Efficacy and safety of bendamustine-containing bridging therapy in R/R LBCL patients receiving CD19 CAR T-cells.

Bridging therapy (BT) after leukapheresis is required in most relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients receiving chimeric antigen receptor (CAR) T cells. Bendamustine-containing regimens are a potential BT option. We aimed to assess if this agent had a negative impact on CAR-T outcomes when it was administered as BT. We included R/R LBCL patients from six centers who received systemic BT after leukapheresis from February 2019 to September 2022; patients who only received steroids or had pre-apheresis bendamustine exposure were excluded. Patients were divided into two BT groups, with and without bendamustine. Separate safety and efficacy analyses were carried out for axi-cel and tisa-cel. Of 243 patients who received BT, bendamustine (benda) was included in 62 (26%). There was a higher rate of BT progressors in the non-benda group (62% vs. 45%, p = 0.02). Concerning CAR-T efficacy, complete responses were comparable for benda versus non-benda BT cohorts with axi-cel (70% vs. 53%, p = 0.12) and tisa-cel (44% vs. 36%, p = 0.70). Also, 12-month progression-free and overall survival were not significantly different between BT groups with axi-cel (56% vs. 43% and 71% vs. 63%) and tisa-cel (25% vs. 26% and 52% vs. 48%); there were no differences when BT response was considered. CAR T-cell expansion for each construct was similar between BT groups. Regarding safety, CRS G ≥3 (6% vs. 6%, p = 0.79), ICANS G ≥3 (15% vs. 17%, p = 0.68), severe infections, and neutropenia post-infusion were comparable among BT regimens. BT with bendamustine-containing regimens is safe for patients requiring disease control during CAR T-cell manufacturing.

The chronology of the human colonization of the Canary Islands.

The human colonization of the Canary Islands represents the sole known expansion of Berber communities into the Atlantic Ocean and is an example of marine dispersal carried out by an African population. While this island colonization shows similarities to the populating of other islands across the world, several questions still need to be answered before this case can be included in wider debates regarding patterns of initial colonization and human settlement, human-environment interactions, and the emergence of island identities. Specifically, the chronology of the first human settlement of the Canary Islands remains disputed due to differing estimates of the timing of its first colonization. This absence of a consensus has resulted in divergent hypotheses regarding the motivations that led early settlers to migrate to the islands, e.g., ecological or demographic. Distinct motivations would imply differences in the strategies and dynamics of colonization; thus, identifying them is crucial to understanding how these populations developed in such environments. In response, the current study assembles a comprehensive dataset of the most reliable radiocarbon dates, which were used for building Bayesian models of colonization. The findings suggest that i) the Romans most likely discovered the islands around the 1st century BCE; ii) Berber groups from western North Africa first set foot on one of the islands closest to the African mainland sometime between the 1st and 3rd centuries CE; iii) Roman and Berber societies did not live simultaneously in the Canary Islands; and iv) the Berber people rapidly spread throughout the archipelago.

El Hierro Genome Study: A Genomic and Health Study in an Isolated Canary Island Population.

El Hierro is the smallest and westernmost island of the Canary Islands, whose population derives from an admixture of different ancestral components and that has been subjected to genetic isolation. We established the "El Hierro Genome Study" to characterize the health status and the genetic composition of ~10% of the current population of the island, accounting for a total of 1054 participants. Detailed demographic and clinical data and a blood sample for DNA extraction were obtained from each participant. Genomic genotyping was performed with the Global Screening Array (Illumina). The genetic composition of El Hierro was analyzed in a subset of 416 unrelated individuals by characterizing the mitochondrial DNA (mtDNA) and Y-chromosome haplogroups and performing principal component analyses (PCAs). In order to explore signatures of isolation, runs of homozygosity (ROHs) were also estimated. Among the participants, high blood pressure, hypercholesterolemia, and diabetes were the most prevalent conditions. The most common mtDNA haplogroups observed were of North African indigenous origin, while the Y-chromosome ones were mainly European. The PCA showed that the El Hierro population clusters near 1000 Genomes' European population but with a shift toward African populations. Moreover, the ROH analysis revealed some individuals with an important portion of their genomes with ROHs exceeding 400 Mb. Overall, these results confirmed that the "El Hierro Genome" cohort offers an opportunity to study the genetic basis of several diseases in an unexplored isolated population.

