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Few non-invasive approaches are available for improving coronary function in intermediate-risk chronic coronary syndrome (CCS) patients. Over the past 30&#xa0;years, enhanced external counterpulsation (EECP) has been widely accepted and recommended for treating CCS in clinical guidelines. However, the effect of EECP on coronary function remains to be quantitatively validated in intermediate-risk CCS patients. Fractional flow reserve (FFR) is a gold standard (quantitative index) of coronary artery function, and FFR&#x2009;<&#x2009;0.80 is regarded as an indicator for percutaneous coronary intervention (PCI) in clinical decision-making. However, FFR is invasive and cannot be performed repeatedly within a short time interval; therefore, FFR is not suitable for large-scale verification of the effect before and after EECP treatment. Conversely, with advancements in numerical theory and computation hardware, FFR derived from coronary computed tomography angiography (FFRCT) performs similarly to FFR used in coronary artery function measurement. Additionally, FFRCT is non-invasive and highly acceptable to patients. Therefore, in this study, we aim to explore whether EECP therapy can improve FFRCT in patients with intermediate-risk CCS and further enhance the long-term prognosis of CCS. This prospective, multicentre, randomised controlled trial is blinded to the examination executors and analysts. One hundred four participants will be recruited, and they will be divided into the EECP and control groups. The primary outcome of this study is the between-group difference in FFRCT changes from baseline to follow-up. The secondary outcomes refer to between-group differences in &#x394;FFRCT, wall shear stress, axial plaque stress, total exercise time, time to 1 mm ST-segment depression, Seattle Angina Questionnaire score, and cardiovascular-related composite endpoint events. This is the first study to use the non-invasive coronary artery function index, FFRCT, to evaluate the efficacy of EECP in patients with CCS. It comprehensively evaluates the treatment efficacy from multiple dimensions, including exercise capacity, symptom changes, and prognosis. Therefore, this will potentially provide reliable evidence to inform treatment strategies for CCS. Trial registration number: ChiCTR2400079915. Registered on January 16, 2024 (retrospectively registered), https://www.chictr.org.cn/about.html.

Spaceflight-associated neuro-ocular syndrome (SANS) poses significant ocular health risks in long-duration missions, yet its molecular mechanisms remain incompletely understood. Oxidative stress and apoptosis are candidate drivers, but their transcriptomic-phenotypic relationships in spaceflight-exposed retinal tissue have not been systematically characterized. We applied a machine learning ensemble to predict two ocular phenotypes: 4-hydroxynonenal (4-HNE) endothelial cell density as a marker of oxidative damage, and TUNEL endothelial cell density as a marker of apoptosis. In this observational study, we use transcriptomic data from a controlled experiment with ground control and spaceflown mice to predict these phenotypes. Gene Ontology pathway enrichment was performed using the most predictive genes for each phenotype. Genes predicting 4-HNE converge on membrane-associated pathways, photoreceptor modification, synaptic dysfunction, and extracellular matrix dysregulation, including B2m, Trf, Cnga1, mt-Nd1, Snap25, and Efemp1. Genes predicting TUNEL emphasize stress-induced apoptosis, rod photoreceptor degeneration, and endoplasmic reticulum dysfunction, with Ddit4, Nrl, Rom1, Reep6, and Gabarapl1 emerging as central regulators. Oxidative lipid peroxidation and apoptotic cell death represent complementary and molecularly distinct pathological mechanisms in spaceflight-exposed murine retinal tissue. The gene signatures provide a putative molecular framework for developing noninvasive biomarkers and therapeutic targets to monitor and protect astronaut visual health during long-duration and deep-space missions.

Minor histocompatibility antigens (MiHA) are polymorphic peptides presented by HLA molecules on recipient cells in allogeneic hematopoietic cell transplantation (allo-HCT) and are derived from proteins with genetic variants that differ between recipient and donor. Following allo-HCT, hematopoietic-restricted MiHA enable selective targeting of residual recipient-derived hematopoiesis, including malignant cells. Advances in engineering T cells with high-affinity MiHA-specific T-cell receptors (TCR; TCR-T) are enabling clinical translation of MiHA T cell immunotherapy. Early-phase trials of HA-1 and HA-2-specific TCR-T demonstrate safety, persistence, and durable anti-leukemic activity in high-risk or relapsed disease. To accelerate translation, the field should expand TCR-T development to additional MiHA targets to broaden HLA and population coverage, integrate MiHA genotyping into donor selection, and devise platform trials to include patients with various MiHA/HLA genotypes and to efficiently test combination therapies. MiHA-directed TCR-T represents a genetically precise, potentially routine HCT adjunct that promises to fortify graft-versus-leukemia effects and improve relapse-free survival.

