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Conventional superconductivity emerges from pairing of charge carriers-electrons or holes-mediated by phonons1. In many unconventional superconductors, the pairing mechanism is conjectured to be mediated by magnetic correlations2, as captured by models of mobile charges in doped antiferromagnets3. However, a precise understanding of the underlying mechanism in real materials is still lacking and has been driving experimental and theoretical research for the past 40 years. Early theoretical studies predicted magnetic-mediated pairing of dopants in ladder systems4-8, in which idealized theoretical toy models explained how pairing can emerge despite repulsive interactions9. Here we experimentally observe this long-standing theoretical prediction, reporting hole pairing due to magnetic correlations in a quantum gas of ultracold atoms. By engineering doped antiferromagnetic ladders with mixed-dimensional couplings10, we suppress Pauli blocking of holes at short length scales. This results in a marked increase in binding energy and decrease in pair size, enabling us to observe pairs of holes predominantly occupying the same rung of the ladder. We find a hole-hole binding energy of the order of the superexchange energy and, upon increased doping, we observe spatial structures in the pair distribution, indicating repulsion between bound hole pairs. By engineering a configuration in which binding is strongly enhanced, we delineate a strategy to increase the critical temperature for superconductivity.
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Topology in quantum many-body systems has profoundly changed our understanding of quantum phases of matter. The model that has played an instrumental role in elucidating these effects is the antiferromagnetic spin-1 Haldane chain1,2. Its ground state is a disordered state, with symmetry-protected fourfold-degenerate edge states due to fractional spin excitations. In the bulk, it is characterized by vanishing two-point spin correlations, gapped excitations and a characteristic non-local order parameter3,4. More recently it has been understood that the Haldane chain forms a specific example of a more general classification scheme of symmetry-protected topological phases of matter, which is based on ideas connected to quantum information and entanglement5-7. Here, we realize a finite-temperature version of such a topological Haldane phase with Fermi-Hubbard ladders in an ultracold-atom quantum simulator. We directly reveal both edge and bulk properties of the system through the use of single-site and particle-resolved measurements, as well as non-local correlation functions. Continuously changing the Hubbard interaction strength of the system enables us to investigate the robustness of the phase to charge (density) fluctuations far from the regime of the Heisenberg model, using a novel correlator.
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ABSTRACT: Multiple myeloma is characterized by a huge heterogeneity at the molecular level. The RAS/RAF pathway is the most frequently mutated, in â¼50% of the patients. However, these mutations are frequently subclonal, suggesting a secondary event. Because these genes are part of our routine next-generation sequencing panel, we analyzed >10 000 patients with different plasma cell disorders to describe the RAS/RAF landscape. In this large cohort of patients, almost 61% of the patients presented a RAS/RAF mutation at diagnosis or relapse, but much lower frequencies occurred in presymptomatic cases. Of note, the mutations were different from that observed in solid tumors (higher proportions of Q61 mutations). In 29 patients with 2 different mutations, we were able to perform single-cell sequencing, showing that in most cases, mutations occurred in different subclones, suggesting an ongoing mutational process. These findings suggest that the RAS/RAF pathway is not an attractive target, both on therapeutic and residual disease assessment points of view.
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Mieloma Múltiplo , Mutação , Humanos , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Plasmócitos/metabolismo , Plasmócitos/patologia , Proteínas ras/genética , Proteínas ras/metabolismo , Quinases raf/genética , Quinases raf/metabolismo , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
The prognostic significance of hypercalcemia in lymphoma has only been studied on small series to date. We conducted a retrospective, monocentric, matched-control study that aimed to compare the outcome of patients diagnosed with any histological subtype of lymphoma associated with hypercalcemia, at diagnosis or relapse, with a group of controls matched for histological and prognostic factors. Sixty-two and 118 comparable patients treated between 2000 and 2016 were included in hypercalcemia and control cohorts, respectively. Hypercalcemia was found mainly at diagnosis (71%) in higher-risk patients (prognosis scores ≥ 3, 76%) and those with diffuse large B cell lymphoma (67.7%), stage III/IV disease (91.9%), and elevated LDH (90.3%). Two-year progression-free survival (PFS) was shorter in the hypercalcemia than control cohort [30.1% (95% confidence interval (95% CI) 18.3-41.9) vs 63.9% (95% CI 5.1-72.7), p < 0.001]. Two-year overall survival (OS) was 40.6% (95% CI 28.1-53.1) and 77.7% (95% CI 70.1-85.3) in the hypercalcemia and control cohorts, respectively (p < 0.001). Hypercalcemia was independently associated with poor PFS [HR = 2.5 (95% CI 1.4-3.5)] and OS [HR = 4.7 (95% CI 2.8-7.8)] in multivariate analysis. Among the 40 patients who received autologous stem cell transplantation (ASCT), hypercalcemia was still associated with shorter OS [2-year OS: 65% (95% CI 40.1-89.9) vs 88.0 (95% CI 75.3-100), p = 0.04]. Hypercalcemia may be associated with chemo-resistance, given its impact on PFS and OS. Hence, these data suggest that alternate strategies for lymphoma patients with hypercalcemia should be developed.
