Strategy for the management of acute postoperative pain in day surgery centres in Spain. DUCMA 2.0. project.

INTRODUCTION: Adequate treatment of acute postoperative pain is one of the quality requirements in ambulatory surgery and its suboptimal management is associated with delayed discharge, unplanned admissions and late admissions after home discharge. The aim of the present study was to learn about the organizational strategy for the management of postoperative pain in ambulatory surgery units (ASU) in Spain. METHODS: A cross-sectional, multicenter study was carried out based on an electronic survey on aspects related to the management of acute postoperative pain in different ASUs in our country. RESULTS: We recruited 133 ASUs of which 85 responded to the questions on the management of postoperative pain. Of the ASUs that responded, 80% had specific protocols for pain management and 37.6% provided preoperative information on the analgesic plan. The assessment of postoperative pain is carried out in 88.2% of the ASUs in the facility and only 56.5% at home. All ASUs use multimodal analgesia protocols; however, 68.2% report the use of opioids for the treatment of moderate to severe pain. Home invasive analgesia strategies are minimally used by the surveyed ASUs. CONCLUSIONS: The DUCMA study highlights that the practice of pain treatment in day surgery remains a challenge in our country and is not always in agreement with national guidelines. The results suggest the need to establish strategies to improve clinical practice and homogenize pain management in ambulatory surgery.

Effect of teak wood lignocellulose pretreatment on the performance of cellulose-graft-(net-poly(acrylamide-co-acrylic acid)) for water absorption and dye removal.

Cellulose modified hydrogels can be produced directly from raw biopolymers in novel cellulose solvents such as NaOH/urea aqueous solution. The effect of cellulose characteristics on the synthesis of a cellulose-graft-(net-poly(acrylamide-co-acrylic acid)) and its performance as water absorbent/methylene blue dye removal material is analyzed. Three cellulose samples, one analytical grade and two obtained from teak wood sawdust with different pretreatments (one alkaline and the other, a novel one known as (gas phase) acid pretreatment) were compared. The starting raw celluloses were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray diffraction (XRD) and viscosity in cupri ethylenediamine hydroxide (CED) solution, whereas the chemically modified materials were characterized by SEM, FTIR, and TGA. The pretreatment used influences composition, crystallinity index and degree of polymerization (DP) of the cellulose obtained. The modified material produced with cellulose from alkaline pretreatment showed the highest swelling ratio in water absorption tests at room temperature (12,714 %); in contrast, the one with cellulose from acid pretreatment showed the lowest swelling ratio (7,470 %). However, this difference is not so significative in dye removal tests, where absorption capacity is 139 and 140 mg/g, respectively. The results indicate that cellulose composition, particularly structures with significant hemicellulose and lignin remaining content, has a major effect on the performance of modified materials for water absorption, and degree of polymerization has a major effect on adsorption capacity of methylene blue.

Synergistic impact of innate immunity hyper-activation and endothelial dysfunction on the magnitude of organ failure in the infection-sepsis continuum.

OBJECTIVES: Identifying host response biomarkers implicated in the emergence of organ failure during infection is key to improving the early detection of this complication. METHODS: Twenty biomarkers of innate immunity, T-cell response, endothelial dysfunction, coagulation, and immunosuppression were profiled in 180 surgical patients with infections of diverse severity (IDS) and 53 with no infection (nIDS). Those better differentiating IDS/nIDS in the area under the curve were combined to test their association with the sequential organ failure assessment score by linear regression analysis in IDS. Results were validated in another IDS cohort of 174 patients. RESULTS: C-reactive protein, procalcitonin, pentraxin-3, lipocalin-2 (LCN2), tumoral necrosis factor-α, angiopoietin-2, triggering receptor expressed on myeloid cells-1 (TREM-1) and interleukin (IL)-15 yielded an area under the curve ≥0.75 to differentiate IDS from nIDS. The combination of LCN2, IL-15, TREM-1, angiopoietin-2 (Dys-4) showed the strongest association with sequential organ failure assessment score in IDS (adjusted regression coefficient; standard error; P): Dys-4 (3.55;0.44; <0.001), LCN2 (2.24; 0.28; <0.001), angiopoietin-2 (1.92; 0.33; <0.001), IL-15 (1.78; 0.40; <0.001), TREM-1(1.74; 0.46; <0.001), tumoral necrosis factor-α (1.60; 0.31; <0.001), pentraxin-3 (1.12; 0.18; <0.001), procalcitonin (0.85; 0.12; <0.001). Dys-4 provided similar results in the validation cohort. CONCLUSIONS: There is a synergistic impact of innate immunity hyper-activation (LCN2, IL-15, TREM-1) and endothelial dysfunction (angiopoietin-2) on the magnitude of organ failure during infection.

