We assessed the prognostic value of minimal residual disease (MRD) detection in multiple myeloma (MM) patients using a sequencing-based platform in bone marrow samples from 133 MM patients in at ...least very good partial response (VGPR) after front-line therapy. Deep sequencing was carried out in patients in whom a high-frequency myeloma clone was identified and MRD was assessed using the IGH-VDJH, IGH-DJH, and IGK assays. The results were contrasted with those of multiparametric flow cytometry (MFC) and allele-specific oligonucleotide polymerase chain reaction (ASO-PCR). The applicability of deep sequencing was 91%. Concordance between sequencing and MFC and ASO-PCR was 83% and 85%, respectively. Patients who were MRD– by sequencing had a significantly longer time to tumor progression (TTP) (median 80 vs 31 months; P < .0001) and overall survival (median not reached vs 81 months; P = .02), compared with patients who were MRD+. When stratifying patients by different levels of MRD, the respective TTP medians were: MRD ≥10−3 27 months, MRD 10−3 to 10−5 48 months, and MRD <10−5 80 months (P = .003 to .0001). Ninety-two percent of VGPR patients were MRD+. In complete response patients, the TTP remained significantly longer for MRD– compared with MRD+ patients (131 vs 35 months; P = .0009).
•MRD assessment by sequencing is prognostic of TTP and OS in multiple myeloma patients.•Among patients in complete response, MRD assessment by sequencing enables identification of 2 distinct subgroups with different TTP.
Abstract Objective To establish the cardiovascular (CV) morbidity and associated risk factors for CV disease (CVD) in Spanish patients with chronic inflammatory rheumatic diseases (CIRD) and ...unexposed individuals attending rheumatology clinics. Methods Analysis of data from the baseline visit of a 10-year prospective study CARdiovascular in rheuMAtology (CARMA) project that includes a cohort of patients with CIRD rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) and another cohort of matched individuals without CIRD attending outpatient rheumatology clinics from 67 hospitals in Spain. Prevalence of CV morbidity, CV risk factors, and systematic coronary risk evaluation (SCORE) assessment were analyzed. Results A total of 2234 patients (775 RA, 738 AS, and 721 PsA) and 677 unexposed subjects were included. Patients had low disease activity at the time of recruitment. PsA patients had more commonly classic CV risk factors and metabolic syndrome features than did the remaining individuals. The prevalence of CVD was higher in RA (10.5%) than in AS (7.6%), PsA (7.2%), and unexposed individuals (6.4%). A multivariate analysis adjusted for the presence of classic CV risk factors and disease duration revealed a positive trend for CVD in RA (OR = 1.58; 95% CI: 0.90–2.76; p = 0.10) and AS (OR = 1.77; 95% CI: 0.96–3.27; p = 0.07). Disease duration in all CIRD groups and functional capacity (HAQ) in RA were associated with an increased risk of CVD (OR = 2.15; 95% CI: 1.29–3.56; p = 0.003). Most patients had a moderate CV risk according to the SCORE charts. Conclusions Despite recent advances in the management of CIRD, incidence of CVD remains increased in Spanish subjects with CIRD attending outpatient rheumatology clinics.
Imaging studies help to understand the evolution of key cognitive processes related to aging, such as working memory (WM). This study aimed to test three hypotheses in older adults. First, that the ...brain activation pattern associated to WM processes in elderly during successful low load tasks is located in posterior sensory and associative areas; second, that the prefrontal and parietal cortex and basal ganglia should be more active during high-demand tasks; third, that cerebellar activations are related to high-demand cognitive tasks and have a specific lateralization depending on the condition.
We used a neuropsychological assessment with functional magnetic resonance imaging and a core N-back paradigm design that was maintained across the combination of four conditions of stimuli and two memory loads in a sample of twenty elderly subjects.
During low-loads, activations were located in the visual ventral network. In high loads, there was an involvement of the basal ganglia and cerebellum in addition to the frontal and parietal cortices. Moreover, we detected an executive control role of the cerebellum in a relatively symmetric fronto-parietal network. Nevertheless, this network showed a predominantly left lateralization in parietal regions associated presumably with an overuse of verbal storage strategies. The differential activations between conditions were stimuli-dependent and were located in sensory areas.
Successful WM processes in the elderly population are accompanied by an activation pattern that involves cerebellar regions working together with a fronto-parietal network.
Objective
To evaluate the impact of comorbidities on physical function in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA).
Methods
This was a cross‐sectional analysis of the ...baseline visit from the Cardiovascular in Rheumatology study. Multivariate models with physical function as the dependent variable (Bath Ankylosing Spondylitis Functional Index and Health Assessment Questionnaire for AS and PsA, respectively) were performed. Independent variables were a proxy for the Charlson Comorbidity Index (CCIp; range 0–27), sociodemographic data, disease activity (erythrocyte sedimentation rate ESR and Bath Ankylosing Spondylitis Disease Activity Index BASDAI in AS; Disease Activity Score in 28 joints DAS28 using the ESR in PsA), disease duration, radiographic damage, and treatments. Results were reported as beta coefficients, 95% confidence intervals (95% CIs), and P values.
