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Background Tumors rewire their metabolism to achieve robust anabolism and resistance against therapeutic interventions like cisplatin treatment. For example, a prolonged exposure to cisplatin causes downregulation of pyridoxal kinase (PDXK), the enzyme that generates the active vitamin B6, and upregulation of poly ADP-ribose (PAR) polymerase-1 (PARP1) activity that requires a supply of nicotinamide (vitamin B3) adenine dinucleotide. We investigated the impact of the levels of PDXK and PAR on the local immunosurveillance (ie, density of the antigen presenting cells and adaptive immune response by CD8 T lymphocytes) in two different tumor types. Methods Tumors from patients with locally advanced cervical carcinoma (LACC) and non-small cell lung cancer (NSCLC) were stained for PAR, PDXK, dendritic cell lysosomal associated membrane glycoprotein (DC-LAMP) and CD8 T cell infiltration. Their correlations and prognostic impact were assessed. Cisplatin-resistant NSCLC cell clones isolated from Lewis-lung cancer (LLC) cells were evaluated for PAR levels by immunoblot. Parental (PARlow) and cisplatin-resistant (PARhigh) clones were subcutaneously injected into the flank of C57BL/6 mice. Tumors were harvested to evaluate their immune infiltration by flow cytometry. Results The infiltration of tumors by CD8 T and DC-LAMP+ cells was associated with a favorable overall survival in patients with LACC (p=0.006 and p=0.008, respectively) and NSCLC (p<0.001 for both CD8 T and DC-LAMP cells). We observed a positive correlation between PDXK expression and the infiltration by DC-LAMP (R=0.44, p=0.02 in LACC, R=0.14, p=0.057 in NSCLC), and a negative correlation between PAR levels and CD8 T lymphocytes (R=−0.39, p=0.034 in LACC, R=−0.18, p=0.017 in NSCLC). PARP1 is constitutively hyperactivated in cisplatin-resistant LLC cells manifesting elevated intracellular levels of poly(ADP-ribosyl)ated proteins (PARhigh). Tumors formed by such cancer cells injected into immunocompetent mice were scarcely infiltrated by CD8 T (p=0.028) and antigen presenting cells (p=0.086). Conclusions Oncometabolic features can impact local immunosurveillance, providing new functional links between cisplatin resistance and therapeutic failure.
Adrien Joseph; Pan Juncheng; Michele Mondini; Nizar Labaied; Mauro Loi; Julien Adam; Antoine Lafarge; Valentina Astesana; Florine Obrist; Christophe Klein; Norma Bloy; Gautier Stoll; Nicolas Signolle; Catherine Genestie; Diane Damotte; Marco Alifano; Alexandra Leary; Patricia Pautier; Philippe Morice; Sebastien Gouy; Eric Deutsch; Cyrus Chargari; Marie-Caroline Dieu-Nosjean; Isabelle Cremer; Judith Michels; Guido Kroemer; Maria Castedo. Metabolic features of cancer cells impact immunosurveillance. Journal for ImmunoTherapy of Cancer 2021, 9, e002362 .
AMA StyleAdrien Joseph, Pan Juncheng, Michele Mondini, Nizar Labaied, Mauro Loi, Julien Adam, Antoine Lafarge, Valentina Astesana, Florine Obrist, Christophe Klein, Norma Bloy, Gautier Stoll, Nicolas Signolle, Catherine Genestie, Diane Damotte, Marco Alifano, Alexandra Leary, Patricia Pautier, Philippe Morice, Sebastien Gouy, Eric Deutsch, Cyrus Chargari, Marie-Caroline Dieu-Nosjean, Isabelle Cremer, Judith Michels, Guido Kroemer, Maria Castedo. Metabolic features of cancer cells impact immunosurveillance. Journal for ImmunoTherapy of Cancer. 2021; 9 (6):e002362.
Chicago/Turabian StyleAdrien Joseph; Pan Juncheng; Michele Mondini; Nizar Labaied; Mauro Loi; Julien Adam; Antoine Lafarge; Valentina Astesana; Florine Obrist; Christophe Klein; Norma Bloy; Gautier Stoll; Nicolas Signolle; Catherine Genestie; Diane Damotte; Marco Alifano; Alexandra Leary; Patricia Pautier; Philippe Morice; Sebastien Gouy; Eric Deutsch; Cyrus Chargari; Marie-Caroline Dieu-Nosjean; Isabelle Cremer; Judith Michels; Guido Kroemer; Maria Castedo. 2021. "Metabolic features of cancer cells impact immunosurveillance." Journal for ImmunoTherapy of Cancer 9, no. 6: e002362.
In mice, the plasma concentrations of the appetite-stimulatory and autophagy-inhibitory factor acyl-coenzyme A binding protein (ACBP, also called diazepam-binding inhibitor, DBI) acutely increase in response to starvation, but also do so upon chronic overnutrition leading to obesity. Here, we show that knockout of Acbp/Dbi in adipose tissue is sufficient to prevent high-fat diet-induced weight gain in mice. We investigated ACBP/DBI plasma concentrations in several patient cohorts to discover a similar dual pattern of regulation. In relatively healthy subjects, ACBP/DBI concentrations independently correlated with body mass index (BMI) and age. The association between ACBP/DBI and BMI was lost in subjects that underwent major weight gain in the subsequent 3–9 years, as well as in advanced cancer patients. Voluntary fasting, undernutrition in the context of advanced cancer, as well as chemotherapy were associated with an increase in circulating ACBP/DBI levels. Altogether, these results support the conclusion that ACBP/DBI may play an important role in body mass homeostasis as well as in its failure.
