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Measurable residual disease by mass spectrometry and next-generation flow to assess treatment response in myeloma.
No full text20.500.12530/87855Quantitative immunoprecipitation mass spectrometry (QIP-MS) allows the identification of the M-protein in patients with multiple myeloma (MM) otherwise in complete response, and could be considered suitable for measurable residual disease (MRD) evaluation in peripheral blood. In the context of the GEM2012MENOS65 and GEM2014MAIN trials, we compared the performance of QIP-MS in serum with next-generation flow (NGF) cytometry in bone marrow to assess MRD in paired samples obtained postinduction, transplant, consolidation and after 24 cycles of maintenance. At each time point, both NGF and QIP-MS were able to segregate 2 groups of patients with significantly different progression-free survival; when the evolution of the results obtained with either method was considered, maintaining or converting to MRD negativity was associated with longer survival, significantly better when compared with sustaining or converting to MRD positivity. Reemergence of MRD by QIP-MS was associated with high risk of imminent clinical progression. In conclusion, MRD evaluation by NGF and MS achieves similar prognostic value based in single time point assessments and kinetics. Thus, the minimally invasive nature of MRD monitoring by MS represents a breakthrough in highly sensitive response assessment in MM. The trials were registered at www.clinicaltrials.gov as #NCT01916252 (GEM2012MENOS65) and at EudraCT as #2012-005683-10; and as #NCT02406144 (GEM2014MAIN) and at EudraCT as 2014-00055410
Financial toxicity in allogeneic haematopoietic stem cell transplant patients from a social determinants of health perspective.
No full text20.500.12530/87858Financial toxicity (FT) refers to the subjective perception of financial distress resulting from objective economic strain due to illness, exerting a detrimental influence on health outcomes. This study aimed to describe FT among allogeneic haematopoietic stem cell transplant (allo-HSCT) recipients within a public health framework, employing a social determinants of health approach. A multi-centre cross-sectional study involving adult allo-HSCT patients was conducted across three public hospitals in Madrid. FT was assessed using a validated COST scale (range 0-44; lower scores indicating higher FT). Patient-administered paper/online questionnaires were utilized to collect data on sociodemographic, socioeconomic, clinical, and healthcare access variables. Descriptive, non-parametric univariate statistical analysis and multiple linear regression models were performed. Sixty-six patients, with a mean age: 52.5 years (SD: 11.5), 50% women, 28.7% displaced to Madrid for HSCT, and 71.4% lacking financial support were included. The median FT score was 20 points (IQR 12-27.25). Independent factors associated with higher FT included being females (Coef = -3.26; p = 0.079), perceived income loss after HSCT (Coef = -6.81; p 2500 € (Coef = 15.75; p Despite the limited sample size, our findings underscore the presence of financial toxicity among allo-HSCT patients, shaped by social determinants of health. Recognizing and addressing FT within the HSCT process is essential to mitigate social inequalities in health
Do patients with axial spondyloarthritis with active disease suffer from greater disease burden and work impairment? Results from the International Map of Axial Spondyloarthritis (IMAS).
No full text20.500.12530/87913To assess the prevalence of clinically active disease in axial spondyloarthritis (axSpA) and its associated factors in a large global sample of patients from the International Map of Axial Spondyloarthritis (IMAS) study. IMAS is a cross-sectional online survey (2017-2022) of 5557 axSpA patients. Patients were divided between those with active disease (BASDAI ≥4) and without active disease (BASDAI In the present study, 5295 patients who had responded to the BASDAI scale were included in the present study: 3231 were from Europe, 770 from North America, 600 from Asia, 548 from Latin America, and 146 from Africa. The mean age was 43.8±12.9 years and 55.4% were females. Patients reported a mean BASDAI of 5.4 (±2.1) with 75% having active disease (BASDAI ≥4). In South Africa, 87.0% of patients reported having active disease, compared to 68.5% in Asia. Multivariable logistic regression showed an association of active disease with higher functional limitation, greater spinal stiffness, difficulty finding a job due to axSpA and worse mental health in both genders. For males, younger age and shorter diagnostic delay, and for females, no physical activity and presence of inflammatory bowel disease were associated with active disease. Three quarters of patients with axSpA reported clinically active disease, with higher proportion of patients with active disease in South Africa and lower proportion in Asia. Our results underline the complexity of the clinical disease activity concept in axSpA and the need for a holistic approach in the patient management, care and treatment
Attributable mortality of infections caused by carbapenem-resistant Enterobacterales: results from a prospective, multinational case-control-control matched cohorts study (EURECA).
No full text20.500.12530/87908To assess the mortality attributable to infections caused by carbapenem-resistant Enterobacterales (CRE) and to investigate the effect of clinical management on differences in observed outcomes in a multinational matched cohort study. A prospective matched-cohorts study (NCT02709408) was performed in 50 European hospitals from March 2016 to November 2018. The main outcome was 30-day mortality with an active post-discharge follow-up when applied. The CRE cohort included patients with complicated urinary tract infections, complicated intra-abdominal infections, pneumonia, or bacteraemia from other sources because of CRE. Two control cohorts were selected: patients with infection caused by carbapenem-susceptible Enterobacterales (CSE) and patients without infection. Matching criteria included type of infection for the CSE group, hospital ward of CRE detection, and duration of hospital admission up to CRE detection. Multivariable and stratified Cox regression was applied. The cohorts included 235 patients with CRE infection, 235 patients with CSE infection, and 705 non-infected patients. The 30-day mortality (95% CI) was 23.8% (18.8-29.6), 10.6% (7.2-15.2), and 8.4% (6.5-10.6), respectively. The difference in 30-day mortality rates between patients with CRE infection when compared with patients with CSE infection was 13.2% (95% CI, 6.3-20.0), (HR, 2.57; 95% CI, 1.55-4.26; p CRE infections are associated with significant attributable mortality and increased adjusted hazard of mortality when compared with CSE infections or patients without infection. Underlying patient characteristics and a delay in appropriate treatment play an important role in the CRE mortality
Association of socioeconomic status with prognosis in hypertensive patients over age 65: a cohort study in the community setting.
No full text20.500.12530/87858To examine whether socioeconomic status is associated with prognosis after the diagnosis of hypertension (HTN), in a population older than 65 years, in the community setting. Retrospective cohort study. All the primary care centres of the Community of Madrid (n=392). All patients (>65 years) with a new diagnosis of HTN in 2007-08, without previous kidney or cardiovascular (K/CV) events (n=21 754).Patient records from primary care electronic health records and Spanish mortality database were analysed from January 2007 through December 2018. Sociodemographic data such as age, gender, Area Deprivation Index (MEDEA-Mortalidad en áreas pequeñas Españolas y Desigualdades Socioeconómicas y Ambientales-Index in quintiles), and characteristics, such as smoking, type 2 diabetes mellitus and hypercholesterolaemia, were collected at the time of enrolment. The occurrence of K/CV events (including mortality from these causes) and total mortality were evaluated using Cox regression. Patients had a mean age of 73.5 (SD 6.5) years, and 63.5% were women. The median follow-up was 128.7 months (IQR: 110.6-136.7 months). There were 10 648 first K/CV events, including 1508 deaths from these causes and 4273 deaths from other causes. Adjusted for age, gender, smoking, diabetes and hypercholesterolaemia, when comparing the third, fourth and last quintiles (less affluent) of the Deprivation Index with respect to the first quintile, the hazard of K/CV events increased by 14.8% (95% CI: 3.3 to 27.6%), 16.0% (95% CI: 6.4 to 26.4%) and 19.1% (95% CI: 8.9 to 30.2%), respectively. The MEDEA Index was not associated with differences in adjusted total mortality. Living in a low socioeconomic status area is associated with an increase in kidney or cardiovascular events in hypertensive patients diagnosed after age 65 years, which will result in a significant increase in disease burden even if not related to an increase in total mortality
Invasive group A<i> Streptococcus</i> infection (<i> Streptococcus</i><i> pyogenes):</i> Current situation in Spain