Exploring the impact of pharmacogenetics on personalized medicine: A systematic review. / [Artículo traducido] Exploración del impacto de la farmacogenética en la medicina personalizada: una revisión sistemática.

INTRODUCTION: Pharmacogenetics evaluates how genetic variations influence drug responses. Nowadays, genetic tests have advanced, becoming more affordable, and its integration is supported by stronger clinical evidence. Guidelines such as those from CPIC (Clinical Pharmacogenetics Implementation Consortium) and resources like PharmGKB facilitate genotype-based prescribing; and organizations like the FDA promote genetic testing before initiating certain medications. Preventive pharmacogenetic panels seem promising, but further research on biomarkers and diverse populations is needed. The aim of this review is to analyze recent evidence on the genotype-drug response relationship to examine how the genetic profile of patients influences the clinical response to treatments, and analyze the areas of research that need further study to advance towards a genetic-based precision medicine. MATERIALS AND METHODS: A systematic search was conducted on PubMed to identify articles investigating the genotype-drug response relationship. The search strategy included terms such as "pharmacogenetics", "personalized treatment", "precision medicine", "dose adjustment", "individualized dosing", "clinical routine" and "clinical practice." Clinical trials, observational studies, and meta-analyses published in English or Spanish between 2013 and 2023 were included. The initial search resulted in a total of 136 articles for analysis. RESULTS: 49 articles were included for the final analysis following review by two investigators. A relationship between genetic polymorphisms and drug response or toxicity was found for drugs such as opioids, GLP-1 agonists, tacrolimus, oral anticoagulants, antineoplastics, atypical antipsychotics, efavirenz, clopidogrel, lamotrigine, anti-TNF-α agents, voriconazole, antidepressants, or statins. However, for drugs like metformin, quetiapine, irinotecan, bisoprolol, and anti-VEGF agents, no statistically significant association between genotype and response was found. CONCLUSION: The studies analyzed in this review suggest a strong correlation between genetic variability and individual drug responses, supporting the use of pharmacogenetics for treatment optimization. However, for certain drugs like metformin or quetiapine, the influence of genotype on their response remains unclear. More studies with larger sample sizes, greater ethnic diversity, and consideration of non-genetic factors are needed. The lack of standardization in analysis methods and accessibility to genetic testing are significant challenges in this field. As a conclusion, pharmacogenetics shows immense potential in personalized medicine, but further research is required.

KRAGEN: a knowledge graph-enhanced RAG framework for biomedical problem solving using large language models.

MOTIVATION: Answering and solving complex problems using a large language model (LLM) given a certain domain such as biomedicine is a challenging task that requires both factual consistency and logic, and LLMs often suffer from some major limitations, such as hallucinating false or irrelevant information, or being influenced by noisy data. These issues can compromise the trustworthiness, accuracy, and compliance of LLM-generated text and insights. RESULTS: Knowledge Retrieval Augmented Generation ENgine (KRAGEN) is a new tool that combines knowledge graphs, Retrieval Augmented Generation (RAG), and advanced prompting techniques to solve complex problems with natural language. KRAGEN converts knowledge graphs into a vector database and uses RAG to retrieve relevant facts from it. KRAGEN uses advanced prompting techniques: namely graph-of-thoughts (GoT), to dynamically break down a complex problem into smaller subproblems, and proceeds to solve each subproblem by using the relevant knowledge through the RAG framework, which limits the hallucinations, and finally, consolidates the subproblems and provides a solution. KRAGEN's graph visualization allows the user to interact with and evaluate the quality of the solution's GoT structure and logic. AVAILABILITY AND IMPLEMENTATION: KRAGEN is deployed by running its custom Docker containers. KRAGEN is available as open-source from GitHub at: https://github.com/EpistasisLab/KRAGEN.

Immune checkpoint inhibitors-associated thrombosis in patients with head and neck cancer: a study of the Spanish society of medical oncology (SEOM) thrombosis and cancer group.

