Search Results (60)

Background/Objectives: Older adults may experience healthcare encounters in which their voices are discounted, redirected through family members, or interpreted through age-related assumptions about cognitive decline. Although such problems are often discussed through dignity, communication, ageism, person-centred care, or shared decision-making, this conceptual review argues that they also involve epistemic harms: harms that occur when older adults are not recognized as credible knowers of their own bodies, needs, values, histories, and care priorities. Methods: This article develops a conceptual and critical analysis of Fricker’s account of testimonial and hermeneutical injustice, later critiques of epistemic injustice, and the nursing and gerontological literature on dignity, person-centred nursing, documentation, dementia care, and shared decision-making. Results: The analysis distinguishes ordinary communication failure, institutional restriction of interpretive space, testimonial injustice, and hermeneutical injustice. It identifies interacting interpersonal and institutional mechanisms through which older adults’ knowledge may be discounted or rendered invisible and develops five theoretically derived principles: credibility-oriented listening, narrative recognition, supported participation, relational decision-making, and epistemic documentation. For each principle, the framework identifies the epistemic failure addressed, its added value beyond general person-centred practice, and responsibilities at both individual and organizational levels. Conclusions: An epistemic-justice lens does not replace dignity, person-centred care, shared decision-making, or professional judgement. It adds a focused analysis of credibility, interpretive authority, knowledge visibility, and whose account shapes care. The proposed framework is a conceptual and normative contribution that requires empirical evaluation before its effects can be established. Full article

Chimeric antigen receptor T-cell therapy and bispecific T-cell engagers have transformed treatment of relapsed and refractory hematologic malignancies, achieving unprecedented response rates. However, their clinical adoption has revealed a complex spectrum of cardiovascular toxicities, differing in frequency and pattern between the two technologies. Manifestations range from common hemodynamic perturbations—hypotension and tachycardia—to severe events, including malignant arrhythmias, left ventricular dysfunction, myocardial infarction, and cardiogenic shock. These complications seem to have different pathophysiological pathways that are yet to be completely understood: on the one hand, they are frequently intertwined with cytokine release syndrome, the hallmark immune complication of T-cell-redirecting therapies, as seen with chimeric antigen receptor T-cell therapy; on the other, a substantial proportion of cardiovascular events—particularly with bispecific T-cell engagers—occur independently of cytokine release syndrome. Proposed cardiotoxic mechanisms include on-target, off-tumor antigen recognition and consequent damage; interleukin-6-driven systemic inflammation; and off-target, off-tumor antigen cross-reactivity. Effective management requires proactive baseline risk stratification, serial cardiac biomarker monitoring, and timely immunosuppressive intervention—primarily tocilizumab—to mitigate cytokine release syndrome-driven injury. Despite rapid clinical expansion, critical gaps remain: long-term cardiovascular outcomes are poorly characterized, validated surveillance protocols are lacking, and cardiovascular endpoints are rarely included in pivotal trials. This narrative review appraises the pathophysiology, clinical spectrum, and management of cardiovascular toxicities associated with these therapies, aiming to define this emerging cardio-oncology frontier, inform multidisciplinary care frameworks and propose a clinical management algorithm. Full article

Background/Objectives: The treatment landscape of relapsed/refractory multiple myeloma (RRMM) has significantly evolved with the introduction of novel classes of agents and, more recently, of T-cell-redirecting therapies, including bispecific antibodies (BsAbs). It is essential to enhance and harmonize the therapeutic management of BsAbs within clinical practice. Methods: We performed a modified Delphi expert consensus study on the use of BsAbs targeting the B-Cell Maturation Antigen (BCMA) in patients with triple-class-exposed (TCE) RRMM. The study was conducted in April–November 2025 following established guidelines and best practices for defining consensus. The key phases in the use of anti-BCMA BsAbs were identified and explored. Results: Fifteen Italian hematologists with expertise in the care of TCE RRMM completed two Delphi rounds. Agreement (defined as ≥67% of panelists) was achieved on most of the topics evaluated. In particular, all panelists considered the step-up dosing phase feasible in an outpatient setting, under specific circumstances, and dosing de-escalation in responding patients to reduce the risk of adverse events. For most of them, anti-BCMA BsAb treatment is also feasible in several challenging subgroups, including frail patients (93% agreement) and those with high-risk cytogenetics (93%), extramedullary disease (93%), end-stage renal disease (86%), active plasma cell leukemia (79%), and central nervous system involvement (67%). In addition, agreement (93%) was reached on the possible sequential use of BCMA-targeting therapies, preferentially BsAbs following CAR-T, though a switch in the target antigen should primarily be considered. Conclusions: In this article, we address the main challenges related to the real-world use of anti-BCMA BsAbs in patients with TCE RRMM, offering expert recommendations to complement existing guidelines and support clinical practice. Full article

