tbuckley/cabot-search huggingface dataset:
Lassa fever in Nigeria
Authors: Paul Adepoju
Journal: The Lancet Microbe (2024)

As of June 30, the Nigeria Centre for Disease Control and Prevention (NCDC) has reported 928 confirmed cases of Lassa fever and 162 associated deaths, a case fatality rate of 17·5%. Over 30 cases have been confirmed among health-care workers, an even male-to-female ratio among confirmed cases has been observed, individuals aged 21–30 years are the most affected age group, and the number of suspected cases has increased compared to the same period last year. NCDC has established a national technical working group to coordinate response activities at all levels. Lassa fever is an acute viral haemorrhagic disease caused by Lassa virus (LASV) that is primarily found in multimammate rodents in west Africa.
Multifunctional polymeric nanocapsules with enhanced cartilage penetration and retention for osteoarthritis treatment
Authors: Hongxiang Mei, Chuanlu Sha, Qinyi Lv, Hai Liu, Linli Jiang, Qiantao Song, Yiwei Zeng, Jiawei Zhou, Yule Zheng, Wenbin Zhong, Jiajing Zhou, Juan Li
Journal: Journal of Controlled Release (2024)
Enhancing RNA-lipid nanoparticle delivery: Organ- and cell-specificity and barcoding strategies
Authors: Pu-Sheng Wei, Nagasri Thota, Gresham John, Evelyn Chang, Sunjae Lee, Yuanjun Wang, Zitao Ma, Yu-Husan Tsai, Kuo-Ching Mei
Journal: Journal of Controlled Release (2024)

Recent advancements in RNA therapeutics highlight the critical need for precision gene delivery systems that target specific organs and cells. Lipid nanoparticles (LNPs) have emerged as key vectors in delivering mRNA and siRNA, offering protection against enzymatic degradation, enabling targeted delivery and cellular uptake, and facilitating RNA cargo release into the cytosol. This review discusses the development and optimization of organ- and cell-specific LNPs, focusing on their design, mechanisms of action, and therapeutic applications. We explore innovations such as DNA/RNA barcoding, which facilitates high-throughput screening and precise adjustments in formulations. We address major challenges, including improving endosomal escape, minimizing off-target effects, and enhancing delivery efficiencies. Notable clinical trials and recent FDA approvals illustrate the practical applications and future potential of LNP-based RNA therapies. Our findings suggest that while considerable progress has been made, continued research is essential to resolve existing limitations and bridge the gap between pre-clinical and clinical evaluation of the safety and efficacy of RNA therapeutics. This review highlights the dynamic progress in LNP research. It outlines a roadmap for future advancements in RNA-based precision medicine.
Prevalence of group B Streptococcus colonisation in mother–newborn dyads in low-income and middle-income south Asian and African countries: a prospective, observational study
Authors: Gaurav Kwatra, Alane Izu, Clare Cutland, Godwin Akaba, Musa Mohammed Ali, Zabed Ahmed, Manisha Madhai Beck, Hellen Cherono Barsosio, James A Berkley, Tolossa E Chaka, Anélsio Cossa, Sowmitra Chakraborty, Nisha Dhar, Phurb Dorji, Maksuda Islam, Adama Mamby Keita, Stella Mwakio, Salim Mwarumba, Nubwa Medugu, Helio Mucavele, Viviana Mabombo, Stephen Obaro, Betuel Sigaúque, Samba O Sow, Samir K Saha, Sridhar Santhanam, Ragunath Sharma, Eric A F Simoes, Rani Diana Sahni, Milagritos D Tapia, Balaji Veeraraghavan, Shabir A Madhi
Journal: The Lancet Microbe (2024)

