Generation and external validation of a histological transformation risk model for patients with follicular lymphoma.

Follicular lymphoma (FL) is the most frequent indolent lymphoma. 10-15% of patients suffer histological transformation (HT) to a more aggressive lymphoma, usually diffuse large B cell lymphoma (DLBCL). This study aimed to validate and improve a genetic risk model to predict HT at diagnosis. We collected mutational data from diagnosis biopsies of 64 FL patients. We combined them with the data from a previously published cohort (total n = 104, 62 from non-transformed, and 42 from patients who did transform to DLBCL). This combined cohort was used to develop a nomogram to estimate the risk of HT. Prognostic mutated genes and clinical variables were assessed using Cox regression analysis to generate a risk model. The model was internally validated by bootstrapping and externally validated in an independent cohort. Its performance was evaluated using a concordance index and a calibration curve. The clinicogenetic nomogram included the mutational status of three genes (HIST1HE1, KMT2D, and TNFSR14) and high-risk FLIPI and predicted HT with a concordance index of 0.746. Patients were classified as being at low or high risk of transformation. The probability HT function at 24 months was 0.90 in the low-risk group vs. 0.51 in the high-risk group and, at 60 months, 0.69 vs. 0.15, respectively. In the external validation cohort, the probability HT function in the low-risk group was 0.86 vs. 0.54 in the high-risk group at 24 months, and 0.71 vs. 0.32 at 60 months. The concordance index in the external cohort was 0.552. In conclusion, we propose a clinicogenetic risk model to predict FL HT to DLBLC, combining genetic alterations in HIST1H1E, KMT2D, and TNFRSF14 genes and clinical features (FLIPI) at diagnosis. This model could improve the management of FL patients and allow treatment strategies that would prevent or delay transformation.

Penetrance of Dilated Cardiomyopathy in Genotype-Positive Relatives.

BACKGROUND: Disease penetrance in genotype-positive (G+) relatives of families with dilated cardiomyopathy (DCM) and the characteristics associated with DCM onset in these individuals are unknown. OBJECTIVES: This study sought to determine the penetrance of new DCM diagnosis in G+ relatives and to identify factors associated with DCM development. METHODS: The authors evaluated 779 G+ patients (age 35.8 ± 17.3 years; 459 [59%] females; 367 [47%] with variants in TTN) without DCM followed at 25 Spanish centers. RESULTS: After a median follow-up of 37.1 months (Q1-Q3: 16.3-63.8 months), 85 individuals (10.9%) developed DCM (incidence rate of 2.9 per 100 person-years; 95% CI: 2.3-3.5 per 100 person-years). DCM penetrance and age at DCM onset was different according to underlying gene group (log-rank P = 0.015 and P <0.01, respectively). In a multivariable model excluding CMR parameters, independent predictors of DCM development were: older age (HR per 1-year increase: 1.02; 95% CI: 1.0-1.04), an abnormal electrocardiogram (HR: 2.13; 95% CI: 1.38-3.29); presence of variants in motor sarcomeric genes (HR: 1.92; 95% CI: 1.05-3.50); lower left ventricular ejection fraction (HR per 1% increase: 0.86; 95% CI: 0.82-0.90) and larger left ventricular end-diastolic diameter (HR per 1-mm increase: 1.10; 95% CI: 1.06-1.13). Multivariable analysis in individuals with cardiac magnetic resonance and late gadolinium enhancement assessment (n = 360, 45%) identified late gadolinium enhancement as an additional independent predictor of DCM development (HR: 2.52; 95% CI: 1.43-4.45). CONCLUSIONS: Following a first negative screening, approximately 11% of G+ relatives developed DCM during a median follow-up of 3 years. Older age, an abnormal electrocardiogram, lower left ventricular ejection fraction, increased left ventricular end-diastolic diameter, motor sarcomeric genetic variants, and late gadolinium enhancement are associated with a higher risk of developing DCM.

A Nomogram for Predicting ADHD and ASD in Child and Adolescent Mental Health Services (CAMHS).