Glioblastoma remains the most lethal primary malignancy of the central nervous system, and the modest gains achieved with maximal surgery, radiotherapy and temozolomide have not been matched by the immune checkpoint inhibitors and antigen-specific vaccines that reshaped the treatment of many extracranial cancers. The recurrent disappointment of these approaches has been attributed less to a single molecular lesion than to a confluence of obstacles: profound intratumoural heterogeneity, a densely immunosuppressive and myeloid-rich microenvironment, sequestration and exhaustion of conventional T cells, and the practical difficulty of delivering effectors across the blood–brain barrier. Against this background, γδ T cells have attracted interest as an unconventional effector population that recognises transformed cells through stress-associated and metabolic cues rather than peptide–major histocompatibility complex (MHC) complexes, that kills in an MHC-unrestricted manner, and that can be expanded from healthy donors for allogeneic, off-the-shelf use with little expectation of graft-versus-host disease. This narrative review examines, with a deliberately critical lens, the biological rationale and the experimental evidence for γδ T cell-based immunotherapy of glioblastoma. We summarise the developmental biology and functional subsets of human γδ T cells, the natural killer group 2 member D (NKG2D)-, DNAX accessory molecule 1 (DNAM-1)- and T-cell-receptor-dependent mechanisms through which they engage glioblastoma cells and glioma stem-like cells, and the in vitro and animal-model studies that underpin the field, taking care not to overstate efficacy that has so far been demonstrated only in preclinical or early-phase settings. We then weigh the principal opportunities—locoregional and repeated dosing, combination with chemoradiotherapy, checkpoint blockade and antibody-based redirection—against barriers that include limited persistence, uncertain intratumoural trafficking, donor and manufacturing variability, and the unsettled requirements of potency testing and trial design. We give particular weight to what becomes of γδ T cells inside a hostile tumour—the exhaustion-like dysfunction that follows chronic stimulation, the oxygen and glucose dependence of their effector programme, the interleukin-17-polarising signals generated by activated microglia and by genotoxic therapy, and the confounding effect of corticosteroids—together with the engineering and pharmacological strategies proposed to counter them. The first peer-reviewed phase 1 report of intracranially delivered, drug-resistant γδ T cells has now appeared and documents tolerability in a small, single-arm cohort without establishing survival benefit. Throughout, γδ T cells are presented as a biologically plausible but still investigational strategy whose clinical value will be determined by adequately powered trials rather than by mechanistic appeal alone. Full article

Gender Equality Plans (GEPs) have been an eligibility requirement for Horizon Europe funding since 2022, yet formal adoption does not necessarily alter organizational routines, culture, or resource allocation. This article examines the process of moving from compliance toward institutionalized practice through a longitudinal single-case study of the University of Primorska (UP), a smaller university in a resource-constrained Widening-country context. We compare the first analytical observation period (2021–2025), based on its 2021–2027 GEP, with GEP 2.0 (2026–2030). Evidence combines documentary analysis, selected gender-disaggregated indicators, three focus groups (n = 24), and aggregated staff-survey results for 2024–2025. We develop the Gender Equality Plan Maturity Index (GEP-MI), an unweighted six-dimensional heuristic scored from 0 to 18. The document-based, triangulated score rises from 7 to 15, indicating more explicit governance, data routines, and resourcing, but not durable implementation outcomes. Qualitative evidence illustrates three overlapping categories associated with the paper–practice gap: passive resistance (skepticism and box-ticking), active ideological resistance (naturalization and denial), and structural implementation constraints (including administrative infeasibility and unequal care burdens). A documentary comparison with the Universities of Ljubljana and Maribor contextualizes differences in formal design; it does not establish the prevalence of these categories beyond UP. We define audit-induced decoupling under constrained resources as the risk that audited requirements redirect scarce capacity toward demonstrable compliance rather than substantive change. The case offers a transparent monitoring heuristic and suggests that proportionate capacity support warrants consideration alongside European conditionality. Full article