Robust Isolated Attosecond Pulse Generation with Self-Compressed Subcycle Drivers from Hollow Capillary Fibers.

High-order harmonic generation (HHG) arising from the nonperturbative interaction of intense light fields with matter constitutes a well-established tabletop source of coherent extreme-ultraviolet and soft X-ray radiation, which is typically emitted as attosecond pulse trains. However, ultrafast applications increasingly demand isolated attosecond pulses (IAPs), which offer great promise for advancing precision control of electron dynamics. Yet, the direct generation of IAPs typically requires the synthesis of near-single-cycle intense driving fields, which is technologically challenging. In this work, we theoretically demonstrate a novel scheme for the straightforward and compact generation of IAPs from multicycle infrared drivers using hollow capillary fibers (HCFs). Starting from a standard, intense multicycle infrared pulse, a light transient is generated by extreme soliton self-compression in a HCF with decreasing pressure and is subsequently used to drive HHG in a gas target. Owing to the subcycle confinement of the HHG process, high-contrast IAPs are continuously emitted almost independently of the carrier-envelope phase (CEP) of the optimally self-compressed drivers. This results in a CEP-robust scheme which is also stable under macroscopic propagation of the high harmonics in a gas target. Our results open the way to a new generation of integrated all-fiber IAP sources, overcoming the efficiency limitations of usual gating techniques for multicycle drivers.

Corrigendum: Impact of disease burden and late loss of B cell aplasia on the risk of relapse after CD19 chimeric antigen receptor T Cell (Tisagenlecleucel) infusion in pediatric and young adult patients with relapse/refractory acute lymphoblastic leukemia: role of B-cell monitoring.

[This corrects the article DOI: 10.3389/fimmu.2023.1280580.].

Is there a common pattern of dental specialties in the world? Orthodontics, the constant element.

BACKGROUND: There is a lack of studies comparing the status of dental specialties worldwide. Therefore, this study aimed to analyze the differences and similarities between the number and types of dental specialties in 31 countries, including every continent, in the world. MATERIALS AND METHODS: Available official documents and webpages from regulatory bodies, official colleges and councils, and dental institutions were collected from 31 countries and analyzed to obtain reliable data on dental specialties. Differences were analyzed using the Lorentz curve and Gini test. Additionally, a cluster analysis was performed to obtain groups of countries with similar patterns in the number and types of dental specialties. RESULTS: A total of 32 different specialties were officially recognized among all the analyzed countries. Orthodontics and oral surgery (100% and 93.1%, respectively) were the two most frequently officially recognized dental specialties worldwide. The total global degree of inequality in the 31 analyzed countries was 42.4%. The Anglo-Saxon countries showed the greatest similarity, approximately 15-fold higher than the European countries. Cluster analysis differentiated six main groups of countries according to the number and types of dental specialties. European countries formed one of the two largest clusters, and the other cluster was of Anglo-Saxon, Asian, African, and several Eastern European countries with a high number of specialties. CONCLUSIONS: Officially recognized dental specialties in the different continents and countries show an asymmetric organization. The number, names, and skills of officially recognized dental specialties exhibited significant differences, showing inequalities in their organization. The Anglo-Saxon pattern of dental specialties showed greater equality than the European pattern. Orthodontics was the only constant element among the different patterns.

Trabectedin and low-dose radiation therapy in patients with advanced leiomyosarcoma.