Adrien Joseph; Hui Chen; Gerasimos Anagnostopoulos; Léa Montégut; Antoine Lafarge; Omar Motiño; Maria Castedo; Maria Chiara Maiuri; Karine Clément; Safae Terrisse; Anne Laure Martin; Ines Vaz-Luis; Fabrice Andre; Franziska Grundler; Françoise Wilhelmi de Toledo; Frank Madeo; Laurence Zitvogel; François Goldwasser; Benoit Blanchet; Frédéric Fumeron; Ronan Roussel; Isabelle Martins; Guido Kroemer. Effects of acyl-coenzyme A binding protein (ACBP)/diazepam-binding inhibitor (DBI) on body mass index. Cell Death & Disease 2021, 12, 1 -14.
AMA StyleAdrien Joseph, Hui Chen, Gerasimos Anagnostopoulos, Léa Montégut, Antoine Lafarge, Omar Motiño, Maria Castedo, Maria Chiara Maiuri, Karine Clément, Safae Terrisse, Anne Laure Martin, Ines Vaz-Luis, Fabrice Andre, Franziska Grundler, Françoise Wilhelmi de Toledo, Frank Madeo, Laurence Zitvogel, François Goldwasser, Benoit Blanchet, Frédéric Fumeron, Ronan Roussel, Isabelle Martins, Guido Kroemer. Effects of acyl-coenzyme A binding protein (ACBP)/diazepam-binding inhibitor (DBI) on body mass index. Cell Death & Disease. 2021; 12 (6):1-14.
Chicago/Turabian StyleAdrien Joseph; Hui Chen; Gerasimos Anagnostopoulos; Léa Montégut; Antoine Lafarge; Omar Motiño; Maria Castedo; Maria Chiara Maiuri; Karine Clément; Safae Terrisse; Anne Laure Martin; Ines Vaz-Luis; Fabrice Andre; Franziska Grundler; Françoise Wilhelmi de Toledo; Frank Madeo; Laurence Zitvogel; François Goldwasser; Benoit Blanchet; Frédéric Fumeron; Ronan Roussel; Isabelle Martins; Guido Kroemer. 2021. "Effects of acyl-coenzyme A binding protein (ACBP)/diazepam-binding inhibitor (DBI) on body mass index." Cell Death & Disease 12, no. 6: 1-14.
Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) is a form of thrombotic microangiopathy secondary to an infection by an enterohemorrhagic E. coli. Historically considered a pediatric disease, its presentation has been described as typical, with bloody diarrhea at the forefront. However, in adults, the clinical presentation is more diverse and makes the early diagnosis hazardous. In this review, we review the epidemiology, most important outbreaks, physiopathology, clinical presentation and prognosis of STEC-HUS, focusing on the differential features between pediatric and adult disease. We show that the clinical presentation of STEC-HUS in adults is far from typical and marked by the prevalence of neurological symptoms and a poorer prognosis. Of note, we highlight knowledge gaps and the need for studies dedicated to adult patients. The differences between pediatric and adult patients have implications for the treatment of this disease, which remains a public health threat and lack a specific treatment.
Benoit Travert; Cédric Rafat; Patricia Mariani; Aurélie Cointe; Antoine Dossier; Paul Coppo; Adrien Joseph. Shiga Toxin-Associated Hemolytic Uremic Syndrome: Specificities of Adult Patients and Implications for Critical Care Management. Toxins 2021, 13, 306 .
AMA StyleBenoit Travert, Cédric Rafat, Patricia Mariani, Aurélie Cointe, Antoine Dossier, Paul Coppo, Adrien Joseph. Shiga Toxin-Associated Hemolytic Uremic Syndrome: Specificities of Adult Patients and Implications for Critical Care Management. Toxins. 2021; 13 (5):306.
Chicago/Turabian StyleBenoit Travert; Cédric Rafat; Patricia Mariani; Aurélie Cointe; Antoine Dossier; Paul Coppo; Adrien Joseph. 2021. "Shiga Toxin-Associated Hemolytic Uremic Syndrome: Specificities of Adult Patients and Implications for Critical Care Management." Toxins 13, no. 5: 306.
Malignant cells adapt to the hostile tumor microenvironment by escaping from, or actively suppressing, anticancer immune responses. In the past, we reported that reduced synthesis of active vitamin B6 (due to downregulation of pyridoxal kinase) or overactivation of poly(ADP-ribose) polymerase confers resistance to chemotherapy with cisplatin. Recently, we found that these prognostically adverse alterations in oncometabolism also correlate with the rarefaction of immune effectors in the tumor bed.
Adrien Joseph; Juncheng Pan; Judith Michels; Guido Kroemer; Maria Castedo. Pyridoxal kinase and poly(ADP-ribose) affect the immune microenvironment of locally advanced cancers. OncoImmunology 2021, 10, 1 .
AMA StyleAdrien Joseph, Juncheng Pan, Judith Michels, Guido Kroemer, Maria Castedo. Pyridoxal kinase and poly(ADP-ribose) affect the immune microenvironment of locally advanced cancers. OncoImmunology. 2021; 10 (1):1.
Chicago/Turabian StyleAdrien Joseph; Juncheng Pan; Judith Michels; Guido Kroemer; Maria Castedo. 2021. "Pyridoxal kinase and poly(ADP-ribose) affect the immune microenvironment of locally advanced cancers." OncoImmunology 10, no. 1: 1.
Anti-CD20 monoclonal antibodies are widely used for the treatment of hematological malignancies or autoimmune disease but may be responsible for a secondary humoral deficiency. In the context of COVID-19 infection, this may prevent the elicitation of a specific SARS-CoV-2 antibody response. We report a series of 17 consecutive patients with profound B-cell lymphopenia and prolonged COVID-19 symptoms, negative immunoglobulin G (IgG)-IgM SARS-CoV-2 serology, and positive RNAemia measured by digital polymerase chain reaction who were treated with 4 units of COVID-19 convalescent plasma. Within 48 hours of transfusion, all but 1 patient experienced an improvement of clinical symptoms. The inflammatory syndrome abated within a week. Only 1 patient who needed mechanical ventilation for severe COVID-19 disease died of bacterial pneumonia. SARS-CoV-2 RNAemia decreased to below the sensitivity threshold in all 9 evaluated patients. In 3 patients, virus-specific T-cell responses were analyzed using T-cell enzyme-linked immunospot assay before convalescent plasma transfusion. All showed a maintained SARS-CoV-2 T-cell response and poor cross-response to other coronaviruses. No adverse event was reported. Convalescent plasma with anti–SARS-CoV-2 antibodies appears to be a very promising approach in the context of protracted COVID-19 symptoms in patients unable to mount a specific humoral response to SARS-CoV-2.