Objectives: To enhance the early detection of Attention Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) by leveraging clinical variables collected at child and adolescent mental health services (CAMHS). Methods: This study included children diagnosed with ADHD and/or ASD (n = 857). Three logistic regression models were developed to predict the presence of ADHD, its subtypes, and ASD. The analysis began with univariate logistic regression, followed by a multicollinearity diagnostic. A backward logistic regression selection strategy was then employed to retain variables with p < 0.05. Ethical approval was obtained from the local ethics committee. The models' internal validity was evaluated based on their calibration and discriminative abilities. Results: The study produced models that are well-calibrated and validated for predicting ADHD (incorporating variables such as physical activity, history of bone fractures, and admissions to pediatric/psychiatric services) and ASD (including disability, gender, special education needs, and Axis V diagnoses, among others). Conclusions: Clinical variables can play a significant role in enhancing the early identification of ADHD and ASD.

Effectiveness of a Serious Video Game (MOON) for Attention Deficit Hyperactivity Disorder: Protocol for a Randomized Clinical Trial.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in childhood and adolescence, with a prevalence of 5% and associated difficulties and worse prognosis if undetected. Multimodal treatment is the treatment of choice. However, sometimes treatment can be insufficient or have drawbacks. OBJECTIVE: This study protocol aims to demonstrate the effectiveness of cognitive training through the serious video game The Secret Trail of Moon (MOON) in improving emotional regulation in people with ADHD. METHODS: This is a prospective, unicenter, randomized, unblinded, pre- and postintervention study. The groups will be randomized (MOON vs control) via an electronic case report form. The MOON intervention will be performed 2 times per week for 10 weeks (30 minutes per session). The first 5 weeks (10 sessions) will be conducted face-to-face at the Puerta de Hierro University Hospital, and the remaining weeks will be conducted via the internet at the participants' homes. The total sample consists of 152 patients aged between 7 and 18 years. All participants have a clinical diagnosis of ADHD under pharmacological treatment. Data collection will be used to obtain demographic and clinical data. The data will be recorded using REDCap. Measures will be made through clinical scales for parents and objective tests of cognitive functioning in patients. Additional information on academic performance will be collected. The study has a power greater than 80% to detect differences. Student t test, 2-factor analysis of variance (ANOVA), and Mann-Whitney analyses will be performed according to each variable's characteristics. RESULTS: The study was approved by the Research Ethics Committee of the Puerta de Hierro University Hospital on December 14, 2022. As of September 26, 2023, we have enrolled 62 participants, and 31 participants have completed the study. This clinical trial was funded by the Comunidad de Madrid (IND2020/BMD-17544). The approximate completion date is March 2024. CONCLUSIONS: Serious video games such as MOON can be motivational tools that complement multimodal treatment for ADHD. TRIAL REGISTRATION: ClinicalTrials.gov; NCT06006871; https://clinicaltrials.gov/study/NCT06006871. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53191.

Randomized trial to assess the efficacy and safety of xyloglucan for the treatment of acute gastroenteritis in children.

Acute gastroenteritis is one of the most common diseases in children and an important cause of morbidity and mortality worldwide. No specific treatment is available; therefore, management is exclusively symptomatic. Xyloglucan has been approved in Europe as a class IIa medical device for restoration of the physiological functions of the intestinal wall. Our objective was to assess efficacy and safety of xyloglucan for the treatment of acute gastroenteritis in children. We performed a triple-blind, randomized placebo-controlled clinical trial in four primary care centers and one continued care hospital center. The study population comprised children with acute gastroenteritis aged >3 months and <5 years. Our primary endpoint was time (in hours) of resolution of diarrhea, defined as the time to resolution of stool consistency (Bristol Stool Form Scale ≤5 or Amsterdam Stool Form Scale B or C) or time until deposition frequency resumes to normality, whichever occurred first. We also recorded intravenous rehydration, hospitalization, stools per day, Vesikari scale, vomiting, relapse, weight loss, drugs prescribed, and adverse events. Eighty children were included in the intention-to-treat population (43 xyloglucan and 37 placebo) and 74 (93%) in the per-protocol population. Time to resolution of diarrhea was similar in both groups with (median, 95% CI) 24, 17-24 h in the xyloglucan group versus 24, 19-24 h in the placebo group, p = .680. Significant differences were observed for patients with moderate-to-severe diarrhea (Vesikari scale ≥9): xyloglucan group (20 [15-24] h) versus placebo group (85 [51-120] h) (p = .04). No other significant differences were found. Xyloglucan can be considered safe and other studies should be performed to confirm the usefulness in patients with moderate-to-severe diarrhea.