Hypophosphatasia (HPP) encompasses a group of inherited metabolic bone disorders characterized by defective skeletal mineralization and variable clinical severity in childhood. Substantial allelic heterogeneity contributes to a broad pediatric clinical spectrum, ranging from life-threatening perinatal disease to milder phenotypes characterized by chronic functional impairment. Historically, management relied primarily on supportive interventions aimed at sustaining survival, without modifying the underlying enzymatic defect. The introduction of enzyme replacement therapy (ERT) with asfotase alfa has fundamentally altered the natural history of pediatric HPP by supplementing deficient alkaline phosphatase activity at sites of active mineralization, thereby improving skeletal integrity, enhancing survival in severe forms, and supporting long-term functional gains. This therapeutic shift has redirected clinical priorities from survival alone toward sustained functional development and health-related quality of life. Nevertheless, variability in disease expression and therapeutic response persists, reflecting both diagnostic timing and the molecular heterogeneity of ALPL variants, whose phenotypic consequences cannot be predicted with complete certainty. Growing recognition of the importance of early diagnosis has prompted exploratory efforts toward systematic identification strategies, including neonatal screening initiatives reported in selected populations, which suggest the potential for earlier therapeutic intervention during active skeletal development. Together, these considerations highlight pediatric HPP as a model of precision-oriented management in rare metabolic bone disease, where timely diagnosis and targeted enzyme replacement must be aligned with long-term, multidisciplinary care to optimize outcomes. Full article

Background: T-cell redirecting therapies (TCRTs), including CAR T-cell therapies and bispecific antibodies, have transformed treatment for relapsed/refractory multiple myeloma (MM), yet real-world adoption remains limited by awareness and access barriers across patients, caregivers, and physicians. Methods: We conducted a cross-sectional study (June–September 2025) using IRB-approved REDCap surveys distributed to patients with MM (via MyChart), caregivers of TCRT recipients (via email), and community physicians (via email). Surveys assessed TCRT familiarity, perceived barriers, and access challenges. The primary objective was to compare TCRT utilization across racial groups among previously treated patients. Results: A total of 428 respondents participated (346 patients, 51 caregivers, 31 physicians). Among patients, 18% were Black. Overall, 26% were unfamiliar with TCRT, with higher unawareness among Black patients (32% vs. 25%) and those with ≤high school education (42% vs. 23%). Higher education was associated with twice the odds of TCRT utilization (p = 0.05). Among patients reporting prior MM treatment, TCRT utilization was similar across racial groups (39% Black vs. 38% non-Black). Among patients reporting TCRT receipt, Black patients more frequently reported receiving therapy through clinical trials compared with non-Black patients (44% vs. 34%). Among caregivers, 53% reported effects on mental/emotional wellness, 61% moderate-to-high stress during treatment, and 33% provided >40 h/week of care during month one. Among physicians, 71% referred patients for TCRT, but 48% reported <25% of referrals resulted in treatment. Patient hesitancy was the most cited referral barrier. Conclusions: Awareness gaps disproportionately affect Black patients and those with lower education. Caregivers experience substantial emotional and time burden. Patient hesitancy remains the primary barrier to TCRT referrals. Clinical trials may serve as an alternative access pathway for some patients. Multi-level interventions targeting education, caregiver support, and care coordination are needed to improve equitable TCRT access. Full article

Dysgeusia is a clinically consequential, but still under-standardized, toxicity of cancer treatment. In the immunotherapy era, taste disturbances are increasingly relevant for patients receiving immune checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapies and T-cell-redirecting bispecific antibodies, with G protein-coupled receptor family C group 5 member D (GPRC5D)-directed treatment in multiple myeloma representing a particularly instructive high-burden model. We performed a structured critical narrative review with evidence mapping. PubMed/MEDLINE was searched from database inception to June 2026, complemented by citation tracking in Google Scholar, ClinicalTrials.gov searches and guideline documents relevant to oncology nutrition, oral supportive care and cancer-related taste dysfunction. Search concepts covered cancer-related dysgeusia, immunotherapy-associated oral toxicity, GPRC5D/talquetamab-associated dysgeusia, oncology nutrition, oral–gut microbiome biology, natural taste modulators and miraculin-based interventions. Dysgeusia can reduce appetite, food enjoyment, dietary diversity and protein energy intake, thereby contributing to weight loss, malnutrition risk, distress, social withdrawal and, in severe cases, treatment modification or discontinuation. Available evidence is heterogeneous: general cancer-treatment-associated dysgeusia is supported by broader observational and interventional literature; immunotherapy-associated dysgeusia is less systematically characterized; and GPRC5D/talquetamab-associated dysgeusia represents the most clinically visible and target-specific immunotherapy-associated phenotype. Emerging pilot data suggest that dried miracle berry or miraculin-containing products may improve selected taste perception and nutritional parameters in cancer-related dysgeusia, but direct evidence in immunotherapy-associated dysgeusia is not yet established. We, therefore, propose a claim-disciplined precision supportive-care framework integrating systematic taste phenotyping, early nutritional risk assessment, oral health evaluation, microbiome-aware but hypothesis-generating endpoints, individualized flavor and texture adaptation, cautious use of natural taste modulators in selected patients and iterative monitoring of patient-centered outcomes. Future trials should test whether dysgeusia-focused nutritional and taste-modulating supportive care interventions can improve intake, quality of life and treatment persistence without compromising immunotherapy safety or efficacy. Full article