Thomas Hueso; Cécile Pouderoux; Hélène Péré; Anne-Lise Beaumont; Laure-Anne Raillon; Florence Ader; Lucienne Chatenoud; Déborah Eshagh; Tali-Anne Szwebel; Martin Martinot; Fabrice Camou; Etienne Crickx; Marc Michel; Matthieu Mahevas; David Boutboul; Elie Azoulay; Adrien Joseph; Olivier Hermine; Claire Rouzaud; Stanislas Faguer; Philippe Petua; Fanny Pommeret; Sébastien Clerc; Benjamin Planquette; Fatiha Merabet; Jonathan London; Valérie Zeller; David Ghez; David Veyer; Amani Ouedrani; Pierre Gallian; Jérôme Pacanowski; Arsène Mékinian; Marc Garnier; France Pirenne; Pierre Tiberghien; Karine Lacombe. Convalescent plasma therapy for B-cell–depleted patients with protracted COVID-19. Blood 2020, 136, 2290 -2295.
AMA StyleThomas Hueso, Cécile Pouderoux, Hélène Péré, Anne-Lise Beaumont, Laure-Anne Raillon, Florence Ader, Lucienne Chatenoud, Déborah Eshagh, Tali-Anne Szwebel, Martin Martinot, Fabrice Camou, Etienne Crickx, Marc Michel, Matthieu Mahevas, David Boutboul, Elie Azoulay, Adrien Joseph, Olivier Hermine, Claire Rouzaud, Stanislas Faguer, Philippe Petua, Fanny Pommeret, Sébastien Clerc, Benjamin Planquette, Fatiha Merabet, Jonathan London, Valérie Zeller, David Ghez, David Veyer, Amani Ouedrani, Pierre Gallian, Jérôme Pacanowski, Arsène Mékinian, Marc Garnier, France Pirenne, Pierre Tiberghien, Karine Lacombe. Convalescent plasma therapy for B-cell–depleted patients with protracted COVID-19. Blood. 2020; 136 (20):2290-2295.
Chicago/Turabian StyleThomas Hueso; Cécile Pouderoux; Hélène Péré; Anne-Lise Beaumont; Laure-Anne Raillon; Florence Ader; Lucienne Chatenoud; Déborah Eshagh; Tali-Anne Szwebel; Martin Martinot; Fabrice Camou; Etienne Crickx; Marc Michel; Matthieu Mahevas; David Boutboul; Elie Azoulay; Adrien Joseph; Olivier Hermine; Claire Rouzaud; Stanislas Faguer; Philippe Petua; Fanny Pommeret; Sébastien Clerc; Benjamin Planquette; Fatiha Merabet; Jonathan London; Valérie Zeller; David Ghez; David Veyer; Amani Ouedrani; Pierre Gallian; Jérôme Pacanowski; Arsène Mékinian; Marc Garnier; France Pirenne; Pierre Tiberghien; Karine Lacombe. 2020. "Convalescent plasma therapy for B-cell–depleted patients with protracted COVID-19." Blood 136, no. 20: 2290-2295.
Background Immune checkpoint inhibitors have reshaped the standard of care in oncology. However, they have been associated with potentially life-threatening immune-related adverse events. With the growing indications of immune checkpoint inhibitors and their position as a pillar of cancer treatment, intensive care physicians will be increasingly confronted with their side effects. The outcome of patients with severe immune-related adverse events in the intensive care unit remains unknown. This retrospective multicentric study aims to describe the characteristics of patients admitted to the intensive care units of 4 academic hospitals in Paris area while receiving immune checkpoint inhibitor treatment between January 2013 and October 2019. Results Over the study period, 112 cancer patients who received immune checkpoint inhibitors were admitted to the intensive care unit within 60 days after the last dose. ICU admission was related to immune-related adverse events (n = 29, 26%), other intercurrent events (n = 39, 35%), or complications related to tumor progression (n = 44, 39%). Immune-related adverse events were pneumonitis (n = 8), colitis (n = 4), myocarditis (n = 3), metabolic disorders related to diabetes (n = 3), hypophysitis (n = 2), nephritis (n = 2), meningitis or encephalitis (n = 2), hepatitis (n = 2), anaphylaxis (n = 2) and pericarditis (n = 1). Primary tumors were mostly melanomas (n = 14, 48%), non-small-cell lung cancers (n = 7, 24%), and urothelial carcinomas (n = 5, 17%). Diagnosis of melanoma and a neutrophil/lymphocyte ratio < 10 were associated with immune-related diagnosis versus other reasons for ICU admission. During their ICU stay, immune-related adverse events patients needed vasopressors (n = 7), mechanical ventilation (n = 6), and extra-corporeal membrane oxygenation (n = 2). One-year survival was significantly higher for patients admitted for irAE compared to patients admitted for other reasons (p = 0.004). Conclusions Admission to the intensive care unit related to immune-related adverse event was associated with better outcome in cancer patients treated with immune checkpoint inhibitors. Our results support the admission for an intensive care unit trial for patients with suspected immune-related adverse events.
Adrien Joseph; Audrey Simonaggio; Annabelle Stoclin; Antoine Vieillard-Baron; Guillaume Geri; Stéphane Oudard; Jean-Marie Michot; Olivier Lambotte; Elie Azoulay; Virginie Lemiale. Immune-related adverse events: a retrospective look into the future of oncology in the intensive care unit. Annals of Intensive Care 2020, 10, 1 -11.