PURPOSE: Both venous and arterial thrombotic events (VTE/AT) can be associated with Immune Checkpoint Inhibitors (ICI). However, there is a paucity of information apropos patients in routine clinical practice. METHODS: /Patients. This retrospective, multicenter study was promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Individuals with head and neck cancer who initiated ICI between 01/01/2015 and 31/12/2021 were recruited. Minimum follow-up was 6 months (except in cases of demise). The primary objective was to calculate the incidence of ICI-associated VTE/AT, with secondary objectives including the analysis of their impact on survival and the identification of variables predictive of VTE/AT. RESULTS: A total of 143 patients with head and neck cancer were enrolled. The incidence of VTE/AT during follow-up (median 8.6 months) was 2.8%. Survival analysis showed no significant differences (p = 0.644) between the group that developed VTE/AT (median 7.13 months, 95% CI 0-22.9) and the group that did not (median 9.86 months, 95% CI 6.3-13.4). The presence of liver metastases was predictive of VTE/AT (p < 0.05). CONCLUSIONS: Thromboembolic disease associated with immunotherapy in patients with head and neck neoplasia does not significantly impact survival. The presence of liver metastases can predict these events.

Comparison of Continuous Intracortical and Scalp Electroencephalography in Comatose Patients with Acute Brain Injury.

BACKGROUND: Depth electroencephalography (dEEG) is a recent invasive monitoring technique used in patients with acute brain injury. This study aimed to describe in detail the clinical manifestations of nonconvulsive seizures (NCSzs) with and without a surface EEG correlate, analyze their long-standing effects, and provide data that contribute to understanding the significance of certain scalp EEG patterns observed in critically ill patients. METHODS: We prospectively enrolled a cohort of 33 adults with severe acute brain injury admitted to the neurological intensive care unit. All of them underwent multimodal invasive monitoring, including dEEG. All patients were scanned on a 3T magnetic resonance imaging scanner at 6 months after hospital discharge, and mesial temporal atrophy (MTA) was calculated using a visual scale. RESULTS: In 21 (65.6%) of 32 study participants, highly epileptiform intracortical patterns were observed. A total of 11 (34.3%) patients had electrographic or electroclinical seizures in the dEEG, of whom 8 had both spontaneous and stimulus-induced (SI) seizures, and 3 patients had only spontaneous intracortical seizures. An unequivocal ictal scalp correlate was observed in only 3 (27.2%) of the 11 study participants. SI-NCSzs occurred during nursing care, medical procedures, and family visits. Subtle clinical manifestations, such as restlessness, purposeless stereotyped movements of the upper limbs, ventilation disturbances, jerks, head movements, hyperextension posturing, chewing, and oroalimentary automatisms, occurred during intracortical electroclinical seizures. MTA was detected in 18 (81.8%) of the 22 patients. There were no statistically significant differences between patients with MTA with and without seizures or status epilepticus. CONCLUSIONS: Most NCSzs in critically ill comatose patients remain undetectable on scalp EEG. SI-NCSzs frequently occur during nursing care, medical procedures, and family visits. Semiology of NCSzs included ictal minor signs and subtle symptoms, such as breathing pattern changes manifested as patient-ventilator dyssynchrony.

Mapping Plastic and Plastic Additive Cycles in Coastal Countries: A Norwegian Case Study.

The growing environmental consequences caused by plastic pollution highlight the need for a better understanding of plastic polymer cycles and their associated additives. We present a novel, comprehensive top-down method using inflow-driven dynamic probabilistic material flow analysis (DPMFA) to map the plastic cycle in coastal countries. For the first time, we covered the progressive leaching of microplastics to the environment during the use phase of products and modeled the presence of 232 plastic additives. We applied this methodology to Norway and proposed initial release pathways to different environmental compartments. 758 kt of plastics distributed among 13 different polymers was introduced to the Norwegian economy in 2020, 4.4 Mt was present in in-use stocks, and 632 kt was wasted, of which 15.2 kt (2.4%) was released to the environment with a similar share of macro- and microplastics and 4.8 kt ended up in the ocean. Our study shows tire wear rubber as a highly pollutive microplastic source, while most macroplastics originated from consumer packaging with LDPE, PP, and PET as dominant polymers. Additionally, 75 kt of plastic additives was potentially released to the environment alongside these polymers. We emphasize that upstream measures, such as consumption reduction and changes in product design, would result in the most positive impact for limiting plastic pollution.