Background/Objectives: T-cell-redirecting immunotherapies, including chimeric antigen receptor T-cell (CAR-T) therapy and bispecific antibodies (BsAbs), have transformed the treatment of relapsed/refractory multiple myeloma (RRMM). However, pivotal registration trials routinely excluded patients with significant renal impairment (RI), creating a critical evidence gap in a population where kidney disease affects 20–50% of patients at diagnosis. Direct comparisons of outcomes across the estimated glomerular filtration rate (eGFR) spectrum for both modalities are lacking. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, a federated electronic health record research platform. Adult patients with RRMM treated with CAR-T therapy (idecabtagene vicleucel or ciltacabtagene autoleucel) or BsAbs (teclistamab, elranatamab, or talquetamab) were stratified by baseline renal function: severe RI (eGFR <30 mL/min/1.73 m²), moderate RI (eGFR 30–60 mL/min/1.73 m²), and preserved renal function (eGFR >60 mL/min/1.73 m²). Propensity score matching (PSM) (1:1), adjusted for key clinical and demographic covariates, was performed for each comparison within each therapy type. Long-term outcomes (all-cause mortality and time to next treatment [TTNT]) were assessed at 1, 2, and 3 years. Overall survival (OS) was additionally evaluated using Kaplan–Meier analysis. Short-term safety outcomes were assessed at 1, 3, and 6 months. Results: A total of 2716 CAR-T and 3376 BsAb recipients were identified. After matching, 281 pairs (severe RI vs. preserved) and 878 pairs (moderate RI vs. preserved) were analyzed in the CAR-T cohort; 645 and 1158 pairs, respectively, were analyzed in the BsAb cohort. Neither severe nor moderate RI was significantly associated with increased mortality or shorter TTNT after either CAR-T or BsAb therapy. However, patients with RI experienced significantly higher rates of anemia, thrombocytopenia, and acute kidney injury (AKI) across both modalities. Cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and neutropenia rates were comparable across renal strata. In the BsAb cohort, infections were transiently elevated at 1 month in the severe RI group (RR 1.29; 95% CI 1.06–1.58; p = 0.011) but equilibrated by 3 months. Conclusions: In this retrospective analysis, renal impairment was not associated with inferior survival outcomes following CAR-T therapy or BsAb treatment in RRMM, suggesting that RI alone should not preclude the use of these agents. However, RI conferred increased hematologic toxicity and AKI risk, warranting enhanced supportive care and monitoring. These findings support broadening access to T-cell-redirecting immunotherapies for patients with RI with appropriate surveillance, though prospective validation is needed. Full article