Rectovaginal group B Streptococcus (GBS) colonisation in pregnant individuals at the time of labour is a major risk factor for invasive GBS disease by age 7 days (early-onset disease). We aimed to investigate the prevalence of rectovaginal GBS colonisation at the time of labour among pregnant women and vertical transmission to their newborns across selected low-income and middle-income African and south Asian countries.
Controlled bioorthogonal activation of Bromodomain-containing protein 4 degrader by co-delivery of PROTAC and Pd-catalyst for tumor-specific therapy
Authors: Zhiyao Li, Taibai Jiang, Xu Yuan, Bowen Li, Chongzhi Wu, Yecheng Li, Yong Huang, Xin Xie, Weidong Pan, Yuan Ping
Journal: Journal of Controlled Release (2024)
Genome Tunisia Project: paving the way for precision medicine in North Africa
Authors: Yosr Hamdi, Mediha Trabelsi, Kais Ghedira, Maroua Boujemaa, Ikhlas Ben Ayed, Cherine Charfeddine, Amal Souissi, Imen Rejeb, Wafa Kammoun Rebai, Chaima Hkimi, Fadoua Neifar, Nouha Jandoubi, Rahma Mkaouar, Melek Chaouch, Ayda Bennour, Selim Kamoun, Hend Chaker Masmoudi, Nabil Abid, Maha Mezghani Khemakhem, Ahlem Achour, Ines Ouertani, Lilia Kraoua, Rym Meddeb, Sana Skouri, Sana Gabtni, Hela Bellil, Yasmina Elaribi, Syrine Hizem, Houweyda Jilani, Sonia Kchaou, Malek Trigui, Khouloud Rjiba, Hamza Chouk, Marwa Mahdouani, Sarra Dimassi, Soumaya Mougou, Narjess Trabelsi, Yasmine El Abed, Safa Boubaker, Rihen Braham, Salma Najjar, Ahlem Msakni, Fatma Chtioui, Lamia Hammami, Hela Gargouri, Fidaa Jbeli, Riadh Ben Marzough, Mouna Choura, Meriem Ben Said, Yosra Lajmi, Souhir Guidara, Manel Guirat, Nesrine Kerkeni, Maryam Younsi, Sana Karoui, Oussema Souiai, Mariem Hannachi, Houcemeddine Othman, Haifa El Mabrouk, Feriel Bouzid, Cyrine Abid, Nihel Ammouss, Imene Boujelbene, Oussema Khamessi, Abdeljelal Ghram, Amade M’charek, Hamdi Mbarek, Thouraya Mellah, Noomen ElKadri, Houssein Khoujet El Khil, Hassan Chaabane, Maher Kharrat, Raja Gargouri, Lotfi Cherni, Faiza Fakhfakh, Chahnaz Charfi Triki, Saber Masmoudi, Ali Saad, Lamia BenJemaa, Alia BenKahla, Samir Boubaker, Ridha Mrad, Hassen Kamoun, Sonia Abdelhak, Moez Gribaa, Neila Belguith, Najla Kharrat, Dorra Hmida, Ahmed Rebai
Journal: Genome Medicine (2024)

Key discoveries and innovations in the field of human genetics have led to the foundation of molecular and personalized medicine. Here, we present the Genome Tunisia Project, a two-phased initiative (2022-2035) which aims to deliver the reference sequence of the Tunisian Genome and to support the implementation of personalized medicine in Tunisia, a North African country that represents a central hub of population admixture and human migration between African, European, and Asian populations. The main goal of this initiative is to develop a healthcare system capable of incorporating omics data for use in routine medical practice, enabling medical doctors to better prevent, diagnose, and treat patients.
Procalcitonin for Safe Reduction of Unnecessary Blood Cultures in the Emergency Department: Development and Validation of a Prediction Model
Authors: Anna G Kaal, Soufian Meziyerh, Nathalie van Burgel, Martijn Dane, Nikki E Kolfschoten, Prashant Mahajan, Agustín Julián-Jiménez, Ewout W Steyerberg, Cees van Nieuwkoop
Journal: Journal of Infection (2024)

