Childhood-onset systemic lupus erythematosus: characteristics and the prospect of glucocorticoid pulse therapy

Childhood-onset systemic lupus erythematosus (cSLE) is an autoimmune disease that results in significant damage and often needs more aggressive treatment. Compared to adult-onset SLE, cSLE has a stronger genetic background and more prevalent elevated type I Interferon expression. The management of cSLE is more challenging because the disease itself and treatment can affect physical, psychological and emotional growth and development. High dose oral glucocorticoid (GC) has become the rule for treating moderate to severe cSLE activity. However, GC-related side effects and potential toxicities are problems that cannot be ignored. Recent studies have suggested that GC pulse therapy can achieve disease remission rapidly and reduce GC-related side effects with a reduction in oral prednisone doses. This article reviews characteristics, including pathogenesis and manifestations of cSLE, and summarized the existing evidence on GC therapy, especially on GC pulse therapy in cSLE, followed by our proposal for GC therapy according to the clinical effects and pathogenesis

Reduced circulating interleukin 35 is associated with enhanced peripheral T cell function in primary biliary cholangitis

Interleukin 35 (IL-35) mediates immunosuppression of T cells in autoimmune diseases. T cells play an important role in primary biliary cholangitis (PBC) with incompletely elucidated pathogenesis. Thus, we aimed to investigate the role of IL-35 regulation on T cells in PBC patients. Fifty-one PBC patients and 28 controls were enrolled in this study. Plasma IL-35 level was measured. Purified peripheral CD4+ and CD8+ T cells were stimulated with exogenous IL-35 to investigate their functional phenotypes. IL-35-treated CD8+ T cells were cultured with human intrahepatic biliary epithelial cell line to determine the cytotoxicity of CD8+ T cells from PBC patients. Plasma IL-35 concentration was lower in PBC patients and negatively correlated with alkaline phosphatase. CD4+ T cells from PBC patients exhibited elevated transcription factor expressions and cytokine secretion, whereas CD8+ T cells produced increased cytotoxic molecules and cytokines. In vitro IL-35 stimulation suppressed the production of IL-17 and IL-22 by CD4+ T cells from PBC patients. CD8+ T cells treated with IL-35 mediated reduced target cell death in the direct contact co-culture system in PBC patients. This process was accompanied by reduced production of cytotoxic molecules and cytokines and increased expressions of immune checkpoint receptors in CD8+ T cells. Reduced circulating IL-35 might be insufficient to suppress T cell function, leading to the immune dysregulation in PBC patients

Ovarian juvenile granulosa cell tumors with Ollier’s disease in children with IDH1 gene somatic mutation

ObjectiveThe aim of this study was to explore the symptoms, treatment, and pathogenesis of ovarian juvenile granulosa cell tumors with Ollier’s disease in children.MethodsFrom October 2019 to October 2020, clinical data were retrospectively analyzed for one case of ovarian juvenile granulosa cell tumors with Ollier’s disease. Whole-exome sequencing and Sanger sequencing were used to detect gene mutation in ovarian tumor and chondroma tissue. NADP-dependent isocitrate dehydrogenase-1 (IDH1) and S6 ribosomal protein expression levels in cells transfected with wild-type or mutant plasmid were analyzed by Western blot.ResultsThe 4-year-old female showed multiple skeletal deformities, bilateral breast development with chromatosis, and vulvar discharge. Sex hormone assay suggested that estradiol and prolactin were elevated, and the x-ray of limbs suggested enchondroma. Pelvic ultrasound and abdominal CT revealed a right ovarian solid mass. Pathologic examination of the right ovarian solid mass showed a juvenile granulosa cell type. A c.394C>T (p. Arg132Cys) mutation of the IDH1 gene was detected in both the ovarian juvenile granulosa cell tumors and enchondroma. Transfection of HeLa cells with either WT or Mut plasmid caused 4.46- or 3.77-fold overexpression of IDH1 gene compared to non-transfected control cells, respectively. R132C mutation inhibited the phosphorylation of S6 ribosomal protein, which is central to the mTOR pathway. Postoperatively, estradiol and prolactin levels fell to values normal for her age and bilateral breast gradual retraction.ConclusionThe incidence of ovarian juvenile granulosa cell tumors with Ollier’s disease in children may be caused by generalized mesodermal dysplasia; IDH1 gene mutation may play a facilitated role in this process. Surgical operation is the main treatment. We suggest that patients with ovarian juvenile granulosa cell tumors and Ollier’s disease should undergo regular investigation