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Hipercalcemia , Linfoma Difuso de Grandes Células B , Transplante de Células-Tronco , Idoso , Autoenxertos , Intervalo Livre de Doença , Feminino , Humanos , Hipercalcemia/sangue , Hipercalcemia/diagnóstico , Hipercalcemia/mortalidade , Hipercalcemia/terapia , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
The precision of a quantum sensor can overcome its classical counterpart when its constituents are entangled. In Gaussian squeezed states, quantum correlations lead to a reduction of the quantum projection noise below the shot noise limit. However, the most sensitive states involve complex non-Gaussian quantum fluctuations, making the required measurement protocol challenging. Here we measure the sensitivity of nonclassical states of the electronic spin J=8 of dysprosium atoms, created using light-induced nonlinear spin coupling. Magnetic sublevel resolution enables us to reach the optimal sensitivity of non-Gaussian (oversqueezed) states, well above the capability of squeezed states and about half the Heisenberg limit.
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We report on an experimental study of the Lipkin-Meshkov-Glick model of quantum spins interacting at infinite range in a transverse magnetic field, which exhibits a ferromagnetic phase transition in the thermodynamic limit. We use dysprosium atoms of electronic spin J=8, subjected to a quadratic Zeeman light shift, to simulate 2J=16 interacting spins 1/2. We probe the system microscopically using single magnetic sublevel resolution, giving access to the spin projection parity, which is the collective observable characterizing the underlying Z_{2} symmetry. We measure the thermodynamic properties and dynamical response of the system, and we study the quantum critical behavior around the transition point. In the ferromagnetic phase, we achieve coherent tunneling between symmetry-broken states, and we test the link between symmetry breaking and the appearance of a finite order parameter.
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The coexistence of dual hematological neoplasms is very rare. Sequential or synchronous neoplasms in hematology are an uncommon and complex clinical situation. The aim of the Hemo2 study was to describe the clinical characteristics and analyze the outcome of these patients. We performed a retrospective review of all patients diagnosed with sequential or synchronous hematological malignancies in the university hospital of Tours, between 2007 and 2018. We identified 49 patients in our study, with a prevalence of 0.89%. Sequential and synchronous combinations were found in 36 (73%) and 13 (27%) patients, respectively. One patient presented three sequential neoplasms. The median cumulative incidence was 6 years (95% CI 3-7). Among all neoplasms diagnosed (n = 99), we found 79 lymphoid neoplasms (LNs) (80%) and 20 myeloid neoplasms (MNs) (20%). Sex ratio was 1.88 with 65% of males and 35% of females. The most common LNs were Hodgkin lymphoma (n = 16; 16%) and multiple myeloma (n = 11; 11%). The most frequent MN was essential thrombocythemia (n = 5; 5%). The most common combination was Hodgkin lymphoma and follicular lymphoma in five (10%) patients. The overall survival from the first diagnosis (OS1) at 5 years was 82.4% (95% CI 72.1-94.3). The median overall survival from the second diagnosis (OS2) was 98 months (95% CI 44-NR) and 5-year OS2 was 58.7% (95% CI 45.5-75.7). Median progression-free survival from the second diagnosis (PFS) was 47 months (95% CI 27-NR) with 5-year PFS of 49% (95% CI 35.9-67). OS and PFS did not statistically differ between synchronous and sequential dual neoplasms. In this cohort, that the death relative risk (RR) was significantly lower if the second neoplasm appeared after more than 4 years following the first diagnosis (OR 0.37 (95% CI 0.16-0.90)). The Hemo2study confirmed the rarity of dual hematological neoplasms. In this cohort, HL and FL were the most frequent combinations. Our results may support that synchronous and sequential dual neoplasms bear the same prognosis. Further studies are needed to better characterize these uncommon clinical situations.