Blood cultures (BCs) are commonly ordered in emergency departments (EDs), while a minority yields a relevant pathogen. Diagnostic stewardship is needed to safely reduce unnecessary BCs. We aimed to develop and validate a bacteremia prediction model for ED patients, with specific focus on the benefit of incorporating procalcitonin.
A versatile nanoplatform carrying cascade Pt nanozymes remodeling tumor microenvironment for amplified sonodynamic/chemo therapy of thyroid cancer
Authors: Dan Wang, Wenqi Ma, Yuanyuan Zhang, Yufeng Wang, Lei Sun, Jue Jiang, Lianying Jiao, Runqing Li, Yujie Zhang, Mingzhen Zhang, Qi Zhou
Journal: Biomaterials (2024)
MSCs Biomimetic Ultrasonic Phase Change Nanoparticles Promotes Cardiac Functional Recovery after Acute Myocardial Infarction
Authors: Zhuo Wang, Jianfeng Chen, Jiaxu Wang, Mingyuan Xu, Haichao Yang, Haobo Yang, Chen Zhao, Ping Sun, Huan Ji, Jinhong Liu, Jiaxin Shan, Jiawei Tian, Shouqiang Li, Dandan Yu, Chao Wang, Xinhong Yu, Shuo Ding, Wenjun Xu, Ying Zhang, Xiaoping Leng, Thomas R-Porter
Journal: Biomaterials (2024)
A multidimensional analysis reveals distinct immune phenotypes and the composition of immune aggregates in pediatric acute myeloid leukemia
Authors: Joost B. Koedijk, Inge van der Werf, Livius Penter, Marijn A. Vermeulen, Farnaz Barneh, Alicia Perzolli, Joyce I. Meesters-Ensing, Dennis S. Metselaar, Thanasis Margaritis, Marta Fiocco, Hester A. de Groot-Kruseman, Rubina Moeniralam, Kristina Bang Christensen, Billie Porter, Kathleen Pfaff, Jacqueline S. Garcia, Scott J. Rodig, Catherine J. Wu, Henrik Hasle, Stefan Nierkens, Mirjam E. Belderbos, C. Michel Zwaan, Olaf Heidenreich
Journal: Leukemia (2024)

Abstract Because of the low mutational burden and consequently, fewer potential neoantigens, children with acute myeloid leukemia (AML) are thought to have a T cell-depleted or ‘cold’ tumor microenvironment and may have a low likelihood of response to T cell-directed immunotherapies. Understanding the composition, phenotype, and spatial organization of T cells and other microenvironmental populations in the pediatric AML bone marrow (BM) is essential for informing future immunotherapeutic trials about targetable immune-evasion mechanisms specific to pediatric AML. Here, we conducted a multidimensional analysis of the tumor immune microenvironment in pediatric AML and non-leukemic controls. We demonstrated that nearly one-third of pediatric AML cases has an immune-infiltrated BM, which is characterized by a decreased ratio of M2- to M1-like macrophages. Furthermore, we detected the presence of large T cell networks, both with and without colocalizing B cells, in the BM and dissected the cellular composition of T- and B cell-rich aggregates using spatial transcriptomics. These analyses revealed that these aggregates are hotspots of CD8 + T cells, memory B cells, plasma cells and/or plasmablasts, and M1-like macrophages. Collectively, our study provides a multidimensional characterization of the BM immune microenvironment in pediatric AML and indicates starting points for further investigations into immunomodulatory mechanisms in this devastating disease.
Stearoyl-CoA desaturase inhibition is toxic to acute myeloid leukemia displaying high levels of the de novo fatty acid biosynthesis and desaturation
Authors: Vilma Dembitz, Hannah Lawson, Richard Burt, Sirisha Natani, Céline Philippe, Sophie C. James, Samantha Atkinson, Jozef Durko, Lydia M. Wang, Joana Campos, Aoife M. S. Magee, Keith Woodley, Michael J. Austin, Ana Rio-Machin, Pedro Casado, Findlay Bewicke-Copley, Giovanny Rodriguez Blanco, Diego Pereira-Martins, Lieve Oudejans, Emeline Boet, Alex von Kriegsheim, Juerg Schwaller, Andrew J. Finch, Bela Patel, Jean-Emmanuel Sarry, Jerome Tamburini, Jan Jacob Schuringa, Lori Hazlehurst, John A. Copland III, Mariia Yuneva, Barrie Peck, Pedro Cutillas, Jude Fitzgibbon, Kevin Rouault-Pierre, Kamil Kranc, Paolo Gallipoli
Journal: Leukemia (2024)

