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Hadronic resonances are used to probe the hadron gas produced in the late stage of heavy-ion collisions since they decay on the same timescale, of the order of 1 to 10 fm/c, as the decoupling time of the system. In the hadron gas, (pseudo)elastic scatterings among the products of resonances that decayed before the kinetic freeze-out and regeneration processes counteract each other, the net effect depending on the resonance lifetime, the duration of the hadronic phase, and the hadronic cross sections at play. In this context, the Σ(1385)± particle is of particular interest as models predict that regeneration dominates over rescattering despite its relatively short lifetime of about 5.5 fm/c. The first measurement of the Σ(1385)± resonance production at midrapidity in Pb-Pb collisions at sNN−−−√=5.02 TeV with the ALICE detector is presented in this Letter. The resonances are reconstructed via their hadronic decay channel, Λπ, as a function of the transverse momentum (pT) and the collision centrality. The results are discussed in comparison with the measured yield of pions and with expectations from the statistical hadronization model as well as commonly employed event generators, including PYTHIA8/Angantyr and EPOS3 coupled to the UrQMD hadronic cascade afterburner. None of the models can describe the data. For Σ(1385)±, a similar behaviour as K∗(892)0 is observed in data unlike the predictions of EPOS3 with afterburner.
The most precise measurements to date of the 3ΛH lifetime τ and Λ separation energy BΛ are obtained using the data sample of Pb-Pb collisions at √sNN = 5.02 TeV collected by ALICE at the LHC. The 3ΛH is reconstructed via its charged two-body mesonic decay channel (3ΛH → 3He + π− and the charge-conjugate process). The measured values τ = [253 ± 11 (stat) ± 6 (syst)] ps and BΛ = [102 ± 63 (stat) ± 67 (syst)] keV are compatible with predictions from effective field theories and confirm that the 3ΛH structure is consistent with a weakly bound system.
The most precise measurements to date of the 3ΛH lifetime τ and Λ separation energy BΛ are obtained using the data sample of Pb-Pb collisions at √= 5.02 TeV collected by ALICE at the LHC. The 3ΛH is reconsNN structed via its charged two-body mesonic decay channel (3ΛH→ 3He + π− and the charge-conjugate process). The measured values τ=[253±11 (stat.)±6 (syst.)] ps and BΛ=[102±63 (stat.)±67 (syst.)] keV are compatible with predictions from effective field theories and confirm that the 3ΛH structure is consistent with a weakly-bound system.
The production of inclusive, prompt and non-prompt J/ψ was studied for the first time at midrapidity (−1.37 < ycms < 0.43) in p-Pb collisions at √sNN = 8.16 TeV with the ALICE detector at the LHC. The inclusive J/ψ mesons were reconstructed in the dielectron decay channel in the transverse momentum (pT) interval 0 < pT < 14 GeV/c and the prompt and non-prompt contributions were separated on a statistical basis for pT > 2 GeV/c. The study of the J/ψ mesons in the dielectron channel used for the first time in ALICE online single-electron triggers from the Transition Radiation Detector, providing a data sample corresponding to an integrated luminosity of 689 ± 13 μb−1. The proton-proton reference cross section for inclusive J/ψ was obtained based on interpolations of measured data at different centre-of-mass energies and a universal function describing the pT-differential J/ψ production cross sections. The pT-differential nuclear modification factors RpPb of inclusive, prompt, and non-prompt J/ψ are consistent with unity and described by theoretical models implementing only nuclear shadowing.
The production of inclusive, prompt and non-prompt J/ψ was studied for the first time at midrapidity (−1.37<ycms<0.43) in p−Pb collisions at √sNN =8.16 TeV with the ALICE detector at the LHC. The inclusive J/ψ mesons were reconstructed in the dielectron decay channel in the transverse momentum (pT) interval 0<pT<14 GeV/c and the prompt and non-prompt contributions were separated on a statistical basis for pT>2 GeV/c. The study of the J/ψ mesons in the dielectron channel used for the first time in ALICE online single-electron triggers from the Transition Radiation Detector, providing a data sample corresponding to an integrated luminosity of 689±13μb−1. The proton−proton reference cross section for inclusive J/ψ was obtained based on interpolations of measured data at different centre-of-mass energies and a universal function describing the pT-differential J/ψ production cross sections. The pT-differential nuclear modification factors RpPb of inclusive, prompt, and non-prompt J/ψ are consistent with unity and described by theoretical models implementing only nuclear shadowing.