No full text20.500.12530/87872Group A ss-hemolytic Streptococcus (S. pyogenes), also known as GAS, is a Gram-positive bacterium. It can be easily identified in the microbiology laboratory by its ability to hemolyse blood in culture media. This bacterium is highly virulent due to its production of enzymes and toxins, and its ability to cause immunologically mediated diseases such as rheumatic fever and post-streptococcal glomerulonephritis. GAS is the primary cause of bacterial pharyngotonsillitis, although it is typically a benign and non-invasive disease. However, it also has the potential to cause severe skin and soft tissue infections, necrotising fasciitis, bacteraemia and endocarditis, pneumonia and empyema, and streptococcal toxic shock syndrome, without any age or predisposition limits. The term invasive GAS disease (iGAS) is used to refer to this group of conditions. In more developed countries, iGAS disease has declined thanks to improved hygiene and the availability of antibiotics. For example, rheumatic fever has practically disappeared in countries such as Spain. However, recent data suggests a potential increase in some iGAS diseases, although the accuracy of this data is not consistent. Because of this, the COVID and Emerging Pathogens Committee of the Illustrious Official College of Physicians of Madrid (ICOMEM) has posed several questions about invasive GAS infection, especially its current situation in Spain. The committee has enlisted the help of several experts in the field to answer these questions. The following lines contain the answers that we have collaboratively produced, aiming to assist not only the members of ICOMEM but also anyone interested in this topic
Isavuconazole Versus Voriconazole as the First-line Therapy for Solid Organ Transplant Recipients With Invasive Aspergillosis: Comparative Analysis of 2 Multicenter Cohort Studies.
No full textIsavuconazole (ISA) and voriconazole (VORI) are recommended as the first-line treatment for invasive aspergillosis (IA). Despite theoretical advantages of ISA, both triazole agents have not been compared in solid organ transplant recipients. We performed a post hoc analysis of 2 retrospective multicenter cohorts of solid organ transplant recipients with invasive fungal disease (the SOTIS [Solid Organ Transplantation and ISavuconazole] and DiasperSOT [DIagnosis of ASPERgillosis in Solid Organ Transplantation] studies). We selected adult patients with proven/probable IA that were treated for ≥48 h with ISA (n = 57) or VORI (n = 77) as first-line therapy, either in monotherapy or combination regimen. The primary outcome was the rate of clinical response at 12 wk from the initiation of therapy. Secondary outcomes comprised 12-wk all-cause and IA-attributable mortality and the rates of treatment-emergent adverse events and premature treatment discontinuation. Both groups were comparable in their demographics and major clinical and treatment-related variables. There were no differences in the rate of 12-wk clinical response between the ISA and VORI groups (59.6% versus 59.7%, respectively; odds ratio [OR], 0.99; 95% confidence interval [CI], 0.49-2.00). This result was confirmed after propensity score adjustment (OR, 0.81; 95% CI, 0.32-2.05) and matching (OR, 0.79; 95% CI, 0.31-2.04). All-cause and IA-attributable mortality were also similar. Patients in the ISA group were less likely to experience treatment-emergent adverse events (17.5% versus 37.7%; P = 0.011) and premature treatment discontinuation (8.8% versus 23.4%; P = 0.027). Front-line treatment with ISA for posttransplant IA led to similar clinical outcomes than VORI, with better tolerability and higher treatment completion
Inhibition of the AURKA/YAP1 axis is a promising therapeutic option for overcoming cetuximab resistance in colorectal cancer stem cells.