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Neoplasias Hematológicas , Segunda Neoplasia Primária , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/mortalidade , Segunda Neoplasia Primária/patologia , Segunda Neoplasia Primária/terapia , Prevalência , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Tularemia is a rare zoonotic infection caused by bacterium Francisella tularensis. It has been well described in immunocompetent patients but poorly described in immunocompromised patients notably in solid organ transplant recipients. CASE PRESENTATIONS: We report here two cases of tularemia in solid organ transplant recipients including first case after heart transplant. We also carried out an exhaustive review of literature describing characteristics of this infection in solid organ transplant recipients.
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Tularemia/diagnóstico , Zoonoses/diagnóstico , Animais , Antibacterianos/uso terapêutico , Quimioterapia Combinada , Francisella tularensis/isolamento & purificação , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transplante de Órgãos , Índice de Gravidade de Doença , Transplantados , Tularemia/tratamento farmacológico , Tularemia/parasitologia , Tularemia/patologia , Zoonoses/tratamento farmacológico , Zoonoses/parasitologia , Zoonoses/patologiaRESUMO
BACKGROUND: Intra-osseous (IO) access is recommended in cases of pre-hospital emergency or resuscitation when intravascular (IV) route is difficult or impossible. Despite recent improvement in IO devices and increasing indications, it remains rarely used in practice. Various complications have been reported but are uncommon. CASE PRESENTATION: We report a case of massive acute tibial osteomyelitis in an adult male three months after an IO catheter insertion for emergency drug infusion. We review the literature on association between IO access and acute osteomyelitis in children and adults. CONCLUSIONS: Emergency-care givers and radiologists should be informed about this infrequent complication in order to make early diagnosis and initiate adequate antibiotic therapy.
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Infecções Relacionadas a Cateter/etiologia , Overdose de Drogas/terapia , Infusões Intraósseas/efeitos adversos , Osteomielite/etiologia , Ressuscitação , Tíbia/microbiologia , Doença Aguda , Adulto , Infecções Relacionadas a Cateter/microbiologia , Infecções Relacionadas a Cateter/patologia , Serviços Médicos de Emergência , Humanos , Doença Iatrogênica , Masculino , Osteomielite/microbiologia , Osteomielite/patologia , Ressuscitação/efeitos adversos , Ressuscitação/métodos , Infecções Estafilocócicas/etiologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus/isolamento & purificação , Tíbia/patologiaRESUMO
A second autologous stem-cell transplantation (ASCT2) is considered for relapsed multiple myeloma (RMM) patients showing prolonged response after a first ASCT. However, given breakthrough treatments like anti-CD38 and immunotherapy, its role remains debated. We conducted a real-life study in 10 French centers (1996-2017) involving 267 RMM patients receiving ASCT2. The median age was 61 years, with 49% females. Most patients received melphalan 200 mg/m² before ASCT2, with low early mortality (1%). Very good partial response or better (VGPR+) rate post ASCT2 was 78%. Post ASCT2, 48% received consolidation therapy and 40% maintenance therapy. Median event-free survival (EFS) after ASCT2 was 2.6 years (95% confidence interval [CI]: 2.3-2.8), and 2-year EFS estimate was 63% (95% CI: 57-70). Median overall survival (OS) was 8.1 years (95% CI: 5.9-NA), and 2-year OS estimate was 92% (95% CI: 88-95). Multivariate analysis revealed that VGPR+ status and maintenance therapy post ASCT2 were associated with better EFS (hazard ratio [HR]: 0.6; 95% CI: 0.3-0.9, p = 0.012 and HR: 0.4; 95% CI: 0.3-0.6, p < 0.001, respectively) and OS (HR: 0.4; 95% CI: 0.2-0.9, p = 0.017 and HR: 0.2; 95% CI: 0.1-0.4, p < 0.001, respectively), while male sex correlated with poorer outcomes for EFS (HR: 2.5; 95% CI: 1.7-3.7, p < 0.001) and OS (HR: 2.7; 95% CI: 1.4-4.9, p = 0.002). Overall, ASCT2 appeared efficient with low toxicity in RMM. Maintenance therapy was associated with extended EFS and OS, particularly in patients with VGPR+ status post ASCT2. These findings underscore ASCT2's potential in RMM when coupled with maintenance therapy in selected patients.
