Efficacy and safety of nilotinib as third-line therapy in an elderly patient with CML

This case report describes a 74 year old male patient with low Sokal risk chronic myeloid leukemia (CML). Treatment was started four years ago with imatinib, 400 mg/day. The patient achieved complete hematologic response but, after 3 months of treatment, developed grade 3 skin toxicity. Imatinib was stopped and the patient was started on dasatinib, achieving complete cytogenetic and molecular response. Two months later, physical examination revealed bilateral gynecomastia. After 2 years of treatment the patient presented with pleural effusion and the drug dose was reduced but, following relapse of CML, therapy was switched to nilotinib, 800 mg/day. Treatment with nilotinib is currently ongoing and is well tolerated by the patient who is again in complete molecular response, with no signs of pleural effusion. Considering the growing availability of new and more potent tyrosine kinase inhibitors (TKI) it is important for the clinician to be aware of the possible inhibitory effects of these molecules against other members of the tyrosine kinase family. Safety of TKI in frail and elderly patients with CML is a fundamental goal. The results achieved in our patient show that nilotinib is safe and effective even when used as third line therapy

Prophylactic and Preemptive Therapy with Dasatinib after Hematopoietic Stem Cell Transplantation for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

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Mortality risk factors in primary Sjögren syndrome:a real-world, retrospective, cohort study

BACKGROUND: What baseline predictors would be involved in mortality in people with primary Sjögren syndrome (SjS) remains uncertain. This study aimed to investigate the baseline characteristics collected at the time of diagnosis of SjS associated with mortality and to identify mortality risk factors for all-cause death and deaths related to systemic SjS activity measured by the ESSDAI score.METHODS: In this international, real-world, retrospective, cohort study, we retrospectively collected data from 27 countries on mortality and causes of death from the Big Data Sjögren Registry. Inclusion criteria consisted of fulfilling 2002/2016 SjS classification criteria, and exclusion criteria included chronic HCV/HIV infections and associated systemic autoimmune diseases. A statistical approach based on a directed acyclic graph was used, with all-cause and Sjögren-related mortality as primary endpoints. The key determinants that defined the disease phenotype at diagnosis (glandular, systemic, and immunological) were analysed as independent variables.FINDINGS: Between January 1st, 2014 and December 31, 2023, data from 11,372 patients with primary SjS (93.5% women, 78.4% classified as White, mean age at diagnosis of 51.1 years) included in the Registry were analysed. 876 (7.7%) deaths were recorded after a mean follow-up of 8.6 years (SD 7.12). Univariate analysis of prognostic factors for all-cause death identified eight Sjögren-related variables (ocular and oral tests, salivary biopsy, ESSDAI, ANA, anti-Ro, anti-La, and cryoglobulins). The multivariate CPH model adjusted for these variables and the epidemiological features showed that DAS-ESSDAI (high vs no high: HR = 1.68; 95% CI, 1.27-2.22) and cryoglobulins (positive vs negative: HR = 1.72; 95% CI, 1.22-2.42) were independent predictors of all-cause death. Of the 640 deaths with available information detailing the specific cause of death, 14% were due to systemic SjS. Univariate analysis of prognostic factors for Sjögren-cause death identified five Sjögren-related variables (oral tests, clinESSDAI, DAS-ESSDAI, ANA, and cryoglobulins). The multivariate competing risks CPH model adjusted for these variables and the epidemiological features showed that oral tests (abnormal vs normal results: HR = 1.38; 95% CI, 1.01-1.87), DAS-ESSDAI (high vs no high: HR = 1.55; 95% CI, 1.22-1.96) and cryoglobulins (positive vs negative: HR = 1.52; 95% CI, 1.16-2) were independent predictors of SjS-related death.INTERPRETATION: The key mortality risk factors at the time of SjS diagnosis were positive cryoglobulins and a high systemic activity scored using the ESSDAI, conferring a 2-times increased risk of all-cause and SjS-related death. ESSDAI measurement and cryoglobulin testing should be considered mandatory when an individual is diagnosed with SjS.FUNDING: Novartis.</p

Epidemiological profile and north-south gradient driving baseline systemic involvement of primary Sjogren's syndrome

Objective: To characterize the systemic phenotype of primary Sjögren’s syndrome at diagnosis by analysing the EULAR-SS disease activity index (ESSDAI) scores. Methods: The Sjögren Big Data Consortium is an international, multicentre registry based on worldwide data-sharing cooperative merging of pre-existing databases from leading centres in clinical research in Sjögren’s syndrome from the five continents. Results: The cohort included 10 007 patients (9352 female, mean 53 years) with recorded ESSDAI scores available. At diagnosis, the mean total ESSDAI score was 6.1; 81.8% of patients had systemic activity (ESSDAI score ≥1). Males had a higher mean ESSDAI (8.1 vs 6.0, P &lt; 0.001) compared with females, as did patients diagnosed at &lt;35 years (6.7 vs 5.6 in patients diagnosed at &gt;65 years, P &lt; 0.001). The highest global ESSDAI score was reported in Black/African Americans, followed by White, Asian and Hispanic patients (6.7, 6.5, 5.4 and 4.8, respectively; P &lt; 0.001). The frequency of involvement of each systemic organ also differed between ethnic groups, with Black/African American patients showing the highest frequencies in the lymphadenopathy, articular, peripheral nervous system, CNS and biological domains, White patients in the glandular, cutaneous and muscular domains, Asian patients in the pulmonary, renal and haematological domains and Hispanic patients in the constitutional domain. Systemic activity measured by the ESSDAI, clinical ESSDAI (clinESSDAI) and disease activity states was higher in patients from southern countries (P &lt; 0.001). Conclusion: The systemic phenotype of primary Sjögren’s syndrome is strongly influenced by personal determinants such as age, gender, ethnicity and place of residence, which are key geoepidemiological players in driving the expression of systemic disease at diagnosis.

