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1. Prospective Clinical Genomic Profiling of Ewing Sarcoma: ERF and FGFR1 Mutations as Recurrent Secondary Alterations of Potential Biologic and Therapeutic Relevance

Author

Ogura, Koichi, Elkrief, Arielle, Bowman, Anita S, Koche, Richard P, de Stanchina, Elisa, Benayed, Ryma, Mauguen, Audrey, Mattar, Marissa S, Khodos, Inna, Meyers, Paul A, Healey, John H, Tap, William D, Hameed, Meera, Zehir, Ahmet, Shukla, Neerav, Sawyers, Charles, Bose, Rohit, Slotkin, Emily, and Ladanyi, Marc

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Biotechnology, Pediatric Cancer, Genetics, Human Genome, Pediatric, Clinical Research, Cancer, 2.1 Biological and endogenous factors, Aetiology, Adult, Biological Products, Genomics, Humans, Mutation, Neuroectodermal Tumors, Primitive, Peripheral, Prospective Studies, Receptor, Fibroblast Growth Factor, Type 1, Repressor Proteins, Sarcoma, Ewing, United States, Oncology and carcinogenesis
Abstract

PurposeEwing sarcoma (ES) is a primitive sarcoma defined by EWSR1-ETS fusions as the primary driver alteration. To better define the landscape of cooperating secondary genetic alterations in ES, we analyzed clinical genomic profiling data of 113 patients with ES, a cohort including more adult patients (> 18 years) and more patients with advanced stage at presentation than previous genomic cohorts.MethodsThe data set consisted of patients with ES prospectively tested with the US Food and Drug Administration-cleared Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets large panel, hybrid capture-based next-generation sequencing assay. To assess the functional significance of ERF loss, we generated ES cell lines with increased expression of ERF and lines with knockdown of ERF. We assessed cell viability, clonogenic growth, and motility in these ES lines and performed transcriptomic and epigenetic analyses. Finally, we validated our findings in vivo using cell line xenografts.ResultsNovel subsets were defined by recurrent secondary alterations in ERF, which encodes an ETS domain transcriptional repressor, in 7% of patients (five truncating mutations, one deep deletion, and two missense mutations) and in FGFR1 in another 2.7% (one amplification and two known activating mutations). ERF alterations were nonoverlapping with STAG2 alterations. In vitro, increased expression of ERF decreased tumor cell growth, colony formation, and motility in two ES cell lines, whereas ERF loss induced cellular proliferation and clonogenic growth. Transcriptomic analysis of cell lines with ERF loss revealed an increased expression of genes and pathways associated with aggressive tumor biology, and epigenetic, chromatin-based studies revealed that ERF competes with EWSR1-FLI1 at ETS-binding sites.ConclusionOur findings open avenues to new insights into ES pathobiology and to novel therapeutic approaches in a subset of patients with ES.

Published
2022

2. Geriatric risk factors for serious COVID-19 outcomes among older adults with cancer: a cohort study from the COVID-19 and Cancer Consortium

Author

Elkrief, Arielle, Hennessy, Cassandra, Kuderer, Nicole M, Rubinstein, Samuel M, Wulff-Burchfield, Elizabeth, Rosovsky, Rachel P, Vega-Luna, Karen, Thompson, Michael A, Panagiotou, Orestis A, Desai, Aakash, Rivera, Donna R, Khaki, Ali Raza, Tachiki, Lisa, Lynch, Ryan C, Stratton, Catherine, Elias, Rawad, Batist, Gerald, Kasi, Anup, Shah, Dimpy P, Bakouny, Ziad, Cabal, Angelo, Clement, Jessica, Crowell, Jennifer, Dixon, Becky, Friese, Christopher R, Fry, Stacy L, Grover, Punita, Gulati, Shuchi, Gupta, Shilpa, Hwang, Clara, Khan, Hina, Kim, Soo Jung, Klein, Elizabeth J, Labaki, Chris, McKay, Rana R, Nizam, Amanda, Pennell, Nathan A, Puc, Matthew, Schmidt, Andrew L, Shahrokni, Armin, Shaya, Justin A, Su, Christopher T, Wall, Sarah, Williams, Nicole, Wise-Draper, Trisha M, Mishra, Sanjay, Grivas, Petros, French, Benjamin, Warner, Jeremy L, Wildes, Tanya M, and Consortium, COVID-19 and Cancer

Subjects
Epidemiology, Public Health, Health Sciences, Clinical Research, Aging, Cancer, Prevention, Good Health and Well Being, Aged, COVID-19, COVID-19 Testing, Cohort Studies, Humans, Middle Aged, Neoplasms, Risk Factors, SARS-CoV-2, COVID-19 and Cancer Consortium, Public health
Abstract

BackgroundOlder age is associated with poorer outcomes of SARS-CoV-2 infection, although the heterogeneity of ageing results in some older adults being at greater risk than others. The objective of this study was to quantify the association of a novel geriatric risk index, comprising age, modified Charlson comorbidity index, and Eastern Cooperative Oncology Group performance status, with COVID-19 severity and 30-day mortality among older adults with cancer.MethodsIn this cohort study, we enrolled patients aged 60 years and older with a current or previous cancer diagnosis (excluding those with non-invasive cancers and premalignant or non-malignant conditions) and a current or previous laboratory-confirmed COVID-19 diagnosis who reported to the COVID-19 and Cancer Consortium (CCC19) multinational, multicentre, registry between March 17, 2020, and June 6, 2021. Patients were also excluded for unknown age, missing data resulting in unknown geriatric risk measure, inadequate data quality, or incomplete follow-up resulting in unknown COVID-19 severity. The exposure of interest was the CCC19 geriatric risk index. The primary outcome was COVID-19 severity and the secondary outcome was 30-day all-cause mortality; both were assessed in the full dataset. Adjusted odds ratios (ORs) and 95% CIs were estimated from ordinal and binary logistic regression models.Findings5671 patients with cancer and COVID-19 were included in the analysis. Median follow-up time was 56 days (IQR 22-120), and median age was 72 years (IQR 66-79). The CCC19 geriatric risk index identified 2365 (41·7%) patients as standard risk, 2217 (39·1%) patients as intermediate risk, and 1089 (19·2%) as high risk. 36 (0·6%) patients were excluded due to non-calculable geriatric risk index. Compared with standard-risk patients, high-risk patients had significantly higher COVID-19 severity (adjusted OR 7·24; 95% CI 6·20-8·45). 920 (16·2%) of 5671 patients died within 30 days of a COVID-19 diagnosis, including 161 (6·8%) of 2365 standard-risk patients, 409 (18·5%) of 2217 intermediate-risk patients, and 350 (32·1%) of 1089 high-risk patients. High-risk patients had higher adjusted odds of 30-day mortality (adjusted OR 10·7; 95% CI 8·54-13·5) than standard-risk patients.InterpretationThe CCC19 geriatric risk index was strongly associated with COVID-19 severity and 30-day mortality. Our CCC19 geriatric risk index, based on readily available clinical factors, might provide clinicians with an easy-to-use risk stratification method to identify older adults most at risk for severe COVID-19 as well as mortality.FundingUS National Institutes of Health National Cancer Institute Cancer Center.

Published
2022

3. Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: a report from the COVID-19 and Cancer Consortium

Author

Grivas, P, Khaki, AR, Wise-Draper, TM, French, B, Hennessy, C, Hsu, C-Y, Shyr, Y, Li, X, Choueiri, TK, Painter, CA, Peters, S, Rini, BI, Thompson, MA, Mishra, S, Rivera, DR, Acoba, JD, Abidi, MZ, Bakouny, Z, Bashir, B, Bekaii-Saab, T, Berg, S, Bernicker, EH, Bilen, MA, Bindal, P, Bishnoi, R, Bouganim, N, Bowles, DW, Cabal, A, Caimi, PF, Chism, DD, Crowell, J, Curran, C, Desai, A, Dixon, B, Doroshow, DB, Durbin, EB, Elkrief, A, Farmakiotis, D, Fazio, A, Fecher, LA, Flora, DB, Friese, CR, Fu, J, Gadgeel, SM, Galsky, MD, Gill, DM, Glover, MJ, Goyal, S, Grover, P, Gulati, S, Gupta, S, Halabi, S, Halfdanarson, TR, Halmos, B, Hausrath, DJ, Hawley, JE, Hsu, E, Huynh-Le, M, Hwang, C, Jani, C, Jayaraj, A, Johnson, DB, Kasi, A, Khan, H, Koshkin, VS, Kuderer, NM, Kwon, DH, Lammers, PE, Li, A, Loaiza-Bonilla, A, Low, CA, Lustberg, MB, Lyman, GH, McKay, RR, McNair, C, Menon, H, Mesa, RA, Mico, V, Mundt, D, Nagaraj, G, Nakasone, ES, Nakayama, J, Nizam, A, Nock, NL, Park, C, Patel, JM, Patel, KG, Peddi, P, Pennell, NA, Piper-Vallillo, AJ, Puc, M, Ravindranathan, D, Reeves, ME, Reuben, DY, Rosenstein, L, Rosovsky, RP, Rubinstein, SM, Salazar, M, Schmidt, AL, and Schwartz, GK

Subjects
Infectious Diseases, Patient Safety, Cancer, Hematology, Lung, Clinical Research, Prevention, Good Health and Well Being, Aged, COVID-19, COVID-19 Testing, Female, Humans, Male, Neoplasms, Pandemics, SARS-CoV-2, SARS-CoV2, neoplasm, cancer, anticancer therapy, laboratory measurements, outcomes, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundPatients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies.Patients and methodsPatients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients).ResultsA total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality.ConclusionsClinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies.Clinical trial identifierNCT04354701.

Published
2021

4. A Systematic Framework to Rapidly Obtain Data on Patients with Cancer and COVID-19:CCC19 Governance, Protocol, and Quality Assurance

Author

Abidi, Maheen, Aboulafia, David M, Accordino, Melissa K, Acoba, Jared D, Ahluwalia, Manmeet S, Ahmad, Syed A, Ajmera, Archana, Alimohamed, Saif I, Altman, Jessica, Angevine, Anne H, Bakouny, Ziad, Bar, Michael H, Bardia, Aditya, Barnholtz-Sloan, Jill S, Barrow McCollough, Briana, Bashir, Babar, Batist, Gerald, Bekaii-Saab, Tanios S, Berg, Stephanie, Bernicker, Eric H, Bhutani, Divaya, Bilen, Mehmet A, Bindal, Poorva, Bishnoi, Rohit, Blau, Sibel, Bohachek, Pamela, Boland, Genevieve, Bonnen, Mark, Bouchard, Gabrielle, Bouganim, Nathaniel, Bowles, Daniel W, Busser, Fiona J, Butt, Omar, Cabal, Angelo, Cabalona, Wilhelmina D, Cabebe, Elwyn C, Caimi, Paolo, Campian, Jian L, Carducci, Theresa M, Chen, James L, Cheng, Alex, Chism, David D, Choueiri, Toni K, Clark, Melanie J, Clement, Jessica M, Connors, Jean M, Cook, Erin, Curran, Catherine R, Daher, Ahmad, Dailey, Mark E, Davis, Elizabeth J, Dawsey, Scott J, Deeken, John F, Del Prete, Salvatore A, Demetri, George D, Desai, Aakash, Doroshow, Deborah B, Durbin, Eric B, Egan, Pamela C, Elias, Rawad, Elkrief, Arielle, Elms, Destry J, Elshoury, Amro, Faller, Bryan, Farmakiotis, Dimitrios, Fecher, Leslie A, Feldman, Lawrence E, Ferrario, Cristiano, Fiala, Mark A, Flora, Daniel B, French, Benjamin, Friese, Christopher R, Fu, Julie C, Gadgeel, Shirish M, Gainor, Justin, Galsky, Matthew D, Gantt, Gerald, Garcia, Jorge A, Gartrell, Benjamin A, Gatti-Mays, Margaret E, Gill, David M, Gillaspie, Erin A, Giordano, Antonio, Glace, Mary Grace, Glover, Michael J, Goel, Sanjay, Graber, Jerome J, Griffiths, Elizabeth A, Grivas, Petros, Grover, Punita, Gulati, Anthony P, Gulati, Shuchi, Gupta, Shilpa, Gurley, Michael, Hafez, Navid, Halabi, Susan, Halfdanarson, Thorvardur R, Halmos, Balazs, Hausrath, Daniel J, and Hawley, Jessica E

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Biological Sciences, Clinical Research, Cancer, COVID-19, COVID-19 Testing, Data Accuracy, Electronic Health Records, Humans, Neoplasms, Quality Improvement, SARS-CoV-2, COVID-19 and Cancer Consortium. Electronic address: jeremy.warner@vumc.org, COVID-19 and Cancer Consortium, Neurosciences, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

When the COVID-19 pandemic began, formal frameworks to collect data about affected patients were lacking. The COVID-19 and Cancer Consortium (CCC19) was formed to collect granular data on patients with cancer and COVID-19 at scale and as rapidly as possible. CCC19 has grown from five initial institutions to 125 institutions with >400 collaborators. More than 5,000 cases with complete baseline data have been accrued. Future directions include increased electronic health record integration for direct data ingestion, expansion to additional domestic and international sites, more intentional patient involvement, and granular analyses of still-unanswered questions related to cancer subtypes and treatments.