Phosphotyrosine signaling plays a critical role in many biological processes, from cell proliferation to immune response. Despite its importance, proteomic studies of tyrosine phosphorylation have been limited in scale and throughput due to the need for specialized enrichment with costly reagents and labor-intensive protocols. To address these challenges, we developed R2HaPpY, a phosphotyrosine enrichment method that combines highly simplified phosphotyrosine superbinder reagent preparation and automated high-throughput enrichment. Our new reagent binds phosphotyrosine peptides at higher efficiency than other enrichment reagents and reduces both cost and preparation time by 20-fold. We generalized the R2HaPpY method to samples of low and high levels of phosphotyrosine. We benchmarked biological application to study EGF signaling dynamics in HeLa cells. Using only ~1&#x2009;mg of input peptides, we detect and quantify 1651 unique phosphotyrosine sites. These include 878 regulated pY sites, many of which are novel or not previously annotated as EGF-responsive. Our results reveal differential temporal regulation and represent the largest phosphotyrosine dataset of cellular response to EGF stimulation to date. This streamlined, cost-effective, and sensitive method enables quantitative mapping of tyrosine phosphorylation dynamics at a scale of hundreds of samples, facilitating integration of phosphotyrosine signaling into multiomic studies across diverse biological systems and disease states.

Diagnosis and management of porphyrias require appropriate biochemical testing. Tests available to practicing physicians in the US are not consistent and depend greatly on what is offered by individual laboratories. In addition, harmonization, whereby results and interpretations from different laboratories are comparable, is not assured. Members of American Porphyrias Expert Collaborative (APEX) recommend that specific tests should be available to all physicians in the US for diagnosis and monitoring of porphyrias, and that harmonization of laboratory practices and results reporting across laboratories should be achieved. These efforts will lead to the development and more effective implementation of guidelines for the diagnosis and monitoring of porphyrias by both community providers and porphyria expert centers.

Given the rising incidence of bone metastases, computed tomography is widely used worldwide as the initial imaging modality for their detection. Accurate diagnosis of bone metastases demands comprehensive evaluation, yet divergent interpretations among specialists can result in diagnostic discrepancies. In clinical practice, precision diagnosis of bone metastases necessitates multidisciplinary collaboration involving radiologists, pathologists and oncologists. Here, to meet the need for an automated tool that can deliver expert-level insights and predictions by jointly considering multidisciplinary information, we propose BoneCoT, a whole-body skeleton foundation model enhanced through a chain-of-thought (CoT) fine-tuning approach. We pretrained the model on 29.3&#x2009;million computed tomography images from 30,267 patients across 12 skeletal sites and refined it over a graph of 26 clinically relevant tasks spanning diagnosis, complications, tumour type and biomarkers. Evaluated across 26 tasks and multicentre cohorts from 10 hospitals, BoneCoT outperformed state-of-the-art methods by 20% in area under the receiver operating characteristic curve. Critically, BoneCoT achieved a 40% area under the receiver operating characteristic curve improvement in distinguishing primary from metastatic lesions, significantly surpassing experienced radiologists. These findings show how clinician-derived reasoning can move artificial intelligence towards more integrated diagnostic assessment in complex disease.

This study aims to analyse the quantity and content of publicly discoverable statements that US-based medical societies issued regarding the 2023 escalation of violence in Palestine and Israel. We conducted a mixed-methods study using an explanatory sequential design. Inclusion criteria were defined as US-based medical societies from the American Medical Association House of Delegates, Council of Medical Specialty Societies (CMSS), or Association of American Medical Colleges (AAMC) Council for Academic Specialty Societies, yielding 186 US-based professional medical societies. Descriptive statistics and oods ratios (ORs) were used to assess the association between society characteristics and odds of statement issuance. A qualitative inductive and deductive thematic approach was employed to identify themes from public statements made from 7 October 2023 to 7 December 2023. 22 professional medical societies (N=22/186, 11.83%) issued 20 unique public statements regarding violence in Israel and Palestine. Exploratory OR analyses suggested associations between statement issuance and several society characteristics, though CIs were wide and thus underscored uncertainty regarding the magnitude of these associations. Exploratory OR analyses suggested that statement issuance was associated with possession of a lobbying arm (OR 26.83, 95% CI 3.53 to 204.25, p<0.01); a society diversity, equity, and inclusivity initiative (OR 6.57, 95% CI 1.48 to 29.04, p=0.01); a society global health or international initiative (OR 3.11, 95% CI 1.23 to 7.86, p=0.02); a society land acknowledgment or indigenous health initiative (OR 8.47, 95% CI 1.60 to 44.99, p=0.01); and prior issuance of a statement about the Russo-Ukrainian War (OR 38.83, 95% CI 10.63 to 141.75, p<0.01). Of the 20 unique, publicly discoverable statements found, 25% (N=5/20) used verbiage indicating exclusive support for Israeli or Jewish civilians, while none expressed sole support for Palestinian civilians. Our qualitative analysis revealed three main thematic categories of statement content: (1) those expressing support for or condemnation of a specific group, (2) those providing historical context, and (3) those describing a society's approach to statement issuance. Most professional medical societies did not make a public statement regarding violence in Palestine and Israel, and societies that previously engaged in political or international advocacy were more likely to issue a statement. Statements generally avoided any historical, contextual, or geopolitical framing and were more likely to reference Israeli victims than Palestinian victims of violence as well as violence by Hamas than Israeli state violence.

The Health Equity Report Card (HERC) was developed to establish best practice recommendations and promote accountability among health systems in addressing care inequities. Recognizing the growing importance of health equity, particularly in cancer care, this study aims to evaluate the feasibility of implementing the HERC within academic cancer centers and to gather insights on its benefits and challenges during implementation to improve its usability. This quality improvement study used a mixed-methods approach, collecting both quantitative and qualitative data over an 18-month period from April 2022 to October 2024 from 5 NCCN Member Institutions. Participants completed self- and third-party scores, as well as survey evaluations providing feedback on the process of using the HERC. Feedback from stakeholders was systematically collected to assess usability and identify areas for improvement. All participating sites successfully achieved the feasibility objectives by completing the self- and third-party scoring processes using the HERC, with unanimous agreement among the sites regarding the feasibility of the HERC for implementation. Site feedback indicated areas for enhancement, particularly in improving question clarity and simplifying the scoring process. Continuous feedback loops facilitated iterative improvements to the HERC, ultimately enhancing user experience and the scoring process. The HERC demonstrates strong potential as a viable framework for prioritizing and assessing equity in care delivery within academic cancer centers. The successful implementation across multiple sites, along with positive stakeholder feedback, underscores its utility in enhancing accountability and promoting best practices in addressing health inequities. Future studies should explore the long-term impacts of HERC implementation on patient outcomes and equity in care delivery. A study testing the HERC for applicability in community oncology settings is ongoing.

Two-dimensional magnetic semiconductors provide a unique platform where long-range magnetic order coexists with strongly bound excitons. Because excitonic states and magnetic moments originate from the same electronic orbitals and couple via intrinsic exchange interactions, optical excitations in these systems exhibit pronounced sensitivity to magnetic order. Recent experiments show unusually strong magneto-optical responses and direct exciton-magnon coupling, establishing new routes for controlling light-matter interactions with spin degrees of freedom. This Review surveys key developments, focusing on representative material systems, experimental signatures, and theoretical frameworks used to describe these phenomena. We conclude with perspectives on how this rapidly evolving field could enable next-generation optoelectronic and quantum technologies leveraging the coupled dynamics of light, charge and spin.

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Peripheral nerve injuries (PNIs) are a common cause of long-term motor and sensory disability despite advances in microsurgical repair. Functional recovery following PNI depends not only on axonal regeneration, but also on preservation of distal nerve pathways, maintenance of neuromuscular junction integrity, prevention of irreversible muscle degeneration, and adaptive central nervous system reorganization. Electrical rehabilitation modalities have been proposed as adjunctive strategies to enhance recovery across these domains, yet their clinical utility in PNIs remains incompletely defined. This review summarizes the pathophysiology of peripheral nerve injury and critically evaluates the current evidence for commonly used electrical rehabilitation modalities, including transcutaneous electrical nerve stimulation (TENS), neuromuscular and functional electrical stimulation (NMES/FES), and surface electromyographic (sEMG) biofeedback. Across modalities, the existing literature is heterogeneous and limited by small sample sizes, reliance on animal models, and substantial variability in stimulation parameters and timing. While TENS may play a role in pain management during the acute phase and sEMG biofeedback shows promise for facilitating motor relearning-particularly following nerve transfer surgery-robust evidence supporting routine use of electrical muscle stimulation in PNIs is lacking. Future investigations should prioritize standardized protocols, appropriate patient selection, and adequately powered clinical trials to clarify the role of electrical modalities in peripheral nerve rehabilitation.