AMA StyleAdrien Joseph, Audrey Simonaggio, Annabelle Stoclin, Antoine Vieillard-Baron, Guillaume Geri, Stéphane Oudard, Jean-Marie Michot, Olivier Lambotte, Elie Azoulay, Virginie Lemiale. Immune-related adverse events: a retrospective look into the future of oncology in the intensive care unit. Annals of Intensive Care. 2020; 10 (1):1-11.
Chicago/Turabian StyleAdrien Joseph; Audrey Simonaggio; Annabelle Stoclin; Antoine Vieillard-Baron; Guillaume Geri; Stéphane Oudard; Jean-Marie Michot; Olivier Lambotte; Elie Azoulay; Virginie Lemiale. 2020. "Immune-related adverse events: a retrospective look into the future of oncology in the intensive care unit." Annals of Intensive Care 10, no. 1: 1-11.
Outcomes in cancer patients after unplanned ICU admission was reassessed. retrospective cohort of patients with solid tumours admitted to ICU over a 10 years period. 622 patients (age 62 [53–70]) were analysed. The most common primary sites of cancer were lung (n = 133; 21.4%) and digestive tract (n = 126; 20.2%) The ICU mortality rate was 22.2% (n = 138). Among 470 ICU survivors, the 1-year mortality was 41.3% (95% CI, 36–45.9) (n = 167). Factors independently associated with 1-year mortality were ICU admission after 2010 (HR 0.53 (0.37–0.76), p < .001), disease status (respectively, HR = 1.88 (1.0.2–3.45), p = .002) for locally advanced cancer and HR = 2.23 (1.35–3.67), p = .003) for metastatic cancer), poor performance status (HR = 1.58 (1.08–2.31), p = .019), newly diagnosed cancer at ICU admission (HR = 2.02 (1.28–3.20), p = .003), inability to receive oncologic treatment after ICU discharge (HR = 5.34 (3.49–8.18), p < .001) and decision to withhold life-sustaining treatment during ICU stay (HR = 2.34 (1.50–3.65), p < .001). Among the factors associated with one-year mortality after ICU discharge, the possibility of receiving oncologic treatment after ICU discharge seems crucial.
Edith Borcoman; Axelle Dupont; Eric Mariotte; Ludovic Doucet; Adrien Joseph; Akli Chermak; Sandrine Valade; Matthieu Resche-Rigon; Elie Azoulay; Virginie Lemiale. One-year survival in patients with solid tumours discharged alive from the intensive care unit after unplanned admission: A retrospective study. Journal of Critical Care 2020, 57, 36 -41.
AMA StyleEdith Borcoman, Axelle Dupont, Eric Mariotte, Ludovic Doucet, Adrien Joseph, Akli Chermak, Sandrine Valade, Matthieu Resche-Rigon, Elie Azoulay, Virginie Lemiale. One-year survival in patients with solid tumours discharged alive from the intensive care unit after unplanned admission: A retrospective study. Journal of Critical Care. 2020; 57 ():36-41.
Chicago/Turabian StyleEdith Borcoman; Axelle Dupont; Eric Mariotte; Ludovic Doucet; Adrien Joseph; Akli Chermak; Sandrine Valade; Matthieu Resche-Rigon; Elie Azoulay; Virginie Lemiale. 2020. "One-year survival in patients with solid tumours discharged alive from the intensive care unit after unplanned admission: A retrospective study." Journal of Critical Care 57, no. : 36-41.
Rheumatology 2019. doi:10.1093/rheumatology/kez575
Antoine Lafarge; Adrien Joseph; Christian Pagnoux; Xavier Puéchal; Pascal Cohen; Maxime Samson; Mohamed Hamidou; Alexandre Karras; Thomas Quemeneur; Camillo Ribi; Matthieu Groh; Luc Mouthon; Loïc Guillevin; Benjamin Terrier; for the French Vasculitis Study Group (FVSG). Corrigendum to: Predictive factors of severe infections in patients with systemic necrotizing vasculitides: data from 733 patients enrolled in five randomized controlled trials of the French Vasculitis Study Group. Rheumatology 2020, 59, 2653 -2653.
AMA StyleAntoine Lafarge, Adrien Joseph, Christian Pagnoux, Xavier Puéchal, Pascal Cohen, Maxime Samson, Mohamed Hamidou, Alexandre Karras, Thomas Quemeneur, Camillo Ribi, Matthieu Groh, Luc Mouthon, Loïc Guillevin, Benjamin Terrier, for the French Vasculitis Study Group (FVSG). Corrigendum to: Predictive factors of severe infections in patients with systemic necrotizing vasculitides: data from 733 patients enrolled in five randomized controlled trials of the French Vasculitis Study Group. Rheumatology. 2020; 59 (9):2653-2653.
Chicago/Turabian StyleAntoine Lafarge; Adrien Joseph; Christian Pagnoux; Xavier Puéchal; Pascal Cohen; Maxime Samson; Mohamed Hamidou; Alexandre Karras; Thomas Quemeneur; Camillo Ribi; Matthieu Groh; Luc Mouthon; Loïc Guillevin; Benjamin Terrier; for the French Vasculitis Study Group (FVSG). 2020. "Corrigendum to: Predictive factors of severe infections in patients with systemic necrotizing vasculitides: data from 733 patients enrolled in five randomized controlled trials of the French Vasculitis Study Group." Rheumatology 59, no. 9: 2653-2653.
The severity of human infection by one of the many Shiga toxin-producing Escherichia coli (STEC) is determined by a number of factors: the bacterial genome, the capacity of human societies to prevent foodborne epidemics, the medical condition of infected patients (in particular their hydration status, often compromised by severe diarrhea), and by our capacity to devise new therapeutic approaches, most specifically to combat the bacterial virulence factors, as opposed to our current strategies that essentially aim to palliate organ deficiencies. The last major outbreak in 2011 in Germany, which killed more than 50 people in Europe, was evidence that an effective treatment was still lacking. Herein, we review the current knowledge of STEC virulence, how societies organize the prevention of human disease, and how physicians treat (and, hopefully, will treat) its potentially fatal complications. In particular, we focus on STEC-induced hemolytic and uremic syndrome (HUS), where the intrusion of toxins inside endothelial cells results in massive cell death, activation of the coagulation within capillaries, and eventually organ failure.