Published
2020

5. Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study

Author

Kuderer, Nicole M, Choueiri, Toni K, Shah, Dimpy P, Shyr, Yu, Rubinstein, Samuel M, Rivera, Donna R, Shete, Sanjay, Hsu, Chih-Yuan, Desai, Aakash, de Lima Lopes, Gilberto, Grivas, Petros, Painter, Corrie A, Peters, Solange, Thompson, Michael A, Bakouny, Ziad, Batist, Gerald, Bekaii-Saab, Tanios, Bilen, Mehmet A, Bouganim, Nathaniel, Larroya, Mateo Bover, Castellano, Daniel, Del Prete, Salvatore A, Doroshow, Deborah B, Egan, Pamela C, Elkrief, Arielle, Farmakiotis, Dimitrios, Flora, Daniel, Galsky, Matthew D, Glover, Michael J, Griffiths, Elizabeth A, Gulati, Anthony P, Gupta, Shilpa, Hafez, Navid, Halfdanarson, Thorvardur R, Hawley, Jessica E, Hsu, Emily, Kasi, Anup, Khaki, Ali R, Lemmon, Christopher A, Lewis, Colleen, Logan, Barbara, Masters, Tyler, McKay, Rana R, Mesa, Ruben A, Morgans, Alicia K, Mulcahy, Mary F, Panagiotou, Orestis A, Peddi, Prakash, Pennell, Nathan A, Reynolds, Kerry, Rosen, Lane R, Rosovsky, Rachel, Salazar, Mary, Schmidt, Andrew, Shah, Sumit A, Shaya, Justin A, Steinharter, John, Stockerl-Goldstein, Keith E, Subbiah, Suki, Vinh, Donald C, Wehbe, Firas H, Weissmann, Lisa B, Wu, Julie Tsu-Yu, Wulff-Burchfield, Elizabeth, Xie, Zhuoer, Yeh, Albert, Yu, Peter P, Zhou, Alice Y, Zubiri, Leyre, Mishra, Sanjay, Lyman, Gary H, Rini, Brian I, Warner, Jeremy L, Consortium, COVID-19 and Cancer, Abidi, Maheen, Acoba, Jared D, Agarwal, Neeraj, Ahmad, Syed, Ajmera, Archana, Altman, Jessica, Angevine, Anne H, Azad, Nilo, Bar, Michael H, Bardia, Aditya, Barnholtz-Sloan, Jill, Barrow, Briana, Bashir, Babar, Belenkaya, Rimma, Berg, Stephanie, Bernicker, Eric H, Bestvina, Christine, Bishnoi, Rohit, Boland, Genevieve, Bonnen, Mark, Bouchard, Gabrielle, Bowles, Daniel W, Busser, Fiona, Cabal, Angelo, Caimi, Paolo, and Carducci, Theresa

Subjects
Biomedical and Clinical Sciences, Health Sciences, Clinical Sciences, Oncology and Carcinogenesis, Clinical Research, Aging, Prevention, Cancer, Lung, Good Health and Well Being, Aged, Antiviral Agents, Azithromycin, Betacoronavirus, COVID-19, Cause of Death, Comorbidity, Coronavirus Infections, Databases, Factual, Female, Humans, Hydroxychloroquine, Male, Middle Aged, Neoplasms, Pandemics, Pneumonia, Viral, Prognosis, Risk Factors, SARS-CoV-2, COVID-19 Drug Treatment, COVID-19 and Cancer Consortium, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundData on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness.MethodsIn this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020. We collected data on baseline clinical conditions, medications, cancer diagnosis and treatment, and COVID-19 disease course. The primary endpoint was all-cause mortality within 30 days of diagnosis of COVID-19. We assessed the association between the outcome and potential prognostic variables using logistic regression analyses, partially adjusted for age, sex, smoking status, and obesity. This study is registered with ClinicalTrials.gov, NCT04354701, and is ongoing.FindingsOf 1035 records entered into the CCC19 database during the study period, 928 patients met inclusion criteria for our analysis. Median age was 66 years (IQR 57-76), 279 (30%) were aged 75 years or older, and 468 (50%) patients were male. The most prevalent malignancies were breast (191 [21%]) and prostate (152 [16%]). 366 (39%) patients were on active anticancer treatment, and 396 (43%) had active (measurable) cancer. At analysis (May 7, 2020), 121 (13%) patients had died. In logistic regression analysis, independent factors associated with increased 30-day mortality, after partial adjustment, were: increased age (per 10 years; partially adjusted odds ratio 1·84, 95% CI 1·53-2·21), male sex (1·63, 1·07-2·48), smoking status (former smoker vs never smoked: 1·60, 1·03-2·47), number of comorbidities (two vs none: 4·50, 1·33-15·28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs 0 or 1: 3·89, 2·11-7·18), active cancer (progressing vs remission: 5·20, 2·77-9·77), and receipt of azithromycin plus hydroxychloroquine (vs treatment with neither: 2·93, 1·79-4·79; confounding by indication cannot be excluded). Compared with residence in the US-Northeast, residence in Canada (0·24, 0·07-0·84) or the US-Midwest (0·50, 0·28-0·90) were associated with decreased 30-day all-cause mortality. Race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality.InterpretationAmong patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments.FundingAmerican Cancer Society, National Institutes of Health, and Hope Foundation for Cancer Research.

Published
2020

6. Variation of the SOFA score and mortality in patients with severe burns: A cohort study

Author

Julien Calles, Benjamin Cohen, Nathalie Forme, Zahida Guendil, Brice Fermier, Claire Chassier, Laure Elkrief, Antoine Roquilly, Francis Remerand, and Romain Miguel Montanes

Subjects
Cohort Studies, ROC Curve, Organ Dysfunction Scores, Multiple Organ Failure, Emergency Medicine, Humans, Surgery, General Medicine, Middle Aged, Burns, Prognosis, Critical Care and Intensive Care Medicine, Retrospective Studies
Abstract

Multiple organ failure (MOF) is the leading cause of death in patients with burns requiring ICU admission. Quantifying the evolution of MOF, with the SOFA score, over the first few days after a severe burn may provide useful prognostic information. This retrospective cohort study aimed at evaluating the association between the evolution of the SOFA score between day 0 and day 3 and in-hospital mortality. All patients admitted for severe burns at the burn ICU of the Tours University Hospital between 2017 and 2020 and who stayed 3 days or more were included. Severe burns included: total body surface area burned (TBSA) ≥ 20 % or burns of any surface associated with one or more of the following items: (1) organ failure, (2) clinically significant smoke inhalation and/or cyanide poisoning, (3) severe preexisting comorbidities, (4) complex and specialized burn wound care. DeltaSOFA was defined as day 3 minus day 0 SOFA. One hundred and thirty-six patients were included. Median age was 52 years (38-70), median TBSA burned was 24 % (20-38), median day 0 SOFA was 2 (0-4) and median day 3 SOFA was 1 (0-5). In-hospital mortality was 10 %. There was a significant association between deltaSOFA and mortality that persisted after adjustment for age and TBSA (HR 1.37, 95 %CI 1.09-1.72, p 0.01). Area under the receiver operating characteristics curve for the prediction of mortality by day 0 SOFA and deltaSOFA were 0.79 (95 %CI 0.69-0.89) and 0.83 (95 %CI 0.70-0.95) respectively. After exclusion of patients with TBSA burned 15 %, deltaSOFA remained independently associated with mortality (HR 1.42 95 %CI 1.09-1.85, p 0.01). In addition, SOFA variations allowed the identification of subgroups of patients with either very low or very high mortality. In patients with severe burns, SOFA score evolution between day 0 and day 3 may be useful for individualized medical and ethical decisions. Further multicenter studies are required to corroborate the present results.

Published
2023
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7. COVID-19 in liver transplant candidates

Author

Belli, Luca Saverio, Duvoux, Christophe, Cortesi, Paolo Angelo, Facchetti, Rita, Iacob, Speranta, Perricone, Giovanni, Radenne, Sylvie, Conti, Sara, Patrono, Damiano, Berlakovich, Gabriela, Hann, Angus, Pasulo, Luisa, Castells, Lluis, Faitot, Francois, Detry, Olivier, Invernizzi, Federica, Magini, Giulia, De Simone, Paolo, Kounis, Ilias, Morelli, Maria Cristina, Díaz Fontenla, Fernando, Ericzon, Bo-Göran, Loinaz, Carmelo, Johnston, Chris, Gheorghe, Liliana, Lesurtel, Mickael, Romagnoli, Renato, Kollmann, Dagmar, Perera, M Thamara Pr, Fagiuoli, Stefano, Mirza, Darius, Coilly, Audrey, Toso, Christian, Zieniewicz, Krzysztof, Elkrief, Laure, Karam, Vincent, Adam, Rene, den Hoed, Caroline, Merli, Marco, Puoti, Massimo, De Carlis, Luciano, Oniscu, Gabriel C, Piano, Salvatore, Angeli, Paolo, Fondevila, Constantino, Polak, Wojciech G, ELITA-ELTR COVID-19 Registry, Gastroenterology & Hepatology, Surgery, Belli, L, Duvoux, C, Cortesi, P, Facchetti, R, Iacob, S, Perricone, G, Radenne, S, Conti, S, Patrono, D, Berlakovich, G, Hann, A, Pasulo, L, Castells, L, Faitot, F, Detry, O, Invernizzi, F, Magini, G, De Simone, P, Kounis, I, Morelli, M, Diaz Fontenla, F, Ericzon, B, Loinaz, C, Johnston, C, Gheorghe, L, Lesurtel, M, Romagnoli, R, Kollmann, D, Perera, M, Fagiuoli, S, Mirza, D, Coilly, A, Toso, C, Zieniewicz, K, Elkrief, L, Karam, V, Adam, R, Den Hoed, C, Merli, M, Puoti, M, De Carlis, L, Oniscu, G, Piano, S, Angeli, P, Fondevila, C, and Polak, W

Subjects
0301 basic medicine, Male, medicine.medical_specialty, Waiting Lists, medicine.medical_treatment, liver cirrhosis, Pneumonia, Viral, Population, Liver transplantation, 03 medical and health sciences, Liver disease, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Risk Factors, Internal medicine, Cause of Death, Medicine, Humans, Viral, Registries, education, Cause of death, education.field_of_study, ddc:617, liver transplantation, liver cirrhosi, Proportional hazards model, business.industry, SARS-CoV-2, Gastroenterology, COVID-19, Pneumonia, Middle Aged, medicine.disease, Transplant Recipients, Transplantation, Europe, 030104 developmental biology, Respiratory failure, Liver cirrhosis, 030211 gastroenterology & hepatology, Female, Liver Transplantation, business, Cohort study
Abstract

ObjectiveExplore the impact of COVID-19 on patients on the waiting list for liver transplantation (LT) and on their post-LT course.DesignData from consecutive adult LT candidates with COVID-19 were collected across Europe in a dedicated registry and were analysed.ResultsFrom 21 February to 20 November 2020, 136 adult cases with laboratory-confirmed SARS-CoV-2 infection from 33 centres in 11 European countries were collected, with 113 having COVID-19. Thirty-seven (37/113, 32.7%) patients died after a median of 18 (10–30) days, with respiratory failure being the major cause (33/37, 89.2%). The 60-day mortality risk did not significantly change between first (35.3%, 95% CI 23.9% to 50.0%) and second (26.0%, 95% CI 16.2% to 40.2%) waves. Multivariable Cox regression analysis showed Laboratory Model for End-stage Liver Disease (Lab-MELD) score of ≥15 (Model for End-stage Liver Disease (MELD) score 15–19, HR 5.46, 95% CI 1.81 to 16.50; MELD score≥20, HR 5.24, 95% CI 1.77 to 15.55) and dyspnoea on presentation (HR 3.89, 95% CI 2.02 to 7.51) being the two negative independent factors for mortality. Twenty-six patients underwent an LT after a median time of 78.5 (IQR 44–102) days, and 25 (96%) were alive after a median follow-up of 118 days (IQR 31–170).ConclusionsIncreased mortality in LT candidates with COVID-19 (32.7%), reaching 45% in those with decompensated cirrhosis (DC) and Lab-MELD score of ≥15, was observed, with no significant difference between first and second waves of the pandemic. Respiratory failure was the major cause of death. The dismal prognosis of patients with DC supports the adoption of strict preventative measures and the urgent testing of vaccination efficacy in this population. Prior SARS-CoV-2 symptomatic infection did not affect early post-transplant survival (96%).