The value of carcinoembryonic antigen stage in staging, prognosis, and management of colorectal cancer: results from two cohort studies

BackgroundCombining the carcinoembryonic antigen (CEA) level (C stage) with TNM staging can provide a more comprehensive prognostic assessment of colorectal cancer (CRC). However, the clinical value of incorporating CEA status into the TNM staging system needs to be evaluated.MethodsWe used the SEER database (N = 49,350) and a retrospective cohort from China (N = 1,440). A normal CEA level was staged as C0 and an elevated CEA level was staged as C1. Restricted cubic spline analysis was used to examine the dose-response relationship between the CEA level and survival. The Kaplan-Meier method with the log-rank test was used to plot survival curves. Multivariable Cox proportional hazards regression models with forward stepwise variable selection were used to estimate the hazard ratios and 95% confidence intervals.ResultsPatients with C1 were more likely to have advanced disease than those with C0. CEA on a continuous scale was positively associated with mortality risk. Compared with patients with C0 stage, those with C1 stage had significantly lower survival rates. In the SEER dataset, C1 was independently associated with poor prognosis in patients with CRC, with an approximately 70% increased risk of mortality. Patients with C1 stage had significantly lower survival than those with C0 stage at all clinical stages. Incorporating the C stage into the TNM staging refined the prediction of prognosis of patients with CRC, with a gradual decline in prognosis from stage I C0 to stage IV C1. A similar pattern was observed in the present retrospective cohort study. At each lymph node stage, patients with C1 had significantly lower 5-year survival rates than patients with C0. Compared with lymph node positivity, CEA positivity may have a stronger correlation with a worse prognosis.ConclusionOur findings not only validated the independent prognostic significance of CEA in CRC but also demonstrated its enhanced prognostic value when combined with TNM staging. Our study provides evidence supporting the inclusion of C stage in the TNM staging system

Patent ductus arteriosus shunting direction and diameter predict inpatient outcomes in newborns with congenital diaphragmatic hernia

ObjectiveTo evaluate whether the patent ductus arteriosus (PDA) can serve as a predictive factor for inpatient outcomes in congenital diaphragmatic hernia (CDH) patients.MethodsA retrospective cohort study was conducted on 59 CDH patients at the Capital Institute of Pediatrics from January 2020 to August 2022. Echocardiography was performed at least three times: within 2–3 h after birth, pre-operatively, and post-operatively of CDH surgery. Based on the direction of the PDA shunt in the first echocardiogram, patients were classified into three groups: left-to-right shunting or closed PDA (L-R), bi-directional shunting, and right-to-left shunting (R-L).ResultsThe mortality rate was 15.3% (9/59), with all non-survivors having R-L shunting and group mortality of 39.1% (9/23). The direction of the PDA shunt was significantly associated with the duration of ventilation and length of hospital stay (p < 0.05). Decreased PDA diameter or pre-operative shunting direction change towards L-R or bi-directional shunting were associated with higher survival rates, while increased PDA diameter or continuous R-L shunting were associated with higher mortality rates. Pre-operative PDA shunt direction, PDA size after birth and before surgery, gestational age of diagnosis, and shortening fraction before surgery were significantly correlated with patient outcomes. The direction of the preoperative PDA shunt was the most relevant factor among these relationships (p = 0.009, OR 20.6, CI 2.2∼196.1).ConclusionOur findings highlight the importance of monitoring changes in PDA shunt directionality and diameter in the early stage after birth, as these parameters may serve as valuable predictors of patient outcomes