Differential sex-related effect of left ventricular ejection fraction trajectory on the risk of mortality and heart failure readmission following hospitalization for acute heart failure: A longitudinal study.

AIMS: There is limited information on the sex-specific longitudinal changes of left ventricular ejection fraction (LVEF) after an acute heart failure (AHF) hospitalization. We aimed to investigate whether LVEF trajectories over time and their impact on mortality and AHF readmission rates differ between men and women. METHODS AND RESULTS: We conducted a retrospective sex-specific analysis of longitudinal LVEF measurements (n = 9581) in 3383 patients with an index hospitalization for AHF in a single tertiary-level hospital. Statistical techniques suited for longitudinal data analysis were used. The mean age of the sample was 73.8 ± 11.2 years, and 47.9% were women. The mean LVEF was 49.4 ± 15.3%. At a median follow-up of 2.58 years (interquartile range 0.77-5.62), we registered 2197 deaths (64.9%) and 2597 AHF readmissions in 1302 (38.5%) patients. The longitudinal analysis showed that women had consistently higher LVEF values throughout the follow-up with both trajectories characterized by an early peak-approximately at 1 year-followed by decreasing values in men but a plateau in women. Multivariate between-sex comparisons across LVEF categories revealed that women had lower rates of AHF readmissions when LVEF ≤40%. On the contrary, women displayed an excess risk of AHF readmissions when LVEF >60%. A trend in the same direction was found for cardiovascular and all-cause mortality. CONCLUSION: Sex was a significant factor in determining the follow-up trajectory of LVEF and predicting differences in outcomes after an AHF admission. The findings suggest that women have a higher risk of AHF readmissions at higher LVEF values, while men have a higher risk at lower LVEF values. For all-cause and cardiovascular mortality, the same direction of the association was inferred but they were not significant.

Joint Hypermobility Syndrome and Membrane Proteins: A Comprehensive Review.

Ehlers-Danlos syndromes (EDSs) constitute a heterogeneous group of connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Asymptomatic EDSs, joint hypermobility without associated syndromes, EDSs, and hypermobility spectrum disorders are the commonest phenotypes associated with joint hypermobility. Joint hypermobility syndrome (JHS) is a connective tissue disorder characterized by extreme flexibility of the joints, along with pain and other symptoms. JHS can be a sign of a more serious underlying genetic condition, such as EDS, which affects the cartilage, bone, fat, and blood. The exact cause of JHS could be related to genetic changes in the proteins that add flexibility and strength to the joints, ligaments, and tendons, such as collagen. Membrane proteins are a class of proteins embedded in the cell membrane and play a crucial role in cell signaling, transport, and adhesion. Dysregulated membrane proteins have been implicated in a variety of diseases, including cancer, cardiovascular disease, and neurological disorders; recent studies have suggested that membrane proteins may also play a role in the pathogenesis of JHS. This article presents an exploration of the causative factors contributing to musculoskeletal pain in individuals with hypermobility, based on research findings. It aims to provide an understanding of JHS and its association with membrane proteins, addressing the clinical manifestations, pathogenesis, diagnosis, and management of JHS.

IKZF1plus is a frequent biomarker of adverse prognosis in Mexican pediatric patients with B-acute lymphoblastic leukemia.