Published
2021

8. Paroxysmal nocturnal hemoglobinuria and vascular liver disease: Eculizumab therapy decreases mortality and thrombotic complications

Author

Aurélie Plessier, Marina Esposito‐Farèse, Anna Baiges, Akash Shukla, Juan Carlos Garcia Pagan, Emmanuelle De Raucourt, Isabelle Ollivier‐Hourmand, Jean‐Paul Cervoni, Victor De Ledinghen, Zoubida Tazi, Jean‐Baptiste Nousbaum, René Bun, Christophe Bureau, Christine Silvain, Olivier Tournilhac, Mathieu Gerfaud‐Valentin, François Durand, Odile Goria, Luis Tellez, Agustin Albillos, Stefania Gioia, Oliviero Riggio, Andrea De Gottardi, Audrey Payance, Pierre‐Emmanuel Rautou, Louis Terriou, Aude Charbonnier, Laure Elkrief, Regis Peffault de la Tour, Dominique‐Charles Valla, Nathalie Gault, and Flore Sicre de Fontbrune

Subjects
Adult, Male, Liver Diseases, Hemoglobinuria, Paroxysmal, Humans, Female, Thrombosis, Hematology, Antibodies, Monoclonal, Humanized, Retrospective Studies
Abstract

A total of 2%-10% of patients with vascular liver disease (VLD) have paroxysmal nocturnal hemoglobinuria (PNH). Eculizumab reduces complement-mediated haemolytic activity in PNH. This study was aimed at assessing the impact of eculizumab on VLD outcome. Retrospective cohort of PNH patients, in Valdig registry, who had VLD diagnosed between 1997 and 2019 is considered. Eculizumab was the exposure of interest. Studied outcomes were death, venous thrombosis, bleeding, arterial ischemic event, infection, and liver-related complications. We compared survival and new thrombotic events from PNH/VLD cohort to Envie2 non-PNH cohort. Sixty-two patients (33 women), median age 35 years (28-48) and median follow-up VLD diagnosis 4.7 years (1.2-9.5), were included. Clone size was 80% (70-90), median hemoglobin concentration was 10.0 g/dl (8-11), and lactate dehydrogenase (LDH) was 736 IU (482-1744). Forty-two patients (68%) had eculizumab; median exposure time was 40.1 [9.3-72.6] months. Mortality was significantly lower in exposed versus nonexposed period: 2.6 versus 8.7 per 100 (PY), incidence rate ratio (IRR) was 0.29, 95% CI (0.1-0.9), p = .035. Thrombosis recurrence occurred less frequently during the exposure to eculizumab: 0.5 versus 2.8 per 100 PY, IRR 0.22 (0.07-0.64). Other secondary end points (i.e., bleeding, arterial ischemic lesions, infection, and liver complications) were less common during the exposure to eculizumab, although not reaching statistical significance. Six-year thrombosis-free survival was 70%, 95% CI [0.60-0.83] for PNH cohort and 83%, 95% CI [0.70-1.00] for non-PNH Envie 2 patients, (p .001). In conclusion, patients with PNH and VLD are at higher risk of recurrent thrombosis than non-PNH patients. Eculizumab is significantly associated with a lower mortality and less thrombotic recurrence in patients with PNH and VLD.

Published
2022
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9. Clinical features and evolution of bacterial infection-related acute-on-chronic liver failure

Author

Carlo Alessandria, Carmine Gambino, Javier Fernández, Hans Van Vlierberghe, Sophie Restellini, Marcos Girala, Luis Colombato, Tae Hee Lee, Nikolaos Pyrsopoulos, Eduardo Fassio, Sang Gyune Kim, Gisela Pinero, Paolo Caraceni, Shivaram Prasad Singh, Do Seon Song, Ji Won Park, Julio Vorobioff, Dong Joon Kim, C. Toledo, Aleksander Krag, Liane Rabinowich, Preetam Nath, Robert A. de Man, Elza Cotrim Soares, Xavier Verhelst, Tiago Sevá Pereira, Gustavo Romero, Macarena Simón-Talero, Sung Eun Kim, Michele Bartoletti, Alexander L. Gerbes, Sebastián Marciano, Tony Bruns, Hyoung Su Kim, Ki Tae Suk, Nicolas M. Intagliata, Annette Dam Fialla, Adrià Juanola, Manuela Merli, Rita de Cassia Ribeiro Barea, Laure Elkrief, Rakhi Maiwall, Laurentius A Lesmana, Pere Ginès, Vikas Gautam, E.L. Yoon, M. Marino, Paolo Angeli, Kalyan Ram Bhamidimarri, Victor Vargas, Virendra Singh, Juan Pablo Roblero, François Durand, Cosmas A. Rinaldi Lesmana, M. V. Maevskaya, Gustavo Navarro, Adrian Gadano, Florence Wong, Pramod Kumar, Tae Hun Kim, Daniela Campion, Salvatore Piano, Giacomo Zaccherini, Barbara Lattanz, Jae Seok Hwang, Sun Young Yim, Thomas D. Boyer, Jeong Han Kim, Carlos Brodersen, Wong F., Piano S., Singh V., Bartoletti M., Maiwall R., Alessandria C., Fernandez J., Soares E.C., Kim D.J., Kim S.E., Marino M., Vorobioff J., Barea R.D.C.R., Merli M., Elkrief L., Vargas V., Krag A., Singh S.P., Lesmana L.A., Toledo C., Marciano S., Verhelst X., Intagliata N., Rabinowich L., Colombato L., Kim S.G., Gerbes A., Durand F., Roblero J.P., Bruns T., Yoon E.L., Girala M., Pyrsopoulos N.T., Kim T.H., Yim S.Y., Juanola A., Gadano A., Angeli P., Bhamidimarri K., Boyer T.D., Brodersen C., Campion D., Caraceni P., de Man R.A., Fassio E., Fialla A.D., Gambino C., Gautam V., Gines P., Hwang J.S., Kim H.S., Kim J.H., Kumar P., Lattanz B., Lee T.H., Rinaldi Lesmana C.A., Maevskaya M., Nath P., Navarro G., Park J.-W., Pinero G., Restellini S., Romero G., Seva -Pereira T., Simon-Talero M., Song D.S., Suk K.T., Van Vlierberghe H., and Zaccherini G.

Subjects
Male, 0301 basic medicine, Cirrhosis, Organ Dysfunction Scores, Antibiotic resistance, medicine.medical_treatment, Liver transplantation, Severity of Illness Index, 0302 clinical medicine, ACLF, MDR, Epidemiology, Cross Infection, Mortality rate, Age Factors, Bacterial Infections, Middle Aged, Prognosis, Community-Acquired Infections, Europe, Hospitalization, Female, 030211 gastroenterology & hepatology, Alcohol-Related Disorders, medicine.medical_specialty, Sepsi, India, Risk Assessment, Sepsis, 03 medical and health sciences, Sex Factors, Spontaneous bacterial peritonitis, Internal medicine, medicine, Humans, XDR, Cirrhosi, Hepatology, business.industry, Acute-On-Chronic Liver Failure, medicine.disease, Pneumonia, 030104 developmental biology, antibiotic resistance, liver transplantation, sepsis, business
Abstract

Background & Aims: Bacterial infections can trigger the development of organ failure(s) and acute-on-chronic liver failure (ACLF). Geographic variations in bacteriology and clinical practice could lead to worldwide differences in ACLF epidemiology, phenotypes and associated outcomes. Herein, we aimed to evaluate regional differences in bacterial infection-related ACLF in patients with cirrhosis admitted to hospital. Methods: This post hoc analysis included 1,175 patients with decompensated cirrhosis (with bacterial infection on admission or nosocomial infection) from 6 geographic regions worldwide. Clinical, laboratory and microbiological data were collected from the diagnosis of infection. Patients were followed-up for organ failure(s) and ACLF development according to the EASL-CLIF criteria from enrolment to discharge/death. Results: A total of 333 patients (28%) had ACLF at diagnosis of infection, while 230 patients developed ACLF after diagnosis of infection, resulting in an overall rate of bacterial infection related-ACLF of 48%, with rates differing amongst different geographic regions (38% in Southern Europe vs. 75% in the Indian subcontinent). Bacterial infection related-ACLF more frequently developed in younger patients (55 ± 13 vs. 58 ± 14 years), males (73% vs. 62%), patients with alcohol-related cirrhosis (59% vs. 45%) and those with a higher baseline MELD score (25 ± 11 vs. 16 ± 5) (all p

Published
2021
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10. Learning through a Pandemic: The Current State of Knowledge on COVID-19 and Cancer

Author

Arielle Elkrief, Julie T. Wu, Chinmay Jani, Kyle T. Enriquez, Michael Glover, Mansi R. Shah, Hira Ghazal Shaikh, Alicia Beeghly-Fadiel, Benjamin French, Sachin R. Jhawar, Douglas B. Johnson, Rana R. McKay, Donna R. Rivera, Daniel Y. Reuben, Surbhi Shah, Stacey L. Tinianov, Donald Cuong Vinh, Sanjay Mishra, and Jeremy L. Warner

Subjects
Oncology, Neoplasms, COVID-19, Humans, Pandemics, Article
Abstract

The ongoing coronavirus disease 2019 (COVID-19) pandemic has left patients with current or past history of cancer facing disparate consequences at every stage of the cancer trajectory. This comprehensive review offers a landscape analysis of the current state of the literature on COVID-19 and cancer, including the immune response to COVID-19, risk factors for severe disease, and impact of anticancer therapies. We also review the latest data on treatment of COVID-19 and vaccination safety and efficacy in patients with cancer, as well as the impact of the pandemic on cancer care, including the urgent need for rapid evidence generation and real-world study designs. SIGNIFICANCE: Patients with cancer have faced severe consequences at every stage of the cancer journey due to the COVID-19 pandemic. This comprehensive review offers a landscape analysis of the current state of the field regarding COVID-19 and cancer. We cover the immune response, risk factors for severe disease, and implications for vaccination in patients with cancer, as well as the impact of the COVID-19 pandemic on cancer care delivery. Overall, this review provides an in-depth summary of the key issues facing patients with cancer during this unprecedented health crisis.

Published
2021
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11. Venous thrombotic events in patients treated with immune checkpoint inhibitors for non-small cell lung cancer: A retrospective multicentric cohort study

Author

Normand Blais, Wiam Belkaid, Andréanne Gagné, Philippe Joubert, Michèle Orain, Julie Malo, Florence Blais, Corentin Richard, Xavier Deschênes-Simard, François Ghiringhelli, Loïck Galland, Bertrand Routy, Lena Cvetkovic, Arielle Elkrief, Antoine Desilets, and Marc-André Hamel

Subjects
Oncology, medicine.medical_specialty, Lung Neoplasms, 030204 cardiovascular system & hematology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Internal medicine, Humans, Medicine, Cumulative incidence, Clinical significance, Lung cancer, Immune Checkpoint Inhibitors, Aged, Retrospective Studies, business.industry, Incidence (epidemiology), Thrombosis, Hematology, medicine.disease, Pulmonary embolism, 030220 oncology & carcinogenesis, Cohort, business, Complication, Cohort study
Abstract

Venous thrombotic events (VTEs) are a frequent complication of non-small cell lung cancer (NSCLC) and are associated with increased morbidity. Immune checkpoint inhibitors (ICIs) are revolutionizing the management of NSCLC, but little is known about their impact on thrombosis. This study aims to define the incidence and clinical relevance of VTEs in NSCLC patients receiving these treatments.A retrospective multicentric cohort study including 593 patients from three centers in Canada and France was performed. The cumulative incidence of VTEs after ICIs was estimated using competing risk analysis, and the association of these events with survival and response to treatment was determined. Finally, univariate and multivariate tests were performed to identify VTE risk factors.The cumulative incidence of VTEs in the cohort was 14.8% (95% CI = 7.4-22.2%) for an incidence rate of 76.5 (95% CI = 59.9-97.8) thrombosis per 1000 person-years, with most thromboses occurring rapidly after treatment initiation. VTEs were not correlated with overall survival, progression-free survival, or objective response to ICIs. Age ˂ 65 years old (HR = 2.00; 95% CI = 1.11-3.59) and tumors with PD-L1 1-49% (HR = 3.36; 95% CI = 1.19-9.50) or PD-L1 ≥ 50% (HR = 3.22; 95% CI = 1.21-8.57) were associated with more VTEs after 12 months of ICI initiation. Also, a delay of less than 12 months from diagnosis to the first ICI treatment (HR = 2.06; 95% CI = 1.09-3.89) and active smoking (HR = 2.00; 95% CI = 1.12-3.58) are probable risk factors of VTEs.This study suggests that the incidence of VTEs in NSCLC patients treated with ICIs is comparable to what is reported in other cohorts of patients treated with chemotherapy. In our cohort, VTEs were not associated with a decreased survival or response to therapy. Patient age 65 and tumors with PD-L1 ≥ 1% were associated with a higher risk of VTEs under ICIs.