Systemic phenotype related to primary Sjögren's syndrome in 279 patients carrying isolated anti-La/SSB antibodies

OBJECTIVES: To evaluate the systemic phenotype associated with the presence of isolated anti-La/SSB antibodies in a large international registry of patients with primary Sjögren's syndrome (pSS) fulfilling the 2002 classification criteria.METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry created in 2014. Baseline clinical information from leading centres on clinical research in SS of the 5 continents was collected. Combination patterns of anti-Ro/SSA-La/SSB antibodies at the time of diagnosis defined the following four immunological phenotypes: double positive (combined Ro/SSA and La/SSB,) isolated anti-Ro/SSA, isolated anti-La/SSB, and immunonegative.RESULTS: The cohort included 12,084 patients (11,293 females, mean 52.4 years) with recorded ESSDAI scores available. Among them, 279 (2.3%) had isolated anti-La/SSB antibodies. The mean total ESSDAI score at diagnosis of patients with pSS carrying isolated anti-La/SSB was 6.0, and 80.4% of patients had systemic activity (global ESSDAI score ≥1) at diagnosis. The domains with the highest frequency of active patients were the biological (42.8%), glandular (36.8%) and articular (31.2%) domains. Patients with isolated anti-La/SSB showed a higher frequency of active patients in all ESSDAI domains but two (articular and peripheral nerve) in comparison with immune-negative patients, and even a higher absolute frequency in six clinical ESSDAI domains in comparison with patients with isolated anti-Ro/SSA. In addition, patients with isolated anti-La/SSB showed a higher frequency of active patients in two ESSDAI domains (pulmonary and glandular) with respect to the most active immunological subset (double-positive antibodies). Meanwhile, systemic activity detected in patients with isolated anti-La/SSB was overwhelmingly low. Even in ESSDAI domains where patients with isolated anti-La/SSB had the highest frequencies of systemic activity (lymphadenopathy and muscular), the percentage of patients with moderate or high activity was lower in comparison with the combined Ro/SSA and La/SSB group.CONCLUSIONS: Patients carrying isolated La/SSB antibodies represent a very small subset of patients with a systemic SS phenotype characterised by a significant frequency of active patients in most clinical ESSDAI domains but with a relative low frequency of the highest severe organ-specific involvements. Primary SS still remains the best clinical diagnosis for this subset of patients

Systemic phenotype related to primary Sjögren's syndrome in 279 patients carrying isolated anti-La/SSB antibodies

OBJECTIVES: To evaluate the systemic phenotype associated with the presence of isolated anti-La/SSB antibodies in a large international registry of patients with primary Sjögren's syndrome (pSS) fulfilling the 2002 classification criteria.METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry created in 2014. Baseline clinical information from leading centres on clinical research in SS of the 5 continents was collected. Combination patterns of anti-Ro/SSA-La/SSB antibodies at the time of diagnosis defined the following four immunological phenotypes: double positive (combined Ro/SSA and La/SSB,) isolated anti-Ro/SSA, isolated anti-La/SSB, and immunonegative.RESULTS: The cohort included 12,084 patients (11,293 females, mean 52.4 years) with recorded ESSDAI scores available. Among them, 279 (2.3%) had isolated anti-La/SSB antibodies. The mean total ESSDAI score at diagnosis of patients with pSS carrying isolated anti-La/SSB was 6.0, and 80.4% of patients had systemic activity (global ESSDAI score ≥1) at diagnosis. The domains with the highest frequency of active patients were the biological (42.8%), glandular (36.8%) and articular (31.2%) domains. Patients with isolated anti-La/SSB showed a higher frequency of active patients in all ESSDAI domains but two (articular and peripheral nerve) in comparison with immune-negative patients, and even a higher absolute frequency in six clinical ESSDAI domains in comparison with patients with isolated anti-Ro/SSA. In addition, patients with isolated anti-La/SSB showed a higher frequency of active patients in two ESSDAI domains (pulmonary and glandular) with respect to the most active immunological subset (double-positive antibodies). Meanwhile, systemic activity detected in patients with isolated anti-La/SSB was overwhelmingly low. Even in ESSDAI domains where patients with isolated anti-La/SSB had the highest frequencies of systemic activity (lymphadenopathy and muscular), the percentage of patients with moderate or high activity was lower in comparison with the combined Ro/SSA and La/SSB group.CONCLUSIONS: Patients carrying isolated La/SSB antibodies represent a very small subset of patients with a systemic SS phenotype characterised by a significant frequency of active patients in most clinical ESSDAI domains but with a relative low frequency of the highest severe organ-specific involvements. Primary SS still remains the best clinical diagnosis for this subset of patients

Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a $Z$ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 $< p_{\textrm{T}} < 100$ GeV and in the pseudorapidity range $2.5 < \eta < 4$. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb$^{-1}$. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb public pages

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages