Alphabio

Greenhouse gas emissions are a major global concern and reducing them is a key objective for governments and organizations worldwide. One of the largest agricultural contributors to greenhouse gas emissions is enteric methane, produced as a byproduct of microbial fermentation in the rumen during forage digestion. As previously reported, we developed an AI-driven model to address this challenge by predicting the efficacy of feed additives in mitigating methane emissions. Since the wide variety of feed additives available in the market, validating the model across a diverse range of additives is critical for its adoption in commercial farming practices. In this study, we extensively validate the model across ten commercial farms over a three-month period, involving 339 Holstein cows, and using an allicin-based essential oil (Allimax), an organosulfur compound obtained from garlic with potential to reduce enteric methane emissions. The validation process simulated two hypothetical scenarios: (i) a naive scenario in which the feed additive is applied uniformly across all participating farms, and (ii) an optimized scenario, based on a precision agriculture approach, in which the additive is supplied only to farms where the AI-driven model predicted a significant reduction in enteric methane emissions. Our results revealed two key findings: first, the AI-driven model demonstrated high accuracy in predicting the additive’s effect on enteric methane emissions at the farm level. Second, the optimized scenario achieved greater overall methane reductions compared to the naive scenario, underscoring the value of a precision agriculture strategy that incorporates rumen microbiome genetics to guide additive applications. These results, which align with a previous validation using a different commercial feed additive, support the adoption of data-driven, customized additive strategies that enhance sustainability and productivity, promote precision agriculture practices, and facilitate compliance with evolving environmental regulations.

The purpose of this study is to raise awareness of small intestinal bacterial overgrowth (SIBO) and intestinal methanogen overgrowth (IMO) prevalence among patients with endometriosis to improve global recommendations in the standard of care for endometriosis. This case-control study included a cohort of 1027 women who underwent the lactulose breath test (LBT) during their healthcare check-up to diagnose SIBO and/or IMO from November 2021 to June 2023. One hundred and forty-eight endometriosis patients were selected based on magnetic resonance imaging or a histological assessment. Each were matched with an equal number of women without endometriosis based on the exact age. SIBO/IMO prevalence was significantly higher among women with endometriosis, with up to 136 out of 148 who tested positive, 91.9% (95% confidence interval [CI] 86.3-95.7%) against 123 in the control group, 83.1% [76.1-88.8%], P = 0.0223. Women with endometriosis showed a significantly higher incidence of altered transit than those without (85.8 vs. 71%, P = 0.0019) and an increased prevalence of constipation (67.8 vs. 44.7%, P = 0.0017) and dizziness (44.8 vs. 28.7%, P = 0.0245). Overall, methane overgrowth accounted for up to 63.2% in women with endometriosis who tested positive for methane overgrowth. SIBO H2 was associated with a higher risk of developing diarrhea (P = 0.0027), whereas those positive for IMO were at a higher risk of developing acid reflux (P = 0.0132). Abnormal digestive overgrowth should be assessed in all endometriosis cases, as this approach could offer a new therapeutic strategy.

The combination of atezolizumab plus bevacizumab (Atz/Bev) has radically changed the treatment strategy for advanced hepatocellular carcinoma (HCC) but raises questions. Our objectives were to determine survival outcomes and safety in a real-life multicenter French cohort, to investigate the on-treatment prognostic value of the bioinflammatory RECA score, and to perform a matched comparison with patients who previously received tyrosine kinase inhibitors (TKIs). A retrospective analysis of 109 consecutive patients enrolled from September 2020 to January 2023 and a post matched comparison with a TKI cohort ( n = 79) by the propensity score matching method. The Atz/Bev population was mainly nonviral disease patients (69%) with Child-Pugh grade A (90%), performance status 0/1 (90%), and Barcelona Clinic Liver Cancer stage B (38%) or stage C (62%) classification. After a median follow-up of 6.5 months (3.6-11.7), overall survival (OS) was 13.0 (5.1-28.7) months. OS was independently associated with metastasis, increased alkaline phosphatase, and serum bilirubin levels. Treatment-related adverse events were reported in 78% of patients, mostly grade 1 or 2. The RECA score clearly revealed two different prognosis groups after three cycles. No difference in OS was observed after matching between sequential treatment with TKIs and Atz/Bev. This real-life study highlights the importance of liver function when using Atz/Bev combination and the necessity of identifying predictive markers of response to HCC therapies. Our findings suggest a change in practices, with a marked proportion of intermediate stages, and support the on-treatment prognostic value of an inflammatory score.

