Hodgkin lymphoma and liquid biopsy: a story to be told.

Hodgkin lymphoma (HL) represents a neoplasm primarily affecting adolescents and young adults, necessitating the development of precise diagnostic and monitoring tools. Specifically, classical Hodgkin lymphoma (cHL), comprising 90% of cases, necessitating tailored treatments to minimize late toxicities. Although positron emission tomography/computed tomography (PET/CT) has enhanced response assessment, its limitations underscore the urgency for more reliable progression predictive tools. Genomic characterisation of rare Hodgkin Reed-Sternberg (HRS) cells is challenging but essential. Recent studies employ single-cell molecular analyses, mass cytometry, and Next-Generation Sequencing (NGS) to unveil mutational landscapes. The integration of liquid biopsies, particularly circulating tumor DNA (ctDNA), extracellular vesicles (EVs), miRNAs and cytokines, emerge as groundbreaking approaches. Recent studies demonstrate ctDNA's potential in assessing therapy responses and predicting relapses in HL. Despite cHL-specific ctDNA applications being relatively unexplored, studies emphasize its value in monitoring treatment outcomes. Overall, this review underscores the imperative role of liquid biopsies in advancing HL diagnosis and monitoring.

Influence of Quadrupolar Molecular Transitions within Plasmonic Cavities.

Optical nanocavities have revolutionized the manipulation of radiative properties of molecular and semiconductor emitters. Here, we investigate the amplified photoluminescence arising from exciting a dark transition of ß-carotene molecules embedded within plasmonic nanocavities. Integrating a molecular monolayer into nanoparticle-on-mirror nanostructures unveils enhancements surpassing 4 orders of magnitude in the initially light-forbidden excitation. Such pronounced enhancements transcend conventional dipolar mechanisms, underscoring the presence of alternative enhancement pathways. Notably, Fourier-plane scattering spectroscopy shows that the photoluminescence excitation resonance aligns with a higher-order plasmonic cavity mode, which supports strong field gradients. Combining quantum chemistry calculations with electromagnetic simulations reveals an important interplay between the Franck-Condon quadrupole and Herzberg-Teller dipole contributions in governing the absorption characteristics of this dark transition. In contrast to free space, the quadrupole moment plays a significant role in photoluminescence enhancement within nanoparticle-on-mirror cavities. These findings provide an approach to access optically inactive transitions, promising advancements in spectroscopy and sensing applications.

Juvenile Delinquency in the Context of Organized Crime in Mexico: A Systematic Review.

In 2007, Mexico implemented a strategy to combat drug trafficking through military intervention, after which a significant increase in homicides, mainly among young men, was observed and linked to structural problems as well as organized crime, especially the recruitment of youth, with adolescents being particularly vulnerable. Through a systematic review of the literature from 2013 to 2022, we have compiled the reported factors influencing the recruitment of adolescents by organized crime in Mexico and conducted a metasynthesis of the data according to the multiple levels that affect adolescents: individual, family, community, cultural, and social. This research has shown that many of the factors reported are interrelated and need to be studied holistically. In addition, many of the factors are common to other forms of juvenile delinquency, but the main difference is the presence of organized crime itself in the community and culture.

Novel Blood Biomarkers for Response Prediction and Monitoring of Stereotactic Ablative Radiotherapy and Immunotherapy in Metastatic Oligoprogressive Lung Cancer.

Up to 80% of patients under immune checkpoint inhibitors (ICI) face resistance. In this context, stereotactic ablative radiotherapy (SABR) can induce an immune or abscopal response. However, its molecular determinants remain unknown. We present early results of a translational study assessing biomarkers of response to combined ICI and SABR (I-SABR) in liquid biopsy from oligoprogressive patients in a prospective observational multicenter study. Cohort A includes metastatic patients in oligoprogression to ICI maintaining the same ICI due to clinical benefit and who receive concomitant SABR. B is a comparative group of oligometastatic patients receiving only SABR. Blood samples are extracted at baseline (T1), after the first (T2) and last (T3) fraction, two months post-SABR (T4) and at further progression (TP). Response is evaluated by iRECIST and defined by the objective response rate (ORR)-complete and partial responses. We assess peripheral blood mononuclear cells (PBMCs), circulating cell-free DNA (cfDNA) and small RNA from extracellular vesicles. Twenty-seven patients could be analyzed (cohort A: n = 19; B: n = 8). Most were males with non-small cell lung cancer and one progressing lesion. With a median follow-up of 6 months, the last ORR was 63% (26% complete and 37% partial response). A decrease in cfDNA from T2 to T3 correlated with a good response. At T2, CD8+PD1+ and CD8+PDL1+ cells were increased in non-responders and responders, respectively. At T2, 27 microRNAs were differentially expressed. These are potential biomarkers of response to I-SABR in oligoprogressive disease.