Background: Recurrent genetic alterations contributing to leukemogenesis have been identified in pediatric B-cell Acute Lymphoblastic Leukemia (B-ALL), and some are useful for refining classification, prognosis, and treatment selection. IKZF1plus is a complex biomarker associated with a poor prognosis. It is characterized by IKZF1 deletion coexisting with PAX5, CDKN2A/2B, or PAR1 region deletions. The mutational spectrum and clinical impact of these alterations have scarcely been explored in Mexican pediatric patients with B-ALL. Here, we report the frequency of the IKZF1plus profile and the mutational spectrum of IKZF1, PAX5, CDKN2A/2B, and ERG genes and evaluate their impact on overall survival (OS) in a group of patients with B-ALL. Methods: A total of 206 pediatric patients with de novo B-ALL were included. DNA was obtained from bone marrow samples at diagnosis before treatment initiation. A custom-designed next-generation sequencing panel was used for mutational analysis. Kaplan-Meier analysis was used for OS estimation. Results: We identified the IKZF1plus profile in 21.8% of patients, which was higher than that previously reported in other studies. A significantly older age (p=0.04), a trend toward high-risk stratification (p=0.06), and a decrease in 5-year Overall Survival (OS) (p=0.009) were observed, although heterogeneous treatment protocols in our cohort would have impacted OS. A mutation frequency higher than that reported was found for IKZF1 (35.9%) and CDKN2A/2B (35.9%) but lower for PAX5 (26.6%). IKZF1MUT group was older at diagnosis (p=0.0002), and most of them were classified as high-risk (73.8%, p=0.02), while patients with CDKN2A/2BMUT had a higher leukocyte count (p=0.01) and a tendency toward a higher percentage of blasts (98.6%, >50% blasts, p=0.05) than the non-mutated patients. A decrease in OS was found in IKZF1MUT and CDKN2A/2BMUT patients, but the significance was lost after IKZF1plus was removed. Discussion: Our findings demonstrated that Mexican patients with B-ALL have a higher prevalence of genetic markers associated with poor outcomes. Incorporating genomic methodologies into the diagnostic process, a significant unmet need in low- and mid-income countries, will allow a comprehensive identification of relevant alterations, improving disease classification, treatment selection, and the general outcome.

Implementation of a roadmap for the comprehensive diagnosis, follow-up, and research of childhood leukemias in vulnerable regions of Mexico: results from the PRONAII Strategy.

The main objective of the National Project for Research and Incidence of Childhood Leukemias is to reduce early mortality rates for these neoplasms in the vulnerable regions of Mexico. This project was conducted in the states of Oaxaca, Puebla, and Tlaxcala. A key strategy of the project is the implementation of an effective roadmap to ensure that leukemia patients are the target of maximum benefit of interdisciplinary collaboration between researchers, clinicians, surveyors, and laboratories. This strategy guarantees the comprehensive management of diagnosis and follow-up samples of pediatric patients with leukemia, centralizing, managing, and analyzing the information collected. Additionally, it allows for a precise diagnosis and monitoring of the disease through immunophenotype and measurable residual disease (MRD) studies, enhancing research and supporting informed clinical decisions for the first time in these regions through a population-based study. This initiative has significantly improved the diagnostic capacity of leukemia in girls, boys, and adolescents in the regions of Oaxaca, Puebla, and Tlaxcala, providing comprehensive, high-quality care with full coverage in the region. Likewise, it has strengthened collaboration between health institutions, researchers, and professionals in the sector, which contributes to reducing the impact of the disease on the community.

Addressing Mental Health Barriers in HIV Care Coordination Is Crucial to Providing Optimal HIV/AIDS Care.

For people with HIV (PWH) who have psychological comorbidities, effective management of mental health issues is crucial to achieving and maintaining viral suppression. Care coordination programs (CCPs) have been shown to improve outcomes across the HIV care continuum, but little research has focused on the role of care coordination in supporting the mental health of PWH. This study reports qualitative findings from the Program Refinements to Optimize Model Impact and Scalability based on Evidence (PROMISE) study, which evaluated a revised version of an HIV CCP for Ryan White Part A clients in New York City. Semistructured interviews were conducted with 30 providers and 27 clients from 6 CCP-implementing agencies to elucidate barriers and facilitators of program engagement. Transcripts were analyzed for key themes related to clients' mental health needs and providers' successes and challenges in meeting these needs. Providers and clients agreed that insufficiently managed mental health issues are a common barrier to achieving and maintaining viral suppression. Although the CCP model calls for providers to address clients' unmet mental health needs primarily through screening and referrals to psychiatric and/or psychological care, both clients and providers reported that the routine provision of emotional support is a major part of providers' role that is highly valued by clients. Some concerns raised by providers included insufficient training to address clients' mental health needs and an inability to document the provision of emotional support as a delivered service. These findings suggest the potential value of formally integrating mental health services into HIV care coordination provision. ClinicalTrials.gov protocol number: NCT03628287.

New approaches and error assessment to snow cover thickness and density using air temperature data at different heights.