Background/Objectives: Contemporary healthcare systems face compound challenges (including technological acceleration, demographic aging, rising chronic disease burden, and growing patient expectations) that demand models that are simultaneously efficient, high-quality, and person-centered. Despite a substantial body of research addressing organizational design, human capital management, and clinical competencies, these dimensions have largely been theorized in isolation. This study aims to construct and justify an integrated theoretical framework explaining how organizational models, human capital, and transversal competencies may jointly shape care quality, patient safety, and institutional sustainability in healthcare organizations. Methods: A narrative literature review was conducted, integrating contributions from business economics, healthcare management, organizational psychology, and nursing sciences. This design was selected for its suitability in synthesizing heterogeneous, multidisciplinary knowledge into a coherent conceptual framework, a purpose for which systematic meta-analytic approaches are not appropriate. Sources encompassed 79 references: peer-reviewed journals (PubMed, JSTOR, Google Scholar), institutional reports (WHO, OECD, European Commission, Joint Commission), normative standards (ISO 30414:2018), and Italian regulatory frameworks, spanning foundational twentieth-century contributions through the most recent literature (2025). Results: Four principal findings emerged: (1) healthcare organizations are evolving from rigid hierarchical structures toward flexible, value-based configurations, with the Value-Based Healthcare (VBHC) paradigm redirecting institutional attention from service volume to patient-meaningful outcomes per unit of cost; (2) transversal competencies (communication, empathy, emotional intelligence, teamwork, and transformational leadership) are closely associated with care quality and patient safety, with 70–80% of sentinel events associated with communication failures; (3) human capital, encompassing technical expertise and relational capacity, constitutes the primary lever of competitive advantage in healthcare institutions; and (4) the trajectory from pyramidal toward participatory and self-managed models is supported by international evidence, including the Buurtzorg experience in the Netherlands. Conclusions: The integrated three-pillar framework (combining resource-based theory and dynamic capabilities, Value-Based Healthcare, and evolutionary organizational theory) provides a theoretically grounded basis for understanding how organizational structure, human capital, and transversal competencies are jointly associated with clinical performance. Healthcare institutions should systematically integrate soft-skills training into professional education and invest in participatory organizational structures. Health policy should revise financing mechanisms to incentivize patient-meaningful outcomes over service volumes and support the broader transition toward Value-Based Healthcare models. The Italian SSN is discussed as an illustrative national context rather than as the primary empirical focus of the review. Full article

Chronic limb-threatening ischemia (CLTI) in patients with no conventional targets for revascularization presents a formidable challenge in limb salvage. Deep venous arterialization (DVA) is an emerging endovascular approach that redirects arterial blood flow into the venous system to perfuse the ischemic foot. Despite early promising results, appropriate wound management of the ischemic foot following a DVA procedure has been described in the literature, albeit infrequently and with limited standardization. Here, we present a case of an 85-year-old male with multiple comorbidities, including peripheral artery disease and a prior right above-knee amputation (AKA), who underwent a successful left-sided DVA following an open transmetatarsal amputation (TMA) for infection. A staged wound care approach with guillotine amputation, delayed revision and skin grafting ultimately preserved his only remaining limb and allowed for ambulation. This case underscores the potential of DVA as a limb-saving option in complex “no-option” patients when paired with multidisciplinary care and tailored wound management. Full article