Results
We included 738 patients with AS and 721 with PsA; 21% of patients had >1 comorbidity. Comorbidity burden (CCIp) was independently associated with worse adjusted physical function in patients with PsA (β = 0.11). Also, female sex (β = 0.14), disease duration (β = 0.01), disease activity (DAS28‐ESR; β = 0.19), and the use of nonsteroidal antiinflammatory drugs (β = 0.09), glucocorticoids (β = 0.11), and biologics (β = 0.15) were associated with worse function in patients with PsA. A higher education level was associated with less disability (β = –0.14). In patients with AS, age (β = 0.03), disease activity (BASDAI; β = 0.81), radiographic damage (β = 0.61), and the use of biologics (β = 0.51) were independently associated with worse function on multivariate analyses, but CCIp was not.
Conclusion
The presence of comorbidities in patients with PsA is independently associated with worse physical function. The detection and control of the comorbidities may yield an integral management of the disease.
Abstract
Objectives
To determine cardiovascular (CV) mortality and incidence of the first CV event (CVE) in patients with chronic inflammatory rheumatic diseases (CIRD) after 5 years of follow-up.
...Methods
This is an analysis of the CARdiovascular in rheMAatology (CARMA) study after 5 years of follow-up. It includes patients with RA (n = 775), AS (n = 738) and PsA (n = 721), and individuals without CIRD (n = 677) attending outpatient rheumatology clinics from 67 public hospitals in Spain. Descriptive analyses were performed for the CV mortality at 5 years. The Systematic COronary Risk Evaluation (SCORE) function at 5 years was calculated to determine the expected risk of CV mortality. Poisson models were used to estimate the incidence rates of the first CVE. Hazard ratios of the risk factors involved in the development of the first CVE were evaluated using the Weibull proportional hazard model.
Results
Overall, 2382 subjects completed the follow-up visit at 5 years. Fifteen patients died due to CVE. CV deaths observed in the CIRD cohort were lower than that predicted by SCORE risk charts. The highest incidence rate of CVE 7.39 cases per 1000 person-years (95% CI 4.63, 11.18) was found in PsA patients. However, after adjusting for age, sex and CV risk factors, AS was the inflammatory disease more commonly associated with CVE at 5 years hazard ratio 4.60 (P =0.02), compared with those without CIRD.
Conclusions
Cardiovascular mortality in patients with CIRD at 5 years of follow-up is lower than estimated. Patients with AS have a higher risk of developing a first CVE after 5 years of follow-up.
Hormonal Dependence and Cancer in Systemic Lupus Erythematosus Cobo‐Ibáñez, Tatiana; Urruticoechea‐Arana, Ana; Rúa‐Figueroa, Iñigo ...
Arthritis care & research,
February 2020, 2020-Feb, 2020-02-00, 20200201, Letnik:
72, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Objective
To estimate the incidence and analyze any cancer‐associated factors in patients with systemic lupus erythematosus (SLE), differentiating between hormone‐sensitive (HS) and non‐HS cancers.
...Methods
This was a retrospective multicenter study of a patient cohort from the Systemic Lupus Erythematosus Registry of the Spanish Society of Rheumatology. Included were the first cancer post‐SLE diagnosis, clinical and sociodemographic information, cumulative damage, severity, comorbidities, treatments, and refractoriness. Cancers were classified as HS (prostate, breast, endometrium, and ovarian) and non‐HS (the remainder). The standardized incidence ratio (SIR) was calculated and logistic regression models were built.
Results
A total of 3,539 patients (90.4% women) were included, 154 of whom had cancer (91% female), and 44 had HS cancer (100% female). The cancer SIR was 1.37 (95% confidence interval 95% CI 1.15–1.59), with higher values in women age <65 years (SIR 2.38 95% CI 1.84–2.91). The SIR in women with HS versus non‐HS cancer was 1.02 (95% CI 0.13–1.91) and 1.93 (95% CI 0.98–2.89). In HS versus non‐HS cancers, SLE diagnostic age (odds ratio OR 1.04 P = 0.002 versus 1.04 P = 0.019), and period of disease evolution (OR 1.01 P < 0.001 versus 1.00 P = 0.029) were associated with cancer. The Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (OR 1.27 P = 0.022) and angiotensin‐converting enzyme (ACE) inhibitor prescriptions (OR 2.87 P = 0.048) were associated with non‐HS cancers.
Conclusion
Cancer incidence in patients with SLE was higher than in the Spanish population, particularly among young women. This increase might be due to non‐HS cancers, which would be associated with SLE involving greater cumulative damage where more ACE inhibitors are prescribed.