Background: The combination of intermediate-dose cytarabine plus mitoxantrone (IMA) can induce high complete remission rates with acceptable toxicity in elderly patients with acute myeloid leukemia (AML). We present the final results of a randomized-controlled trial comparing IMA with the standard 7 + 3 induction regimen consisting of continuous infusion cytarabine plus daunorubicin (DA).
Patients and methods: Patients with newly diagnosed AML >60 years were randomized to receive either intermediate-dose cytarabine (1000 mg/m2 twice daily on days 1, 3, 5, 7) plus mitoxantrone (10 mg/m2 days 1–3) (IMA) or standard induction therapy with cytarabine (100 mg/m2 continuously days 1–7) plus daunorubicin (45 mg/m2 days 3–5) (DA). Patients in complete remission after DA received intermediate-dose cytarabine plus amsacrine as consolidation treatment, whereas patients after IMA were consolidated with standard-dose cytarabine plus mitoxantrone.
Results: Between February 2005 and October 2009, 485 patients were randomized; 241 for treatment arm DA and 244 for IMA; 76% of patients were >65 years. The complete response rate after DA was 39% [95% confidence interval (95% CI): 33–45] versus 55% (95% CI: 49–61) after IMA (odds ratio 1.89, P = 0.001). The 6-week early-death rate was 14% in both arms. Relapse-free survival curves were superimposable in the first year, but separated afterwards, resulting in 3-year relapse-free survival rates of 29% versus 14% in the DA versus IMA arms, respectively (P = 0.042). The median overall survival was 10 months in both arms (P = 0.513).
Conclusion: The dose escalation of cytarabine in induction therapy lead to improved remission rates in the elderly AML patients. This did not translate into a survival advantage, most likely due to differences in consolidation treatment. Thus, effective consolidation strategies need to be further explored. In combination with an effective consolidation strategy, the use of intermediate-dose cytarabine in induction may improve curative treatment for elderly AML patients.
Objectives: The aim of this multicenter retrospective study was to investigate safety and efficacy of direct acting antiviral (DAA) treatment in the rare subgroup of patients with HCV/HIV-coinfection and advanced liver cirrhosis on the liver transplant waiting list or after liver transplantation, respectively.
Methods: When contacting 54 German liver centers (including all 23 German liver transplant centers), 12 HCV/HIV-coinfected patients on antiretroviral combination therapy were reported having received additional DAA therapy while being on the waiting list for liver transplantation (patient characteristics: Child-Pugh A (n = 6), B (n = 5), C (n = 1); MELD range 7–21; HCC (n = 2); HCV genotype 1a (n = 8), 1b (n = 2), 4 (n = 2)). Furthermore, 2 HCV/HIV-coinfected patients were denoted having received DAA therapy after liver transplantation (characteristics: HCV genotype 1a (n = 1), 4 (n = 1)).
Results: Applied DAA regimens were SOF/DAC (n = 7), SOF/LDV/RBV (n = 3), SOF/RBV (n = 3), PTV/r/OBV/DSV (n = 1), or PTV/r/OBV/DSV/RBV (n = 1), respectively. All patients achieved SVR 12, in the end. In one patient, HCV relapse occurred after 24 weeks of SOF/DAC therapy; subsequent treatment with 12 weeks PTV/r/OBV/DSV achieved SVR 12. One patient underwent liver transplantation while on DAA treatment. Analysis of liver function revealed either stable parameters or even significant improvement during DAA therapy and in follow-up. MELD scores were found to improve in 9/13 therapies in patients on the waiting list for liver transplantation; in only 2 patients a moderate increase of MELD scores persisted at the end of follow-up.
Conclusion: DAA treatment was safe and highly effective in this nation-wide cohort of patients with HCV/HIV-coinfection awaiting liver transplantation or being transplanted.