Automatic Variable Selection Algorithms in Prognostic Factor Research in Neck Pain.

This study aims to compare the variable selection strategies of different machine learning (ML) and statistical algorithms in the prognosis of neck pain (NP) recovery. A total of 3001 participants with NP were included. Three dichotomous outcomes of an improvement in NP, arm pain (AP), and disability at 3 months follow-up were used. Twenty-five variables (twenty-eight parameters) were included as predictors. There were more parameters than variables, as some categorical variables had >2 levels. Eight modelling techniques were compared: stepwise regression based on unadjusted p values (stepP), on adjusted p values (stepPAdj), on Akaike information criterion (stepAIC), best subset regression (BestSubset) least absolute shrinkage and selection operator [LASSO], Minimax concave penalty (MCP), model-based boosting (mboost), and multivariate adaptive regression splines (MuARS). The algorithm that selected the fewest predictors was stepPAdj (number of predictors, p = 4 to 8). MuARS was the algorithm with the second fewest predictors selected (p = 9 to 14). The predictor selected by all algorithms with the largest coefficient magnitude was "having undergone a neuroreflexotherapy intervention" for NP (ß = from 1.987 to 2.296) and AP (ß = from 2.639 to 3.554), and "Imaging findings: spinal stenosis" (ß = from -1.331 to -1.763) for disability. Stepwise regression based on adjusted p-values resulted in the sparsest models, which enhanced clinical interpretability. MuARS appears to provide the optimal balance between model sparsity whilst retaining high predictive performance across outcomes. Different algorithms produced similar performances but resulted in a different number of variables selected. Rather than relying on any single algorithm, confidence in the variable selection may be increased by using multiple algorithms.

Patterns and outcome of unplanned care in lung cancer patients: an observational study in a medical oncology department.

Background: There is increasing interest in unplanned care utilization among lung cancer patients and its evaluation should allow the identification of areas for quality improvement. Being a major priority for transformation in oncology, we aim to measure the risk and burden of unplanned care in a medical oncology department and identify factors that determine acute care. Methods: This was an observational retrospective cohort study that included all lung cancer patients treated at Puerta de Hierro-Majadahonda University Hospital between January 1st 2016 and December 31st 2020. Data cut off: June 30th, 2021. The main objective was to assess the incidence of unplanned care, emergency department (ED) visits and unplanned hospital admissions, from the first visit to the medical oncology service and its potential conditioning variables, considering patient death as a competitive event. As secondary objectives, a description and a quality of unplanned care evaluation was carried out. Results: A total of 821 lung cancer patients, all histologies and stages, were included (median follow-up: 32.8 months). Six hundred and eighty-one patients required consultation in the ED (82.9%), and 558 required an unplanned admission (68%). Eighty-six percent of ED consultations and 80.9% of unplanned hospital admissions were related to cancer or its treatment. The 1-year cumulative incidence for ED consultation and for unplanned hospital admission was 71.3% (95% CI: 67.8-74.5%) and 56.7% (95% CI: 53-60%), respectively. In the multivariable analysis, a higher tumor stage increased the risk of consultation in the ED, while a higher stage, Eastern Cooperative Oncology Group performance status (ECOG PS) 2 compared to ECOG PS 0, male sex, opioid or steroid use at first consultation increased the risk of unplanned admission. Conclusions: Our study shows that lung cancer patients have an extremely high demand for unplanned care. It is an early need and related to cancer in the majority of consultations and admissions and therefore a key issue for the management of oncology departments. We must optimize the follow-up of patients with a higher risk of unplanned care, advanced lung cancer or symptomatic patients, incorporating remote monitoring strategies and early interventions, as developing specific urgent care pathways for a better comprehensive cancer care.