Adrien Joseph; Aurélie Cointe; Patricia Mariani Kurkdjian; Cédric Rafat; Alexandre Hertig. Shiga Toxin-Associated Hemolytic Uremic Syndrome: A Narrative Review. Toxins 2020, 12, 67 .
AMA StyleAdrien Joseph, Aurélie Cointe, Patricia Mariani Kurkdjian, Cédric Rafat, Alexandre Hertig. Shiga Toxin-Associated Hemolytic Uremic Syndrome: A Narrative Review. Toxins. 2020; 12 (2):67.
Chicago/Turabian StyleAdrien Joseph; Aurélie Cointe; Patricia Mariani Kurkdjian; Cédric Rafat; Alexandre Hertig. 2020. "Shiga Toxin-Associated Hemolytic Uremic Syndrome: A Narrative Review." Toxins 12, no. 2: 67.
Reduction in cyclophosphamide cumulative dose and introduction of newer immunosuppressive drugs may reduce the malignant burden of systemic necrotising vasculitis (SNV).1 2 This study aimed to describe malignancies recorded in five randomised controlled trials in SNV conducted by the French Vasculitis Study Group and to identify predictive factors. CHUSPAN, CHUSPAN 2, WEGENT, CORTAGE and MAINRITSAN trials evaluated different therapeutic strategies, summarised in online supplementary table S1, for the treatment of newly diagnosed or relapsing SNV. Informations regarding methods and references are provided in the online supplementary materials. The primary endpoint was the occurrence of malignancy.### Supplementary data [annrheumdis-2019-216452supp001.pdf] A total of 733 patients included between 1993 and 2012 were pooled. Baseline characteristics of the population are summarised in table 1. During a 4485.9 person-years (PY) observation period, 39 (5.3%) patients developed malignancies (869.5 per 100 000 PY), including solid cancers in 34 (4.6%) cases (757.9 per 100000 PY) and …
Antoine Lafarge; Adrien Joseph; Christian Pagnoux; Xavier Puechal; Pacal Cohen; Maxime Samson; Mohamed Hamidou; Alexandre Karras; Matthieu Groh; Thomas Quemeneur; Camillo Ribi; Luc Mouthon; Loic Guillevin; Benjamin Terrier. Risk of malignancy in patients treated for systemic necrotising vasculitis. Annals of the Rheumatic Diseases 2019, 79, 431 -433.
AMA StyleAntoine Lafarge, Adrien Joseph, Christian Pagnoux, Xavier Puechal, Pacal Cohen, Maxime Samson, Mohamed Hamidou, Alexandre Karras, Matthieu Groh, Thomas Quemeneur, Camillo Ribi, Luc Mouthon, Loic Guillevin, Benjamin Terrier. Risk of malignancy in patients treated for systemic necrotising vasculitis. Annals of the Rheumatic Diseases. 2019; 79 (3):431-433.
Chicago/Turabian StyleAntoine Lafarge; Adrien Joseph; Christian Pagnoux; Xavier Puechal; Pacal Cohen; Maxime Samson; Mohamed Hamidou; Alexandre Karras; Matthieu Groh; Thomas Quemeneur; Camillo Ribi; Luc Mouthon; Loic Guillevin; Benjamin Terrier. 2019. "Risk of malignancy in patients treated for systemic necrotising vasculitis." Annals of the Rheumatic Diseases 79, no. 3: 431-433.
The expression of two metabolic enzymes, i.e., aldehyde dehydrogenase 7 family, member A1 (ALDH7A1) and lipase C, hepatic type (LIPC) by malignant cells, has been measured by immunohistochemical methods in non-small cell lung carcinoma (NSCLC) biopsies, and has been attributed negative and positive prognostic value, respectively. Here, we demonstrate that the protein levels of ALDH7A1 and LIPC correlate with the levels of the corresponding mRNAs. Bioinformatic analyses of gene expression data from 4921 cancer patients revealed that the expression of LIPC positively correlates with abundant tumor infiltration by myeloid and lymphoid cells in NSCLC, breast carcinoma, colorectal cancer and melanoma samples. In contrast, high levels of ALDH7A1 were associated with a paucity of immune effectors within the tumor bed. These data reinforce the notion that the metabolism of cancer cells has a major impact on immune and inflammatory processes in the tumor microenvironment, pointing to hitherto unsuspected intersections between oncometabolism and immunometabolism.
Gautier Stoll; Margerie Kremer; Normal Bloy; Adrien Joseph; Maria Castedo; Guillaume Meurice; Christophe Klein; Lorenzo Galluzzi; Judith Michels; Guido Kroemer. Metabolic enzymes expressed by cancer cells impact the immune infiltrate. OncoImmunology 2019, 8, e1571389 .
AMA StyleGautier Stoll, Margerie Kremer, Normal Bloy, Adrien Joseph, Maria Castedo, Guillaume Meurice, Christophe Klein, Lorenzo Galluzzi, Judith Michels, Guido Kroemer. Metabolic enzymes expressed by cancer cells impact the immune infiltrate. OncoImmunology. 2019; 8 (6):e1571389.
Chicago/Turabian StyleGautier Stoll; Margerie Kremer; Normal Bloy; Adrien Joseph; Maria Castedo; Guillaume Meurice; Christophe Klein; Lorenzo Galluzzi; Judith Michels; Guido Kroemer. 2019. "Metabolic enzymes expressed by cancer cells impact the immune infiltrate." OncoImmunology 8, no. 6: e1571389.