Lenalidomide (LEN) maintenance (MT) post autologous stem cell transplantation (ASCT) is standard of care in newly diagnosed multiple myeloma (MM) but has not been compared to other agents in clinical trials. We retrospectively compared bortezomib (BTZ; n = 138) or LEN (n = 183) MT from two subsequent GMMG phase III trials. All patients received three cycles of BTZ-based triplet induction and post-ASCT MT. BTZ MT (1.3 mg/m2 i.v.) was administered every 2 weeks for 2 years. LEN MT included two consolidation cycles (25 mg p.o., days 1–21 of 28 day cycles) followed by 10–15 mg/day for 2 years. The BTZ cohort more frequently received tandem ASCT (91% vs. 33%) due to different tandem ASCT strategies. In the LEN and BTZ cohort, 43% and 46% of patients completed 2 years of MT as intended (p = 0.57). Progression-free survival (PFS; HR = 0.83, p = 0.18) and overall survival (OS; HR = 0.70, p = 0.15) did not differ significantly with LEN vs. BTZ MT. Patients with <nCR after first ASCT were assigned tandem ASCT in both trials. In patients with <nCR and tandem ASCT (LEN: n = 54 vs. BTZ: n = 84), LEN MT significantly improved PFS (HR = 0.61, p = 0.04) but not OS (HR = 0.46, p = 0.09). In conclusion, the significant PFS benefit after eliminating the impact of different tandem ASCT rates supports the current standard of LEN MT after ASCT.
Background: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity.
Objective: To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus.
Methods: Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%).
Results: Seropositive patients were found to be predominantly female (p < 0.0003), to more often have signs of co-existing autoimmunity (p < 0.00001), and to experience more severe clinical attacks. A visual acuity of ≤ 0.1 during acute optic neuritis (ON) attacks was more frequent among seropositives (p < 0.002). Similarly, motor symptoms were more common in seropositive patients, the median Medical Research Council scale (MRC) grade worse, and MRC grades ≤ 2 more frequent, in particular if patients met the 2006 revised criteria (p < 0.005, p < 0.006 and p < 0.01, respectively), the total spinal cord lesion load was higher (p < 0.006), and lesions ≥ 6 vertebral segments as well as entire spinal cord involvement more frequent (p < 0.003 and p < 0.043). By contrast, bilateral ON at onset was more common in seronegatives (p < 0.007), as was simultaneous ON and myelitis (p < 0.001); accordingly, the time to diagnosis of NMO was shorter in the seronegative group (p < 0.029). The course of disease was more often monophasic in seronegatives (p < 0.008). Seropositives and seronegatives did not differ significantly with regard to age at onset, time to relapse, annualized relapse rates, outcome from relapse (complete, partial, no recovery), annualized EDSS increase, mortality rate, supratentorial brain lesions, brainstem lesions, history of carcinoma, frequency of preceding infections, oligoclonal bands, or CSF pleocytosis. Both the time to relapse and the time to diagnosis was longer if the disease started with ON (p < 0.002 and p < 0.013). Motor symptoms or tetraparesis at first myelitis and > 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome.
Conclusion: This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients
Background: Atypical EGFR mutations occur in 10%-30% of non-small-cell lung cancer (NSCLC) patients with EGFR mutations and their sensitivity to classical epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) is highly heterogeneous. Patients harboring one group of uncommon, recurrent EGFR mutations (G719X, S768I, L861Q) respond to EGFR-TKI. Exon 20 insertions are mostly insensitive to EGFR-TKI but display sensitivity to exon 20 inhibitors. Clinical outcome data of patients with very rare point and compound mutations upon systemic treatments are still sparse to date.
Patients and methods: In this retrospective, multicenter study of the national Network Genomic Medicine (nNGM) in Germany, 856 NSCLC cases with atypical EGFR mutations including co-occurring mutations were reported from 12 centers. Clinical follow-up data after treatment with different EGFR-TKIs, chemotherapy and immune checkpoint inhibitors were available from 260 patients. Response to treatment was analyzed in three major groups: (i) uncommon mutations (G719X, S7681, L861Q and combinations), (ii) exon 20 insertions and (iii) very rare EGFR mutations (very rare single point mutations, compound mutations, exon 18 deletions, exon 19 insertions).
Results: Our study comprises the largest thus far reported real-world cohort of very rare EGFR single point and compound mutations treated with different systemic treatments. We validated higher efficacy of EGFR-TKI in comparison to chemotherapy in group 1 (uncommon), while most exon 20 insertions (group 2) were not EGFR-TKI responsive. In addition, we found TKI sensitivity of very rare point mutations (group 3) and of complex EGFR mutations containing exon 19 deletions or L858R mutations independent of the combination partner. Notably, treatment responses in group 3 (very rare) were highly heterogeneous. Co-occurring TP53 mutations exerted a non-significant trend for a detrimental effect on outcome in EGFR-TKI-treated patients in groups 2 and 3 but not in group 1.
Conclusions: Based on our findings, we propose a novel nNGM classification of atypical EGFR mutations.