Transfusion-associated adverse events incidence and severity after the implementation of an active hemovigilance program with 24 h follow-up. A prospective cohort study.

BACKGROUND: Hemovigilance (HV) is usually based on voluntary reports (passive HV). Our aim is to ascertain credible incidence, severity, and mortality of transfusion-associated adverse events (TAAEs) using an active HV program. STUDY DESIGN AND METHODS: Prospective cohort study to estimate transfusion risk after 46,488 transfusions in 5830 patients, using an active HV program with follow-up within the first 24 h after transfusion. We compared these results to those with the previously established passive HV program during the same 30 months of the study. We explored factors associated with the occurrence of TAAEs using generalized estimating equations models. RESULTS: With the active HV program TAAEs incidence was 57.3 (95% CI, 50.5-64.2) and mortality 1.1 (95% CI, 0.13-2.01) per 10,000 transfusions. Incidence with the new surveillance model was 14.0 times higher than with the passive. Most events occurred when transfusions had already finished (60.2%); especially pulmonary events (80.4%). Three out of five deaths and 50.3% of severe TAAEs were pulmonary. In the multivariate analysis surgical patients had half TAAEs risk when compared to medical patients (OR, 0.53; 95% CI, 0.34-0.78) and women had nearly twice the risk of a pulmonary event compared to men (OR, 1.84; 95% CI, 1.03-3.32). Patient's age, blood component type, or blood component shelf-life were unrelated to TAAEs risk. DISCUSSION: Active hemovigilance programs provide additional data which may lead to better recognition and understanding of TAAEs and their frequency and severity.

Monitoring with circulating tumor cells in the perioperative setting of patients with surgically treated stages I-IIIA NSCLC.

Background: Surgery is regarded as the treatment's cornerstone for early stage and locally advanced non-small cell lung cancer (NSCLC) whenever the tumor is considered resectable. Liquid biopsy is one of the most promising research areas in oncology in the last 10 years, providing a useful non-invasive tool to detect and monitor cancer. The prognostic value of circulating tumor cells (CTCs) has been studied in different cancer types and had been related with a higher risk of relapse and worse prognosis. The aim of this study is to evaluate the prognostic value of CTC detection in patients with stage I-IIIA NSCLC treated with surgery. Methods: We conducted a prospective, single-center study of 180 consecutive patients with resected and pathological confirmed stage I to IIIA (TNM AJCC/UICC 8th edition) NSCLC. Patients' blood samples were processed and CTCs were characterized before and after the surgery. A cohort of patients had CTC determination after chemotherapy and surgery. Cut-off points were established in 1 and 5 CTCs for statistical analysis. Results: A proportion of 76.7% had at least 1 CTC before the surgery, and 30.6% had 5 or more, while 55.9% had at least 1 CTC after surgery, and 8.3% had 5 or more. We found no correlation between preoperative CTC detection for a cut-off of 5 with neither overall survival (OS) [hazard ratio (HR): 0.99, P=0.887], disease-free survival (DFS) (HR: 0.95, P=0.39) nor relapse (32.7% vs. 28.8%, P=0.596). We also did not find a correlation between postoperative CTCs detection for a cut-off of 5 with either OS (HR: 1.01, P=0.808), DFS (HR: 0.95, P=0.952) or relapse (26.7% vs. 29.5%, P=0.83). The mean change in the number of CTCs over time between preoperative and postoperative samples was 2.13, with a standard deviation of 6.78. Conclusions: Despite the large cohort of patients included in this study, CTC monitoring in the perioperative setting was not correlated with relapse, DFS or OS in our study, and therefore cannot be recommended as a reliable biomarker for minimal residual disease (MRD) after surgery.

Tunneled antibiotic-impregnated vs. bolt-connected, non-coated external ventricular drainage: a comparison of complications.