Background and objectives: Dimensional response is an unmet need in second lines of advanced soft tissue sarcomas (STS). Indeed, the three approved drugs, pazopanib, trabectedin, and eribulin, achieved an overall response rate (ORR) of less than 10%. This fact potentially hinders the options for fast symptomatic relief or surgical rescue. The combination of trabectedin plus low-dose radiation therapy (T-XRT) demonstrated a response rate of 60% in phase I/II trial, while real-life data achieved 32.5% ORR, probably due to a more relaxed timing between treatments. These results were obtained in progressing and advanced STS. In this study, the merged databases (trial plus real life) have been analyzed, with a special focus on leiomyosarcoma patients. Design and methods: As responses were seen in a wide range of sarcoma histologies (11), this study planned to analyze whether leiomyosarcoma, the largest subtype with 26 cases (30.6%) in this series, exhibited a better clinical outcome with this therapeutic strategy. In addition, four advanced and progressing leiomyosarcoma patients, all with extraordinarily long progression-free survival of over 18 months, were collected. Results: A total of 847 cycles of trabectedin were administered to 85 patients, with the median number of cycles per patient being 7 (1-45+). A trend toward a longer progression-free survival (PFS) was observed in leiomyosarcoma patients with median PFS (mPFS) of 9.9 months [95% confidence interval (CI): 1.1-18.7] versus 5.6 months (95% CI: 3.2-7.9) for the remaining histologies, p = 0.25. When leiomyosarcoma and liposarcoma were grouped, this difference reached statistical significance, probably due to the special sensitivity of myxoid liposarcoma. The mPFS for L-sarcomas was 12.7 months (95% CI: 7-18.5) versus 4.3 months (95% CI: 3.3-5.3) for the remaining histologies, p = 0.001. Cases with long-lasting disease control are detected among leiomyosarcoma patients. Conclusion: Even when extraordinarily long-lasting responses do exist among leiomyosarcoma patients treated with T-XR, we were unable to demonstrate a significant difference favoring leiomyosarcoma patients in clinical outcomes.

Differences in the Ratios of General and Dental Specialists in Europe.

BACKGROUND: The European Economic Area (EEA) is composed of member states with a multitude of different regions. This study aimed to analyse the ratios of general dentists and dental specialists to the total population and the proportion of dental specialists to general dentists in 24 European countries and to explore specific intranational differences within 2 countries: France and Germany. METHODS: Available official documents and webpages from the United Kingdom and 23 of the 30 countries comprising the EEA were analysed. Data were expressed as absolute values, ratios of general dentists and dental specialists in the total of population, and percentages of dental specialists/dentists. The Mann-Whitney U test was used to clarify the main ratios that distinguish France from Germany, and cluster analysis was employed to determine similar areas. RESULTS: Significant differences were found between countries, with Ireland and Austria having the lowest ratio of dentists and Romania and Greece having the highest. The Czech Republic, the Netherlands, France, and Denmark had the lowest ratios of dental specialists to the total population. Lithuania, Sweden, and Germany had the highest number of dental specialists. Orthodontists were the most numerous specialists (5.0% of dentists), followed by oral surgeons (2.7%). In France, differences between departments were pronounced and associated with the presence of dental schools and per capita income. In Germany, only the correlation between per capita income and the density of oral surgeons was significant. CONCLUSIONS: Diverse ratios of general dentists and dental specialists to the total population and the proportion of dental specialists to general dentists were discovered within the examined countries, and their maximum values were 2.5, 5.7, and 4.1 times the minimum values, respectively. Differences were even found within the same country, as was the case in France and, to a lesser extent, in Germany.

Amelioration of Tau and ApoE4-linked glial lipid accumulation and neurodegeneration with an LXR agonist.