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The therapeutic management of patients with multiple myeloma (MM) is complex. Despite substantial advances, MM remains incurable, and management involves cycles of treatment response, disease relapse, and further therapy. Currently, evidence to support the therapeutic decision is limited. Thus, the EMMY longitudinal, real-world study was designed to annually assess therapeutic management of MM in France to provide evidence to support physicians. During an annual prespecified 3-month recruitment period, eligible patients will be identified from their medical records. Adults aged ≥18 years diagnosed with symptomatic MM and requiring systemic treatment will be eligible. The primary objective, the evolution of MM therapeutic management, will be described, as well as the impact on the following outcomes: time-to-next treatment (TTNT), progression-free survival (PFS), and overall survival (OS). The study plans to recruit 5000 patients over 6 years: 700 to 900 patients annually. EMMY is a unique opportunity to collect real-world data to describe the evolving MM therapeutic landscape and record outcomes in France. These data will provide annual snapshots of various aspects of MM management. This knowledge will provide physicians with real-life, evidence-based data for therapeutic decision-making and ultimately improve treatment for MM patients.
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OBJECTIVES: Bispecific antibodies (BsAbs) are an effective treatment used in relapsed or refractory multiple myeloma. Despite a well-tolerated safety profile, infectious events appear to be frequent in clinical trials. Real-world data on epidemiology, characteristics, risk factors, and outcomes of infections in patients treated with BsAb are still needed. METHODS: A retrospective, multicentre study in BsAb-treated patients with multiple myeloma was performed in 14 French centres from December 2020 to February 2023. The primary objective was to describe the incidence of infections that required hospitalization, specific treatment, or adaptation in BsAb administration. RESULTS: Among 229 patients with multiple myeloma treated with BsAb, 153 (67%) received teclistamab, 47 (20%) received elranatamab, and 29 (13%) talquetamab. We reported a total of 234 infections, including 123 (53%) of grade of ≥3. Predominant infections affected the respiratory tract (n = 116, 50%) followed by bacteraemias (n = 36, 15%). The hospitalization rate was 56% (n = 131), and 20 (9%) infections resulted in death. Global cumulative incidence of the first infection was 70% in all patients, 73% in patients treated with B-cell maturation antigen-targeting, and 51% with GPRC5D-targeting BsAb. In univariate analyses, corticosteroids for cytokine release syndrome (CRS)/immune effector cell-associated neurotoxicity syndrome (ICANS) were associated with a higher risk of first infection (HR = 2.13; 95% CI, 1.38-3.28), whereas GPRC5D-targeting BsAb and anti-bacterial prophylaxis were associated with a lower risk (HR = 0.53; 95% CI, 0.3-0.94 and HR = 0.65; 95% CI, 0.46-0.9). Fine and Gray multivariate model found that only corticosteroids for CRS/ICANS were correlated with a higher risk of first infection (HR = 2.01; 95% CI, 1.27-3.19). DISCUSSIONS: The implementation of preventive measures that aim to mitigate the risk of infection under BsAb is pivotal, notably in patients who received corticosteroids for CRS/ICANS.