Published
2021
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12. Prospective Clinical Genomic Profiling of Ewing Sarcoma

Author

Koichi, Ogura, Arielle, Elkrief, Anita S, Bowman, Richard P, Koche, Elisa, de Stanchina, Ryma, Benayed, Audrey, Mauguen, Marissa S, Mattar, Inna, Khodos, Paul A, Meyers, John H, Healey, William D, Tap, Meera, Hameed, Ahmet, Zehir, Neerav, Shukla, Charles, Sawyers, Rohit, Bose, Emily, Slotkin, and Marc, Ladanyi

Subjects
Adult, Repressor Proteins, Biological Products, Mutation, Humans, Genomics, Neuroectodermal Tumors, Primitive, Peripheral, Prospective Studies, Receptor, Fibroblast Growth Factor, Type 1, Sarcoma, Ewing, United States
Abstract

Ewing sarcoma (ES) is a primitive sarcoma defined by EWSR1-ETS fusions as the primary driver alteration. To better define the landscape of cooperating secondary genetic alterations in ES, we analyzed clinical genomic profiling data of 113 patients with ES, a cohort including more adult patients (18 years) and more patients with advanced stage at presentation than previous genomic cohorts.The data set consisted of patients with ES prospectively tested with the US Food and Drug Administration-cleared Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets large panel, hybrid capture-based next-generation sequencing assay. To assess the functional significance ofNovel subsets were defined by recurrent secondary alterations inOur findings open avenues to new insights into ES pathobiology and to novel therapeutic approaches in a subset of patients with ES.

Published
2022

13. Helicobacter pylori serology is associated with worse overall survival in patients with melanoma treated with immune checkpoint inhibitors

Author

Marion Tonneau, Alexis Nolin-Lapalme, Suzanne Kazandjian, Edouard Auclin, Justin Panasci, Myriam Benlaifaoui, Mayra Ponce, Afnan Al-Saleh, Wiam Belkaid, Sabrine Naimi, Catalin Mihalcioiu, Ian Watson, Mickael Bouin, Wilson Miller, Marie Hudson, Matthew K. Wong, Rossanna C. Pezo, Simon Turcotte, Karl Bélanger, Rahima Jamal, Paul Oster, Dominique Velin, Corentin Richard, Meriem Messaoudene, Arielle Elkrief, and Bertrand Routy

Subjects
Carcinoma, Non-Small-Cell Lung/drug therapy, Helicobacter Infections/drug therapy, Helicobacter Infections/microbiology, Helicobacter pylori/physiology, Humans, Immune Checkpoint Inhibitors/therapeutic use, Lung Neoplasms/drug therapy, Melanoma/drug therapy, Syndrome, Metastatic melanoma, helicobacter pylori, immune checkpoint inhibitor therapy, microbiome, non-small cell lung cancer, onco-immunology, Oncology, Immunology, Immunology and Allergy
Abstract

The microbiome is now regarded as one of the hallmarks of cancer and several strategies to modify the gut microbiota to improve immune checkpoint inhibitor (ICI) activity are being evaluated in clinical trials. Preliminary data regarding the upper gastro-intestinal microbiota indicated that Helicobacter pylori seropositivity was associated with a negative prognosis in patients amenable to ICI. In 97 patients with advanced melanoma treated with ICI, we assessed the impact of H. pylori on outcomes and microbiome composition. We performed H. pylori serology and profiled the fecal microbiome with metagenomics sequencing. Among the 97 patients, 22% were H. pylori positive (Pos). H. pylori Pos patients had a significantly shorter overall survival (p = .02) compared to H. pylori negative (Neg) patients. In addition, objective response rate and progression-free survival were decreased in H. pylori Pos patients. Metagenomics sequencing did not reveal any difference in diversity indexes between the H. pylori groups. At the taxa level, Eubacterium ventriosum, Mediterraneibacter (Ruminococcus) torques, and Dorea formicigenerans were increased in the H. pylori Pos group, while Alistipes finegoldii, Hungatella hathewayi and Blautia producta were over-represented in the H. pylori Neg group. In a second independent cohort of patients with NSCLC, diversity indexes were similar in both groups and Bacteroides xylanisolvens was increased in H. pylori Neg patients. Our results demonstrated that the negative impact of H. pylori on outcomes seem to be independent from the fecal microbiome composition. These findings warrant further validation and development of therapeutic strategies to eradicate H. pylori in immuno-oncology arena.

Published
2022
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14. Gemcitabine-Containing Chemotherapy for the Treatment of Metastatic Myxofibrosarcoma Refractory to Doxorubicin: A Case Series

Author

Arielle Elkrief, Suzanne Kazandjian, and Thierry Alcindor

Subjects
Oncology, Adult, medicine.medical_specialty, sarcoma, medicine.medical_treatment, chemotherapy, Deoxycytidine, Undifferentiated Pleomorphic Sarcoma, Refractory, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Doxorubicin, RC254-282, Retrospective Studies, Chemotherapy, business.industry, Brief Report, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Myxofibrosarcoma, medicine.disease, Gemcitabine, Cohort, myxofibrosarcoma, Sarcoma, Neoplasm Recurrence, Local, business, medicine.drug
Abstract

Background: Myxofibrosarcoma is a type of soft-tissue sarcoma that is associated with high rates of local recurrence and distant metastases. The first-line treatment for metastatic soft-tissue sarcoma has conventionally been doxorubicin-based. Recent evidence suggests that myxofibrosarcoma may be molecularly similar to undifferentiated pleomorphic sarcoma (UPS), which is particularly sensitive to gemcitabine-based therapy. The goal of this study was to evaluate the activity of gemcitabine-containing regimens for the treatment of metastatic myxofibrosarcoma refractory to doxorubicin. Material and Methods: We retrospectively evaluated seven consecutive cases of metastatic myxofibrosarcoma at our institution treated with gemcitabine-based therapy in the second-line setting, after progression on doxorubicin. Baseline clinical and baseline characteristics were collected. Primary endpoints were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: After progression on first-line doxorubicin, a partial, or complete radiological response was observed in four of seven patients who received gemcitabine-based chemotherapy. With a median follow-up of 14 months, median progression-free and overall survival were 8.5 months and 11.4 months, respectively. Conclusions: Gemcitabine-based chemotherapy was associated with encouraging response rates in this cohort, similar to those seen in UPS. Both entities could be studied together for novel gemcitabine-based regimens.

Published
2021

15. Durvalumab therapy following chemoradiation compared with a historical cohort treated with chemoradiation alone in patients with stage III non–small cell lung cancer: A real-world multicentre study

Author

Victor Cohen, Chloé Charbonneau, Rui Kitadai, Lena Cvetkovic, Penelope A. Bradbury, Normand Blais, Julie Malo, Marie Florescu, Félix Blanc-Durand, S. Lau, Wiam Belkaid, Natasha B. Leighl, Arielle Elkrief, Adrian G. Sacher, Corentin Richard, Kevin Jao, Suzanne Kazandjian, Geoffrey Liu, Mustapha Tehfe, Taiki Hakozaki, Frances A. Shepherd, Jason Agulnik, Nathalie Daaboul, Benjamin Shieh, S. Owen, Houda Bahig, Nicolas Marcoux, Meriem Messaoudene, Bertrand Routy, and Antoine Desilets

Subjects
Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Durvalumab, Cohort Studies, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Internal medicine, medicine, Humans, Stage (cooking), Survival analysis, Aged, Neoplasm Staging, Retrospective Studies, Pneumonitis, Univariate analysis, business.industry, Incidence (epidemiology), Hazard ratio, Antibodies, Monoclonal, Chemoradiotherapy, medicine.disease, Confidence interval, 030104 developmental biology, 030220 oncology & carcinogenesis, Female, business
Abstract

The PACIFIC trial demonstrated that durvalumab therapy following chemoradiation (CRT) was associated with improved overall survival (OS) in patients with stage III non-small cell lung cancer (NSCLC). It is unclear whether the results obtained as part of randomised controlled trials are a reflection of real-world (RW) data. Several questions remain unanswered with regard to RW durvalumab use, such as optimal time to durvalumab initiation, incidence of pneumonitis and response in PD-L1 subgroups.In this multicentre retrospective analysis, 147 patients with stage III NSCLC treated with CRT followed by durvalumab were compared with a historical cohort of 121 patients treated with CRT alone. Survival curves were estimated using the Kaplan-Meier method and compared with the log-rank test in univariate analysis. Multivariate analysis was performed to evaluate the effect of standard prognostic factors for durvalumab use.Median OS was not reached in the durvalumab group, compared with 26.9 months in the historical group (hazard ratio [HR]: 0.56, 95% confidence interval [CI]: 0.37-0.85, p = 0.001). In the durvalumab group, our data suggest improved 12-month OS in patients with PD-L1 expression ≥50% (100% vs 86%, HR: 0.25, 95% CI: 0.11-0.58, p = 0.007). There was no difference in OS between patients with a PD-L1 expression of 1-49% and patients with PD-L1 expression1%. Delay in durvalumab initiation beyond 42 days did not impact OS. Incidence of pneumonitis was similar in the durvalumab and historical groups. In the durvalumab group, patients who experienced any-grade pneumonitis had a lower 12-month OS than patients without pneumonitis (85% vs 95%, respectively; HR: 3.3, 95% CI: 1.2-9.0, p = 0.006).This multicentre analysis suggests that PD-L1 expression ≥50% was associated with favourable OS in patients with stage III NSCLC treated with durvalumab after CRT, whereas the presence of pneumonitis represented a negative prognostic factor.

Published
2021
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16. Impact of the presence of median arcuate ligament on biliary complications after liver transplantation

Author

Eleftherios Gialamas, Michela Assalino, Laure Elkrief, Fani Apostolidou‐Kiouti, Arthur Piveteau, Graziano Oldani, Philippe Compagnon, and Thierry Berney

Subjects
Transplantation, Hepatic Artery, Ligaments, Case-Control Studies, Humans, Liver Transplantation, Retrospective Studies
Abstract

The presence of median arcuate ligament (MAL) during orthotopic liver transplantation (OLT) may cause a significant reduction in the arterial hepatic flow. The aim of the present study is to investigate the impact of MAL on biliary complications in patients who underwent OLT.We performed a retrospective case-control study among patients who underwent OLT in Geneva University Hospital between 2007 and 2017, depending on the presence or absence of MAL. The matching was performed according to age, gender, lab-MELD score at the time of OLT and type of donor (living or dead). The presence of MAL was assessed by an expert liver radiologist on the preoperative CT angiographic evaluation.The incidence of MAL was 6.1% (19 patients). Baseline characteristics were comparable between the two groups. No significant difference in biliary complications was found between patients with and without MAL (37% and 24%, respectively). No patient presented hepatic artery thrombosis. After logistic regression, in patients with MAL, the MAL release and gastroduodenal artery preservation compared to no treatment, showed an odds ratio for post-OLT biliary complications of 1.5 and 1.25, respectively. There was no difference in overall graft survival and in hazard for biliary complications between patients with and without MAL.In the present study, we did not find any difference in the prevalence of biliary and arterial complications between patients with and without MAL. The choice of MAL treatment did not influence in a significant way the overall outcome and development of complications. However, if, at the end of arterial reconstruction, the arterial flow is not adequately established, MAL needs to be treated with the least invasive technique.