Thrombotic microangiopathy syndromes are a heterogeneous group of severe diseases that often require ICU admission. Prompt initiation of targeted therapies is required for atypical hemolytic uremic syndrome and thrombotic thrombocytopenic purpura, whereas there is no specific consensus therapy for Shiga toxin–associated hemolytic uremic syndrome. We sought to compare the characteristics of Shiga toxin–associated hemolytic uremic syndrome, atypical hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura patients at admission in the ICU to allow early differentiation of Shiga toxin–associated hemolytic uremic syndrome from other thrombotic microangiopathy syndromes and help to tailor initial treatment. Retrospective cohort study. Two ICUs part of the French reference center for thrombotic microangiopathy syndromes. Adult patients presenting with features of thrombotic microangiopathy syndromes. Other causes than Shiga toxin–associated hemolytic uremic syndrome, atypical hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura were excluded. None. From September 2003 to January 2017, 236 thrombotic microangiopathy syndrome patients were admitted, including 12 Shiga toxin–associated hemolytic uremic syndrome, 21 atypical hemolytic uremic syndrome, and 91 thrombotic thrombocytopenic purpura. Shiga toxin–associated hemolytic uremic syndrome patients were older than other thrombotic microangiopathy syndromes patients (64 yr [interquartile range, 50–72 yr] vs 42 yr [31–54 yr]; p = 0.007) and presented with more frequent digestive symptoms (92% vs 42%; p Conclusions: Adult Shiga toxin–associated hemolytic uremic syndrome patients are older, present more frequently with digestive symptoms and display higher hemoglobin and fibrinogen levels than other thrombotic microangiopathy syndromes. However, overlap across the three thrombotic microangiopathy syndromes remains substantial, putting forward the need to implement early plasma therapy until thrombotic thrombocytopenic purpura and atypical hemolytic uremic syndrome can be ruled out.
Adrien Joseph; Cédric Rafat; Lara Zafrani; Patricia Mariani-Kurkdjian; Agnès Veyradier; Alexandre Hertig; Eric Rondeau; Eric Mariotte; Elie Azoulay. Early Differentiation of Shiga Toxin–Associated Hemolytic Uremic Syndrome in Critically Ill Adults With Thrombotic Microangiopathy Syndromes. Critical Care Medicine 2018, 46, e904 -e911.
AMA StyleAdrien Joseph, Cédric Rafat, Lara Zafrani, Patricia Mariani-Kurkdjian, Agnès Veyradier, Alexandre Hertig, Eric Rondeau, Eric Mariotte, Elie Azoulay. Early Differentiation of Shiga Toxin–Associated Hemolytic Uremic Syndrome in Critically Ill Adults With Thrombotic Microangiopathy Syndromes. Critical Care Medicine. 2018; 46 (9):e904-e911.
Chicago/Turabian StyleAdrien Joseph; Cédric Rafat; Lara Zafrani; Patricia Mariani-Kurkdjian; Agnès Veyradier; Alexandre Hertig; Eric Rondeau; Eric Mariotte; Elie Azoulay. 2018. "Early Differentiation of Shiga Toxin–Associated Hemolytic Uremic Syndrome in Critically Ill Adults With Thrombotic Microangiopathy Syndromes." Critical Care Medicine 46, no. 9: e904-e911.
Cisplatin is the most widely used chemotherapeutic agent, and resistance of neoplastic cells against this cytoxicant poses a major problem in clinical oncology. Here, we explored potential metabolic vulnerabilities of cisplatin‐resistant non‐small human cell lung cancer and ovarian cancer cell lines. Cisplatin‐resistant clones were more sensitive to killing by nutrient deprivation in vitro and in vivo than their parental cisplatin‐sensitive controls. The susceptibility of cisplatin‐resistant cells to starvation could be explained by a particularly strong dependence on glutamine. Glutamine depletion was sufficient to restore cisplatin responses of initially cisplatin‐resistant clones, and glutamine supplementation rescued cisplatin‐resistant clones from starvation‐induced death. Mass spectrometric metabolomics and specific interventions on glutamine metabolism revealed that, in cisplatin‐resistant cells, glutamine is mostly required for nucleotide biosynthesis rather than for anaplerotic, bioenergetic or redox reactions. As a result, cisplatin‐resistant cancers became exquisitely sensitive to treatment with antimetabolites that target nucleoside metabolism. Synopsis Cisplatin‐resistant cancers acquire a vulnerability to nutrient depletion depending on glutamine‐fueled nucleotide biosynthesis, suggesting new opportunities for combination therapies. Cisplatin‐resistant cancer cells are sensitive to starvation in vitro and in vivo. Glutamine suppresses starvation‐induced cell death. Glutamine rescues cisplatin‐resistant cells from starvation‐induced death by elevating the intracellular concentrations of nucleosides. Cisplatin‐resistant cells become exclusively sensitive to antimetabolites targeting nucleotide biosynthesis.
Florine Obrist; Judith Michels; Sylvere Durand; Alexis Chery; Jonathan Pol; Sarah Levesque; Adrien Joseph; Valentina Astesana; Federico Pietrocola; Gen Sheng Wu; Maria Castedo; Guido Kroemer. Metabolic vulnerability of cisplatin‐resistant cancers. The EMBO Journal 2018, 37, e98597 .
AMA StyleFlorine Obrist, Judith Michels, Sylvere Durand, Alexis Chery, Jonathan Pol, Sarah Levesque, Adrien Joseph, Valentina Astesana, Federico Pietrocola, Gen Sheng Wu, Maria Castedo, Guido Kroemer. Metabolic vulnerability of cisplatin‐resistant cancers. The EMBO Journal. 2018; 37 (14):e98597.
Chicago/Turabian StyleFlorine Obrist; Judith Michels; Sylvere Durand; Alexis Chery; Jonathan Pol; Sarah Levesque; Adrien Joseph; Valentina Astesana; Federico Pietrocola; Gen Sheng Wu; Maria Castedo; Guido Kroemer. 2018. "Metabolic vulnerability of cisplatin‐resistant cancers." The EMBO Journal 37, no. 14: e98597.