No full text20.500.12530/87857Primary resistance to anti-EGFR therapies affects 40% of metastatic colorectal cancer patients harbouring wild-type RAS/RAF. YAP1 activation is associated with this resistance, prompting an investigation into AURKA's role in mediating YAP1 phosphorylation at Ser397, as observed in breast cancer. We used transcriptomic analysis along with in vitro and in vivo models of RAS/RAF wild-type CRC to study YAP1 Ser397 phosphorylation as a potential biomarker for cetuximab resistance. We assessed cetuximab efficacy using CCK8 proliferation assays and cell cycle analysis. Additionally, we examined the effects of AURKA inhibition with alisertib and created a dominant-negative YAP1 Ser397 mutant to assess its impact on cancer stem cell features. The RAS/RAF wild-type CRC models exhibiting primary resistance to cetuximab prominently displayed elevated YAP1 phosphorylation at Ser397 primarily mediated by AURKA. AURKA-induced YAP1 phosphorylation was identified as a key trigger for cancer stem cell reprogramming. Consequently, we found that AURKA inhibition had the capacity to effectively restore cetuximab sensitivity and concurrently suppress the cancer stem cell phenotype. AURKA inhibition holds promise as a therapeutic approach to overcome cetuximab resistance in RAS/RAF wild-type colorectal cancer, offering a potential means to counter the development of cancer stem cell phenotypes associated with cetuximab resistance
Dynamics of virological and immunological markers of HIV persistence after allogeneic haematopoietic stem-cell transplantation in the IciStem cohort: a prospective observational cohort study.
No full text20.500.12530/87910Allogeneic haematopoietic stem-cell transplantation (allo-HSCT) markedly reduces HIV reservoirs, but the mechanisms by which this occurs are only partly understood. In this study, we aimed to describe the dynamics of virological and immunological markers of HIV persistence after allo-HSCT. In this prospective observational cohort study, we analysed the viral reservoir and serological dynamics in IciStem cohort participants with HIV who had undergone allo-HSCT and were receiving antiretroviral therapy, ten of whom had received cells from donors with the CCR5Δ32 mutation. Participants from Belgium, Canada, Germany, Italy, the Netherlands, Spain, Switzerland, and the UK were included in the cohort both prospectively and retrospectively between June 1, 2014 and April 30, 2019. In the first 6 months after allo-HSCT, participants had monthly assessments, with annual assessments thereafter, with the protocol tailored to accommodate for the individual health status of each participant. HIV reservoirs were measured in blood and tissues and HIV-specific antibodies were measured in plasma. We used the Wilcoxon signed-rank test to compare data collected before and after allo-HSCT in participants for whom longitudinal data were available. When the paired test was not possible, we used the Mann-Whitney U test. We developed a mathematical model to study the factors influencing HIV reservoir reduction in people with HIV after allo-HSCT. We included 30 people with HIV with haematological malignancies who received a transplant between Sept 1, 2009 and April 30, 2019 and were enrolled within the IciStem cohort and included in this analysis. HIV reservoirs in peripheral blood were reduced immediately after full donor chimerism was achieved, generally accompanied by undetectable HIV-DNA in bone marrow, ileum, lymph nodes, and cerebrospinal fluid, regardless of donor CCR5 genotype. HIV-specific antibody levels and functionality values declined more slowly than direct HIV reservoir values, decaying significantly only months after full donor chimerism. Mathematical modelling suggests that allogeneic immunity mediated by donor cells is the main viral reservoir depletion mechanism after massive reservoir reduction during conditioning chemotherapy before allo-HSCT (half-life of latently infected replication-competent cells decreased from 44 months to 1·5 months). Our work provides, for the first time, data on the effects of allo-HSCT in the context of HIV infection. Additionally, we raise the question of which marker can serve as the last reporter of the residual viraemia, postulating that the absence of T-cell immune responses might be a more reliable marker than antibody decline after allo-HSCT. amfAR (American Foundation for AIDS Research; ARCHE Program), National Institutes of Health, National Institute of Allergy and Infectious Diseases, and Dutch Aidsfonds