Published
2022

17. Childhood maltreatment mediates the effect of the genetic background on psychosis risk in young adults

Author

Marchi, Mattia, Elkrief, Laurent, Alkema, Anne, van Gastel, Willemijn, Schubart, Chris D., van Eijk, Kristel R, Luykx, Jurjen J, Branje, Susan, Mastrotheodoros, Stefanos, Galeazzi, Gian M., Van Os, Jim, Cecil, Charlotte A., Boks, Marco P., Trauma and Grief, Adolescent development: Characteristics and determinants, Leerstoel Branje, Child and Adolescent Psychiatry / Psychology, and Epidemiology

Subjects
Cellular and Molecular Neuroscience, Psychiatry and Mental health, Young Adult, Psychotic Disorders, SDG 3 - Good Health and Well-being, Child, Genetic Background, Genetic Predisposition to Disease, Humans, Cannabis, Child Abuse, Schizophrenia, Biological Psychiatry
Abstract

Childhood maltreatment (CM) and genetic vulnerability are both risk factors for psychosis, but the relations between them are not fully understood. Guided by the recent identification of genetic risk to CM, this study investigates the hypothesis that genetic risk to schizophrenia also increases the risk of CM and thus impacts psychosis risk. The relationship between schizophrenia polygenetic risk, CM, and psychotic-like experiences (PLE) was investigated in participants from the Utrecht Cannabis Cohort (N = 1262) and replicated in the independent IMAGEN cohort (N = 1740). Schizophrenia polygenic risk score (SZ-PRS) were calculated from the most recent GWAS. The relationship between CM, PRS, and PLE was first investigated using multivariate linear regression. Next, mediation of CM in the pathway linking SZ-PRS and PLE was examined by structural equation modeling, while adjusting for a set of potential mediators including cannabis use, smoking, and neuroticism. In agreement with previous studies, PLE were strongly associated with SZ-PRS (B = 0.190, p = 0.009) and CM (B = 0.575, p B = 0.171, p = 0.001), and substantially mediated the effects of SZ-PRS on PLE (proportion mediated = 29.9%, p = 0.001). In the replication cohort, the analyses yielded similar results, confirming equally strong mediation by CM (proportion mediated = 34.7%, p = 0.009). Our results suggest that CM acts as a mediator in the causal pathway linking SZ-PRS and psychosis risk. These findings open new perspectives on the relations between genetic and environmental risks and warrant further studies into potential interventions to reduce psychosis risk in vulnerable people.

Published
2022

18. Dissecting the clinicopathologic, genomic, and immunophenotypic correlates of KRAS

Author

B, Ricciuti, J V, Alessi, A, Elkrief, X, Wang, A, Cortellini, Y Y, Li, V R, Vaz, H, Gupta, F, Pecci, A, Barrichello, G, Lamberti, T, Nguyen, J, Lindsay, B, Sharma, K, Felt, S J, Rodig, M, Nishino, L M, Sholl, D A, Barbie, M V, Negrao, J, Zhang, A D, Cherniack, J V, Heymach, M, Meyerson, C, Ambrogio, P A, Jänne, K C, Arbour, D J, Pinato, F, Skoulidis, A J, Schoenfeld, M M, Awad, and J, Luo

Subjects
Proto-Oncogene Proteins p21(ras), Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Mutation, Programmed Cell Death 1 Receptor, Humans, Forkhead Transcription Factors, Genomics, B7-H1 Antigen
Abstract

Allele-specific KRAS inhibitors are an emerging class of cancer therapies. KRAS-mutant (KRASClinicopathologic and genomic information were collected from patients with NSCLCs harboring a KRAS mutation at the Dana-Farber Cancer Institute (DFCI), Memorial Sloan Kettering Cancer Center, MD Anderson Cancer Center, and Imperial College of London. Multiplexed immunofluorescence for CK7, programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), Foxp3, and CD8 was carried out on a subset of samples with available tissue at the DFCI. Clinical outcomes to PD-(L)1 inhibition ± chemotherapy were analyzed according to KRAS mutation subtype.Of 2327 patients with KRAS-mutated (KRASKRAS

Published
2022

19. Gut microbiota signatures are associated with toxicity to combined CTLA-4 and PD-1 blockade

Author

Catalin Mihalcioiu, Charlotte E. Ariyan, Michael K. Wong, Aurélie Fluckiger, Julie M. Simon, Rossanna C. Pezo, Michael G. White, Padmanee Sharma, Michael A. Postow, Sapna Pradyuman Patel, Adi Diab, Isabella C. Glitza, Elizabeth M. Burton, Whijae Roh, Zachary A. Cooper, Laurence Zitvogel, Maria Paula Roberti, Wen-Jen Hwu, Alexandria P. Cogdill, Miles C. Andrews, Gladys Ferrere, Abdul Wadud Khan, Scott E. Woodman, Robert R. Jenq, Christine N. Spencer, James P. Allison, Lisa Derosa, Curtis Gumbs, Wei Shen Chen, Stephanie S. Watowich, Irina Fernandez Curbelo, Michael A. Davies, Paule Opolon, Connie P.M. Duong, Jennifer A. Wargo, Maryam Tidjani Alou, Courtney W. Hudgens, Vancheswaran Gopalakrishnan, Pierre Olivier Gaudreau, Michael T. Tetzlaff, Didier Raoult, Arielle Elkrief, Khalida Wani, Jeffrey E. Gershenwald, Margaret K. Callahan, Sarah B. Johnson, Alexandre Reuben, Joseph F. Petrosino, Latasha Little, Peter A. Prieto, Matthew Lastrapes, Valerio Iebba, Bertrand Routy, Matthew Adamow, Alexander J. Lazar, Jennifer L. McQuade, Nadim J. Ajami, Golnaz Morad, Rodabe N. Amaria, Matthew C. Wong, Erez N. Baruch, Hussein Abdul-Hassan Tawbi, Satoru Yonekura, Li Zhao, Reetakshi Arora, Luis M Vence, Lauren E. Haydu, Luigi Nezi, Patrick Hwu, P. Andrew Futreal, Jianhua Zhang, The University of Texas M.D. Anderson Cancer Center [Houston], Olivia Newton-John Cancer Research Institute [Heidelberg, VIC, Australia], Monash University [Melbourne], Institut Gustave Roussy (IGR), Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Saclay, Morsani College of Medicine [Tampa, USA], University of South Florida [Tampa] (USF), The Parker Institute, University of Copenhagen = Københavns Universitet (UCPH), AstraZeneca, Gaithersburg, MD, USA, University of Rochester Medical Center (URMC), Memorial Sloane Kettering Cancer Center [New York], Istituto Europeo di Oncologia, Milan, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), McGill University Health Center [Montreal] (MUHC), University of Toronto, Baylor College of Medicine (BCM), Baylor University, ANR-16-RHUS-0008,LUMIERE,LUMIERE(2016), ANR-10-IAHU-0003,Méditerranée Infection,I.H.U. Méditerranée Infection(2010), European Project: 825410,ONCOBIOME, COMBE, Isabelle, LUMIERE - - LUMIERE2016 - ANR-16-RHUS-0008 - RHUS - VALID, Instituts Hospitalo-Universitaires - I.H.U. Méditerranée Infection - - Méditerranée Infection2010 - ANR-10-IAHU-0003 - IAHU - VALID, European Union’s Horizon 2020 research and innovation programme under grant agreement. - ONCOBIOME - 825410 - INCOMING, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Department of Radiology, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France, University of Copenhagen = Københavns Universitet (KU), Immunologie anti-tumorale et immunothérapie des cancers (ITIC), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Faculté de médecine de l'Université Paris-Sud [Kremlin Bicêtre, Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Malaria : parasites et hôtes - Malaria : parasites and hosts, Institut Pasteur [Paris], Ottawa Hospital Research Institute [Ottawa] (OHRI), Andrews, M. C., Duong, C. P. M., Gopalakrishnan, V., Iebba, V., Chen, W. -S., Derosa, L., Khan, M. A. W., Cogdill, A. P., White, M. G., Wong, M. C., Ferrere, G., Fluckiger, A., Roberti, M. P., Opolon, P., Alou, M. T., Yonekura, S., Roh, W., Spencer, C. N., Curbelo, I. F., Vence, L., Reuben, A., Johnson, S., Arora, R., Morad, G., Lastrapes, M., Baruch, E. N., Little, L., Gumbs, C., Cooper, Z. A., Prieto, P. A., Wani, K., Lazar, A. J., Tetzlaff, M. T., Hudgens, C. W., Callahan, M. K., Adamow, M., Postow, M. A., Ariyan, C. E., Gaudreau, P. -O., Nezi, L., Raoult, D., Mihalcioiu, C., Elkrief, A., Pezo, R. C., Haydu, L. E., Simon, J. M., Tawbi, H. A., Mcquade, J., Hwu, P., Hwu, W. -J., Amaria, R. N., Burton, E. M., Woodman, S. E., Watowich, S., Diab, A., Patel, S. P., Glitza, I. C., Wong, M. K., Zhao, L., Zhang, J., Ajami, N. J., Petrosino, J., Jenq, R. R., Davies, M. A., Gershenwald, J. E., Futreal, P. A., Sharma, P., Allison, J. P., Routy, B., Zitvogel, L., and Wargo, J. A.

Subjects
[SDV]Life Sciences [q-bio], medicine.medical_treatment, Interleukin-1beta, Programmed Cell Death 1 Receptor, Cancer immunotherapy, Gut flora, Inbred C57BL, Mice, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, CTLA-4 Antigen, Melanoma, ComputingMilieux_MISCELLANEOUS, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Tumor, biology, General Medicine, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 030220 oncology & carcinogenesis, Toxicity, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Human, General Biochemistry, Genetics and Molecular Biology, Cell Line, 03 medical and health sciences, Immune system, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Cell Line, Tumor, Animals, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Microbiome, Colitis, 030304 developmental biology, Animal, business.industry, medicine.disease, biology.organism_classification, Mice, Inbred C57BL, Gastrointestinal Microbiome, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Immune checkpoint, CTLA-4, Immunology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business
Abstract

International audience; Treatment with combined immune checkpoint blockade (CICB) targeting CTLA-4 and PD-1 is associated with clinical benefit across tumor types, but also a high rate of immune-related adverse events. Insights into biomarkers and mechanisms of response and toxicity to CICB are needed. To address this, we profiled the blood, tumor and gut microbiome of 77 patients with advanced melanoma treated with CICB, with a high rate of any ≥grade 3 immune-related adverse events (49%) with parallel studies in pre-clinical models. Tumor-associated immune and genomic biomarkers of response to CICB were similar to those identified for ICB monotherapy, and toxicity from CICB was associated with a more diverse peripheral T-cell repertoire. Profiling of gut microbiota demonstrated a significantly higher abundance of Bacteroides intestinalis in patients with toxicity, with upregulation of mucosal IL-1β in patient samples of colitis and in pre-clinical models. Together, these data offer potential new therapeutic angles for targeting toxicity to CICB.

Published
2021
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20. Microcirculatory changes in the liver of patients with refractory ascites and their relationship with diabetes and alcohol

Author

Xavière Panhard, Sophie Buyse, L. Elkrief, François Durand, Nathalie Gault, Dominique Valla, Pierre Bedossa, Valérie Paradis, Jacques Belghiti, Richard Moreau, Pierre-Emmanuel Rautou, and Clotilde Baudry

Subjects
Liver Cirrhosis, medicine.medical_specialty, Cirrhosis, Hepatology, business.industry, Microcirculation, medicine.medical_treatment, Microangiopathy, Fatty liver, Gastroenterology, Ascites, Odds ratio, Liver transplantation, medicine.disease, Fibrosis, Diabetes mellitus, Internal medicine, Diabetes Mellitus, Humans, Medicine, medicine.symptom, business, Retrospective Studies
Abstract

OBJECTIVES The determinants of refractory ascites have not been fully characterized. The aims of this study were to assess liver histopathological alterations associated with refractory ascites and their relationship with comorbidities. METHODS Consecutive patients with cirrhosis who underwent liver transplantation were retrospectively included. Patients' characteristics at the time of listing were analysed. The native livers were reviewed and lesions associated with refractory ascites were examined. RESULTS Out of the 89 patients included, 30 had refractory ascites and 59 did not (including 35 without ascites and 24 with diuretic-sensitive ascites). Patients with and without refractory ascites had a similar amount of fibrous tissue and features of fatty liver disease. By contrast, microvascular changes, namely sinusoidal dilatation (P < 0.001), diffuse perisinusoidal fibrosis (P = 0.001), hepatic venous thromboses (P = 0.004) and vascular proliferation (P = 0.01) were more frequently observed in the livers of patients with refractory ascites. Diabetes (57% vs. 31%, P = 0.02) and alcohol as a causal factor for cirrhosis (80% vs. 42%, P = 0.001) were more frequent in patients with refractory ascites than in those without. By multivariate analysis, refractory ascites was independently associated with diabetes mellitus [odds ratio (OR) (95% confidence interval, CI) 6.15 (1.47-25.71); P = 0.01], alcohol as a causal factor for cirrhosis [OR (95% CI) 4.63 (1.07-20.02); P = 0.04], higher Model For End Stage Liver Diseases [OR (95% CI) 1.21 (1.05-1.38); P = 0.008] and lower serum sodium [OR (95% CI) 0.87 (0.78-0.98); P = 0.03]. CONCLUSION Liver microcirculatory changes are associated with refractory ascites. Diabetes and alcohol may explain refractory ascites by causing microangiopathy.