Background: External ventricular drainage (EVD) is a common emergency neurosurgical procedure, but it is not free of adverse events. The aim of this study is to compare the complication rate of two frequently used EVD types, namely, tunneled antibiotic-impregnated catheters (Bactiseal©) and bolt-connected non-coated devices (Camino©). Methods: All EVDs placed between 1 March 2015 and 31 December 2017 were registered. Procedures performed with any catheter different from Bactiseal© or Camino© EVD with incomplete follow-up and those EVDs placed due to infectious disease were excluded. Demographic and clinical variables, as well as the overall complication rate (infection, hemorrhage, obstruction, malposition of the catheter, and involuntary pull-out of the device) and the need for replacement of the EVD, were collected. Results: A total of 77 EVDs were finally considered for analysis (40 Bactiseal® and 37 Camino®). There was a statistically significant difference in diagnosis and also in the location of the procedure, as more bolt-connected EVD was placed outside the operating room (97.3 vs. 23.5%, p < 0.001) due to emergent pathologies such as vascular diseases and spontaneous hemorrhages. In the univariate analysis, a statistically significantly higher rate of catheter involuntary pull-out (29.7 vs. 7.5%, p = 0.012) and the need for EVD replacement (32.4 vs. 12.5%, p = 0.035) was found in the Camino cohort. However, those differences could not be confirmed with multivariable analysis, which showed no association between the type of catheter and any of the studied complications. Ventriculostomy duration was identified as a risk factor for infection (OR 1.09, 95% CI 1.02-1.18). Conclusion: No significant differences were observed regarding infection, hemorrhage, obstruction, malposition, involuntary catheter pull-out, and the need for EVD replacement when comparing non-impregnated bolt-connected EVDs (Camino®) with tunneled antibiotic-impregnated catheters (Bactiseal®). The duration of EVD was associated with an increased risk of infection.

The Management of Metastatic Spinal Cord Compression in Routine Clinical Practice.

(1) Background: Whether clinical management of spinal metastatic disease (SMD) matches evidence-based recommendations is largely unknown. (2) Patients and Methods: A questionnaire was distributed through Spanish Medical Societies, exploring routine practice, interpretation of the SINS and ESCC scores and agreement with items in the Tokuhashi and SINS scales, and NICE guideline recommendations. Questionnaires were completed voluntarily and anonymously, without compensation. (3) Results: Eighty specialists participated in the study. A protocol for patients with SMD existed in 33.7% of the hospitals, a specific multidisciplinary board in 33.7%, 40% of radiological reports included the ESCC score, and a prognostic scoring method was used in 73.7%. While 77.5% of the participants were familiar with SINS, only 60% used it. The different SINS and ESCC scores were interpreted correctly by 57.5-70.0% and 30.0-37.5% of the participants, respectively. Over 70% agreed with the items included in the SINS and Tokuhashi scores and with the recommendations from the NICE guideline. Differences were found across private/public sectors, hospital complexity, number of years of experience, number of patients with SMD seen annually and especially across specialties. (4) Conclusions: Most specialists know and agree with features defining the gold standard treatment for patients with SCC, but many do not apply them.

Pathological N1/N2 in Clinical Stage I Bronchogenic Carcinoma. Analysis From a Prospective Multicentre Database

Objectives: To determine the incidence of occult N1/N2 nodal metastases and associated risk factors in patients with non-small cell lung cancer no larger than 3cm and deemed cN0 by CT and PET-CT in a prospective, multicentre national database. Methods: Patients with a NSCLC no larger than 3cm, deemed cN0 by PET-CT and CT scan, who had undergone at least a lobectomy, were selected from a national multicentre database of 3533 patients who had undergone anatomic lung resection between 2016 and 2018. Clinical and pathological variables of patients with pN0 and patients with pN1/N2 were compared to identify factors associated with the presence of lymph node metastases. Chi2 and the Mann–Whitney U test were used for categorical and numerical variables, respectively. All variables with p<0.2 in the univariate analysis were included in the multivariate logistic regression analysis. Results: The study included 1205 patients from the cohort. The incidence of occult pN1/N2 disease was 10.70% (95%CI, 9.01–12.58). The multivariable analysis revealed that the degree of differentiation, size, location (central or peripheral) and SUV of the tumour in PET, surgeon experience and number of lymph nodes resected were associated with occult N1/N2 metastases. Conclusions: The incidence of occult N1/N2 in patients with bronchogenic carcinoma with cN0 tumours no larger than 3cm is no negligible. Data about the degree of differentiation, tumour size in CT scan, maximal uptake of the tumour in PET-CT, location (central or peripheral), number of lymph nodes resected and surgeon seniority is relevant in order to detect patients at risk. (AU)

Survival following vertebral compression fractures in population over 65 years old.