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Anticorpos Biespecíficos , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/imunologia , Estudos Retrospectivos , Masculino , Feminino , Anticorpos Biespecíficos/uso terapêutico , Anticorpos Biespecíficos/efeitos adversos , Pessoa de Meia-Idade , Incidência , Idoso , Fatores de Risco , França/epidemiologia , Adulto , Idoso de 80 Anos ou mais , Hospitalização/estatística & dados numéricos , Infecções/epidemiologia , Infecções/etiologiaRESUMO
CD38-targeting immunotherapy is approved in combination with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma (NDMM) that are transplant ineligible (TI) and is considered the best standard of care (SOC). To improve current SOC, we evaluated the added value of weekly bortezomib (V) to isatuximab plus lenalidomide and dexamethasone (IsaRd versus Isa-VRd). This Intergroupe Francophone of Myeloma phase 3 study randomized 270 patients with NDMM that were TI, aged 65-79 years, to IsaRd versus Isa-VRd arms. The primary endpoint was a minimal residual disease (MRD) negativity rate at 10-5 by next-generation sequencing at 18 months from randomization. Key secondary endpoints included response rates, MRD assessment rates, survival and safety. The 18-month MRD negativity rates at 10-5 were reported in 35 patients (26%, 95% confidence interval (CI) 19-34) in IsaRd versus 71 (53%, 95% CI 44-61) in Isa-VRd (odds ratio for MRD negativity 3.16, 95% CI 1.89-5.28, P < 0.0001). The MRD benefit was consistent across subgroups at 10-5 and 10-6, and was already observed at month 12. The proportion of patients with complete response or better at 18 months was higher with Isa-VRd (58% versus 33%; P < 0.0001), as was the proportion of MRD negativity and complete response or better (37% versus 17%; P = 0.0003). At a median follow-up of 23.5 months, no difference was observed for survival times (immature data). The addition of weekly bortezomib did not significantly affect the relative dose intensity of IsaRd. Isa-VRd significantly increased MRD endpoints, including the 18-month negativity rate at 10-5, the primary endpoint, compared with IsaRd. This study proposes Isa-VRd as a new SOC for patients with NDMM that are TI. ClinicalTrials.gov identifier: NCT04751877 .
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The role of high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) in the treatment of myeloma (MM) patients with severe and/or dialysis-dependent renal impairment remains uncertain. We report on the outcomes of 110 patients (median age 57 years) who had become dialysis-dependent pre-ASCT and who underwent a first ASCT between 1997 and 2017. Sixty-three (57%) patients had light chain MM. All patients required dialysis (94% hemodialysis and 6% peritoneal). Forty-four of 71 (62%) patients received bortezomib-based induction regimens and 42 (39%) patients had achieved at least a very good partial response (VGPR) pre-ASCT. Melphalan dosing was as follows: ≤140 mg/m2 (82%), and >140 mg/m2 (18%). The median PFS after ASCT was 35 months (95% CI: 21.5-42.2) and the median OS 102 months (95% CI: 70.4-129.1). At 1, 2, and 5 years after ASCT, 8% (95% CI 3-14%), 13% (6-20%), and 20% (12-29%) of patients, respectively, had achieved dialysis independence. In multivariate analyses of OS and PFS including age at ASCT, response at ASCT, and year of ASCT, younger age at ASCT and better response at ASCT (CR/VGPR/PR vs. MR/SD/progression) were significantly associated with better OS and PFS.
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Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Bortezomib/uso terapêutico , Resultado do Tratamento , Transplante Autólogo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Diálise Renal , Transplante de Células-Tronco , Estudos RetrospectivosRESUMO
BACKGROUND: Shulman's disease, or eosinophilic fasciitis (EF), is a rare autoimmune disease, characterized by sclerodermic skin lesions with progressive induration and thickening of the soft tissues. Chronic graft-versus-host-disease (GVHD) presenting as EF is a very rare manifestation of cutaneous GVHD. CASE PRESENTATION: We report an unusual case of EF in a 46-year-old Caucasian male patient who had received an allogenic hematopoietic stem cell transplantation in the context of relapsed/refractory multiple myeloma. The diagnosis was challenging, with the patient presenting hepatic dysfunction, normal eosinophils count, and incomplete clinical signs. Magnetic resonance imaging (MRI) and skin biopsy confirmed the diagnosis of EF. Early initiation of specific treatment with corticosteroids and prednisolone achieved complete response. CONCLUSION: In practice, incomplete signs in this rare complication should lead to MRI as it is a major tool to guide decision-making based on the skin biopsy, allowing a rapid diagnosis and the initiation of treatment without delay.