Published
2020
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21. Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study

Author

Dimitrios Farmakiotis, Susie Owenby, Arturo Loaiza-Bonilla, Mansi R. Shah, Matthew Puc, Vadim S. Koshkin, Ahmad Daher, Prakash Peddi, Cameron Rink, Heloisa P. Soares, Eneida R. Nemecek, Mehmet Asim Bilen, Sanjay Mishra, Lidia Schapira, Amit Verma, Ali Raza Khaki, Chih-Yuan Hsu, Sandy DiLullo, Mark Bonnen, Jeanna Knoble, Carla Casulo, Umit Topaloglu, Jorge A. Garcia, Geoffrey Shouse, Praveen Vikas, Clarke A. Low, Archana Ajmera, George D. Demetri, Leyre Zubiri, Grace Glace, Shannon K. McWeeney, Susan Yackzan, Pamela C Egan, Rachel P. Rosovsky, Salvatore Del Prete, Anthony P. Gulati, Lane R. Rosen, Andy Futreal, Merry Jennifer Markham, Sabitha Prabhakaran, Alicia K. Morgans, Sarah Nagle, Lisa Weissmann, Albert C. Yeh, Ziad Bakouny, Stephanie Berg, David Gill, Marcus Messmer, Ryan Nguyen, Terence Duane Rhodes, Vikram M. Narayan, Matthew D. Galsky, Arielle Elkrief, Lori J. Rosenstein, Roy S. Herbst, Justin Shaya, Thorvardur R. Halfdanarson, Douglas B. Johnson, Orestis A. Panagiotou, Sanjay G. Revankar, Toni K. Choueiri, Yu Shyr, Fiona Busser, Kaitlin M. Kelleher, Nicole M. Kuderer, Paul L. Weinstein, Anup Kasi, Grace Shaw, Adam J. Olszewski, Catherine Curran, Samuel M. Rubinstein, Angelo Cabal, Michael H. Bar, John F. Deeken, Vivek Subbiah, Abdul Hai Mansoor, Hina Khan, Rana R. McKay, Catherine Stratton, Saurabh Dahiya, Marc A. Rovito, John Philip, Sanjay Shete, Oscar K. Serrano, Julie Fu, Daniel W. Bowles, Candice Schwartz, Tian Zhang, Pier Vitale Nuzzo, Eric H. Bernicker, Wenxin Xu, Genevieve M. Boland, Sarah Wall, Babar Bashir, Solange Peters, Neeta K. Venepalli, Sandeep H. Mashru, William A. Wood, Anne H. Angevine, Mary F. Mulcahy, Gilberto Lopes, Justin F. Gainor, Jessica Hawley, Monika Joshi, Christopher R. Friese, Navid Hafez, Heather H. Nelson, Gregory J. Riely, Jordan Kharofa, Nilo Azad, Chintan Shah, Gerald Batist, Mary Salazar, Rosemary Zacks, Alice Zhou, Lawrence E. Feldman, Paul Fu, Gary H. Lyman, Nathaniel Bouganim, John A. Steinharter, Shilpa Gupta, Matthias Weiss, Peter Paul Yu, Susan Van Loon, Jamie Stratton, Karen Vega-Luna, Tyler Masters, Christopher Lemmon, Aakash Desai, Bryan A. Faller, Jessica M. Clement, Zhuoer Xie, Keith Stockerl-Goldstein, Corrie A. Painter, Gabrielle Bouchard, Rulla M. Tamimi, Daruka Mahadevan, Rimma Belenkaya, Jill S. Barnholtz-Sloan, Jarushka Naidoo, Amelie G. Ramirez, Philip E. Lammers, Elizabeth A. Griffiths, Michael J. Gurley, X. Li, Jonathan Riess, Syed A. Ahmad, Daniel Blake Flora, Salma K. Jabbour, Jared D. Acoba, Neeraj Agarwal, Ang Li, Sarah Mushtaq, Firas Wehbe, Tanios Bekaii-Saab, Donald C. Vinh, Emily Hsu, Ryan Monahan, Petros Grivas, Harry Menon, John M. Nakayama, Janice M. Mehnert, Elizabeth Marie Wulff-Burchfield, Sara Matar, Paul E. Oberstein, Mary M. Pasquinelli, Axel Grothey, Jack West, John C. Leighton, Dawn L. Hershman, Leslie A. Fecher, Aditya Bardia, Sumit A. Shah, Barbara Logan, Kerry L. Reynolds, Michael A. Thompson, Robert L. Rice, Erin Cook, Trisha Wise-Draper, Christine Bestvina, Daniel Castellano, Paolo Caimi, K. M.Steve Lo, Ruben A. Mesa, Maheen Z. Abidi, Alvaro G. Menendez, Daniel G. Stover, Colleen Lewis, Bertrand Routy, Deborah B. Doroshow, Carmen C. Solorzano, M. Wasif Saif, Rohit Bishnoi, Michael Glover, David D. Chism, Briana Barrow, Christopher McNair, Dimpy P. Shah, Erin A. Gillaspie, Andrea J. Zimmer, Andrew Schmidt, Jessica K. Altman, Michelle Marcum, Rawad Elias, Balazs Halmos, Karen Stauffer, Gayathri Nagaraj, Ardaman Shergill, Mark E. Dailey, Catherine Handy Marshall, Pramod K. Srivastava, Shuchi Gulati, Alokkumar Jha, Mateo Bover Larroya, Mark A. Lewis, Young Soo Rho, James L. Chen, Eli Van Allen, Julie Tsu Yu Wu, Antonio Giordano, Amit Kulkarni, Joerg Rathmann, Donna R. Rivera, Narjust Duma, Maryam B. Lustberg, Theresa M. Carducci, Jeremy L. Warner, Elizabeth Robilotti, Patricia LoRusso, Rohit Jain, Amit Sanyal, Nizar M. Tannir, Kent Hoskins, Nathan A. Pennell, Brian I. Rini, Suki Subbiah, COVID-19 and Cancer Consortium, Abidi, M., Acoba, J.D., Agarwal, N., Ahmad, S., Ajmera, A., Altman, J., Angevine, A.H., Azad, N., Bar, M.H., Bardia, A., Barnholtz-Sloan, J., Barrow, B., Bashir, B., Belenkaya, R., Berg, S., Bernicker, E.H., Bestvina, C., Bishnoi, R., Boland, G., Bonnen, M., Bouchard, G., Bowles, D.W., Busser, F., Cabal, A., Caimi, P., Carducci, T., Casulo, C., Chen, J.L., Clement, J.M., Chism, D., Cook, E., Curran, C., Daher, A., Dailey, M., Dahiya, S., Deeken, J., Demetri, G.D., DiLullo, S., Duma, N., Elias, R., Faller, B., Fecher, L.A., Feldman, L.E., Friese, C.R., Fu, P., Fu, J., Futreal, A., Gainor, J., Garcia, J., Gill, D.M., Gillaspie, E.A., Giordano, A., Glace, M.G., Grothey, A., Gulati, S., Gurley, M., Halmos, B., Herbst, R., Hershman, D., Hoskins, K., Jain, R.K., Jabbour, S., Jha, A., Johnson, D.B., Joshi, M., Kelleher, K., Kharofa, J., Khan, H., Knoble, J., Koshkin, V.S., Kulkarni, A.A., Lammers, P.E., Leighton, J.C., Lewis, M.A., Li, X., Li, A., Lo, KMS, Loaiza-Bonilla, A., LoRusso, P., Low, C.A., Lustberg, M.B., Mahadevan, D., Mansoor, A.H., Marcum, M., Markham, M.J., Handy Marshall, C., Mashru, S.H., Matar, S., McNair, C., McWeeney, S., Mehnert, J.M., Menendez, A., Menon, H., Messmer, M., Monahan, R., Mushtaq, S., Nagaraj, G., Nagle, S., Naidoo, J., Nakayama, J.M., Narayan, V., Nelson, H.H., Nemecek, E.R., Nguyen, R., Nuzzo, P.V., Oberstein, P.E., Olszewski, A.J., Owenby, S., Pasquinelli, M.M., Philip, J., Prabhakaran, S., Puc, M., Ramirez, A., Rathmann, J., Revankar, S.G., Rho, Y.S., Rhodes, T.D., Rice, R.L., Riely, G.J., Riess, J., Rink, C., Robilotti, E.V., Rosenstein, L., Routy, B., Rovito, M.A., Saif, M.W., Sanyal, A., Schapira, L., Schwartz, C., Serrano, O., Shah, M., Shah, C., Shaw, G., Shergill, A., Shouse, G., Soares, H.P., Solorzano, C.C., Srivastava, P.K., Stauffer, K., Stover, D.G., Stratton, J., Stratton, C., Subbiah, V., Tamimi, R., Tannir, N.M., Topaloglu, U., Van Allen, E., Van Loon, S., Vega-Luna, K., Venepalli, N., Verma, A.K., Vikas, P., Wall, S., Weinstein, P.L., Weiss, M., Wise-Draper, T., Wood, W.A., Xu, W.V., Yackzan, S., Zacks, R., Zhang, T., Zimmer, A.J., and West, J.

Subjects
Prognostic variable, medicine.medical_specialty, business.industry, Cancer, General Medicine, Odds ratio, Aged, Antiviral Agents/therapeutic use, Azithromycin/therapeutic use, Betacoronavirus, Cause of Death, Comorbidity, Coronavirus Infections/drug therapy, Coronavirus Infections/epidemiology, Coronavirus Infections/mortality, Databases, Factual, Female, Humans, Hydroxychloroquine/therapeutic use, Male, Middle Aged, Neoplasms/epidemiology, Neoplasms/mortality, Neoplasms/therapy, Pandemics, Pneumonia, Viral/drug therapy, Pneumonia, Viral/epidemiology, Pneumonia, Viral/mortality, Prognosis, Risk Factors, 030204 cardiovascular system & hematology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Cohort, Clinical endpoint, Medicine, 030212 general & internal medicine, business, Cause of death, Cohort study
Abstract

Summary Background Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness. Methods In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020. We collected data on baseline clinical conditions, medications, cancer diagnosis and treatment, and COVID-19 disease course. The primary endpoint was all-cause mortality within 30 days of diagnosis of COVID-19. We assessed the association between the outcome and potential prognostic variables using logistic regression analyses, partially adjusted for age, sex, smoking status, and obesity. This study is registered with ClinicalTrials.gov, NCT04354701, and is ongoing. Findings Of 1035 records entered into the CCC19 database during the study period, 928 patients met inclusion criteria for our analysis. Median age was 66 years (IQR 57–76), 279 (30%) were aged 75 years or older, and 468 (50%) patients were male. The most prevalent malignancies were breast (191 [21%]) and prostate (152 [16%]). 366 (39%) patients were on active anticancer treatment, and 396 (43%) had active (measurable) cancer. At analysis (May 7, 2020), 121 (13%) patients had died. In logistic regression analysis, independent factors associated with increased 30-day mortality, after partial adjustment, were: increased age (per 10 years; partially adjusted odds ratio 1·84, 95% CI 1·53–2·21), male sex (1·63, 1·07–2·48), smoking status (former smoker vs never smoked: 1·60, 1·03–2·47), number of comorbidities (two vs none: 4·50, 1·33–15·28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs 0 or 1: 3·89, 2·11–7·18), active cancer (progressing vs remission: 5·20, 2·77–9·77), and receipt of azithromycin plus hydroxychloroquine (vs treatment with neither: 2·93, 1·79–4·79; confounding by indication cannot be excluded). Compared with residence in the US-Northeast, residence in Canada (0·24, 0·07–0·84) or the US-Midwest (0·50, 0·28–0·90) were associated with decreased 30-day all-cause mortality. Race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality. Interpretation Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments. Funding American Cancer Society, National Institutes of Health, and Hope Foundation for Cancer Research.

