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Helicobacter pylori (Hp) eradication therapy alters gut microbiota, provoking gastrointestinal (GI) symptoms that could be improved by probiotics. The study aim was to assess the effect in Hp patients of a Test fermented milk containing yogurt and Lacticaseibacillus (L. paracasei CNCM I-1518 and I-3689, L. rhamnosus CNCM I-3690) strains on antibiotic associated diarrhea (AAD) (primary aim), GI-symptoms, gut microbiota, and metabolites. A randomised, double-blind, controlled trial was performed on 136 adults under 14-day Hp treatment, receiving the Test or Control product for 28 days. AAD and GI-symptoms were reported and feces analysed for relative and quantitative gut microbiome composition, short chain fatty acids (SCFA), and calprotectin concentrations, and viability of ingested strains. No effect of Test product was observed on AAD or GI-symptoms. Hp treatment induced a significant alteration in bacterial and fungal composition, a decrease of bacterial count and alpha-diversity, an increase of Candida and calprotectin, and a decrease of SCFA concentrations. Following Hp treatment, in the Test as compared to Control group, intra-subject beta-diversity distance from baseline was lower (padj = 0.02), some Enterobacteriaceae, including Escherichia-Shigella (padj = 0.0082) and Klebsiella (padj = 0.013), were less abundant, and concentrations of major SCFA (p = 0.035) and valerate (p = 0.045) were higher. Viable Lacticaseibacillus strains were detected during product consumption in feces. Results suggest that, in patients under Hp treatment, the consumption of a multi-strain fermented milk can induce a modest but significant faster recovery of the microbiota composition (beta-diversity) and of SCFA production and limit the increase of potentially pathogenic bacteria.

Derived neutrophil-to lymphocyte ratio (dNLR) change between baseline and cycle 2 is correlated with benefit during immune-checkpoint inhibitors (ICI) in advanced nonesmall-cell lung cancer (NSCLC) patients.

Given the very poor prognosis for children with recurrent medulloblastoma, we aimed to identify prognostic factors for survival post-relapse in children with childhood medulloblastoma. We retrospectively collected clinico-biological data at diagnosis and main clinical characteristics at relapse of children newly diagnosed with a medulloblastoma between 2007 and 2017 at Gustave Roussy and Necker Hospital. At a median follow-up of 6.6 years (range, 0.4–12.3 years), relapse occurred in 48 out 155 patients (31%). The median time from diagnosis to relapse was 14.3 months (range, 1.2–87.2 months). Relapse was local in 9, metastatic in 22 and combined (local and metastatic) in 17 patients. Second-line treatment consisted of chemotherapy in 31 cases, radiotherapy in 9, SHH-inhibitor in four and no treatment in the remaining four. The 1-year overall survival rate post-relapse was 44.8% (CI 95%, 31.5% to 59.0%). While molecular subgrouping at diagnosis was significantly associated with survival post-relapse, the use of radiotherapy at relapse and time to first relapse (>12 months) might also have a potential impact on post-relapse survival.

Background A current critical need remains in the identification of prognostic and predictive markers in early breast cancer. It appears that a distinctive trait of cancer cells is their addiction to hyperactivation of ribosome biogenesis. Thus, ribosome biogenesis might be an innovative source of biomarkers that remains to be evaluated. Methods Here, fibrillarin (FBL) was used as a surrogate marker of ribosome biogenesis due to its essential role in the early steps of ribosome biogenesis and its association with poor prognosis in breast cancer when overexpressed. Using 3,275 non-metastatic primary breast tumors, we analysed FBL mRNA expression levels and protein nucleolar organisation. Usage of TCGA dataset allowed transcriptomic comparison between the different FBL expression levels-related breast tumours. Results We unexpectedly discovered that in addition to breast tumours expressing high level of FBL, about 10% of the breast tumors express low level of FBL. A correlation between low FBL mRNA level and lack of FBL detection at protein level using immunohistochemistry was observed. Interestingly, multivariate analyses revealed that these low FBL tumors displayed poor outcome compared to current clinical gold standards. Transcriptomic data revealed that FBL expression is proportionally associated with distinct amount of ribosomes, low FBL level being associated with low amount of ribosomes. Moreover, the molecular programs supported by low and high FBL expressing tumors were distinct. Conclusion Altogether, we identified FBL as a powerful ribosome biogenesis-related independent marker of breast cancer outcome. Surprisingly we unveil a dual association of the ribosome biogenesis FBL factor with prognosis. These data suggest that hyper- but also hypo-activation of ribosome biogenesis are molecular traits of distinct tumors.

associated with progression (PD) and poor outcomes. We reported that pretreatment dNLR ((neutrophils/[leucocytes-neutrophils]; high>3) correlated with immune checkpoint inhibitor (ICI) outcomes in advanced (a) NSCLC pts. Although neutrophil population is heterogeneous, the immature neutrophils (i.e. CD15+CD244-CD16 low , among others) seem to be a key subpopulation linked to PD. Tumor-associated neutrophils (TAN) can be also modulator on the microenvironment. We aimed to assess the role of pretreatment circulating immature-neutrophils and tissue-TAN, combined with dNLR, on ICI outcomes in aNSCLC pts. Method: aNSCLC pts treated with ICI at our institution between 11/2012 and 08/2018 were eligible. Pretreatment immunophenotyping of monocytes, monocytic MDSC (mMDSC) and granulocytes (CD15, CD11b, CD33, CD244, CD16, CD14, CD32, CD64, HLA-DR) was prospectively performed by flow cytometry in fresh whole blood in 58 pts; we defined immature-neutrophils as CD15+CD244-CD16 low. TAN in the stroma were assessed using H&E staining from archival specimen, available from 80 pts. dNLR was retrospectively collected; available from 343 pts. Correlation between baseline circulating neutrophils phenotype, TAN and dNLR was evaluated as well as their impact on outcomes: progression-free survival (PFS), overall (OS), including death before 12 weeks (12wk-death) (fast-PD) Result: 366 pts included; 320 (90%) smokers, median age 63; 280 (77%) nonsquamous, 117 (64%) 1%PDL1 and 183 missing. Median PFS (mPFS) was 1.93 months (m) [95%CI, 1.8-2.3] and mOS 8.8m [6.5-11.6]. Overall, 12wk-death rate was 31% [25.9-35.6]. Pretreatment high-dNLR (143/343; 42%) was correlated with poor PFS (P¼0.002), OS P¼0.0003) and a 12wk-death rate of 43% [34.5-50.9]. Pretreatment high immature-neutrophils (30/58; 53%), defined by logrank maximization method (>0.22%), were also associated with poor PFS (P¼0.04), OS (P¼0.0007) and a 12wk-death rate of 48.7% [26.7-64.1]. TAN (9/80; 11%) were not correlated with outcomes. There was not a correlation between immature-neutrophils, tissue-TAN and dNLR. When evaluating pretreatment immature-neutrophils and dNLR together, we identified a fast-PD phenotype (high immature-neutrophils/high-dNLR, 10/58; 17%), with a mOS of 1.3m [0.73-not reached (NR)] and 12wk-death rate of 60% [14.5-81.3] compared to a responder-phenotype (low immature-neutrophils/low-dNLR, 12/58; 21%), associated with good outcomes: mOS NR [18.23-NR] (P¼0.002). Conclusion: Pretreatment high circulating immature-neutrophils (CD15+CD244-CD16 low) correlate with early failure to ICI and fast-PD phenotype. The combination of circulating immature-neutrophils and dNLR could improve the identification of this population. The impact of immature-neutrophils on ICI should be more deeply explored.