Abstract Identification of specific and therapeutically actionable vulnerabilities, ideally present across multiple mutational backgrounds, is needed to improve acute myeloid leukemia (AML) patients’ outcomes. We identify stearoyl-CoA desaturase (SCD), the key enzyme in fatty acid (FA) desaturation, as prognostic of patients' outcomes and, using the clinical-grade inhibitor SSI-4, show that SCD inhibition (SCDi) is a therapeutic vulnerability across multiple AML models in vitro and in vivo. Multiomic analysis demonstrates that SCDi causes lipotoxicity, which induces AML cell death via pleiotropic effects. Sensitivity to SCDi correlates with AML dependency on FA desaturation regardless of mutational profile and is modulated by FA biosynthesis activity. Finally, we show that lipotoxicity increases chemotherapy-induced DNA damage and standard chemotherapy further sensitizes AML cells to SCDi. Our work supports developing FA desaturase inhibitors in AML while stressing the importance of identifying predictive biomarkers of response and biologically validated combination therapies to realize their full therapeutic potential.
Antibiotic-loaded nanoparticles for the treatment of intracellular methicillin-resistant Staphylococcus Aureus infections: In vitro and in vivo efficacy of a novel antibiotic
Authors: Gabriella Costabile, Domizia Baldassi, Christoph Müller, Birgit Groß, Francesca Ungaro, Sören Schubert, Steven M Firestine, Olivia M Merkel
Journal: Journal of Controlled Release (2024)

Antimicrobial resistance is considered one of the biggest threats to public health worldwide. Methicillin-resistant S. aureus is the causative agent of a number of infections and lung colonization in people suffering from cystic fibrosis. Moreover, a growing body of evidence links the microbiome to the development of cancer, as well as to the success of the treatment. In this view, the development of novel antibiotics is of critical importance, and SV7, a novel antibiotic active against MRSA at low concentrations, represents a promising candidate. However, the low aqueous solubility of SV7 hampers its therapeutic translation. In this study, SV7 was encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) to improve the solubility profile, to ensure sustained release and eventually support deposition in the airways. Furthermore, PLGA NPs were formulated as dry powder to extend their shelf-life and were shown to efficiently target intracellular infections. After identifying a formulation with suitable physico-chemical characteristics, SV7-loaded NPs were investigated in vitro in terms of inhibitory activity against MRSA, and their safety profile in lung epithelial cells. Subsequently, the activity against MRSA intracellular infections was investigated in a co-culture model of MRSA and macrophages. To test the translatability of our findings, SV7-loaded NPs were tested in vivo in a Galleria mellonella infection model. In conclusion, SV7-loaded NPs showed a safe profile and efficient inhibitory activity against MRSA at low concentrations. Furthermore, their activity against intracellular infections was confirmed, and was retained in vivo, rendering them a promising candidate for treatment of MRSA lung infections.
The Impact of Normal Hepatobiliary Cell Zonation Programs on the Phenotypes and Functions of Primary Liver Tumors
Authors: Tomoko Aoki, Naoshi Nishida, Yasunori Minami, Masatoshi Kudo
Journal: Liver Cancer (2024)

Background: Traditional tumor classifications have relied on cellular origin, pathological morphological features, gene expression profiles, and more recently, the tumor immune microenvironment. While these classifications provide valuable insights, incorporating physiological classifications focusing on liver metabolic functions may lead to new discoveries. Summary: We proposed to reclassify benign and malignant hepatocellular neoplasms based on their physiological functions such as albumin production, bile acid production, glycolysis, glycogenesis, and adipogenesis. We further demonstrated the homology between signal pathways activated by the differentiation program of the normal hepatobiliary cells and those activated by genetic abnormalities in tumors. Specifically, Wnt/β-catenin, RAS, NOTCH, and TGF-β signaling not only contribute to cell differentiation via activation of liver-enriched transcription factors but also determine the tumor traits. Examining the distinctions between hepatocellular carcinomas (HCCs) that maintain or lose metabolic functions can yield valuable insights into the drivers of biological malignancy and tumor plasticity. Key Messages: To confirm the homology between the differentiation programs of normal hepatobiliary cells, hepatocellular adenomas (HCA), and HCC we identify liver-specific functions such as catabolism and anabolism within tumors. HCCs and HCAs that have lost these metabolic functions exhibit characteristics such as dedifferentiation, resemblance to biliary cells, or increased glycolysis. Focusing on this underexplored area will likely stimulate active research into new tumor characteristics.
Efficacy of a Therapeutic Pelvic Yoga Program Versus a Physical Conditioning Program on Urinary Incontinence in Women
Authors: Alison J. Huang, Margaret Chesney, Michael Schembri, Harini Raghunathan, Eric Vittinghoff, Wendy Berry Mendes, Sarah Pawlowsky, Leslee L. Subak
Journal: Annals of Internal Medicine (2024)