Background: The management of diabetic foot disease and knee osteoarthritis (OA) with smart orthotics holds significant importance during the early stages of these conditions, given their potential consequences, including functional impairment, chronic pain, and economic burden. Real-time monitoring of plantar foot pressure enables early detection of abnormal force distribution and gait biomechanics, allowing for the redirection of forces away from affected ulcers or arthritic joints. This is the first systematic review to synthesise clinical evidence for smart orthotics technology with real-time plantar pressure sensor biofeedback across both diabetic foot ulcer prevention and knee osteoarthritis management simultaneously. A search of the PROSPERO register confirmed no existing registration covers this specific combination. Objectives: To examine the clinical evidence for the use of standard and smart orthotics in the prevention and management of diabetic foot ulcers (DFUs) and knee OA, and to evaluate their impact on plantar pressure redistribution, ulcer recurrence, pain, biomechanics, and economic burden. Eligibility criteria: Studies published in English involving human adult participants (≥18 years) with a clinical diagnosis of diabetes mellitus (at risk of DFU or with peripheral neuropathy) or knee OA, where the intervention involved any orthotic device or smart/intelligent insole with clinical outcomes reported, were included. Studies on healthy individuals only, those not reporting participant age, and non-weight-bearing protocols not differentiated from weight-bearing were excluded. Information sources: Five databases were searched: CINAHL (EBSCO Information Services, Ipswich, MA, USA), PubMed Advanced (National Library of Medicine, Bethesda, MD, USA), Wiley Online Library (John Wiley & Sons, Hoboken, NJ, USA), Cochrane Library (Cochrane Collaboration, London, UK), and Google Scholar (Google LLC, Mountain View, CA, USA). Searches were completed in May 2026. Methods: We conducted a comprehensive literature review. This review was structured and reported with reference to the PRISMA 2020 statement (Preferred Reporting Items for Systematic Reviews and Meta-Analysis; University of Ottawa, Ottawa, ON, Canada) to guide transparency of reporting. It does not constitute a full Cochrane-style systematic review; risk of bias assessment was applied to key included studies and GRADE (Grading of Recommendations Assessment, Development and Evaluation; McMaster University, Hamilton, ON, Canada) certainty ratings were applied informally and narratively rather than as formal per-outcome evidence profiles. Five databases were searched yielding 92,637 records. After removal of 398 duplicates by Rayyan, 92,239 records remained. A subsequent automated keyword-based relevance filter applied within Rayyan (Rayyan AI, Doha, Qatar), prior to human screening, excluded 84,572 records that did not contain any terms related to orthotics, diabetic foot, or knee osteoarthritis, yielding 7667 records for human title/abstract screening. A narrative synthesis approach was adopted owing to the heterogeneity of study designs and outcome measures across included studies, which precluded meta-analysis. This review was not prospectively registered. A complete list of all 78 included studies, including those not individually discussed in the results and discussion. Results: The available clinical studies report promising findings for orthotics and smart orthotics in pain reduction, ulcer prevention, and potential reduction in economic burden, though conclusions are limited by small sample sizes, heterogeneity, and predominantly open-label designs. Recent research found that orthotics can be used to alter the gait pattern that influences knee OA by reducing excessive force on the affected joint. A randomised controlled trial demonstrated an 80% relative risk reduction in DFU recurrence (RR = 0.20; 95% CI: 0.06–0.79; p = 0.022), with absolute event rates of 6.3% in the intervention group versus 30.8% in controls (ARR = 24.5%); a second trial reported a 71% reduction in ulcer incidence over 18 months; and a third randomised controlled trial demonstrated statistically significant plantar pressure reduction (p < 0.01) in patients with diabetic neuropathy. Conclusions: The available evidence suggests that orthotics may be associated with improved pressure redistribution, reduced ulcer incidence, and benefit in the management of knee OA. Although the number of studies directly comparing smart orthotics with standard orthotics remains limited, the limited comparative studies suggested that smart orthotics showed promising results in reducing ulcer incidence, providing the patient with real-time feedback to offload via their electronic devices. These findings, while preliminary, highlight the potential of smart orthotic technology as an adjunct to standard orthotic care in reducing the overall burden of diabetic foot disease and knee osteoarthritis. Limitations: The primary methodological limitation of this review is the open-label design of all included smart orthotic trials, which precludes participant blinding and introduces performance bias. However, this limitation is structural and inherent to the wearable technology field—analogous to surgical trials—and is substantially mitigated by the use of objective primary outcome measures (plantar pressure and ulcer recurrence) across the three included RCTs, the consistency of effect direction across independent RCTs conducted in different countries, and a narrative sensitivity analysis confirming robustness of findings (Risk of Bias Across Studies Section). Formal per-outcome GRADE evidence profiles were not produced; overall certainty of evidence was assessed narratively with reference to GRADE domains and is judged to be low to moderate for smart orthotics in DFU prevention and low for knee OA management, consistent with the Level 2–3 evidence base and open-label study designs. Future adequately powered, multi-site RCTs with standardised outcome reporting, minimum 24-month follow-up, and integrated health economic modelling are the highest priority to extend these preliminary findings. Registration: This review was not prospectively registered. Full article

Background and Objectives: Relapsed or refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHL) remain associated with poor outcomes despite advances in chemoimmunotherapy and chimeric antigen receptor (CAR) T-cell therapy. Many patients are ineligible for or relapse after cellular therapies, highlighting the need for effective off-the-shelf immunotherapeutic approaches. CD20 × CD3 bispecific antibodies (BsAbs) redirect endogenous T cells against malignant B cells and have emerged as a promising therapeutic class in B-NHL. To summarize current clinical evidence regarding mosunetuzumab, glofitamab, epcoritamab, and odronextamab in B-NHL, focusing on efficacy, safety, and emerging therapeutic applications. Materials and Methods: A structured review of published phase I–III clinical trials evaluating the four currently approved CD20 × CD3 BsAbs in B-NHL was conducted. Efficacy outcomes, durability of response, and safety data were assessed across indolent and aggressive lymphoma subtypes. Results: CD20 × CD3 BsAbs demonstrated substantial and durable clinical activity in heavily pretreated B-NHL, including patients with prior CAR T-cell exposure. Mosunetuzumab showed high response rates and durable remissions in follicular lymphoma (FL), while glofitamab demonstrated significant efficacy in aggressive lymphomas, particularly diffuse large B-cell lymphoma (DLBCL). Epcoritamab exhibited consistent activity across lymphoma subtypes with favorable tolerability supported by subcutaneous administration and step-up dosing. Odronextamab also demonstrated clinically meaningful responses in both FL and DLBCL, including high-risk populations. Across studies, cytokine release syndrome (CRS) was the most common adverse event, predominantly low grade and manageable with established mitigation strategies. Immune effector cell-associated neurotoxicity syndrome (ICANS) was uncommon. Infections and hematologic toxicities, particularly neutropenia, represented clinically relevant adverse events across all treatment programs, highlighting the need for special supportive care. Conclusions: CD20 × CD3 BsAbs represent a major therapeutic advancement in R/R B-NHL, combining high clinical activity, manageable toxicity, and off-the-shelf availability. Their expanding integration into earlier treatment settings and combination strategies is expected to further reshape the therapeutic landscape of B-NHL. Full article