Apolipoprotein E (APOE) is a strong genetic risk factor for late-onset Alzheimer's disease (LOAD). APOE4 increases and APOE2 decreases risk relative to APOE3. In the P301S mouse model of tauopathy, ApoE4 increases tau pathology and neurodegeneration when compared with ApoE3 or the absence of ApoE. However, the role of ApoE isoforms and lipid metabolism in contributing to tau-mediated degeneration is unknown. We demonstrate that in P301S tau mice, ApoE4 strongly promotes glial lipid accumulation and perturbations in cholesterol metabolism and lysosomal function. Increasing lipid efflux in glia via an LXR agonist or Abca1 overexpression strongly attenuates tau pathology and neurodegeneration in P301S/ApoE4 mice. We also demonstrate reductions in reactive astrocytes and microglia, as well as changes in cholesterol biosynthesis and metabolism in glia of tauopathy mice in response to LXR activation. These data suggest that promoting efflux of glial lipids may serve as a therapeutic approach to ameliorate tau and ApoE4-linked neurodegeneration.

Recent Bendamustine Treatment Before Apheresis Has a Negative Impact on Outcomes in Patients With Large B-Cell Lymphoma Receiving Chimeric Antigen Receptor T-Cell Therapy.

PURPOSE: Approximately 30%-40% of patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) infused with CD19-targeted chimeric antigen receptor (CAR) T cells achieve durable responses. Consensus guidelines suggest avoiding bendamustine before apheresis, but specific data in this setting are lacking. We report distinct outcomes after CAR T-cell therapy according to previous bendamustine exposure. METHODS: The study included CAR T-cell recipients from seven European sites. Safety, efficacy, and CAR T-cell expansion kinetics were analyzed according to preapheresis bendamustine exposure. Additional studies on the impact of the washout period and bendamustine dose were performed. Inverse probability treatment weighting (IPTW) and propensity score matching (PSM) analyses were carried out for all efficacy comparisons between bendamustine-exposed and bendamustine-naïve patients. RESULTS: The study included 439 patients with R/R LBCL infused with CD19-targeted commercial CAR T cells, of whom 80 had received bendamustine before apheresis. Exposed patients had significantly lower CD3+ cells and platelets at apheresis. These patients had a lower overall response rate (ORR, 53% v 72%; P < .01), a shorter progression-free survival (PFS, 3.1 v 6.2 months; P = .04), and overall survival (OS, 10.3 v 23.5 months; P = .01) in comparison with the bendamustine-naïve group. Following adjustment methods for baseline variables, these differences were mitigated. Focusing on the impact of bendamustine washout before apheresis, those with recent (<9 months) exposure (N = 42) displayed a lower ORR (40% v 72%; P < .01), shorter PFS (1.3 v 6.2 months; P < .01), and OS (4.6 v 23.5 months; P < .01) in comparison with bendamustine-naïve patients. These differences remained significant after IPTW and PSM analysis. Conversely, the cumulative dose of bendamustine before apheresis did not affect CAR-T efficacy outcomes. CONCLUSION: Recent bendamustine exposure before apheresis was associated with negative treatment outcomes after CD19-targeted CAR T-cell therapy and should be therefore avoided in CAR T-cell candidates.

Causes of mortality among adults with Down syndrome before and after the COVID-19 pandemic in Spain.

BACKGROUND: The life expectancy of people with Down syndrome (DS) is limited by Alzheimer's disease (AD)-related deaths, mainly due to respiratory infections. The emergence of the COVID-19 pandemic could have changed known, past trends in mortality in this population. We analysed the differences in causes of mortality between individuals with DS deceased before and after the onset of the pandemic. METHOD: This is a cross-sectional study of adults with DS recruited at a tertiary, university outpatient clinic in Madrid, Spain. Demographic and clinical data were retrospectively collected from their medical records, including information on their deaths, if any. RESULTS: Five hundred seventy-two adults were included in the study, and 67 (11.7%) died. The main cause of death was respiratory infections, which occurred in 36 participants [9 (45.0%) before, and 27 (58.7%) after the appearance of COVID-19]. No significant differences were found in the determinants of pre-pandemic and post-pandemic death after adjusting for age and AD, except for an association between the use of psychotropic medication and death in the post-pandemic period (odds ratio: 2.24; 95% confidence interval: 1.04-4.82). Vaccination against COVID-19 showed a marked protective effect against mortality (odds ratio: 0.0002; 95% confidence interval: 6.7e10-6 to 0.004). CONCLUSIONS: The appearance of COVID-19 has not impacted the overall trend of increase in mean age of death of adults with DS in our milieu, probably thanks to the very important protective effect of vaccination, which supports prioritising people with DS in future immunisation campaigns. The association between psychotropic medication use and mortality requires further exploration.