Brownian Motion Governs the Plasmonic Enhancement of Colloidal Upconverting Nanoparticles.

Upconverting nanoparticles are essential in modern photonics due to their ability to convert infrared light to visible light. Despite their significance, they exhibit limited brightness, a key drawback that can be addressed by combining them with plasmonic nanoparticles. Plasmon-enhanced upconversion has been widely demonstrated in dry environments, where upconverting nanoparticles are immobilized, but constitutes a challenge in liquid media where Brownian motion competes against immobilization. This study employs optical tweezers for the three-dimensional manipulation of an individual upconverting nanoparticle, enabling the exploration of plasmon-enhanced upconversion luminescence in water. Contrary to expectation, experiments reveal a long-range (micrometer scale) and moderate (20%) enhancement in upconversion luminescence due to the plasmonic resonances of gold nanostructures. Comparison between experiments and numerical simulations evidences the key role of Brownian motion. It is demonstrated how the three-dimensional Brownian fluctuations of the upconverting nanoparticle lead to an "average effect" that explains the magnitude and spatial extension of luminescence enhancement.

CD8+ NKs as a potential biomarker of complete response and survival with lenalidomide plus R-GDP in the R2-GDP-GOTEL trial in recurrent/refractory diffuse large B cell lymphoma.

Background: Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. DLBCL is an aggressive disease that can be cured with upfront standard chemoimmunotherapy schedules. However, in approximately 35-40% of the patients DLBCL relapses, and therefore, especially in this setting, the search for new prognostic and predictive biomarkers is an urgent need. Natural killer (NK) are effector cells characterized by playing an important role in antitumor immunity due to their cytotoxic capacity and a subset of circulating NK that express CD8 have a higher cytotoxic function. In this substudy of the R2-GDP-GOTEL trial, we have evaluated blood CD8+ NK cells as a predictor of treatment response and survival in relapsed/refractory (R/R) DLBCL patients. Methods: 78 patients received the R2-GDP schedule in the phase II trial. Blood samples were analyzed by flow cytometry. Statistical analyses were carried out in order to identify the prognostic potential of CD8+ NKs at baseline in R/R DLBCL patients. Results: Our results showed that the number of circulating CD8+ NKs in R/R DLBCL patients were lower than in healthy donors, and it did not change during and after treatment. Nevertheless, the level of blood CD8+ NKs at baseline was associated with complete responses in patients with R/R DLBCL. In addition, we also demonstrated that CD8+ NKs levels have potential prognostic value in terms of overall survival in R/R DLBCL patients. Conclusion: CD8+ NKs represent a new biomarker with prediction and prognosis potential to be considered in the clinical management of patients with R/R DLBCL. Clinical trial registration: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001620-29 EudraCT, ID:2014-001620-29.

Epigenetic targets to enhance antitumor immune response through the induction of tertiary lymphoid structures.

Tertiary lymphoid structures (TLS) are ectopic lymphoid aggregates found in sites of chronic inflammation such as tumors and autoimmune diseases. The discovery that TLS formation at tumor sites correlated with good patient prognosis has triggered extensive research into various techniques to induce their formation at the tumor microenvironment (TME). One strategy is the exogenous induction of specific cytokines and chemokine expression in murine models. However, applying such systemic chemokine expression can result in significant toxicity and damage to healthy tissues. Also, the TLS formed from exogenous chemokine induction is heterogeneous and different from the ones associated with favorable prognosis. Therefore, there is a need to optimize additional approaches like immune cell engineering with lentiviral transduction to improve the TLS formation in vivo. Similarly, the genetic and epigenetic regulation of the different phases of TLS neogenesis are still unknown. Understanding these molecular regulations could help identify novel targets to induce tissue-specific TLS in the TME. This review offers a unique insight into the molecular checkpoints of the different stages and mechanisms involved in TLS formation. This review also highlights potential epigenetic targets to induce TLS neogenesis. The review further explores epigenetic therapies (epi-therapy) and ongoing clinical trials using epi-therapy in cancers. In addition, it builds upon the current knowledge of tools to generate TLS and TLS phenotyping biomarkers with predictive and prognostic clinical potential.