The relationship between sodium intake and cardiovascular events is controversial, but most large epidemiological studies estimated sodium intake using formulae based on single urine samples, the validity of which is debated. We evaluated sodium intake estimating formulae in a large cohort of adult patients. Patients were asked to collect 24-h urine the day before admission. Validity of the 24-h urine collection was assessed by comparing creatinine clearance from this collection to the mean creatinine clearance from six fractionated urine samples. Only collections with creatinine clearance within ±15% of fractionated clearance were considered valid. The Kawasaki, INTERSALT and Tanaka formulae, using a morning fasting urine sample obtained upon admission, were compared with 24-h urine sodium excretion. The relationship between sodium intake, either measured or estimated, and blood pressure was assessed. Amongst 2278 patients referred to our physiology department between September 2006 and August 2016, 1018 had complete 24-h urine collections and were included in this analysis. Mean age was 51 ± 14 years and mean sodium excretion was 3624 ± 1614 mg/day. The intraclass correlation coefficient was higher for the Kawasaki (0.54; 95% confidence interval, 0.48–0.60), than for the INTERSALT (0.38; 0.33–0.42, P < 0.001), and Tanaka (0.42; 0.37–0.46, P < 0.001) formulae. The Kawasaki formula displayed the lowest mean bias (248; 157–339 mg/day). There was a significant positive association between measured sodium intake and blood pressure, and the Kawasaki formula yielded a similar association. All formulae have poor precision and accuracy and are not suitable for estimating individual sodium intake. This does not dismiss their potential value for assessment of sodium intake in population studies.
Emmanuelle Vidal-Petiot; Adrien Joseph; Matthieu Resche-Rigon; Anne Boutten; Jimmy Mullaert; Marie-Pia D’ Ortho; Francois Vrtovsnik; Ph. Gabriel Steg; Martin Flamant. External validation and comparison of formulae estimating 24-h sodium intake from a fasting morning urine sample. Journal of Hypertension 2018, 36, 785 -792.
AMA StyleEmmanuelle Vidal-Petiot, Adrien Joseph, Matthieu Resche-Rigon, Anne Boutten, Jimmy Mullaert, Marie-Pia D’ Ortho, Francois Vrtovsnik, Ph. Gabriel Steg, Martin Flamant. External validation and comparison of formulae estimating 24-h sodium intake from a fasting morning urine sample. Journal of Hypertension. 2018; 36 (4):785-792.
Chicago/Turabian StyleEmmanuelle Vidal-Petiot; Adrien Joseph; Matthieu Resche-Rigon; Anne Boutten; Jimmy Mullaert; Marie-Pia D’ Ortho; Francois Vrtovsnik; Ph. Gabriel Steg; Martin Flamant. 2018. "External validation and comparison of formulae estimating 24-h sodium intake from a fasting morning urine sample." Journal of Hypertension 36, no. 4: 785-792.
Despite substantial improvements in the management of multiple myeloma, renal failure remains an important burden that tremendously impairs prognosis. The purpose of this study was to describe the characteristics and to establish prognostic factors of renal recovery in myeloma patients admitted to the intensive care unit (ICU) for acute kidney injury (AKI) Stage 3 treated with renal replacement therapy (RRT). A retrospective single-centre cohort study was performed, including consecutive myeloma patients admitted to one medical ICU between 1 January 2007 and 1 September 2015 and treated with RRT. Patients were evaluated 60 days after initiation of RRT and divided into three groups: alive without dialysis, alive and dialysis-dependent or deceased. A univariate analysis was performed to identify factors associated with renal recovery (alive without dialysis 60 days after initiation of RRT). Fifty patients were included in the study. Mean age was 63 (interquartile range: 58-70) years and 32 (64%) were male. Patients were admitted to the ICU 4 (1-7) years after the diagnosis of myeloma. Twenty-one (42%) had already been treated with high-dose therapy combined with autologous stem cell transplantation. Baseline renal function evaluated by estimated glomerular filtration rate (GFR) before ICU admission was 63 (44-90) mL/min/1.73 m2. The mean SOFA score at Day 1 was 7 (4-8). The three main reasons for ICU admission were AKI (n = 31, 62%), acute pulmonary oedema (n = 17, 32%) and sepsis (n = 10, 20%). During ICU stay, RRT was implemented in all patients, 16 (32%) patients required invasive mechanical ventilation and 12 (24%) received vasopressors. The mean ICU and hospital length of stay were 6 (1-7) and 28 (13-34) days, respectively. At Day 60, 23 (46%) patients were alive without dialysis, 17 (32%) had died and 10 (20%) were still undergoing dialysis. Among the 23 patients who recovered, the mean duration of dialysis was 6 (2-18) days and renal function was not significantly different from baseline [estimated GFR at baseline = 65 (25-74) mL/min/1.73 m2 versus 63 (56-70) mL/min/1.73 m2 at Day 60, P = 0.70]. By univariate analysis, two factors were associated with nonrecovery of renal function at Day 60: a history of high-dose therapy combined with autologous stem cell transplantation [odds ratio (OR) = 6.1, 95% confidence interval (CI) 1.7-21.6; P = 0.008] and a proteinuria at ICU admission >370 mg/mmol creatinine (OR = 4.2, 95% CI 1.1-17; P = 0.02). None of the other variables related to the haematological malignancy or to the ICU stay was associated with renal recovery at Day 60. AKI Stage 3 in critically ill myeloma patients was associated with a lower than expected hospital mortality. Patients with a high level of proteinuria and a history of high-dose therapy combined with autologous stem cell transplantation were less likely to recover their renal function at Day 60. dialysis, intensive care, multiple myeloma, prognosis, proteinuria.
Adrien Joseph; Stephanie Harel; Marion Venot; Sandrine Valade; Eric Mariotte; Claire Pichereau; Akli Chermak; Lara Zafrani; Elie Azoulay; Emmanuel Canet. Renal recovery after severe acute kidney injury in critically ill myeloma patients: a retrospective study. Clinical Kidney Journal 2017, 11, 20 -25.