Snow poles are inexpensive systems composed of a wooden mast with temperature sensors affixed at varying heights with the purpose of estimating the snow depth. They are frequently utilised in cold, remote regions where the maintenance of complex monitoring instruments becomes impractical. In this study, snow cover thickness is determined using different methods, based on the thermal behaviour of air temperature measured by a snow pole on Deception Island, Antarctica. The methods are compared to high-resolution measurements of snow depth obtained using an ultrasonic sensor at the same site. A new modified method is proposed and shown to give the best results. Errors and sensitivity to chosen thresholds of the various methods have been compared. Sensitivity tests have been also conducted to evaluate the impact of missing data from some of the sensors. Finally, the insulating effect on the thermal signal produced by the snow is used to obtain information on the snowpack density. Promising results have been found from this effort, opening new possibilities for the usage of snow poles and may lead to future studies.

Epidemiology of childhood acute leukemias in marginalized populations of the central-south region of Mexico: results from a population-based registry.

Introduction: Acute leukemias (AL) are the main types of cancer in children worldwide. In Mexico, they represent one of the main causes of death in children under 20 years of age. Most of the studies on the incidence of AL in Mexico have been developed in the urban context of Greater Mexico City and no previous studies have been conducted in the central-south of the country through a population-based study. The aim of the present work was to identify the general and specific incidence rates of pediatric AL in three states of the south-central region of Mexico considered as some of the marginalized populations of Mexico (Puebla, Tlaxcala, and Oaxaca). Methods: A population-based study was conducted. Children aged less than 20 years, resident in these states, and newly diagnosed with AL in public/private hospitals during the period 2021-2022 were identified. Crude incidence rates (cIR), standardized incidence rates (ASIRw), and incidence rates by state subregions (ASIRsr) were calculated. Rates were calculated using the direct and indirect method and reported per million children under 20 years of age. In addition, specific rates were calculated by age group, sex, leukemia subtype, and immunophenotype. Results: A total of 388 cases with AL were registered. In the three states, the ASIRw for AL was 51.5 cases per million (0-14 years); in Puebla, it was 53.2, Tlaxcala 54.7, and Oaxaca de 47.7. In the age group between 0-19 years, the ASIRw were 44.3, 46.4, 48.2, and 49.6, in Puebla, Tlaxcala, and Oaxaca, respectively. B-cell acute lymphoblastic leukemia was the most common subtype across the three states. Conclusion: The incidence of childhood AL in the central-south region of Mexico is within the range of rates reported in other populations of Latin American origin. Two incidence peaks were identified for lymphoblastic and myeloid leukemias. In addition, differences in the incidence of the disease were observed among state subregions which could be attributed to social factors linked to the ethnic origin of the inhabitants. Nonetheless, this hypothesis requires further investigation.

Factors Contributing to Negative Outcomes Associated with Medications and Drug-Related Problems in Kidney Replacement Therapy-A Hospital-Based Prospective Observational Study.

BACKGROUND: Negative outcomes associated with medications (NOM) and drug-related problems (DRP) significantly impact individuals with kidney replacement therapy (KRT) given the complexities of managing kidney disease and associated comorbidities. The present study aims to assess the frequency of NOMs/DRPs among KRT patients and identify contributing factors. METHODS: A cross-sectional study was conducted at Virgen de las Nieves University Hospital (Granada, Spain), involving 117 outpatient adults with KRT. Data were collected from February 2021 to July 2023 using electronic records, semi-structured interviews (Dáder Method), and discussions with nephrology specialists. NOMs/DRPs were identified following treatment guidelines. Binary logistic regression was used to determine associated factors (p-value < 0.05). RESULTS: Across 117 patients, 2436 NOMs and 3303 DRPs were identified, averaging 20.82 NOMs and 28.23 DRPs per patient. Prevalent NOMs included untreated conditions (58.95%), quantitative ineffectiveness (35.43%), and non-quantitative safety problems (5.13%). Dominant DRPs were undertreated conditions (37.63%), wrong dose/posology/length (33.00%), risk of adverse drug reactions (ADR) (16.14%), and non-adherence (6.87%). Patients with ADR, undertreated conditions, and anemia were associated with quantitative ineffectiveness. Risk of ADR and vitamin D deficiency/insufficiency correlated with non-quantitative safety problems. CONCLUSIONS: KRT patients exhibited a substantial prevalence of NOMs/DRPs. Further research is needed to deepen our understanding of these complexities for improved patient care.

A multinational study on artificial intelligence adoption: Clinical implementers' perspectives.