Assessment of Full-Fat Tenebrio molitor as Feed Ingredient for Solea senegalensis: Effects on Growth Performance and Lipid Profile.

Tenebrio molitor (TM) is considered as one of the most promising protein sources for replacing fish meal in aquafeeds, among other things because it is rich in protein, a good source of micronutrients and has a low carbon footprint and land use. However, the main drawback of TM is its fatty acid profile, in particular its low content of n-3 PUFA. This study evaluates the effects of partially replacing plant or marine-derived with full-fat TM meal at two different levels on growth performance and lipid profiles of Senegalese sole (Solea senegalensis). For this purpose, a control diet (CTRL) and four experimental isoproteic (53%) and isolipidic (16%) diets were formulated containing 5 and 10% TM meal replacing mostly fish meal (FM5 and FM10), or 10 and 15% TM meal replacing mostly plant meal (PP10 and PP15). Fish (215 g) were fed at 1% of their body weight for 98 days. The final body weight of fish fed the experimental diets containing TM meal was not different from that of fish fed the CTRL diet (289 g). However, the inclusion of TM meal resulted in a gradual improvement in growth rate and feed efficiency in both cases (replacement of fish or plant meals), and significant differences in specific growth rate (SGR) were observed between fish fed the CTRL diet (SGR = 0.30% day-1) and those fed diets with the highest TM meal content (PP15; SGR = 0.35% day-1). The experimental groups did not show any differences in the protein content of the muscle (19.6% w/w). However, significant differences were observed in the total lipid content of the muscle, with the FM10, PP10, and PP15 groups having the lowest muscle lipid contents (2.2% ww). These fish also showed the lowest neutral lipid content in muscle (6.6% dw), but no differences were observed in the total phospholipid content (2.6% dw). Regarding the fatty acid profile, fish fed FM10, PP10 and PP15 had lower levels of linoleic acid (18:2n-6) and higher levels of oleic acid (18:1n-9) in liver and muscle compared to fish fed CTRL. However, no differences were found between fish fed CTRL and TM-based diets for docosahexaenoic acid (22:6n-3) and total n-3 PUFA in liver and muscle. In conclusion, our study demonstrated that full-fat TM inclusion up to 15% in S. senegalensis diets had no negative effects or even some positive effects on fish survival, growth performance, nutrient utilization and flesh quality.

[Design of the evaluation of the socio-educational groups for men in primary care]. / Diseño de la evaluación de los grupos socioeducativos para hombres en atención primaria.

The Public Health System of Andalusia develops the Socio-Educational Groups Strategy (GRUSE), focused on promoting the health and emotional well-being of those who present somatic symptoms without organic cause in primary care health centers. This intervention began with groups of women and has been extended to groups of men, after verifying that the unemployment caused by the economic crisis, generated discomfort due to the loss of the "productive role". A mixed methodology research has been designed to measure the effects of GRUSE in male participants. The quantitative design has longitudinal and quasi-experimental section, in which a battery of scales are used as instruments for collecting information. The qualitative design includes semi-structured interviews and focus groups. The objective of this article is to present the design of the research, with which it is expected to collect evidence of the impact of the intervention.

Indicators to evaluate quality of care in head and neck cancer in Spain.

PURPOSE: This study aimed to develop a set of criteria and indicators to evaluate the quality of care of patients with head and neck cancer (HNC). METHODS: A systematic literature review was conducted to identify valuable criteria/indicators for the assessment of the quality of care in HNC. With the aid of a technical group, a scientific committee of oncologists specialised in HNC used selected criteria to propose indicators that were evaluated with a two-round Delphi method. Indicators on which consensus was achieved were then prioritised by the scientific committee to develop a final set of indicators. RESULTS: We proposed a list of 50 indicators used in the literature or developed by us to be evaluated with a Delphi method. There was consensus on the appropriateness of 47 indicators in the first round; the remaining 3 achieved consensus in the second round. The 50 indicators were scored to prioritise them, leading to a final selection of 29 indicators related to structure (3), process (22), or outcome (4) and covering diagnosis, treatment, follow-up, and health outcomes in patients with HNC. Easy-to-use index cards were developed for each indicator, with their criterion, definition, formula for use in real-world clinical practice, rationale, and acceptable level of attainment. CONCLUSIONS: We have developed a set of 29 evidence-based and expert-supported indicators for evaluating the quality of care in HNC, covering diagnosis, treatment, follow-up, and health outcomes.