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Eosinofilia , Fasciite , Doença Enxerto-Hospedeiro , Eosinofilia/diagnóstico , Eosinofilia/tratamento farmacológico , Eosinófilos , Fasciite/diagnóstico , Fasciite/tratamento farmacológico , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: In ineffective erythropoiesis, hepcidin synthesis is suppressed by erythroid regulators, namely erythroferrone and growth differentiation factor-15. For the first time, the hypothesis that iron overload in megaloblastic anemia may be related to ineffective erythropoiesis is explored by describing the kinetics of hepcidin, erythroferrone, and growth differentiation factor-15 levels in a patient diagnosed with megaloblastic anemia associated with iron overload. CASE PRESENTATION: An 81-year-old Caucasian male was admitted for fatigue. He had type-2 diabetes previously treated with metformin, ischemic cardiac insufficiency, and stage-3 chronic kidney disease. Vitiligo was observed on both hands. Biological tests revealed normocytic non-regenerative anemia associated with hemolysis, thrombocytopenia, and elevated sideremia, ferritin, and transferrin saturation levels. Megaloblastic anemia was confirmed with undetectable blood vitamin B12 and typical cytological findings like hyper-segmented neutrophils in blood and megaloblasts in bone marrow. The patient received vitamin B12 supplementation. At 3 months, biological parameters reached normal values. Hepcidin kinetics from diagnosis to 3 months inversely correlated with those of erythroferrone and growth differentiation factor-15. CONCLUSIONS: This case suggests that iron-overload mechanisms of dyserythropoietic anemias may apply to megaloblastic anemias.
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Anemia Megaloblástica , Anemia , Sobrecarga de Ferro , Idoso de 80 Anos ou mais , Anemia Megaloblástica/diagnóstico , Anemia Megaloblástica/tratamento farmacológico , Eritropoese , Humanos , Ferro , Sobrecarga de Ferro/tratamento farmacológico , MasculinoRESUMO
OBJECTIVES: Patients with haematological malignancies (HM) receive more aggressive treatments near the end-of-life (EOL) than patients with solid tumours. Palliative care (PC) needs are less widely acknowledged in patients with multiple myeloma (MM) than in other HM. The main objective of our study was to describe EOL care and PC referral in a population of older patients with MM. METHODS: We retrospectively included deceased inpatients and outpatients with an MM previously diagnosed at the age of 70 and over in two tertiary centres in France. We reported EOL characteristics regarding treatments considered to be aggressive-antimyeloma therapies, hospitalisations, blood product transfusions, intensive care units (ICUs) or emergency admissions-and PC referral. RESULTS: We included 119 patients. In their last month of life, 75 (63%) were hospitalised for fever, pain, asthenia, anaemia or bleeding, 49 (41%) were admitted in the emergency department and 12 (10%) in ICU, 76 (64%) still received antimyeloma therapy and 45 (38%) had at least two transfusions. Only 24 (20%) received PC intervention for pain, global care, family support, anxiety, social care or confusion. Median follow-up until death was 20 days. CONCLUSIONS: Our study found a high rate of hospitalisations and antimyeloma therapies in the last month of life. The PC referral rate was low, often once specific treatments were stopped. Our results suggest the need for more effective collaboration between PC teams and haematologists in order to respond to the specific needs of these patients and to improve their quality of care at EOL.
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Coherent superposition states of a mesoscopic quantum object play a major role in our understanding of the quantum to classical boundary, as well as in quantum-enhanced metrology and computing. However, their practical realization and manipulation remains challenging, requiring a high degree of control of the system and its coupling to the environment. Here, we use dysprosium atoms-the most magnetic element in its ground state-to realize coherent superpositions between electronic spin states of opposite orientation, with a mesoscopic spin size J = 8. We drive coherent spin states to quantum superpositions using non-linear light-spin interactions, observing a series of collapses and revivals of quantum coherence. These states feature highly non-classical behavior, with a sensitivity to magnetic fields enhanced by a factor 13.9(1.1) compared to coherent spin states-close to the Heisenberg limit 2J = 16-and an intrinsic fragility to environmental noise.