Background: Patients described as high-need, high-cost (HNHC) represent a subset of individuals with complex multimorbidity whose healthcare trajectories are characterised by recurrent instability and intensive use of acute care services. Concepts such as trajectory disruption, resilience, and complex adaptive behaviour are widely discussed in health systems research, yet linking these ideas to longitudinal patient care remains limited. The PaJR (Patient Journey Record) relational system was designed using principles from complex adaptive systems theory, enabling longitudinal observation of patient trajectories in real-world care. Objective: This study develops a middle-range theory grounded in longitudinal relational monitoring data. Methods: Two datasets (MonashWatch and Irish cohorts) provide empirical grounding through descriptive analysis of signal clustering, distribution, and multi-domain patterns. Monitoring calls capture structured patient-reported signals across multiple domains, including illness, medication, healthcare utilisation, social support, environmental factors, and self-care. Results: Results demonstrate long-tail signal distributions, temporal clustering, and multi-domain instability preceding admission. Alerts frequently occurred in clusters across consecutive monitoring calls 88% of alert calls were part of a consecutive alert sequence, with approximately 64% of alert calls occurring immediately after a previous alert. Alerts were also commonly multi-domain, with approximately 64% involving disturbances across more than one domain simultaneously. Conclusions: Longitudinal relational monitoring reveals instability patterns in patient journeys that are not visible in episodic health-system data. Recognising these instability phases may enable earlier, more adaptive responses for patients with complex healthcare needs and provides empirical grounding for emerging theories of healthcare trajectories within complex adaptive systems. Although grounded in relational monitoring data, the instability–plasticity framework may extend to inform interpretation across physiological and connected health monitoring systems. Full article

Tryptophan (Trp) metabolism sits at the intersection of nutrition, the microbiome, mucosal immunity, and tumor adaptation. The broad observation that microbial indoles can support barrier function, whereas tumors exploit kynurenine-pathway metabolism to suppress immunity, is already established in publications. The specific contribution of this review is to organize that literature into a context- and network-based translational framework. Rather than treating indoleamine 2,3-dioxygenase 1 (IDO1) as a single bottleneck, we frame tumor Trp metabolism as a compensatory system linking IDO1, tryptophan 2,3-dioxygenase (TDO2), interleukin-4-induced gene 1 (IL4I1), amino-acid transport, amino-acid stress sensing, and downstream aryl hydrocarbon receptor (AHR) signaling. In healthy tissue, especially the gut, dietary Trp and microbiota-derived indoles can promote epithelial integrity, interleukin-22 (IL-22)-associated programs, and mucosal restraint. In tumors, the same substrate pool is redirected toward Kynurenine, kynurenic acid, indole-3-pyruvate, and related catabolites that impair cytotoxic lymphocytes, expand regulatory T-cell (Treg) and suppressive myeloid compartments, and reinforce invasion and treatment resistance. We also argue that the potential metabolite biomarker interpretation should be context-dependent. Finally, we propose a clinical-context–specific framework for intervention. Dietary and microbiome-based strategies may be most effective in prevention, premalignant states, or supportive care, whereas established cancers are more likely to require biomarker-guided targeting of tumor-associated catabolic pathways and convergent signaling mechanisms. The “paradox” is therefore not that Trp changes chemistry across settings, but that the same nutrient is routed through different cellular contexts, enzymes, ligands, and cell states. Full article