The
(Telomerase Reverse Transcriptase) gene promoter mutation is one of the most prevalent mutations in urothelial bladder tumors and this mutation is related to bladder tumor progression. Our ...purpose was to evaluate the presence of this mutation in a population of patients who were first diagnosed at age ≤ 40 years and to examine its relationship with tumor characteristics and progression. A molecular study was performed to detect the two most prevalent mutations in the
promoter (C228T and C250T). The study included 29 patients, with a mean follow-up of 152 months. There were no statistically significant differences in the clinical or tumor characteristics according to the presence or absence of the mutation. Although the mutation group showed poorer recurrence-free survival (RFS), there was no statistically significant difference and there was no difference in progression-free survival by group (
> 0.05). The
mutations in bladder tumor cells occurred less frequently in younger patients than in older patients, a finding that could indicate different mechanisms of carcinogenesis. The trend towards lower RFS in patients with mutated
needs to be confirmed by further studies, given the small number of patients included in these studies due to the low incidence of bladder tumors in this age group.
In this randomized phase 2 study (GEM-KyCyDex), the combination of weekly carfilzomib 70 mg/m2, cyclophosphamide and dexamethasone was compared to carfilzomib and dexamethasone (Kd) in ...relapsed/refractory multiple myeloma (RRMM) after 1-3 prior lines (PLs). 197 patients were included and randomized 1:1 to receive KCd (97 patients) or Kd (100 patients) in 28-day cycles until progressive disease or unacceptable toxicity occurred. Patient median age was 70 years, and the median number of PLs was 1 (1-3). More than 90% of patients had previously been exposed to proteasome inhibitors, ≈70% to immunomodulators, and ≈50% were refractory to their last line (mainly lenalidomide) in both groups. After a median follow-up of 37 months, median progression-free survival (PFS) was 19.1 and 16.6 months in KCd and Kd, respectively (P=0.577). Of note, in the post hoc analysis of the lenalidomiderefractory population, the addition of cyclophosphamide to Kd resulted in a significant benefit in terms of PFS: 18.4 vs. 11.3 months (Hazard ratio 1.7 1.1-2.7; P=0.043). The overall response rate and the percentage of patients who achieved complete response was around 70% and 20% in both groups. The addition of cyclophosphamide to Kd did not result in any safety signal, except for severe infections (7% vs. 2%). In conclusion, the combination of cyclophosphamide with Kd 70 mg/m2 weekly does not improve outcomes as compared with Kd alone in RRMM after 1-3 PLs, but a significant benefit in PFS was observed with the triplet in the lenalidomide-refractory population. The administration of weekly carfilzomib 70 mg/m2 was safe and convenient, and, overall, the toxicity was manageable in both arms.
Although rituximab is generally well‐tolerated, infusion‐related reactions (IRRs) are common with the initial dose when administered intravenously according to standard recommendations. To prevent ...IRRs, premedication and low‐speed infusion rates have been recommended. Consequently, intravenous (i.v.) infusion of rituximab can become a labor‐intensive process. Rapid i.v. rituximab infusion over 90 min has demonstrated a favorable safety profile for the second and subsequent infusions during the course of therapy. The aim of this study was to investigate the safety and tolerability of 90‐min rapid infusion of Sandoz rituximab biosimilar (SDZ‐RTX) for patients with CD20+ lymphoma or chronic lymphocytic leukemia (CLL). We retrospectively reviewed all patients with CD20+ lymphoma or CLL who received SDZ‐RTX infusions in 90 min from July 2019 to July 2021 at seven Spanish hospitals. The primary end point was the incidence of IRRs. We identified 124 patients and 576 rapid administrations of SDZ‐RTX, with an average of five rapid infusions per patient. Most rapid infusions of SDZ‐RTX were in combination with CHOP/CHOP‐like therapy (48.4%), followed by SDZ‐RTX alone (15.1%), in combination with bendamustine (14.5%), or with other regimens (22%). The 90‐min SDZ‐RTX infusion schedule was well‐tolerated with no grade 3/4 IRRs. The incidence of any grade IRR during the first rapid infusion was 1% (5 grade 1 IRRs and 1 grade 2 IRR). In conclusion, rapid 90‐min i.v. administration of SDZ‐RTX for the second and subsequent infusions during the course of therapy is well‐tolerated in patients with CD20+ lymphoma or CLL.
Summary
Available data have proved insufficient to develop consensus recommendations on the prevention of thrombosis and bleeding in myelofibrosis (MF). We evaluated the incidence and risk factors of ...vascular complications in 1613 patients from the Spanish Myelofibrosis Registry. Over a total of 6981 patient‐years at risk, 6.4% of the study population had at least one thrombotic event after MF diagnosis, amounting to an incidence rate of 1.65 per 100 patient‐years. Prior history of thrombosis, the JAK2 mutation, and the intermediate‐2/high‐risk International Prognostic Scoring System (IPSS) categories conferred an increased thrombotic risk after adjustment for the risk‐modifying effect of anti‐thrombotic and cytoreductive treatments. History of thrombosis and the JAK2 mutation allowed us to pinpoint a group of patients at higher risk of early thrombosis. No decreased incidence of thrombosis was observed while patients were on anti‐thrombotic or cytoreductive treatment. An increased risk of venous thrombosis was found during treatment with immunomodulatory agents. A total of 5.3% of patients had at least one episode of major bleeding, resulting in an incidence rate of 1.5 events per 100 patient‐years. Patients in the intermediate‐2/high‐risk IPSS categories treated with anti‐coagulants had an almost sevenfold increased risk of major bleeding. These findings should prove useful for guiding decision‐making in clinical practice.