BACKGROUND: Despite substantial progress in AI research for healthcare, translating research achievements to AI systems in clinical settings is challenging and, in many cases, unsatisfactory. As a result, many AI investments have stalled at the prototype level, never reaching clinical settings. OBJECTIVE: To improve the chances of future AI implementation projects succeeding, we analyzed the experiences of clinical AI system implementers to better understand the challenges and success factors in their implementations. METHODS: Thirty-seven implementers of clinical AI from European and North and South American countries were interviewed. Semi-structured interviews were transcribed and analyzed qualitatively with the framework method, identifying the success factors and the reasons for challenges as well as documenting proposals from implementers to improve AI adoption in clinical settings. RESULTS: We gathered the implementers' requirements for facilitating AI adoption in the clinical setting. The main findings include 1) the lesser importance of AI explainability in favor of proper clinical validation studies, 2) the need to actively involve clinical practitioners, and not only clinical researchers, in the inception of AI research projects, 3) the need for better information structures and processes to manage data access and the ethical approval of AI projects, 4) the need for better support for regulatory compliance and avoidance of duplications in data management approval bodies, 5) the need to increase both clinicians' and citizens' literacy as respects the benefits and limitations of AI, and 6) the need for better funding schemes to support the implementation, embedding, and validation of AI in the clinical workflow, beyond pilots. CONCLUSION: Participants in the interviews are positive about the future of AI in clinical settings. At the same time, they proposenumerous measures to transfer research advancesinto implementations that will benefit healthcare personnel. Transferring AI research into benefits for healthcare workers and patients requires adjustments in regulations, data access procedures, education, funding schemes, and validation of AI systems.

T-FINDER: A highly sensitive, pan-HLA platform for functional T cell receptor and ligand discovery.

Effective, unbiased, high-throughput methods to functionally identify both class II and class I HLA-presented T cell epitopes and their cognate T cell receptors (TCRs) are essential for and prerequisite to diagnostic and therapeutic applications, yet remain underdeveloped. Here, we present T-FINDER [T cell Functional Identification and (Neo)-antigen Discovery of Epitopes and Receptors], a system to rapidly deconvolute CD4 and CD8 TCRs and targets physiologically processed and presented by an individual's unmanipulated, complete human leukocyte antigen (HLA) haplotype. Combining a highly sensitive TCR signaling reporter with an antigen processing system to overcome previously undescribed limitations to target expression, T-FINDER both robustly identifies unknown peptide:HLA ligands from antigen libraries and rapidly screens and functionally validates the specificity of large TCR libraries against known or predicted targets. To demonstrate its capabilities, we apply the platform to multiple TCR-based applications, including diffuse midline glioma, celiac disease, and rheumatoid arthritis, providing unique biological insights and showcasing T-FINDER's potency and versatility.

Selinexor, daratumumab, bortezomib and dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma: results of the phase II, nonrandomized, multicenter GEM-SELIBORDARA study.

The treatment landscape for multiple myeloma has significantly evolved in the last decade. Notwithstanding, a large proportion of patients continue to relapse and novel combinations continue to be needed. In this phase II study, selinexor, a first-in-class inhibitor of exportin-1 was evaluated in combination with standard daratumumab-bortezomib-dexamethasone (DVd), for the treatment of relapsed and refractory multiple myeloma (RRMM). The aim of the trial was to assess the efficacy and safety of the combination of selinexor with DVd (S-DVd). A total of 57 patients were enrolled in the two parts of the study. Part 1 enrolled a heavily pretreated population with at least three prior lines (PL) of therapy and part 2 enrolled an early relapse population with at least one PL of therapy. The primary endpoint was complete response (CR) rate in part 2 and overall response rate (ORR) in part 1. In the latter, 24 patients were treated with a median of three PL. Overall response rate (ORR) was 50% with two CR. Median progression- free survival (PFS) was 7 months. In part 2, 33 patients were enrolled, with a median of one PL. ORR was 82% and CR or better was 33%. Median PFS was 24 months. In lenalidomide-refractory patients, a median PFS of 22.1 months was observed. Thrombocytopenia was the most common hematological adverse event (69%; grade 3-4: 34%) and nausea, the most frequent non-hematological adverse event (38%; grade 3-4: 6%). Sixty-two percent of the patients required dose modifications. In summary, although the primary endpoint of the study was not met, the combination of S-DVd showed encouraging clinical efficacy with a generally manageable safety profile representing a potential option for the treatment of RRMM patients.