BACKGROUND: Lower mortality has been demonstrated when vertebral compression fractures (VCFs) are treated surgically (vertebral augmentation) vs. conservatively. AIMS: To analyze the overall survival in patients over 65 who suffer a VCF, to review the principal causes of death, and to detect which factors are associated with a greater risk of mortality. METHODS: Patients over 65 years old diagnosed with acute, non-pathologic thoracic or lumbar VCF, treated consecutively from January 2017 to December 2020, were retrospectively selected. Those patients with follow-ups under 2 years or who required arthrodesis were excluded. Overall survival was estimated by the Kaplan-Meier method. Differences in survival were tested through the log-rank test. Multivariable Cox regression was used to assess the association of covariates and time to death. RESULTS: A total of 492 cases were included. Overall mortality was 36.2%. Survival rate at 1-, 12-, 24-, 48-, and 60-month follow-up was 97.4%, 86.6%, 78.0%, 64.4%, and 59.4%, respectively. Infection was the leading cause of death. The independent factors associated with a higher mortality risk were age, male, oncologic history, non-traumatic mechanism, and comorbidity during hospitalization. No statistical difference was found when comparing the two survival curves by treatment (vertebral augmentation vs. conservative) over time. CONCLUSION: Overall mortality rate was 36.2% after a median follow-up of 50.5 months (95% CI 48.2; 54.2). Age, male sex, history of oncological disease, non-traumatic mechanism of the fracture, and any comorbidity during hospitalization were identified as variables independently associated with a higher risk of mortality following a VCF in the elderly.

Pathological N1/N2 in Clinical Stage I Bronchogenic Carcinoma. Analysis From a Prospective Multicentre Database.

OBJECTIVES: To determine the incidence of occult N1/N2 nodal metastases and associated risk factors in patients with non-small cell lung cancer no larger than 3cm and deemed cN0 by CT and PET-CT in a prospective, multicentre national database. METHODS: Patients with a NSCLC no larger than 3cm, deemed cN0 by PET-CT and CT scan, who had undergone at least a lobectomy, were selected from a national multicentre database of 3533 patients who had undergone anatomic lung resection between 2016 and 2018. Clinical and pathological variables of patients with pN0 and patients with pN1/N2 were compared to identify factors associated with the presence of lymph node metastases. Chi2 and the Mann-Whitney U test were used for categorical and numerical variables, respectively. All variables with p<0.2 in the univariate analysis were included in the multivariate logistic regression analysis. RESULTS: The study included 1205 patients from the cohort. The incidence of occult pN1/N2 disease was 10.70% (95%CI, 9.01-12.58). The multivariable analysis revealed that the degree of differentiation, size, location (central or peripheral) and SUV of the tumour in PET, surgeon experience and number of lymph nodes resected were associated with occult N1/N2 metastases. CONCLUSIONS: The incidence of occult N1/N2 in patients with bronchogenic carcinoma with cN0 tumours no larger than 3cm is no negligible. Data about the degree of differentiation, tumour size in CT scan, maximal uptake of the tumour in PET-CT, location (central or peripheral), number of lymph nodes resected and surgeon seniority is relevant in order to detect patients at risk.

Effectiveness of a Personalized, Chess-Based Training Serious Video Game in the Treatment of Adolescents and Young Adults With Attention-Deficit/Hyperactivity Disorder: Randomized Controlled Trial.