Clinical characteristics associated with elevated levels of lipoprotein(a) in patients with vascular risk.

Objectives: Lipoprotein(a) (Lp(a)) is increasingly used in the evaluation of patients with vascular risk due to its association with cardiovascular events. The purpose of this study was to identify the clinical characteristics of patients with elevated levels of Lp(a) attended in an outpatient vascular risk unit. Methods: An observational, retrospective study was conducted to assess the clinical characteristics of patients with elevated levels of Lp(a) (≥50 mg/dL), as compared to patients with normal values (<50 mg/dL). The sample was composed of 878 patients identified as having a high vascular risk due to a diagnosis of vascular disease, attended in a vascular risk unit between 2021 and 2022. Results: The highest levels of Lp(a) were independently associated with a higher probability of having a history of peripheral arterial disease (p=0.024), polygenic familial hypercholesterolemia (PH, p=0.030) and combined familial hypercholesterolemia (CFH, p=0.015); and using PCSK9 inhibitor treatment (p=0.029) and combination therapy with statins and ezetimibe (p=0.018). In contrast, there were no significant differences in relation to familial history of early cardiovascular disease (p=0.143) or personal history of cardiovascular disease (p=0.063), which contrasts with other series. Conclusions: Elevated levels of Lp(a) were associated with a history of peripheral arterial disease, diagnosis of FHP and CFH, and need for more intense lipid-lowering treatments.

Efectos de un programa de intervención escolar para promover el desplazamiento activo en bicicleta de los adolescentes / Effects of a School-Based Intervention Program to Promote Adolescents' Active Commuting by Cycling / Efeitos de um programa de intervenção escolar para promover o ciclismo ativo entre adolescentes

Resumen: Objetivo: El objetivo del presente estudio fue evaluar los efectos de un programa escolar sobre la satisfacción de la competencia y la predisposición a participar en una Unidad Didáctica (UD) de bicicleta todo terreno (BTT) en Educación Física, así como el estado de la conducta de desplazarse en bicicleta. Método: Se realizó un diseño cuasiexperimental, sin grupo control, en el que participaron 98 estudiantes españoles (M=13.95±0.67; 50% chicas) de un centro educativo. El programa de intervención, basado en estrategias de apoyo a la competencia, consistió en una UD de BTT (12 sesiones), el plan de acción tutorial (4 sesiones) y una actividad extraescolar. Resultados: Se encontró un incremento en la satisfacción de competencia (únicamente en los chicos) y la predisposición hacia la UD de BTT en los dos géneros. Asimismo, se incrementó en un 39 % en los chicos y 43 % en las chicas, los estados de "Acción" y "Mantenimiento" en la conducta de desplazarse en bicicleta. Conclusión: Este programa multicomponente, basado en estrategias de apoyo a la competencia, parece ser efectivo para promover el desplazamiento activo en bicicleta entre los adolescentes.

Abstract: Objective: This study aimed to evaluate the effects of a school-based intervention program on competence satisfaction, the predisposition to participate in a cycling Didactic Unit (DU) in Physical Education, and the behavior of commuting by bicycle. Method: The study had a quasi-experimental design without a control group, in which 98 Spanish students (M=13.95±0.67; 50% girls) from a high school participated. The intervention program based on supporting competence consisted of a cycling DU (12 sessions), a tutorial action plan (4 sessions), and an extracurricular activity. Results: An increase in competence satisfaction was found only in boys, and the predisposition towards cycling DU was found in both genders. Likewise, the states of "Action" and "Maintenance" in the behavior of commuting by bicycle increased by 39% in boys and 43% in girls. Conclusion: This multi-component program based on strategies to support competence effectively promotes active bicycle commuting among adolescents.