Le méthotrexate (MTX) présente de nombreuses indications notamment à haute dose (> 500 mg/m 2 ) dans les hémopathies malignes (HM). La toxicité rénale (conséquence du retard d’élimination du MTX) induite par le MTX haute dose (MTX-HD) est une problématique inhérente à son utilisation. Son incidence est estimée entre 2 et 10 %. Malgré une utilisation depuis de nombreuses années, aucune donnée avec un niveau de preuve suffisant ne permet d’anticiper cette toxicité. L’objectif principal est d’isoler des covariables liées à la survenue du retard d’élimination. Nous chercherons ensuite, à explorer s’il existe un lien entre retard d’élimination et survenue de toxicités hématologiques, et son impact sur la survie des patients. Nous étudierons aussi des covariables impactant le délai de survenue d’une aplasie. Les données de 69 patients traités par MTX-HD pour HM entre 2013 et 2020 ont été recueillies. Le recueil a concerné des covariables cliniques, paracliniques, pharmacocinétiques, thérapeutiques et iatrogéniques, recueillies à l’aide des logiciels Chimio®, Pharma®, Axigate®, VisualPatient®. Les données de survie ont été recueillies jusqu’en 2022. L’analyse statistique a été faite via R version 4.3.1. Nous avions 14 cures en retard d’élimination, avec des méthotrexatémies moyennes de 2,4 ± 2,8 μM à 48 h. Quatre des covariables testées avaient un impact statistiquement significatif sur la survenue du retard d’élimination : le sexe masculin, la prise de sulfamethoxazole/trimethoprime et de paracétamol, et la présence d’une contre-indication. En focalisant sur le retard d’élimination en première cure, une hyperhydratation (HH) non conforme, a eu un impact significatif sur sa survenue. Aucune différence de survie n’était observée entre le groupe retard d’élimination et le groupe sans retard d’élimination. Sur le délai de survenue de l’aplasie, 6 covariables sont significatives : la prise de pénicilline, un suivi de pH non conforme, une HH non conforme, une réduction de dose, le poids et la surface corporelle des patients. Nous constatons que 4 de ces covariables relèvent de l’analyse pharmaceutique des prescriptions. Nous avions un faible taux de retards d’élimination, ceci pouvant s’expliquer par une application stricte du protocole d’HH et de suivi du pH. Les covariables impactant significativement la survenue d’un retard d’élimination, et de l’aplasie sont liées à l’analyse pharmaceutique. Une lacune dans cette analyse était plus importante dans les groupes retard d’élimination et survenue d’aplasie, ce qui renforce l’importance de la place du pharmacien dans l’équipe de soin. Mener une étude multicentrique permettrait de valider les covariables isolées sur ce travail, d’harmoniser les pratiques sur l’administration du MTX-HD, et d’améliorer la sécurité de prise en charge des patients traités par MTX-HD.

Data on the management of Hepatitis B-Delta (HB-D) by hepatogastroenterologists (HGs) practicing in nonacademic hospitals or private practices are unknown in France. We aimed to evaluate the knowledge and practices of HGs practicing in nonacademic settings regarding HB-D. A Google form document was sent to those HGs from May to September 2021. A total of 130 HGs (mean age, 45 years) have participated in this survey. Among HBsAg-positive patients, Delta infection was sought in only 89% of cases. Liver fibrosis was assessed using FibroScan in 77% of the cases and by liver biopsy in 81% of the cases. A treatment was proposed for patients with >F2 liver fibrosis in 49% of the cases regardless of transaminase levels and for all the patients by 39% of HGs. Responding HGs proposed a treatment using pegylated interferon in 50% of cases, bulevirtide in 45% of cases and a combination of pegylated interferon and bulevirtide in 40.5% of cases. Among the criteria to evaluate the treatment efficacy, a decrease or a normalization of transaminases was retained by 89% of responding HGs, a reduction of liver fibrosis score for 70% of them, an undetectable delta RNA and HBsAg for 55% of them and a 2 log 10 decline in delta viremia for 62% of the cases. Hepatitis Delta screening was not systematically performed in HBsAg-positive patients despite the probable awareness and knowledge of the few responders who were able to prescribe treatments of hepatitis delta.