BACKGROUND: Compared with traditional approaches, gaming strategies are promising interventions for the treatment of attention-deficit/hyperactivity disorder (ADHD). We developed a serious game, The Secret Trail of Moon (TSTM), for ADHD treatment. OBJECTIVE: The main objective of this clinical trial was to demonstrate the effectiveness of an add-on, either TSTM or Therapeutic Chess (TC), in previously optimally drug-titrated, clinically stable patients with ADHD. METHODS: This study is a prospective, unicentric, randomized clinical trial in clinically stable patients with ADHD, aged 12 to 22 years. The TSTM (n=35) and TC groups (n=34) performed 12 weekly sessions of their respective treatments. The control group (CG) patients (n=35) were called by phone every week, but they received no cognitive intervention. The primary end point was the change from baseline to end point in the parent "Behavior Rating Inventory of Executive Function-2" (BRIEF-2; patients' parents) in the per-protocol population (31 serious videogame: 24 TC and 34 CG). RESULTS: Our study failed to probe clear-cut improvements in the global score of the BRIEF-2. However, the TC group showed improvements in measures of emotional control, emotional regulation, and inattention. The TSTM group showed improvements in measures of emotional regulation, inattention, and school context. CONCLUSIONS: TSTM and TC did not improve executive function symptoms, but they improved ADHD symptomatology related to emotional regulation. Further studies with bigger samples are required to confirm these preliminary findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04355065; https://clinicaltrials.gov/ct2/show/NCT04355065.

Long-term outcomes in Hodgkin lymphoma survivors. Temporary trends and comparison with general population.

The high cure rates of Hodgkin lymphoma (HL) make this oncological disease among those with the greatest number of long-term survivors. This single-institution study including 383 HL patients with up to 45 years of follow-up, analyses the morbidity and mortality of this population after treatments in comparison with the overall Spanish population, and investigates whether it has changed over time stratifying by periods of time, as a consequence of therapeutic optimization. The median age was 34.8 years (range 15-87) with median overall survival of 30 years, significantly higher in women (HR 0.58, 95% CI 0.42-0.79) (p = 0.0002). 185 late-stage diseases were noted (35% patients), cardiovascular disease (CVD) being the most frequent (23.2%). 30% of patients developed at least one second malignant neoplasm (SMN) to give a total of 174 SMNs. 20.9% of the patients died from HL and 67.0% died from non-HL causes (32.2% from SMN, 17% from CVD). The overall standardized mortality ratio (SMR) was 3.57 (95% CI: 3.0-4.2), with striking values of 7.73 (95% CI: 5.02-8.69) and of 14.75 (95% CI: 11.38-19.12) for women and patients <30 years at diagnosis, respectively. Excluding HL as the cause of death, the SMRs of those diagnosed before 2000 and from 2000 were proved to be similar (3.88 vs 2.73), maintaining in this last period an unacceptable excess of mortality due to secondary toxicity in patients cured of HL. Our study confirm that HL treatment substantially reduces the life expectancy of patients cured of HL. In recent periods, despite therapeutic optimization, deaths from toxicity continue to occur, mainly from CVD and SMN. Risk-factor monitoring should be intensified, prevention programs developed, and therapeutic optimization of LH investigated, especially in two vulnerable groups: those aged <30 years at diagnosis, and women.

Endocannabinoid levels in peripheral blood mononuclear cells of multiple sclerosis patients treated with dimethyl fumarate.

The endocannabinoid system (ECS), a signalling network with immunomodulatory properties, is a potential therapeutic target in multiple sclerosis (MS). Dimethyl fumarate (DMF) is an approved drug for MS whose mechanism of action has not been fully elucidated; the possibility exists that its therapeutic effects could imply the ECS. With the aim of studying if DMF can modulate the ECS, the endocannabinoids 2-arachidonoylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) were determined by liquid chromatography-mass spectrometry in peripheral blood mononuclear cells from 21 healthy donors (HD) and 32 MS patients at baseline and after 12 and 24 months of DMF treatment. MS patients presented lower levels of 2-AG and PEA compared to HD. 2-AG increased at 24 months, reaching HD levels. AEA and PEA remained stable at 12 and 24 months. OEA increased at 12 months and returned to initial levels at 24 months. Patients who achieved no evidence of disease activity (NEDA3) presented the same modulation over time as EDA3 patients. PEA was modulated differentially between females and males. Our results show that the ECS is dysregulated in MS patients. The increase in 2-AG and OEA during DMF treatment suggests a possible role of DMF in ECS modulation.