Resumo: Objetivo: O objetivo do presente estudo era avaliar os efeitos de um programa escolar sobre a satisfação com a competição e a predisposição para participar de uma Unidade Didática (UD) relativa ao ciclismo de montanha (MTB) em Educação Física, bem como o estado do comportamento do ciclista. Métodos: noventa e oito estudantes espanhóis (M=13,95±0,67; 50% meninas) de uma escola participaram de um projeto quase experimental, sem grupo de controle. O programa de intervenção, baseado em estratégias de apoio à competência, consistiu em um MTB UD (12 sessões), o plano de ação tutorial (4 sessões) e uma atividade extracurricular. Resultados: Encontramos um aumento na satisfação com a competência (somente em meninos) e predisposição para a MTB em ambos os sexos. Além disso, os estados de "Ação" e "Manutenção" no comportamento ciclístico aumentaram em 39% nos meninos e 43% nas meninas. Conclusão: Este programa multicomponente, baseado em estratégias de apoio à competência, parece ser eficaz na promoção do ciclismo ativo entre os adolescentes.

Are 24-hour movement recommendations associated with obesity-related indicators in the young population? A meta-analysis.

OBJECTIVE: This study aimed to determine the relationship between meeting all three 24-hour movement recommendations (i.e., physical activity, sleep duration, and screen time) and obesity-related indicators among young people. METHODS: Four databases were systematically searched (PubMed, Scopus, Web of Science, and Cochrane Library). RESULTS: Meeting the 24-hour movement recommendations was cross-sectionally associated with lower overall obesity-related indicators (r = -0.09, 95% CI: -0.11 to -0.06), but no longitudinal association was found. Regarding each obesity-related indicator separately, meeting all three recommendations was related to lower odds of overweight/obesity (odds ratio = 0.65, 95% CI: 0.56 to 0.76) and obesity alone (odds ratio = 0.28, 95% CI: 0.16 to 0.50). An inverse relationship between meeting 24-hour movement recommendations and BMI, BMI z score, waist circumference, and body fat was also found. Regarding subgroup analysis, the association between 24-hour movement recommendations and overall obesity-related indicators was similar regardless of sex, comparison used (meeting all three vs. not meeting [i.e., those who met zero to two of the movement behaviors] or meeting all three vs. none), and type of measure to assess 24-hour movement recommendations (i.e., self-reported or accelerometer-based measures). CONCLUSIONS: Meeting all 24-hour movement recommendations may be a crucial factor in maintaining a healthy weight status in the young population.

Post-Chemoradiation Metastatic, Persistent and Resistant Nodes in Locally Advanced Rectal Cancer: Metrics and Their Impact on Long-Term Outcome.

BACKGROUND: The purpose of this study was to evaluate the long-term oncological progression pattern of locally advanced rectal cancer patients with post-neoadjuvant nodal metastatic disease (ypN+) and correlate potential prognostic features associated with proven radiochemoresistant nodal biology. METHODS: Individual patient data (100 variables) from a 20-year consecutive single-institution multidisciplinary experience (1995-2015), delivering multimodal therapy to rectal cancer patient candidates for radical treatment, including a neoadjuvant component and surgical resection with or without intraoperative radiotherapy followed by optional adjuvant chemotherapy. The ypN+ disease data was registered in the context of initial staging categories post-neoadjuvant T status (ypT). RESULTS: Data on 487 patients showed histologically confirmed diagnoses of metastatic nodal disease in 108 specimens (ypN+, 22.1). There was a significant age difference (p = 0.009) between the ypN groups: age ≥ 65 was 57.6% in pN0 and 43.5% in ypN+ and patients aged < 65 constituted 42.4% of pN0 and 56.5% of ypN+. According to the clinical stage there were statistically significant differences (p = 0.001) in the categories' distribution: ypN+ patients 10.8% were stage II and 89.2% were stage III. Univariant analysis on outcome variables showed statistically significant differences in overall survival at 7 years (63.8% vs. 55.7%, p = 0.016) disease-free survival (DFS) (78% vs. 53.8%, p = 0.000) and local recurrence-free survival (LRFS) (93.6% vs. 84%, p = 0.002). CONCLUSIONS: The presence of nodal metastases (ypN+) after neoadjuvant therapy containing long-course pelvic irradiation severely impacts the long-term outcome for patients with locally advanced rectal cancer and correlates with multiple clinical and therapeutic variable metrics. Implementation of local and systemic therapies should be adapted and intensified in relation to the finding of ypN+ category in surgical specimens.