Pelvic floor yoga has been recommended as a complementary treatment strategy for urinary incontinence (UI) in women, but evidence of its efficacy is lacking.
Sodium–Glucose Cotransporter-2 Inhibitors, Dulaglutide, and Risk for Dementia
Authors: Bin Hong, Sungho Bea, Hwa Yeon Ko, Woo Jung Kim, Young Min Cho, Ju-Young Shin
Journal: Annals of Internal Medicine (2024)

Both sodium–glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may have neuroprotective effects in patients with type 2 diabetes (T2D). However, their comparative effectiveness in preventing dementia remains uncertain.
A Dual-Payload Antibody-Drug Conjugate Targeting CD276/B7-H3 Elicits Cytotoxicity and Immune Activation in Triple-Negative Breast Cancer
Authors: Zhuoxin “Zora” Zhou, Yingnan Si, Jiashuai Zhang, Kai Chen, Ashley George, Seulhee Kim, Lufang Zhou, Xiaoguang “Margaret” Liu
Journal: Cancer Research (2024)

Triple-negative breast cancer (TNBC) is a highly aggressive and heterogeneous disease that often relapses following treatment with standard radiotherapies and cytotoxic chemotherapies. Combination therapies have potential for treating refractory metastatic TNBC. In this study, we aimed to develop an antibody-drug conjugate with dual payloads (DualADC) as a chemoimmunotherapy for TNBC. The overexpression of an immune checkpoint transmembrane CD276 (also known as B7-H3) was associated with angiogenesis, metastasis, and immune tolerance in more than 60% of patients with TNBC. Development of a mAb capable of targeting the extracellular domain of surface CD276 enabled delivery of payloads to tumors, and a platform was established for concurrent conjugation of a traditional cytotoxic payload and an immunoregulating Toll-like receptor 7/8 agonist to the CD276 mAb. The DualADC effectively killed multiple TNBC subtypes, significantly enhanced immune functions in the tumor microenvironment, and reduced tumor burden by up to 90% to 100% in animal studies. Single-cell RNA sequencing, multiplex cytokine analysis, and histology elucidated the impact of treatment on tumor cells and the immune landscape. This study suggests that the developed DualADC could represent a promising targeted chemoimmunotherapy for TNBC. Significance: An anti-CD276 monoclonal antibody conjugated with both a cytotoxic drug and an immune boosting reagent effectively targets triple-negative breast cancer by inducing tumor cell death and stimulating immune cell infiltration.
TROPHY-U-01 Cohort 2: A Phase II Study of Sacituzumab Govitecan in Cisplatin-Ineligible Patients With Metastatic Urothelial Cancer Progressing After Previous Checkpoint Inhibitor Therapy
Authors: Daniel P. Petrylak, Scott T. Tagawa, Rohit K. Jain, Manojkumar Bupathi, Arjun Balar, Arash Rezazadeh Kalebasty, Saby George, Phillip Palmbos, Luke Nordquist, Nancy Davis, Chethan Ramamurthy, Cora N. Sternberg, Yohann Loriot, Neeraj Agarwal, Chandler Park, Julia Tonelli, Morganna Vance, Huafeng Zhou, Petros Grivas, Daniel P. Petrylak, Scott T. Tagawa, Rohit K. Jain, Manojkumar Bupathi, Arjun Balar, Arash Rezazadeh Kalebasty, Saby George, Phillip Palmbos, Luke Nordquist, Nancy Davis, Chethan Ramamurthy, Cora N. Sternberg, Neeraj Agarwal, Chandler Park, Julia Tonelli, Morganna Vance, Huafeng Zhou, Petros Grivas, Yohann Loriot
Journal: Journal of Clinical Oncology (2024)