From a contextual transdiagnostic approach, this study focuses on the importance of the processes of Experiential Avoidance and Activation in explaining and treating psychological problems. There ...exists widespread empirical evidence to suggest that the response pattern known as Experiential Avoidance, a general unwillingness to remain in contact with particular private experiences through the use of maladaptive avoidance strategies, acts as a functional dimension in various psychological problems. Activation, that is, maintaining contact with experiences/conditions of life and consequently with associated sources of reward, is a condition present in most therapeutic processes. Although a great deal of research has analyzed the relationship of the value of reward with the etiology and maintenance of psychological problems, Activation, as a transdiagnostic factor, has been studied less. The aim of this paper is to carry out an empirical study of the relationship between Activation, EA and emotional state and analyze the capacity of these two conditions to discriminate the intensity and symptomatology type in subjects with emotional distress.
The Hospital Anxiety and Depression Scale (HADS), Environmental Reward Observation Scale (EROS) and Behavioral Activation for Depression Scale (BADS) were completed by 240 health center users.
Of the participants, 55% showed clinically relevant emotional distress. All cases of depression showed clinical anxiety. To discriminate between subjects without (
= 109) and with emotional distress (
= 131), analyses of the ROC curves and logistic regression analysis identified the BADS-Avoidance/Rumination followed by the EROS. To discriminate between subjects with anxiety but without depression (
= 61) and with anxiety and depression (
= 70), the most efficient scales were EROS followed by BADS-Social Impairment.
It was shown that people with no emotional complaints maintained greater contact with life experiences and with environmental sources of reward than those with emotional distress. Response patterns showing Experiential Avoidance and a reduction in Activation responses were associated with clinical distress. A reduction in Activation was the condition which distinguished those people with the greatest distress and also the greatest comorbidity of symptoms of depression and anxiety. These data support the transdiagnostic nature of Activation and suggest greater attention should be paid to this concept.
This study evaluates the impact of breast cancer (BC) in health related quality of life (HRQL) and in psychological distress (PD) during the initial phases of the disease and looks for contributing ...factors. A multicentric case-control study, EpiGEICAM, was carried out. Incident BC cases and age- and residence- matched controls were included. Clinical, epidemiological, HRQL (SF-36) and PD information (GHQ-28) was collected. We used multivariable logistic regression models to estimate OR of low HRQL and of PD in cases compared to controls, and to identify factors associated with low HRQL and with PD. Among 896 BC cases and 890 control women, cases had poorer scores than both, the reference population and the control group, in all SF-36 scales. BC women with lower education, younger, active workers, never smokers, those with comorbidities, in stage IV and with surgical treatment had lower physical HRQL; factors associated with low mental HRQL were dissatisfaction with social support, being current smoker and having children. Cases had a fivefold increased odds of PD compared to controls. Managing comorbidities and trying to promote social support, especially in younger and less educated women, could improve well-being of BC patients.
Thirty to forty percent of patients with Diffuse Large B-cell Lymphoma (DLBCL) have an adverse clinical evolution. The increased understanding of DLBCL biology has shed light on the clinical ...evolution of this pathology, leading to the discovery of prognostic factors based on gene expression data, genomic rearrangements and mutational subgroups. Nevertheless, additional efforts are needed in order to enable survival predictions at the patient level. In this study we investigated new machine learning-based models of survival using transcriptomic and clinical data.
Gene expression profiling (GEP) of in 2 different publicly available retrospective DLBCL cohorts were analyzed. Cox regression and unsupervised clustering were performed in order to identify probes associated with overall survival on the largest cohort. Random forests were created to model survival using combinations of GEP data, COO classification and clinical information. Cross-validation was used to compare model results in the training set, and Harrel's concordance index (c-index) was used to assess model's predictability. Results were validated in an independent test set.
Two hundred thirty-three and sixty-four patients were included in the training and test set, respectively. Initially we derived and validated a 4-gene expression clusterization that was independently associated with lower survival in 20% of patients. This pattern included the following genes: TNFRSF9, BIRC3, BCL2L1 and G3BP2. Thereafter, we applied machine-learning models to predict survival. A set of 102 genes was highly predictive of disease outcome, outperforming available clinical information and COO classification. The final best model integrated clinical information, COO classification, 4-gene-based clusterization and the expression levels of 50 individual genes (training set c-index, 0.8404, test set c-index, 0.7942).
Our results indicate that DLBCL survival models based on the application of machine learning algorithms to gene expression and clinical data can largely outperform other important prognostic variables such as disease stage and COO. Head-to-head comparisons with other risk stratification models are needed to compare its usefulness.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Diffuse Large B-cell Lymphoma (DLBCL) is the most common type of aggressive lymphoma. Approximately 60% of fit patients achieve curation with immunochemotherapy, but the remaining patients relapse or ...have refractory disease, which predicts a short survival. Traditionally, risk stratification in DLBCL has been based on scores that combine clinical variables. Other methodologies have been developed based on the identification of novel molecular features, such as mutational profiles and gene expression signatures. Recently, we developed the LymForest-25 profile, which provides a personalized survival risk prediction based on the integration of transcriptomic and clinical features using an artificial intelligence system. In the present report, we studied the relationship between the molecular variables included in LymForest-25 in the context of the data released by the REMoDL-B trial, which evaluated the addition of bortezomib to the standard treatment (R-CHOP) in the upfront setting of DLBCL. For this, we retrained the machine learning model of survival on the group of patients treated with R-CHOP (N=469) and then made survival predictions for those patients treated with bortezomib plus R-CHOP (N=459). According to these results, the RB-CHOP scheme achieved a 30% reduction in the risk of progression or death for the 50% of DLBCL patients at higher molecular risk (p-value 0.03), potentially expanding the effectiveness of this treatment to a wider patient population as compared with other previously defined risk groups.
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