The genomic history of the indigenous people of the Canary Islands.

The indigenous population of the Canary Islands, which colonized the archipelago around the 3rd century CE, provides both a window into the past of North Africa and a unique model to explore the effects of insularity. We generate genome-wide data from 40 individuals from the seven islands, dated between the 3rd-16rd centuries CE. Along with components already present in Moroccan Neolithic populations, the Canarian natives show signatures related to Bronze Age expansions in Eurasia and trans-Saharan migrations. The lack of gene flow between islands and constant or decreasing effective population sizes suggest that populations were isolated. While some island populations maintained relatively high genetic diversity, with the only detected bottleneck coinciding with the colonization time, other islands with fewer natural resources show the effects of insularity and isolation. Finally, consistent genetic differentiation between eastern and western islands points to a more complex colonization process than previously thought.

Improvement in Quality of Life With the Use of a Technological System Among Patients With Chronic Disease Followed Up in Primary Care (TeNDER Project): Protocol for a Randomized Controlled Trial.

BACKGROUND: Among chronic diseases, cognitive, neurological, and cardiovascular impairments are becoming increasingly prevalent, generating a shift in health and social needs. Technology can create an ecosystem of care integrated with microtools based on biosensors for motion, location, voice, and expression detection that can help people with chronic diseases. A technological system capable of identifying symptoms, signs, or behavioral patterns could provide notification of the development of complications of disease. This would help the self-care of patients with chronic disease and save health care costs, promoting the autonomy and empowerment of patients and their caregivers, improving their quality of life (QoL), and providing health professionals with monitoring tools. OBJECTIVE: The main objective of this study is to evaluate the effectiveness of a technological system (the TeNDER system) to improve quality of life in patients with chronic diseases: Alzheimer disease, Parkinson disease, and cardiovascular disease. METHODS: A multicenter, randomized, parallel-group clinical trial will be conducted with a follow-up of 2 months. The scope of the study will be the primary care health centers of the Community of Madrid belonging to the Spanish public health system. The study population will be patients diagnosed with Parkinson disease, Alzheimer disease, and cardiovascular disease; their caregivers; and health professionals. The sample size will be 534 patients (380 in the intervention group). The intervention will consist of the use of the TeNDER system. The system will monitor the patients by means of biosensors, and their data will be integrated into the TeNDER app. With the information provided, the TeNDER system will generate health reports that can be consulted by patients, caregivers, and health professionals. Sociodemographic variables and technological affinity will be measured, as will views on the usability of and satisfaction with the TeNDER system. The dependent variable will be the mean difference in QoL score between the intervention and control groups at 2 months. To study the effectiveness of the TeNDER system in improving QoL in patients, an explanatory linear regression model will be constructed. All analyses will be performed with the 95% CI and robust estimators. RESULTS: Ethics approval for this project was received on September 11, 2019. The trial was registered on August 14, 2020. Recruitment commenced in April 2021, and the expected results will be available during 2023 or 2024. CONCLUSIONS: This clinical trial among patients with highly prevalent chronic illnesses and the people most involved in their care will provide a more realistic view of the situation experienced by people with long-term illness and their support networks. The TeNDER system is in continuous development based on a study of the needs of the target population and on feedback during its use from the users: patients, caregivers, and primary care health professionals. TRIAL REGISTRATION: ClinicalTrials.gov NCT05681065; https://clinicaltrials.gov/ct2/show/NCT05681065. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47331.