PURPOSE Sacituzumab govitecan (SG) is a Trop-2–directed antibody-drug conjugate with an SN-38 payload, approved for patients with locally advanced (LA) or metastatic urothelial cancer (mUC) who progressed after platinum (PT)-based chemotherapy and a checkpoint inhibitor (CPI). Here, we report results from Cohort 2 of TROPHY-U-01 trial, evaluating the efficacy and safety of SG in patients with mUC. METHODS TROPHY-U-01 (ClinicalTrials.gov identifier: NCT03547973 ) is a multicohort, open-label phase II study. Cohort 2 includes patients with LA or mUC who have had progression or recurrence after a CPI and were cisplatin-ineligible at study initiation. Patients received SG 10 mg/kg on days 1 and 8 of 21-day cycles. The primary end point was objective response rate (ORR) per central review; secondary end points were clinical benefit rate (CBR), duration of response (DOR), and progression-free survival (PFS) per central review and safety. RESULTS Cohort 2 included 38 patients (61% male; median age 72.5 years; 66% visceral metastases [29% liver]; 50% received previous PT-based chemotherapy as previous [neo]adjuvant therapy]). At a median follow-up of 9.3 months, ORR was 32% (95% CI, 17.5 to 48.7), CBR 42% (95% CI, 26.3 to 59.2), median DOR 5.6 months (95% CI, 2.8 to 13.3), median PFS 5.6 months (95% CI, 4.1 to 8.3), and median overall survival 13.5 months (95% CI, 7.6 to 15.6). Grade ≥3 treatment-emergent adverse events occurred in 87% of patients, most commonly neutropenia (34%), anemia (24%), leukopenia (19%), fatigue (18%), and diarrhea (16%). CONCLUSION SG monotherapy demonstrated a relatively high ORR with rapid responses; this was feasible with a manageable toxicity profile in cisplatin-ineligible patients who had progression after CPI therapy. Limitations include a moderate sample size and lack of random assignment. These results warrant further evaluation of SG alone and in combinations in patients with LA/mUC.
Oxaliplatin Added to Fluoropyrimidine/Bevacizumab as Initial Therapy for Unresectable Metastatic Colorectal Cancer in Older Patients: A Multicenter, Randomized, Open-Label Phase III Trial (JCOG1018)
Authors: Atsuo Takashima, Tetsuya Hamaguchi, Junki Mizusawa, Fumio Nagashima, Masahiko Ando, Hitoshi Ojima, Tadamichi Denda, Jun Watanabe, Katsunori Shinozaki, Hideo Baba, Masako Asayama, Seiji Hasegawa, Toshiki Masuishi, Ken Nakata, Shunsuke Tsukamoto, Hiroshi Katayama, Kenichi Nakamura, Haruhiko Fukuda, Yukihide Kanemitsu, Yasuhiro Shimada
Journal: Journal of Clinical Oncology (2024)

PURPOSE Doublet chemotherapy with fluoropyrimidine (FP) and oxaliplatin (OX) plus bevacizumab (BEV) is a standard regimen for unresectable metastatic colorectal cancer (MCRC). However, the efficacy of adding OX to FP plus BEV (FP + BEV) remains unclear for older patients, a population for whom FP + BEV is standard. We aimed to confirm the superiority of adding OX to FP + BEV for this population. METHODS This open-label, randomized, phase III trial was conducted at 42 institutions in Japan. Patients with unresectable MCRC age 70-74 years with Eastern Cooperative Oncology Group performance status (ECOG-PS) 2 and those 75 years and older with ECOG-PS 0-2 were randomly assigned (1:1) to an FP + BEV arm or an OX addition (FP + BEV + OX) arm. Fluorouracil plus levofolinate calcium or capecitabine was declared before enrollment. The primary end point was progression-free survival (PFS). The study was registered in the Japan Registry of Clinical Trials (identifier: jRCTs031180145). RESULTS Between September 2012 and March 2019, 251 patients were randomly assigned to the FP + BEV arm (n = 125) and the FP + BEV + OX arm (n = 126). The median age was 80 and 79 years in the respective arm. The median PFS was 9.4 months (95% CI, 8.3 to 10.3) in the FP + BEV arm and 10.0 months (9.0 to 11.2) in the FP + BEV + OX arm (hazard ratio [HR], 0.84 [90.5% CI, 0.67 to 1.04]; one-sided P = .086). The median overall survival was 21.3 months (18.7 to 24.3) in the FP + BEV arm and 19.7 months (15.5 to 25.5) in the FP + BEV + OX arm (HR, 1.05 [0.81 to 1.37]). The proportion of any grade ≥3 adverse events was higher in the FP + BEV + OX arm (52% v 69%). There was one treatment-related death in the FP + BEV arm and three in the FP + BEV + OX arm. CONCLUSION No benefit of adding OX to FP + BEV as first-line treatment was demonstrated in older patients with MCRC. FP + BEV is recommended for this population.