AMA StyleAdrien Joseph, Stephanie Harel, Marion Venot, Sandrine Valade, Eric Mariotte, Claire Pichereau, Akli Chermak, Lara Zafrani, Elie Azoulay, Emmanuel Canet. Renal recovery after severe acute kidney injury in critically ill myeloma patients: a retrospective study. Clinical Kidney Journal. 2017; 11 (1):20-25.
Chicago/Turabian StyleAdrien Joseph; Stephanie Harel; Marion Venot; Sandrine Valade; Eric Mariotte; Claire Pichereau; Akli Chermak; Lara Zafrani; Elie Azoulay; Emmanuel Canet. 2017. "Renal recovery after severe acute kidney injury in critically ill myeloma patients: a retrospective study." Clinical Kidney Journal 11, no. 1: 20-25.
Emmanuelle Vidal-Petiot; Adrien Joseph; Martin Flamant. Estimation of populational 24-h urinary sodium and potassium excretion from spot urine samples. Journal of Hypertension 2017, 35, 1119 -1120.
AMA StyleEmmanuelle Vidal-Petiot, Adrien Joseph, Martin Flamant. Estimation of populational 24-h urinary sodium and potassium excretion from spot urine samples. Journal of Hypertension. 2017; 35 (5):1119-1120.
Chicago/Turabian StyleEmmanuelle Vidal-Petiot; Adrien Joseph; Martin Flamant. 2017. "Estimation of populational 24-h urinary sodium and potassium excretion from spot urine samples." Journal of Hypertension 35, no. 5: 1119-1120.
Orthostatic hypotension, defined by a drop in blood pressure of at least 20mmHg for systolic blood pressure and at least 10mmHg for diastolic blood pressure within 3minutes of standing up, is a frequent finding, particularly in elderly patients. It is associated with a significant increase in morbidity and mortality. Although it is often multifactorial, the first favoring factor is medications. Other etiologies are divided in neurogenic orthostatic hypotension, characterized by autonomic failure due to central or peripheral nervous system disorders, and non-neurogenic orthostatic hypotension, mainly favoured by hypovolemia. Treatment always requires education of the patient regarding triggering situations and physiological countermanoeuvers. Pharmacological treatment may sometimes be necessary and mainly relies on volume expansion by fludrocortisone and/or a vasopressor agents such as midodrine. There is no predefined blood pressure target, the goal of therapy being the relief of symptoms and fall prevention.
Adrien Joseph; Ruben Wanono; Martin Flamant; Emmanuelle Vidal-Petiot. Orthostatic hypotension: A review. Néphrologie & Thérapeutique 2017, 13, S55 -S67.
AMA StyleAdrien Joseph, Ruben Wanono, Martin Flamant, Emmanuelle Vidal-Petiot. Orthostatic hypotension: A review. Néphrologie & Thérapeutique. 2017; 13 ():S55-S67.
Chicago/Turabian StyleAdrien Joseph; Ruben Wanono; Martin Flamant; Emmanuelle Vidal-Petiot. 2017. "Orthostatic hypotension: A review." Néphrologie & Thérapeutique 13, no. : S55-S67.
Adrien Joseph; Emmanuelle Vidal-Petiot; Yazdan Yazdanpanah; Martin Flamant. Syndrome de Fanconi lié au Tenofovir et récupération à l’arrêt du traitement : considérations physiologiques à propos d’un cas. La Presse Médicale 2017, 46, 233 -236.
AMA StyleAdrien Joseph, Emmanuelle Vidal-Petiot, Yazdan Yazdanpanah, Martin Flamant. Syndrome de Fanconi lié au Tenofovir et récupération à l’arrêt du traitement : considérations physiologiques à propos d’un cas. La Presse Médicale. 2017; 46 (2):233-236.
Chicago/Turabian StyleAdrien Joseph; Emmanuelle Vidal-Petiot; Yazdan Yazdanpanah; Martin Flamant. 2017. "Syndrome de Fanconi lié au Tenofovir et récupération à l’arrêt du traitement : considérations physiologiques à propos d’un cas." La Presse Médicale 46, no. 2: 233-236.
H. Ayari; E. Vidal-Petiot; T. Stehlé; Adrien Joseph; B. Arnulf; F. Vrtovsnik; M. Flamant. Diminution de la sécrétion tubulaire de créatinine : nouveau signe du syndrome de Fanconi. Néphrologie & Thérapeutique 2016, 12, 273 -274.
AMA StyleH. Ayari, E. Vidal-Petiot, T. Stehlé, Adrien Joseph, B. Arnulf, F. Vrtovsnik, M. Flamant. Diminution de la sécrétion tubulaire de créatinine : nouveau signe du syndrome de Fanconi. Néphrologie & Thérapeutique. 2016; 12 (5):273-274.
Chicago/Turabian StyleH. Ayari; E. Vidal-Petiot; T. Stehlé; Adrien Joseph; B. Arnulf; F. Vrtovsnik; M. Flamant. 2016. "Diminution de la sécrétion tubulaire de créatinine : nouveau signe du syndrome de Fanconi." Néphrologie & Thérapeutique 12, no. 5: 273-274.
Thomas Robert; Maren Burbach; Adrien Joseph; Laurent Mesnard. Sodium is the secret re-agent of bicarbonate therapy during hyperkalemia. Kidney International 2016, 90, 450 -451.
AMA StyleThomas Robert, Maren Burbach, Adrien Joseph, Laurent Mesnard. Sodium is the secret re-agent of bicarbonate therapy during hyperkalemia. Kidney International. 2016; 90 (2):450-451.
Chicago/Turabian StyleThomas Robert; Maren Burbach; Adrien Joseph; Laurent Mesnard. 2016. "Sodium is the secret re-agent of bicarbonate therapy during hyperkalemia." Kidney International 90, no. 2: 450-451.