Serum creatinine/cystatin C ratio as a prognostic indicator for patients with colorectal cancer

BackgroundThis study aimed to explore the relationship between creatinine/cystatin C ratio and progression-free survival (PFS) and overall survival (OS) in colorectal cancer (CRC) patients undergoing surgical treatment.MethodsA retrospective analysis was conducted on 975 CRC patients who underwent surgical resection from January 2012 to 2015. Restricted three-sample curve to display the non-linear relationship between PFS/OS and creatinine-cystatin C ratio. Cox regression model and Kaplan-Meier method were used to evaluate the effect of the creatinine-cystatin C ratio on the survival of CRC patients. Prognostic variables with p-value ≤0.05 in multivariate analysis were used to construct prognostic nomograms. The receiver operator characteristic curve was used to compare the efficacy of prognostic nomograms and the traditional pathological stage.ResultsThere was a negative linear relationship between creatinine/cystatin C ratio and adverse PFS in CRC patients. Patients with low creatinine/cystatin C ratio had significantly lower PFS/OS than those with high creatinine/cystatin C ratio (PFS, 50.8% vs. 63.9%, p = 0.002; OS, 52.5% vs. 68.9%, p < 0.001). Multivariate analysis showed that low creatinine/cystatin C ratio was an independent risk factor for PFS (HR=1.286, 95%CI = 1.007–1.642, p=0.044) and OS (HR=1.410, 95%CI=1.087–1.829, p=0.010) of CRC patients. The creatinine/cystatin C ratio-based prognostic nomograms have good predictive performance, with a concordance index above 0.7, which can predict the 1–5-year prognosis.ConclusionCreatinine/cystatin C ratio may be an effective prognostic marker for predicting PFS and OS in CRC patients, aid in pathological staging, and along with tumour markers help in-depth prognostic stratification in CRC patients

Comprehensive comparative analysis of prognostic value of serum systemic inflammation biomarkers for colorectal cancer: Results from a large multicenter collaboration

BackgroundThe incidence of colorectal cancer (CRC) is common and reliable biomarkers are lacking. We aimed to systematically and comprehensively compare the ability of various combinations of serum inflammatory signatures to predict the prognosis of CRC. Moreover, particular attention has been paid to the clinical feasibility of the newly developed inflammatory burden index (IBI) as a prognostic biomarker for CRC.MethodsThe discrimination capacity of the biomarkers was compared using receiver operating characteristic curves and Harrell’s C-index. Kaplan-Meier curves and log-rank tests were used to compare survival differences between the groups. Cox proportional hazard regression analysis was used to determine the independent prognostic factors. Logistic regression analysis was used to assess the relationship between IBI, short-term outcomes, and malnutrition.ResultsIBI had the optimal prediction accuracy among the systemic inflammation biomarkers for predicting the prognosis of CRC. Taking IBI as a reference, none of the remaining systemic inflammation biomarkers showed a gain. Patients with high IBI had significantly worse overall survival than those with low IBI (56.7% vs. 80.2%; log-rank P<0.001). Multivariate Cox regression analysis showed that continuous IBI was an independent risk factor for the prognosis of CRC patients (hazard ratio = 1.165, 95% confidence interval [CI] = 1.043–1.302, P<0.001). High IBI was an independent risk factor for short-term outcomes (odds ratio [OR] = 1.537, 95% CI = 1.258–1.878, P<0.001), malnutrition (OR = 2.996, 95% CI = 1.471–6.103, P=0.003), and recurrence (OR = 1.744, 95% CI = 1.176–2.587, p = 0.006) in CRC patients.ConclusionsIBI, as a reflection of systemic inflammation, is a feasible and promising biomarker for assessing the prognosis of CRC 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