Estrogen receptor alpha (ER&#x3b1;) signaling has metabolic and anti-inflammatory properties in addition to its impact on reproductive function. Compared to females, male mice generally exhibit greater inflammatory activation of microglia and increased susceptibility to diet-induced obesity (DIO). Given the established metabolic protective effects of estrogen, these observations raise the possibility that sex differences in microglial estrogen signaling contribute to this sexual dimorphism. In this study, we assessed metabolic and CNS histopathological properties in a mouse model with inducible microglia-specific ablation of ER&#x3b1; (MG-ER&#x3b1;KO). Male MG-ER&#x3b1;KO mice developed increased weight gain and insulin resistance relative to controls during high-fat diet (HFD) feeding. Indirect calorimetry and food intake analysis revealed that reduced energy expenditure, coupled with an inadequate compensatory reduction in food intake, was the primary driver of the obese phenotype. In contrast, female MG-ER&#x3b1;KO mice fed HFD developed mild insulin resistance, with no change in body weight gain compared to controls, despite a similar reduction in energy expenditure. Immunohistochemical analyses of the microglial activation marker IBA1 in the mediobasal hypothalamus (MBH) revealed that female MG-ER&#x3b1;KO mice had an increased number of microglia without showing morphological signs of activation. In contrast, MBH microglial number was unchanged in MG-ER&#x3b1;KO male mice, but the cells adopted more activated morphological profiles. Finally, HFD-fed MG-ER&#x3b1;KO male mice had increased POMC neuron-microglia interactions but fewer overall hypothalamic POMC neurons, suggesting microglia may disrupt POMC neuron integrity to promote DIO. Together, these findings indicate that sex-specific actions of estrogen in microglia limit the metabolic complications of HFD feeding.

Testing hypotheses of phenotypic modularity involves assessing whether groups of traits covary more strongly with each other than with parts outside the group. Structural Equation Modelling (SEM) is a flexible statistical framework for interrogating complex relationships between sets of variables, making it ideally suited to studies of hierarchical modularity and integration. However, quantifying the modular organization of high-dimensional traits using SEM in a phylogenic context has only recently become possible through new methodological advances. Here, we applied SEM to investigate patterns and correlates of phenotypic modularity in the skull and brain of birds. Birds independently evolved relatively large brains multiple times, as well as a wide range of different skull and brain morphologies. While some have proposed the bird skull is composed of several functional or developmental modules, others have suggested the skull is highly integrated, with share allometric scaling structuring trait correlations. The data best supported a model in which brain shape is influenced by changes in shape of the neurocranium as well as a 'jaw' module consisting of the rostrum shape and jaw musculature. Rostrum shape itself does not strongly covary with other aspects of the skull and brain, suggesting decoupling of beak morphology from the rest of the avian cranium. All variables, with the exception of rostrum shape, are strongly influenced by size, supporting the idea that allometry is a major influence on craniofacial integration in birds. These results provide new insights into likely drivers shaping the evolution of the skull in birds and highlight the usefulness of phyloSEM testing hypotheses of evolutionary modularity and integration.

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Autosomal-dominant frontotemporal lobar degeneration with tau pathology (FTLD-tau) is caused by pathogenic variants in the MAPT gene. Although abnormal tau aggregation is a shared endpoint, MAPT mutations produce distinct cellular phenotypes and regional patterns of tau deposition, the mutation specificity and familial consistency of which remain poorly defined. We performed a systematic neuropathologic and transcriptomic analysis of brains from clinically characterized families carrying MAPT V337M, P301L, or L284L mutations. Multiple affected members per family were examined, with interfamily comparisons for P301L. Quantitative assessment of regional tau burden, cellular morphology, and co-pathologies revealed distinct, mutation-specific signatures. The V337M mutation was characterized by predominantly neuronal tau pathology with vesicular pretangles, scattered neurofibrillary tangles, and fine neurites, with minimal glial involvement. P301L exhibited prominent astrocytic tau pathology, including globular and proximal inclusions, accompanied by neuronal pretangles. L284L produced extensive oligodendroglial tau pathology with thick fibrillar coiled bodies in gray and white matter. Additional distinguishing features included hippocampal sclerosis and TDP-43 pathology in V337M; severe cortical neuronal loss and dentate fascia tau in P301L; and extensive white matter and brainstem tau, including ventral pontine neurons, in L284L. These morphologic profiles were conserved within families and, for P301L, across unrelated families. Transcriptomic analyses suggested mutation-linked expression changes concordant with cellular pathology. These findings define reproducible, mutation-specific neuropathologic and molecular signatures of MAPT-associated FTLD-tau, emphasizing the importance of genotype-driven stratification in studies of tauopathy pathogenesis.

Psychotic experiences are commonly reported in population-based surveys, yet brief self-report screening instruments often yield high false-positive rates by capturing normative, culturally sanctioned, or other non-psychotic phenomena. Large surveys and administrative datasets increasingly include free-text responses that could contextualize these endorsements; however, qualitative data are under-analyzed due to resource constraints. Using data from a US adult online survey, respondents who endorsed at least one item on the abbreviated World Health Organization Composite International Diagnostic Interview (WHO CIDI) psychosis screen were asked whether they could describe their experiences in an open-ended format. Using reflexive thematic analysis, three coders developed codes that were grouped into categories,&#xa0;and ultimately classified responses as probably psychotic, probably not psychotic, or unclear. Content analysis identified 13 thematic categories, including hallucinations, paranoia, emotional distress, interpersonal conflict, spiritual or paranormal beliefs, sleep-related experiences, and unintelligible responses. Nearly half of the responses were classified as unlikely to reflect psychotic experiences, while approximately 9% were deemed probably psychotic and 41% remained unclear due to insufficient context. Many responses reflected affective distress, stress-related interpretations, grief, or ambiguous experiences rather than clear psychotic phenomena. Descriptions capturing distress, functional impact, and insight were clinically informative but were inconsistently reported. Brief qualitative descriptions accompanying psychosis screening items provide valuable context that can clarify whether psychotic experiences reflect clinically meaningful psychotic phenomena or normative experiences. Integrating qualitative free-response fields may improve the interpretability and precision of psychosis screening, inform early detection efforts, and reduce the risk of over-pathologization.

Urine drug testing for tetrahydrocannabinol (THC) is widely performed using lateral flow immunoassay (LFI) kits. However, these tests are vulnerable to adulteration by benzalkonium chloride (BAK), a cationic surfactant that is a common ingredient in consumer products, such as eyedrops and antiseptics, which can produce false-negative THC results. BAK is believed to act by forming micelles around the THC metabolite 11-nor-9-carboxy-tetrahydrocannabinol (THC-COOH), blocking detection. Because BAK is not routinely included in specimen validity testing panels, it remains a significant potential masking agent in urine drug screening. This study evaluated BAK-containing products and confirmed that readily available commercial formulations can effectively mask THC in the urine. For example, when 25 mL of an antiseptic liquid containing BAK at a nominal concentration of 1300 ppm was added to 75 mL of urine, the LFI test was found to flip from true positive to false negative. Consumer products containing lower concentrations of BAK, such as eye drops, typically mask THC detection when added to urine at an equal volume. To address the vulnerability of LFI-based THC testing to BAK addition, a rapid, low-cost, noninstrumental screening approach based on the standard addition method was developed to distinguish true negatives from BAK-induced false negatives. In blinded testing of 45 urine samples, consisting of 15 true positives, 15 true negatives, and 15 false negatives, the method correctly identified all of the adulterated samples. These findings highlight a practical strategy for improving the reliability of THC urine drug screening in settings where LFI kits are routinely used.

In emergency care, clinicians currently have scarce evidence-based guidance on whether to order diagnostic tests for suspected pulmonary embolism in children. We aimed to test whether the Pulmonary Embolism Rule-Out Criteria in Children (PERC-Peds) can safely rule out pulmonary embolism in children. This multicentre, prospective, observational, diagnostic accuracy study was done in 21 paediatric emergency departments across the USA. We enrolled children aged 4-17 years who presented with symptoms prompting the emergency physician to order, or strongly consider ordering, a diagnostic test for pulmonary embolism. Participants formed a consecutive series. At the point of care, clinicians completed a case report form to record the components of the PERC-Peds rule. Diagnostic testing, including D-dimer testing, was done at clinician discretion. Trained research personnel collected patient-reported demographic data, symptoms, medications, and past medical histories prospectively and cross-checked patient-reported past medical histories and medications against data in the electronic health record. Follow-up was done 45 days after enrolment with a standardised, automated SMS message to caregivers. The criterion standard for pulmonary embolism was the outcome of any venous thromboembolism (VTE; including image-proven pulmonary embolism or proximal deep vein thrombosis [DVT; above knee or elbow, but not including isolated saphenous, brachial, or calf vein clots]) within 45 days, as adjudicated by an independent committee of three board-certified paediatric emergency physicians. Adjudicators viewed all imaging reports, information from the 45-day follow-up, and outside medical records. The primary endpoint was safe exclusion by use of PERC-Peds in all participants who were adjudicated, defined as the upper limit of the 95% CI for the false-negative rate not crossing 1&#xb7;5%. Between July 29, 2020, and Sept 29, 2024, 4039 children were enrolled, with 4011 participants adjudicated for pulmonary embolism or proximal DVT. Date of last follow-up was Sept 18, 2025. The median age of the adjudicated population was 15 years (IQR 13-16); 2567 (64&#xb7;0%) were female and 1444 (36&#xb7;0%) were male. 3988 participants had complete data, and 253 (6&#xb7;3%, 95% CI 5&#xb7;6-7&#xb7;2) were diagnosed with pulmonary embolism or proximal DVT within 45 days. The sensitivity of the PERC-Peds rule was 99&#xb7;6% (95% CI 97&#xb7;8-100&#xb7;0), specificity was 19&#xb7;6% (18&#xb7;4-20&#xb7;9), and false-negative rate was 0&#xb7;1% (0&#xb7;0-0&#xb7;8). D-dimer test was ordered in 3161 (78&#xb7;8%) of 4011 participants. Sequential use of PERC-Peds followed by D-dimer test ruled out pulmonary embolism or proximal DVT in 2167 (54&#xb7;3%) with a false-negative rate of 0&#xb7;9% (0&#xb7;6-1&#xb7;4). In this multicentre, prospective, observational, diagnostic accuracy study of children with suspected pulmonary embolism in the emergency department, we found a 6&#xb7;3% prevalence of pulmonary embolism or proximal DVT; in this population, the PERC-Peds negative rule can safely rule out pulmonary embolism. Use of PERC-Peds might reduce low-value diagnostic testing for pulmonary embolism in children and adolescents. US National Institutes of Health.

Patients with plasma cell leukemia (PCL) are generally excluded from pivotal T-cell redirecting bispecific antibody (BsAb) trials. We evaluated real-world outcomes in a multicenter retrospective study of 122 patients with primary or secondary PCL across 15 academic centers, categorized as 'active' (&#x2265;5% circulating plasma cells within 30 days of BsAb initiation) or 'historical'. In a heavily pretreated population, patients received teclistamab (37%), elranatamab (11%), talquetamab as a line of therapy (Tal LOT, 42%), or talquetamab as bridging therapy to CAR-T (Tal Bridge, 11%). Cytokine release syndrome (CRS) was grade 1-2 in 56% and grade 3-4 in 4%, whereas neurotoxicity was grade 1-2 in 16% and grade 3-4 in 5%. Among 110 evaluable patients, the overall response rate (ORR) was 55%, including 61% with Tal LOT, 58% with Tal Bridge, 46% with elranatamab, and 33% with teclistamab. With a median follow-up of 8.3 months, talquetamab demonstrated superior survival. Tal LOT showed a median progression-free survival (mPFS) of 5.5 months and a median overall survival (mOS) of 11.5 months, and both were unreached in the Tal Bridge cohort. In contrast, teclistamab and elranatamab showed a mPFS of 1.2 and 1.6 months and mOS of 8.1 and 3.6 months, respectively (P=0.007, P=0.023). In active PCL, Tal LOT achieved mPFS/mOS of 6.9/12.2 months versus 0.7/1.4 months with teclistamab and 1.0/3.1 months with elranatamab, respectively (P<0.001, P=0.002). Multivariable analysis associated active PCL with worse survival and Tal LOT with improved outcomes. BsAbs were safe in PCL, with talquetamab showing superior outcomes compared with BCMA-directed BsAbs.