The aim of this study is to compare the properties of free-walking at a natural pace between mild Parkinson's disease (PD) patients during the ON-clinical status and two control groups. In-shoe ...pressure-sensitive insoles were used to quantify the temporal and force characteristics of a 5-min free-walking in 11 PD patients, in 16 young healthy controls, and in 12 age-matched healthy controls. Inferential statistics analyses were performed on the kinematic and kinetic parameters to compare groups' performances, whereas feature selection analyses and automatic classification were used to identify the signature of parkinsonian gait and to assess the performance of group classification, respectively. Compared to healthy subjects, the PD patients' gait pattern presented significant differences in kinematic parameters associated with bilateral coordination but not in kinetics. Specifically, patients showed an increased variability in double support time, greater gait asymmetry and phase deviation, and also poorer phase coordination. Feature selection analyses based on the ReliefF algorithm on the differential parameters in PD patients revealed an effect of the clinical status, especially true in double support time variability and gait asymmetry. Automatic classification of PD patients, young and senior subjects confirmed that kinematic predictors produced a slightly better classification performance than kinetic predictors. Overall, classification accuracy of groups with a linear discriminant model which included the whole set of features (i.e., demographics and parameters extracted from the sensors) was 64.1%.
The human brain undergoes structural and functional changes across the lifespan. The study of motor sequence learning in elderly subjects is of particularly interest since previous findings in young ...adults might not replicate during later stages of adulthood. The present functional magnetic resonance imaging (fMRI) study assessed the performance, brain activity and functional connectivity patterns associated with motor sequence learning in late middle adulthood. For this purpose, a total of 25 subjects were evaluated during early stages of learning i.e., fast learning (FL). A subset of these subjects (
= 11) was evaluated after extensive practice of a motor sequence i.e., slow learning (SL) phase. As expected, late middle adults improved motor performance from FL to SL. Learning-related brain activity patterns replicated most of the findings reported previously in young subjects except for the lack of hippocampal activity during FL and the involvement of cerebellum during SL. Regarding functional connectivity, precuneus and sensorimotor lobule VI of the cerebellum showed a central role during improvement of novel motor performance. In the sample of subjects evaluated, connectivity between the posterior putamen and parietal and frontal regions was significantly decreased with aging during SL. This age-related connectivity pattern may reflect losses in network efficiency when approaching late adulthood. Altogether, these results may have important applications, for instance, in motor rehabilitation programs.
•Spent coffee grounds are natural source of antioxidant dietary fibre.•Coffee antioxidant dietary fibre is a food ingredient for use at high temperature.•A food grade ingredient has been obtained ...from spent coffee grounds.•Safety of spent coffee grounds can be easily controlled.•Spent coffee grounds can be used in bakery products and other foodstuffs.
The present research aimed to evaluate the use of spent coffee grounds (SCG) from instant coffee as a food ingredient and its application in bakery products. Data on physicochemical characterization, thermal stability and food safety of SCG were acquired. Evaluation of feasibility as dietary fibre was also determined. Results showed SCG are natural source of antioxidant insoluble fibre, essential amino acids, low glycaemic sugars, resistant to thermal food processing and digestion process, and totally safe. In the present work, SCG were incorporated in biscuit formulations for the first time. Low-calorie sweeteners and oligofructose were also included in the food formulations. Nutritional quality, chemical (acrylamide, hydroxymethylfurfural and advanced glycation end products) and microbiological safety and sensory tests of the biscuits were carried out. Innovative biscuits were obtained according to consumers’ preferences with high nutritional and sensorial quality and potential to reduce the risk of chronic diseases such as obesity and diabetes.
To examine the cross-sectional and longitudinal (2-year follow-up) associations between dietary diversity (DD) and depressive symptoms.
An energy-adjusted dietary diversity score (DDS) was assessed ...using a validated FFQ and was categorised into quartiles (Q). The variety in each food group was classified into four categories of diversity (C). Depressive symptoms were assessed with Beck Depression Inventory-II (Beck II) questionnaire and depression cases defined as physician-diagnosed or Beck II >= 18. Linear and logistic regression models were used.
Spanish older adults with metabolic syndrome (MetS).
A total of 6625 adults aged 55-75 years from the PREDIMED-Plus study with overweight or obesity and MetS.
Total DDS was inversely and statistically significantly associated with depression in the cross-sectional analysis conducted; OR Q4
. Q1 = 0·76 (95 % CI (0·64, 0·90)). This was driven by high diversity compared to low diversity (C3
. C1) of vegetables (OR = 0·75, 95 % CI (0·57, 0·93)), cereals (OR = 0·72 (95 % CI (0·56, 0·94)) and proteins (OR = 0·27, 95 % CI (0·11, 0·62)). In the longitudinal analysis, there was no significant association between the baseline DDS and changes in depressive symptoms after 2 years of follow-up, except for DD in vegetables C4
. C1 = (
= 0·70, 95 % CI (0·05, 1·35)).
According to our results, DD is inversely associated with depressive symptoms, but eating more diverse does not seem to reduce the risk of future depression. Additional longitudinal studies (with longer follow-up) are needed to confirm these findings.