuation of antiviral therapy with entecavir

Registration studies show entecavir (ETV) to be effective and safe in NUC‐naïve patients with chronic hepatitis B, but relapse rates after treatment discontinuation have not been well established. Relapse rates and predictors of relapse were evaluated in naïve HBeAg‐positive and HBeAg‐negative patients treated with ETV. Treatment duration was defined according to international guidelines. Virological relapse was defined as reappearance in serum of hepatitis B virus (HBV) DNA to >2000 IU/mL after discontinuation of treatment. A hundred and sixty‐nine consecutive patients were treated for a median 181 weeks. 61% were HBeAg positive, 23% had cirrhosis, and mean HBV DNA level was 6.88 ± 1.74 log₁₀ IU/mL. Ninety‐two per cent became HBV DNA negative; 71% of HBeAg+ve patients became HBeAg negative and 68% anti‐HBe positive; 14% became HBsAg negative and 13% anti‐HBs positive. At the end of the study, 36 patients discontinued treatment: one due to breakthrough associated with resistant variants and 35 (20%) due to sustained virological response; 33 of these patients developed HBeAg seroconversion and 18 HBsAg seroconversion. Median off‐treatment time was 69 weeks. Nine patients (26%), all HBeAg positive at baseline, developed virological relapse after a median 48 weeks off‐treatment, 3 of them showed HBeAg reversion and 4 lost anti‐HBe. No patient with HBsAg seroconversion relapsed. HBeAg clearance after week 48 of treatment was associated with an increase risk of relapse. After ETV discontinuation, HBsAg seroconversion was maintained in 100% of the patients, HBeAg seroconversion maintained in 90%, and virological relapse rate was 24%.     

Facial porokeratosis: A series of six patients

Porokeratosis is a disorder of epidermal keratinization characterized by annular plaques with an atrophic centre and hyperkeratotic edges, and includes a heterogeneous group of disorders that are mostly inherited in an autosomal dominant fashion. Facial porokeratosis is rare and is not well documented. We present six cases of facial porokeratosis seen over a period of 15 years in a hospital in Lima, Peru. In most of the cases, porokeratosis was found in younger women without any significant past medical history. Oral isotretinoin showed moderate improvement in two of our patients.     

Molar incisor hypomineralization in HIV‐infected children and adolescents

The objective was to determine the prevalence of molar incisor hypomineralization (MIH) among individuals between 7 and 15 years old infected or noninfected with human immunodeficiency virus (HIV). The study was conducted with 33 HIV‐infected individuals (study group; SG) and 66 non‐HIV‐infected schoolchildren (control group; CG), paired by gender and age. Data collection was based on medical records (SG), a questionnaire for caregivers and oral examination for diagnosis of MIH (European Academy of Pediatric Dentistry criteria) and caries (DMFT index and ICDAS). Data were analyzed with Mann‐Whitney, chi‐square, and Fisher's exact tests and logistic regression. In SG, MIH (45.5%) and caries (87.9%) had higher prevalence. MIH was associated with use of protease inhibitors in SG (OR: 2.14; 95% CI: 1.21 to 3.77) and incubator need in CG (OR: 2.80; 95% CI: 1.71 to 9.10). HIV‐infected patients had a higher prevalence of MIH and dental caries in the permanent dentition.