Abstract Background Biologic drugs such as anti-TNFα antibodies are predominantly used in a step-up setting and prescribed for Crohn’s disease (CD) patients who have failed, or are contraindicated for, first-line therapies. However, patient response to biologics is highly variable, with only a minority benefitting from a strong and sustained clinical response. Presently, there is no operationally effective means in clinical care to stratify patients on individual biologic drugs. Consequently, standard of care for those with CD remains inadequate and inefficient. To identify protein biomarkers associating with treatment outcomes, we performed an untargeted proteomics analysis of baseline serum samples from individuals with moderate to severe CD starting anti-TNFα treatment. Methods Biobanked serum samples from 47 (42 from Amsterdam, 5 from Oxford) moderate to severe CD patients starting anti-TNFα treatment (adalimumab, infliximab or their biosimilars) with documented 12 and 26-week treatment response were used for untargeted serum proteomic analysis using SomaLogic’s SomaScan® technology platform. Data was checked for outliers using robust principal component analysis. Supervised machine learning (ML) was used to predict treatment outcome. Results There were 29 responders and 18 non-responders to anti-TNFα treatment (week 26). Untargeted proteomics profiles passing SomaLogic’s quality controls were generated for all samples with 7,596 proteins detected in each sample. Robust principal component analysis for anomaly detection did not reveal any substantial outliers (see Figure 1). Five different ML algorithms independently generated mean AUCs and balanced accuracies from 5x 5-fold cross-validation ranging from 0.47 to 0.53 (see Table 1) indicating no reliable signal in the data. Notably, applying the ML algorithms to detect sample origin, samples from the 2 different clinical sites (Oxford or Amsterdam) could be confidently distinguished suggesting careful protocol alignment for serum collection is essential. Of 26 proteins previously reported to be associated with biologic treatment outcome, only PF4 was found to be significantly different between anti-TNFα responder and non-responders (P=0.0043). Overall, these metrics all fall well below what would be needed for a predictor to have value in the clinic. Conclusion ML analysis of serum proteomics profiles for 47 CD patients did not identify any strong and reliable biomarkers of biologic treatment response suitable for clinical applications. This small study suggests serum proteins are not suitable for anti-TNFα response prediction in this population. In addition, the serum proteomic profile is highly susceptible to differences in serum collection and storage methods.

OBJECTIVES:To identify COVID-19-associated immunophenotyping patterns at hospital admission and to determine if some patterns could predict the need for mechanical ventilation (MV).DESIGN:Prospective observational monocentric cohort study.SETTING:A university-affiliated hospital in Marseille, France.PATIENTS:Thirty patients presenting with laboratory-confirmed COVID-19 pneumonia were enrolled within the first 48 hours of hospital admission and compared with 18 healthy controls.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:Whole-blood leukocytes were immunophenotyped with a rapid and simplified one-step flow cytometry method. Thirty-eight immune and five laboratory parameters were compared first between COVID-19 patients and controls and then between the COVID-19 patients who received or not MV during their stays. The variables that significantly discriminated MV from non-MV patients in univariate analysis were entered into a multiple stepwise logistic regression analysis. The COVID-19 patients were predominantly male (87%), aged 61 years (50–71 yr), and 93% received early corticosteroid therapy. Sixteen patients (53%) were managed with noninvasive respiratory support, and 14 (47%) required MV. Compared with controls, COVID-19 patients were characterized by an immune signature featuring: 1) decreased HLA-DR expression on monocytes; 2) reduced basophils, eosinophils, T-cells, NK cells, and nonclassical monocyte count; and 3) up regulation of CD169 on monocytes, CD64 on neutrophils, the adhesion/migration markers (CD62L and CD11b), and the checkpoint inhibitor CD274 on myeloid cells. Among the COVID-19 patients, those who received MV had lower level of CD4 and HLA-DR on monocytes, lower CD8+ T-cell count, and higher lactate dehydrogenase at hospital admission. In multivariate analysis, only CD4 on monocytes (p = 0.032) and CD8+ T-cell count (p = 0.026) were associated with MV requirement. The model combining these two variables provided an area under curve of 0.97 (95% CI, 0.83–0.99).CONCLUSIONS:The association of low CD4 on monocytes and low CD8+ T-cell count at hospital admission was highly predictive of the need for MV in hospitalized patients with COVID-19 pneumonia.