Electroluminescence as a Probe of Strong Exciton-Plasmon Coupling in Few-Layer WSe2.

The manipulation of coupled quantum excitations is of fundamental importance in realizing novel photonic and optoelectronic devices. We use electroluminescence to probe plasmon-exciton coupling in hybrid structures consisting of a nanoscale plasmonic tunnel junction and few-layer two-dimensional transition-metal dichalcogenide transferred onto the junction. The resulting hybrid states act as a novel dielectric environment that affects the radiative recombination of hot carriers in the plasmonic nanostructure. We determine the plexcitonic spectrum from the electroluminescence and find Rabi splittings exceeding 50 meV in the strong coupling regime. Our experimental findings are supported by electromagnetic simulations that enable us to explore systematically and in detail the emergence of plexciton polaritons as well as the polarization characteristics of their far-field emission. Electroluminescence modulated by plexciton coupling provides potential applications for engineering compact photonic devices with tunable optical and electrical properties.

Diseño de la evaluación de los grupos socioeducativos para hombres en atención primaria / Design of the evaluation of the socio-educational groups for men in primary care

El Sistema Sanitario Público de Andalucía desarrolla la Estrategia Grupos Socioeducativos (GRUSE), enfocada a la promoción de la salud y del bienestar emocional de quienes presentan síntomas somáticos sin causa orgánica en los centros de salud de atención primaria. Esta intervención comenzó con grupos de mujeres y se ha ampliado a grupos de hombres, tras comprobar que el desempleo provocado por la crisis económica generaba malestares por la pérdida del «rol productivo». Se ha diseñado una investigación con metodología mixta para medir los efectos de los GRUSE en los hombres participantes. El diseño cuantitativo tiene corte longitudinal y cuasiexperimental, y se usa una batería de escalas como instrumentos de recogida de la información. El diseño cualitativo contempla la realización de entrevistas semiestructuradas y grupos focales. El objetivo de este artículo es presentar el diseño de la investigación, con la que se espera recoger evidencias del impacto de la intervención. (AU)

The Public Health System of Andalusia develops the Socio-Educational Groups Strategy (GRUSE), focused on promoting the health and emotional well-being of those who present somatic symptoms without organic cause in primary care health centers. This intervention began with groups of women and has been extended to groups of men, after verifying that the unemployment caused by the economic crisis, generated discomfort due to the loss of the “productive role”. A mixed methodology research has been designed to measure the effects of GRUSE in male participants. The quantitative design has longitudinal and quasi-experimental section, in which a battery of scales are used as instruments for collecting information. The qualitative design includes semi-structured interviews and focus groups. The objective of this article is to present the design of the research, with which it is expected to collect evidence of the impact of the intervention. (AU)

Optimizing Clinical Diabetes Diagnosis through Generative Adversarial Networks: Evaluation and Validation.

The escalating prevalence of Type 2 Diabetes (T2D) represents a substantial burden on global healthcare systems, especially in regions such as Mexico. Existing diagnostic techniques, although effective, often require invasive procedures and labor-intensive efforts. The promise of artificial intelligence and data science for streamlining and enhancing T2D diagnosis is well-recognized; however, these advancements are frequently constrained by the limited availability of comprehensive patient datasets. To mitigate this challenge, the present study investigated the efficacy of Generative Adversarial Networks (GANs) for augmenting existing T2D patient data, with a focus on a Mexican cohort. The researchers utilized a dataset of 1019 Mexican nationals, divided into 499 non-diabetic controls and 520 diabetic cases. GANs were applied to create synthetic patient profiles, which were subsequently used to train a Random Forest (RF) classification model. The study's findings revealed a notable improvement in the model's diagnostic accuracy, validating the utility of GAN-based data augmentation in a clinical context. The results bear significant implications for enhancing the robustness and reliability of Machine Learning tools in T2D diagnosis and management, offering a pathway toward more timely and effective patient care.

Immediate-release niacin and a monounsaturated fatty acid-rich meal on postprandial inflammation and monocyte characteristics in men with metabolic syndrome.

BACKGROUND & AIM: When considered separately, long-term immediate-release niacin and fatty meals enriched in monounsaturated fatty acids (MUFA) decrease postprandial triglycerides, but their effects on postprandial inflammation, which is common in individuals with metabolic syndrome, are less known. Moreover, successful combination is lacking and its impact on acute disorders of the innate immune cells in the metabolic syndrome remains unclear. Here, we aimed to establish the effects from combination with niacin of different fats [butter, enriched in saturated fatty acids (SFA), olive oil, enriched in MUFA, and olive oil supplemented with eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids] on plasma inflammatory markers and circulating monocyte subsets, activation and priming at the postprandial period in individuals with metabolic syndrome. METHODS: A random-order within-subject crossover experiment was performed, in which 16 individuals with metabolic syndrome and 16 age-matched healthy volunteers took 2 g immediate-release niacin together with the corresponding fatty meal or a meal with no fat as control. In total, 128 postprandial curves were analysed. We sampled hourly over 6 h for plasma concentrations of soluble inflammatory markers and triglycerides. Circulating monocyte subsets (CD14/CD16 balance), activation (CCL2/CCR2 axis) and priming (M1/M2-like phenotype) at the time of postprandial hypertriglyceridemic peak were also addressed. RESULTS: Dietary SFA (combined with niacin) promote postprandial excursions of circulating IL-6, IL-1ß, TNF-α and CD14/CCR2-rich monocytes with a pro-inflammatory M1-like phenotype, particularly in individuals with metabolic syndrome. In contrast, dietary MUFA (combined with niacin) postprandially increased circulating CD16-rich monocytes with an anti-inflammatory M2-like phenotype. Omega-3 PUFA did not add to the effects of MUFA. CONCLUSION: The co-administration of a single-dose of immediate-release niacin with a fatty meal rich in MUFA, in contrast to SFA, suppresses postprandial inflammation at the levels of both secretory profile and monocyte response in individuals with metabolic syndrome. These findings highlight a potential role of combining niacin and dietary MUFA for the homeostatic control of inflammation and the innate immune system, identifying a new search direction for the management of disorders associated with the metabolic syndrome.

SEOM-GOTEL clinical guidelines on diffuse large B cell lymphoma (2022)

Diffuse large B-cell lymphoma is the most frequent histological subtype of NHL and the paradigm for the management of aggressive lymphoma. An excisional or incisional lymph node biopsy evaluated by an experienced hemopathologist is recommended to establish the diagnosis. Twenty years following its introduction, R-CHOP remains the standard first-line treatment. No modification of this scheme (increased chemotherapy dose intensity, new monoclonal antibodies, or the addition of immunomodulators or anti-target agents) has significatively improved the clinical outcomes, whereas therapy for recurrence or progression is evolving rapidly. The irruption of CART cells, polatuzumab vedotin, tafasitamab, and CD20/CD3 bispecific antibodies are changing the natural history of relapsed patients and will challenge R-CHOP as the benchmark for newly diagnosed patients (AU)

Fluorometric Quantification of Total Cell-Free DNA as a Prognostic Biomarker in Non-Small-Cell Lung Cancer Patients Treated with Immune Checkpoint Blockade.

The present study aimed to investigate the potential of basal cell-free fluorometric DNA (cfDNA) quantification as a prognostic biomarker in advanced non-small cell lung cancer (NSCLC) patients treated with an Immune Checkpoint Blockade (ICB). A discovery and validation cohort of 61 and 31 advanced lung cancer patients treated with ICB were included in this study. Quantification of cfDNA concentration was performed before the start of the treatment and patients were followed up for a median of 34 (30-40) months. The prognostic predicted value of cfDNA was evaluated based on ROC, and Cox regression was conducted via univariate and multivariate analyses to estimate the hazard ratio. We observed that a cfDNA cut-off of 0.55 ng/µL before the ICB determines the overall survival of patients with a log rank p-value of 3.3 × 10-4. That represents median survivals of 3.8 vs. 17.5 months. Similar results were obtained in the validation cohort being the log rank p-value 3.8 × 10-2 with median survivals of 5.9 vs. 24.3. The univariate and multivariate analysis revealed that the cut-off of 0.55 ng/µL before ICB treatment was an independent predictive factor and was significantly associated with a better survival outcome. High cfDNA concentrations identify patients with advanced NSCLC who do not benefit from the ICB. The determination of cfDNA is a simple test that could select a group of patients in whom new therapeutic strategies are needed.

Diabetes Detection Models in Mexican Patients by Combining Machine Learning Algorithms and Feature Selection Techniques for Clinical and Paraclinical Attributes: A Comparative Evaluation.

The development of medical diagnostic models to support healthcare professionals has witnessed remarkable growth in recent years. Among the prevalent health conditions affecting the global population, diabetes stands out as a significant concern. In the domain of diabetes diagnosis, machine learning algorithms have been widely explored for generating disease detection models, leveraging diverse datasets primarily derived from clinical studies. The performance of these models heavily relies on the selection of the classifier algorithm and the quality of the dataset. Therefore, optimizing the input data by selecting relevant features becomes essential for accurate classification. This research presents a comprehensive investigation into diabetes detection models by integrating two feature selection techniques: the Akaike information criterion and genetic algorithms. These techniques are combined with six prominent classifier algorithms, including support vector machine, random forest, k-nearest neighbor, gradient boosting, extra trees, and naive Bayes. By leveraging clinical and paraclinical features, the generated models are evaluated and compared to existing approaches. The results demonstrate superior performance, surpassing accuracies of 94%. Furthermore, the use of feature selection techniques allows for working with a reduced dataset. The significance of feature selection is underscored in this study, showcasing its pivotal role in enhancing the performance of diabetes detection models. By judiciously selecting relevant features, this approach contributes to the advancement of medical diagnostic capabilities and empowers healthcare professionals in making informed decisions regarding diabetes diagnosis and treatment.

Non-Hermitian Anharmonicity Induces Single-Photon Emission.

Single-photon sources are in high demand for quantum information applications. A paradigmatic way to achieve single-photon emission is through anharmonicity in the energy levels, such that the absorption of a single photon from a coherent drive shifts the system out of resonance and prevents absorption of a second one. We identify a novel mechanism for single-photon emission through non-Hermitian anharmonicity, i.e., anharmonicity in the losses instead of in the energy levels. We demonstrate the mechanism in two types of systems, including a feasible setup consisting of a hybrid metallodielectric cavity weakly coupled to a two-level emitter, and show that it induces high-purity single-photon emission at high repetition rates.

DNA Origami Assembled Nanoantennas for Manipulating Single-Molecule Spectral Emission.

The emission spectrum of a dye is given by the energy of all of the possible radiative transitions weighted by their probability. This spectrum can be altered with optical nanoantennas that are able to manipulate the decay rate of nearby emitters by modifying the local density of photonic states. Here, we make use of DNA origami to precisely place an individual dye at different positions around a gold nanorod and show how this affects the emission spectrum of the dye. In particular, we observe a strong suppression or enhancement of the transitions to different vibrational levels of the excitonic ground state, depending on the spectral overlap with the nanorod resonance. This reshaping can be used to experimentally extract the spectral dependence of the radiative decay rate enhancement. Furthermore, for some cases, we argue that the drastic alteration of the fluorescence spectrum could arise from the violation of Kasha's rule.

SEOM-GOTEL clinical guidelines on diffuse large B cell lymphoma (2022).

Diffuse large B-cell lymphoma is the most frequent histological subtype of NHL and the paradigm for the management of aggressive lymphoma. An excisional or incisional lymph node biopsy evaluated by an experienced hemopathologist is recommended to establish the diagnosis. Twenty years following its introduction, R-CHOP remains the standard first-line treatment. No modification of this scheme (increased chemotherapy dose intensity, new monoclonal antibodies, or the addition of immunomodulators or anti-target agents) has significatively improved the clinical outcomes, whereas therapy for recurrence or progression is evolving rapidly. The irruption of CART cells, polatuzumab vedotin, tafasitamab, and CD20/CD3 bispecific antibodies are changing the natural history of relapsed patients and will challenge R-CHOP as the benchmark for newly diagnosed patients.