Published
2020
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22. Geriatric risk factors for serious COVID-19 outcomes among older adults with cancer: a cohort study from the COVID-19 and Cancer Consortium

Author

Arielle Elkrief, Cassandra Hennessy, Nicole M Kuderer, Samuel M Rubinstein, Elizabeth Wulff-Burchfield, Rachel P Rosovsky, Karen Vega-Luna, Michael A Thompson, Orestis A Panagiotou, Aakash Desai, Donna R Rivera, Ali Raza Khaki, Lisa Tachiki, Ryan C Lynch, Catherine Stratton, Rawad Elias, Gerald Batist, Anup Kasi, Dimpy P Shah, Ziad Bakouny, Angelo Cabal, Jessica Clement, Jennifer Crowell, Becky Dixon, Christopher R Friese, Stacy L Fry, Punita Grover, Shuchi Gulati, Shilpa Gupta, Clara Hwang, Hina Khan, Soo Jung Kim, Elizabeth J Klein, Chris Labaki, Rana R McKay, Amanda Nizam, Nathan A Pennell, Matthew Puc, Andrew L Schmidt, Armin Shahrokni, Justin A Shaya, Christopher T Su, Sarah Wall, Nicole Williams, Trisha M Wise-Draper, Sanjay Mishra, Petros Grivas, Benjamin French, Jeremy L Warner, and Tanya M Wildes

Subjects
Cohort Studies, Psychiatry and Mental health, Health (social science), COVID-19 Testing, Risk Factors, SARS-CoV-2, Neoplasms, COVID-19, Humans, Geriatrics and Gerontology, Middle Aged, Family Practice, Aged
Abstract

Older age is associated with poorer outcomes of SARS-CoV-2 infection, although the heterogeneity of ageing results in some older adults being at greater risk than others. The objective of this study was to quantify the association of a novel geriatric risk index, comprising age, modified Charlson comorbidity index, and Eastern Cooperative Oncology Group performance status, with COVID-19 severity and 30-day mortality among older adults with cancer.In this cohort study, we enrolled patients aged 60 years and older with a current or previous cancer diagnosis (excluding those with non-invasive cancers and premalignant or non-malignant conditions) and a current or previous laboratory-confirmed COVID-19 diagnosis who reported to the COVID-19 and Cancer Consortium (CCC19) multinational, multicentre, registry between March 17, 2020, and June 6, 2021. Patients were also excluded for unknown age, missing data resulting in unknown geriatric risk measure, inadequate data quality, or incomplete follow-up resulting in unknown COVID-19 severity. The exposure of interest was the CCC19 geriatric risk index. The primary outcome was COVID-19 severity and the secondary outcome was 30-day all-cause mortality; both were assessed in the full dataset. Adjusted odds ratios (ORs) and 95% CIs were estimated from ordinal and binary logistic regression models.5671 patients with cancer and COVID-19 were included in the analysis. Median follow-up time was 56 days (IQR 22-120), and median age was 72 years (IQR 66-79). The CCC19 geriatric risk index identified 2365 (41·7%) patients as standard risk, 2217 (39·1%) patients as intermediate risk, and 1089 (19·2%) as high risk. 36 (0·6%) patients were excluded due to non-calculable geriatric risk index. Compared with standard-risk patients, high-risk patients had significantly higher COVID-19 severity (adjusted OR 7·24; 95% CI 6·20-8·45). 920 (16·2%) of 5671 patients died within 30 days of a COVID-19 diagnosis, including 161 (6·8%) of 2365 standard-risk patients, 409 (18·5%) of 2217 intermediate-risk patients, and 350 (32·1%) of 1089 high-risk patients. High-risk patients had higher adjusted odds of 30-day mortality (adjusted OR 10·7; 95% CI 8·54-13·5) than standard-risk patients.The CCC19 geriatric risk index was strongly associated with COVID-19 severity and 30-day mortality. Our CCC19 geriatric risk index, based on readily available clinical factors, might provide clinicians with an easy-to-use risk stratification method to identify older adults most at risk for severe COVID-19 as well as mortality.US National Institutes of Health National Cancer Institute Cancer Center.

Published
2022

23. Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in advanced non-small cell lung cancer patients

Author

Derosa, Lisa, Routy, Bertrand, Thomas, Andrew Maltez, Iebba, Valerio, Zalcman, Gerard, Friard, Sylvie, Mazieres, Julien, Audigier-Valette, Clarisse, Moro-Sibilot, Denis, Goldwasser, François, Silva, Carolina Alves Costa, Terrisse, Safae, Bonvalet, Melodie, Scherpereel, Arnaud, Pegliasco, Hervé, Richard, Corentin, Ghiringhelli, François, Elkrief, Arielle, Desilets, Antoine, Blanc-Durand, Felix, Cumbo, Fabio, Blanco, Aitor, Boidot, Romain, Chevrier, Sandy, Daillère, Romain, Kroemer, Guido, Alla, Laurie, Pons, Nicolas, Chatelier, Emmanuelle Le, Galleron, Nathalie, Roume, Hugo, Dubuisson, Agathe, Bouchard, Nicole, Messaoudene, Meriem, Drubay, Damien, Deutsch, Eric, Barlesi, Fabrice, Planchard, David, Segata, Nicola, Martinez, Stéphanie, Zitvogel, Laurence, Soria, Jean-Charles, and Besse, Benjamin

Subjects
Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Humans, Immunologic Factors, Akkermansia, Immunotherapy, Article
Abstract

Aside from PD-L1 expression, biomarkers of response to immune checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC) are needed. We previously reported in 100 NSCLC and kidney cancer patients that fecal Akkermansia muciniphila (Akk) correlated with ICI clinical success. The endpoint of this study was to prospectively validate the prognostic significance of fecal Akk in advanced NSCLC patients treated with first or second line ICI. We performed shotgun metagenomics-based microbiome profiling using two different pipelines in 338 NSCLC patients. Baseline stool Akk was associated with increased objective response rates and overall survival in multivariate analyses, independent of PD-L1 expression, antibiotics and performance status. Intestinal Akk was accompanied by a richer commensalism, including Eubacterium hallii and Bifidobacterium adolescentis and a more inflamed tumor microenvironment in a subset of patients. However, antibiotic use (20% of cases) coincided with a relative dominance of Akk above 4.8% accompanied with the genus Clostridium, both associated with resistance to ICI. Our study shows significant differences in relative abundance of Akk that could be useful for future studies as a tool to aid patient stratification.

Published
2022

24. Contrast-enhanced CT and liver surface nodularity for the diagnosis of porto-sinusoidal vascular disorder: A case-control study

Author

Shantha Ram Valainathan, Riccardo Sartoris, Laure Elkrief, Marta Magaz, Fabian Betancourt, Silvia Pellegrino, Arianna Nivolli, Marco Dioguardi Burgio, Yves Flattet, Sylvain Terraz, Nicolas Drilhon, Marie Lazareth, Julia Herrou, Onorina Bruno, Audrey Payance, Aurélie Plessier, François Durand, Maxime Ronot, Dominique‐Charles Valla, Valérie Paradis, Juan Carlos Garcia‐Pagan, Valérie Vilgrain, and Pierre‐Emmanuel Rautou

Subjects
Liver Cirrhosis, Hepatology, Liver, Case-Control Studies, Hypertension, Portal, Humans, Vascular Diseases, Tomography, X-Ray Computed, Fibrosis, Retrospective Studies
Abstract

Porto-sinusoidal vascular disorder (PSVD) is a rare and commonly overlooked cause of portal hypertension. The interest of CT analysis, including quantification of liver surface nodularity (LSN) for PSVD diagnosis has not been established. This study aimed at assessing the performance of LSN and CT features for a PSVD diagnosis in patients with signs of portal hypertension.This retrospective case-control study included a learning cohort consisting of 50 patients with histologically proven PSVD, according to VALDIG criteria, and 100 control patients with histologically proven cirrhosis, matched on ascites. All patients and controls had at least one sign of portal hypertension and CT available within 1 year of liver biopsy. Principal component analysis of CT features separated patients with PSVD from patients with cirrhosis. Patients with PSVD had lower median LSN than those with cirrhosis (2.4 vs. 3.1, p 0.001). Multivariate analysis identified LSN 2.5 and normal-sized or enlarged segment IV as independently associated with PSVD. Combination of these two features had a specificity of 90% for PSVD and a diagnostic accuracy of 84%. Even better results were obtained in an independent multicenter validation cohort including 53 patients with PSVD and 106 control patients with cirrhosis (specificity 94%, diagnostic accuracy 87%).This study that included a total of 103 patients with PSVD and 206 patients with cirrhosis demonstrates that LSN 2.5 combined with normal-sized or enlarged segment IV strongly suggests PSVD in patients with signs of portal hypertension.

Published
2022

25. A Natural Polyphenol Exerts Antitumor Activity and Circumvents Anti–PD-1 Resistance through Effects on the Gut Microbiota

Author

Meriem Messaoudene, Reilly Pidgeon, Corentin Richard, Mayra Ponce, Khoudia Diop, Myriam Benlaifaoui, Alexis Nolin-Lapalme, Florent Cauchois, Julie Malo, Wiam Belkaid, Stephane Isnard, Yves Fradet, Lharbi Dridi, Dominique Velin, Paul Oster, Didier Raoult, François Ghiringhelli, Romain Boidot, Sandy Chevrier, David T. Kysela, Yves V. Brun, Emilia Liana Falcone, Geneviève Pilon, Florian Plaza Oñate, Oscar Gitton-Quent, Emmanuelle Le Chatelier, Sylvere Durand, Guido Kroemer, Arielle Elkrief, André Marette, Bastien Castagner, Bertrand Routy, COMBE, Isabelle, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), McGill University = Université McGill [Montréal, Canada], McGill University Health Center [Montreal] (MUHC), Centre de recherche du CHU de Québec-Université Laval (CRCHUQ), CHU de Québec–Université Laval, Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] (ICMUB), Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université du Québec à Montréal = University of Québec in Montréal (UQAM), Institut de Recherches Cliniques de Montréal (IRCM), Université de Montréal (UdeM), Université Laval [Québec] (ULaval), MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Gustave Roussy (IGR), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), and École Pratique des Hautes Études (EPHE)

Subjects
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Bacteria, Polyphenols, Fecal Microbiota Transplantation, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Gastrointestinal Microbiome, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Mice, Oncology, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Animals, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Abstract

Several approaches to manipulate the gut microbiome for improving the activity of cancer immune-checkpoint inhibitors (ICI) are currently under evaluation. Here, we show that oral supplementation with the polyphenol-rich berry camu-camu (CC; Myrciaria dubia) in mice shifted gut microbial composition, which translated into antitumor activity and a stronger anti–PD-1 response. We identified castalagin, an ellagitannin, as the active compound in CC. Oral administration of castalagin enriched for bacteria associated with efficient immunotherapeutic responses (Ruminococcaceae and Alistipes) and improved the CD8+/FOXP3+CD4+ ratio within the tumor microenvironment. Moreover, castalagin induced metabolic changes, resulting in an increase in taurine-conjugated bile acids. Oral supplementation of castalagin following fecal microbiota transplantation from ICI-refractory patients into mice supported anti–PD-1 activity. Finally, we found that castalagin binds to Ruminococcus bromii and promoted an anticancer response. Altogether, our results identify castalagin as a polyphenol that acts as a prebiotic to circumvent anti–PD-1 resistance. Significance: The polyphenol castalagin isolated from a berry has an antitumor effect through direct interactions with commensal bacteria, thus reprogramming the tumor microenvironment. In addition, in preclinical ICI-resistant models, castalagin reestablishes the efficacy of anti–PD-1. Together, these results provide a strong biological rationale to test castalagin as part of a clinical trial. This article is highlighted in the In This Issue feature, p. 873

Published
2022
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27. PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis

Author

William Bernal, Agustín Albillos, Alex Amoros, Wim Laleman, Michael Manns, Javier Martínez, Maximilian J. Brol, Pere Ginès, Alessandra Pohlmann, Joerg Tobiasch Moritz, Francois Smits, Elisabet Garcia-Lopez, Joan Clària, Jennifer Lehmann, Jonel Trebicka, Christoph Welsch, Vicente Arroyo, Richard Moreau, Tony Bruns, Monica Mesquita, Christian Jansen, Peter Jarcuska, Harald Rupprechter, Martin Janicko, Thierry Gustot, Macarena Simón-Talero, Giacomo Zaccherini, Cristina Ripoll, Luise Aamann, Oliviero Riggio, Martina Rizzo, Karen Vagner Danielsen, Javier Romaní Fernández, Jelte J Schaapman, Frank Erhard Uschner, Juan Acevedo, Miguel Á. Rodríguez, David Semela, Carlo Alessandria, Carmine Gambino, Lise Lotte Gluud, Paolo Caraceni, Emanuela Ciraci, István Altorjay, Cristina Solé, Salvatore Piano, Minneke J. Coenraad, Pierre Nahon, Haluk Tarik Kani, Faouzi Saliba, Agnese Antognoli, Andrea De Gottardi, Osman Ozdogan, Henning Grønbæk, Christian J. Steib, Anna Curto, Hans Van Vlierberghe, Manuel Romero-Gómez, T.M. Welzel, Roland Amathieu, Sylvie Tresson, Carla Pitarch, Frederik Nevens, Alexander Zipprich, Christian Trautwein, Ilaria Giovo, Victor Vargas, Laure Elkrief, Giorgio Maria Saracco, Johannes Chang, Mattias Mandorfer, Paul Horn, Thomas Berg, Nesrine Amari, Sara Mareso, Heinz Zoller, Osagie Akpata, Mária Papp, Adam Herber, Thomas Reiberger, Flemming Bendtsen, Elsa Solà, Ferran Aguilar, Jose Presa Ramos, Miriam Maschmeier, Tamas Tornai, Manuela Merli, Rajiv Jalan, Martina Gagliardi, Cornelius Engelmann, Rafael Bañares, Daniela Campion, Antonella Putignano, Natalie Van den Ende, Claire Francoz, Marco Pavesi, Paola Ponzo, Rita Garcia, Sven Francque, Vish Patel, Esau Moreno, Alessandra Brocca, Rudolf E. Stauber, Zsuzsanna Vitális, Rajeshwar P. Mookerjee, Ahmed Elsharkawy, Eleonora Bertoli, Michael Praktiknjo, Stephen D. Ryder, Cristina Sanchez, Boglarka Balogh, Debbie L. Shawcross, Manuel Tufoni, Paolo Angeli, Florian Rainer, Pavel Strnad, István Tornai, Edilmar Alvarado-Tapias, Alexander L. Gerbes, Didier Samuel, Maurizio Baldassarre, Cesar Jimenez, Stefan Zeuzem, Pietro Gatti, Germán Soriano, Robert Schierwagen, Ana Clemente, Mauro Bernardi, Daniel Markwardt, Trebicka, Jonel, Fernandez, Javier, Papp, Maria, Caraceni, Paolo, Laleman, Wim, Gambino, Carmine, Giovo, Ilaria, Uschner, Frank Erhard, Jansen, Christian, Jimenez, Cesar, Mookerjee, Rajeshwar, Gustot, Thierry, Albillos, Agustin, Bañares, Rafael, Jarcuska, Peter, Steib, Christian, Reiberger, Thoma, Acevedo, Juan, Gatti, Pietro, Shawcross, Debbie L, Zeuzem, Stefan, Zipprich, Alexander, Piano, Salvatore, Berg, Thoma, Bruns, Tony, Danielsen, Karen Vagner, Coenraad, Minneke, Merli, Manuela, Stauber, Rudolf, Zoller, Heinz, Ramos, José Presa, Solé, Cristina, Soriano, Germán, de Gottardi, Andrea, Gronbaek, Henning, Saliba, Faouzi, Trautwein, Christian, Kani, Haluk Tarik, Francque, Sven, Ryder, Stephen, Nahon, Pierre, Romero-Gomez, Manuel, Van Vlierberghe, Han, Francoz, Claire, Manns, Michael, Garcia-Lopez, Elisabet, Tufoni, Manuel, Amoros, Alex, Pavesi, Marco, Sanchez, Cristina, Praktiknjo, Michael, Curto, Anna, Pitarch, Carla, Putignano, Antonella, Moreno, Esau, Bernal, William, Aguilar, Ferran, Clària, Joan, Ponzo, Paola, Vitalis, Zsuzsanna, Zaccherini, Giacomo, Balogh, Boglarka, Gerbes, Alexander, Vargas, Victor, Alessandria, Carlo, Bernardi, Mauro, Ginès, Pere, Moreau, Richard, Angeli, Paolo, Jalan, Rajiv, Arroyo, Vicente, Banares, Rafael, Reiberger, Thomas, Shawcross, Debbie L., Berg, Thomas, Ramos, Jose Presa, Sole, Cristina, Soriano, German, Van Vlierberghe, Hans, Claria, Joan, Gines, Pere, Maschmeier, Miriam, Semela, David, Elkrief, Laure, Elsharkawy, Ahmed, Tornai, Tamas, Tornai, Istvan, Altorjay, Istvan, Antognoli, Agnese, Baldassarre, Maurizio, Gagliardi, Martina, Bertoli, Eleonora, Mareso, Sara, Brocca, Alessandra, Campion, Daniela, Saracco, Giorgio Maria, Rizzo, Martina, Lehmann, Jennifer, Pohlmann, Alessandra, Brol, Maximilian J., Chang, Johannes, Schierwagen, Robert, Sola, Elsa, Amari, Nesrine, Rodriguez, Miguel, Nevens, Frederik, Clemente, Ana, Janicko, Martin, Markwardt, Daniel, Mandorfer, Mattias, Welsch, Christoph, Welzel, Tanja M., Ciraci, Emanuela, Patel, Vish, Ripoll, Cristina, Herber, Adam, Horn, Paul, Bendtsen, Flemming, Gluud, Lise Lotte, Schaapman, Jelte, Riggio, Oliviero, Rainer, Florian, Moritz, Joerg Tobiasch, Mesquita, Monica, Alvarado-Tapias, Edilmar, Akpata, Osagie, Aamann, Luise, Samuel, Didier, Tresson, Sylvie, Strnad, Pavel, Amathieu, Roland, Simon-Talero, Macarena, Smits, Francois, van den Ende, Natalie, Martinez, Javier, Garcia, Rita, Rupprechter, Harald, Engelmann, Cornelius, and Ozdogan, Osman Cavit

Subjects
0301 basic medicine, Liver Cirrhosis, Male, Cirrhosis, Organ Dysfunction Scores, acute complication, Chronic liver disease, Acute complications, Non-elective admission, Outcome, Risk factors, 0302 clinical medicine, Preventive Health Services, Medicine and Health Sciences, Gastro-entérologie, risk factors, 610 Medicine & health, Medical History Taking, factors, Toxic encephalopathy, Bacterial Infections, Middle Aged, Prognosis, Europe, Cohort, Disease Progression, outcome, 030211 gastroenterology & hepatology, Female, medicine.symptom, Needs Assessment, Risk, medicine.medical_specialty, Alcoholic hepatitis, 03 medical and health sciences, Internal medicine, medicine, Humans, Decompensation, Medical history, Inflammation, Hepatology, business.industry, Hepatitis, Alcoholic, Organ dysfunction, Acute-On-Chronic Liver Failure, chronic liver disease, medicine.disease, Precipitating Factors, 030104 developmental biology, Human medicine, business, non-elective admission
Abstract

Acute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (AD-No ACLF), or with ACLF phenotype (AD-ACLF) defined by organ failure(s). Precipitants may induce AD. This multicenter, prospective, observational PREDICT study (NCT03056612) analyzes and characterizes the precipitants leading to both of these AD phenotypes., info:eu-repo/semantics/published

Published
2021
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28. Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer

Author

Lisa Derosa, Bertrand Routy, Andrew Maltez Thomas, Valerio Iebba, Gerard Zalcman, Sylvie Friard, Julien Mazieres, Clarisse Audigier-Valette, Denis Moro-Sibilot, François Goldwasser, Carolina Alves Costa Silva, Safae Terrisse, Melodie Bonvalet, Arnaud Scherpereel, Hervé Pegliasco, Corentin Richard, François Ghiringhelli, Arielle Elkrief, Antoine Desilets, Felix Blanc-Durand, Fabio Cumbo, Aitor Blanco, Romain Boidot, Sandy Chevrier, Romain Daillère, Guido Kroemer, Laurie Alla, Nicolas Pons, Emmanuelle Le Chatelier, Nathalie Galleron, Hugo Roume, Agathe Dubuisson, Nicole Bouchard, Meriem Messaoudene, Damien Drubay, Eric Deutsch, Fabrice Barlesi, David Planchard, Nicola Segata, Stéphanie Martinez, Laurence Zitvogel, Jean-Charles Soria, Benjamin Besse, Derosa, Lisa, Routy, Bertrand, Thomas, Andrew Maltez, Iebba, Valerio, Zalcman, Gerard, Friard, Sylvie, Mazieres, Julien, Audigier-Valette, Clarisse, Moro-Sibilot, Deni, Goldwasser, Françoi, Silva, Carolina Alves Costa, Terrisse, Safae, Bonvalet, Melodie, Scherpereel, Arnaud, Pegliasco, Hervé, Richard, Corentin, Ghiringhelli, Françoi, Elkrief, Arielle, Desilets, Antoine, Blanc-Durand, Felix, Cumbo, Fabio, Blanco, Aitor, Boidot, Romain, Chevrier, Sandy, Daillère, Romain, Kroemer, Guido, Alla, Laurie, Pons, Nicola, Le Chatelier, Emmanuelle, Galleron, Nathalie, Roume, Hugo, Dubuisson, Agathe, Bouchard, Nicole, Messaoudene, Meriem, Drubay, Damien, Deutsch, Eric, Barlesi, Fabrice, Planchard, David, Segata, Nicola, Martinez, Stéphanie, Zitvogel, Laurence, Soria, Jean-Charle, and Besse, Benjamin

Subjects
metagenomics, Lung Neoplasms, Microbiota, Programmed Cell Death 1 Receptor, biomarkers, kidney cancer, General Medicine, Akkermansia, patients stratification, NSCLC, General Biochemistry, Genetics and Molecular Biology, B7-H1 Antigen, Microbiome, immunotherapy, Akkermansia muciniphila, cancer, immune checkpoint inhibitors (ICIs), tumor microenvironment, Carcinoma, Non-Small-Cell Lung, Tumor Microenvironment, biomarker, Humans, metagenomic, Retrospective Studies
Abstract

Aside from PD-L1 expression, biomarkers of response to immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) are needed. In a previous retrospective analysis, we documented that fecal Akkermansia muciniphila (Akk) was associated with clinical benefit of ICI in patients with NSCLC or kidney cancer. In the current study, we performed shotgun-metagenomics-based microbiome profiling in a large cohort of patients with advanced NSCLC (n = 338) treated with first- or second-line ICIs to prospectively validate the predictive value of fecal Akk. Baseline stool Akk was associated with increased objective response rates and overall survival in multivariate analyses, independent of PD-L1 expression, antibiotics, and performance status. Intestinal Akk was accompanied by a richer commensalism, including Eubacterium hallii and Bifidobacterium adolescentis, and a more inflamed tumor microenvironment in a subset of patients. However, antibiotic use (20% of cases) coincided with a relative dominance of Akk above 4.8% accompanied with the genus Clostridium, both associated with resistance to ICI. Our study shows significant differences in relative abundance of Akk that may represent potential biomarkers to refine patient stratification in future studies.

Published
2020

29. First experience of SARS-CoV-2 infections in solid organ transplant recipients in the Swiss Transplant Cohort Study

Author

Tschopp, Jonathan, LHuillier, Arnaud G., Mombelli, Matteo, Mueller, Nicolas J., Khanna, Nina, Garzoni, Christian, Meloni, Dario, Papadimitriou‐Olivgeris, Matthaios, Neofytos, Dionysios, Hirsch, Hans H., Schuurmans, Macé M., Müller, Thomas, Berney, Thierry, Steiger, Jürg, Pascual, Manuel, Manuel, Oriol, Delden, Christian, Amico, Patrizia, Aubert, John‐David, Banz, Vanessa, Beldi, Guido, Benden, Christian, Berger, Christoph, Binet, Isabelle, Bochud, Pierre‐Yves, Branca, Sanda, Bucher, Heiner, Carell, Thierry, Catana, Emmanuelle, Chalandon, Yves, Geest, Sabina, Rougemont, Olivier, Dickenmann, Michael, Duchosal, Michel, Elkrief, Laure, Fehr, Thomas, Ferrari‐Lacraz, Sylvie, Soccal, Paola Gasche, Gaudet, Christophe, Giostra, Emiliano, Golshayan, Déla, Hadaya, Karine, Halter, Jörg, Hauri, Dimitri, Heim, Dominik, Hess, Christoph, Hillinger, Sven, Hirsch, Hans H, Hofbauer, Günther, Huynh‐Do, Uyen, Immer, Franz, Klaghofer, Richard, Koller, Michael, Laesser, Bettina, Laube, Guido, Lehmann, Roger, Lovis, Christian, Majno, Pietro, Marti, Hans‐Peter, Martin, Pierre Yves, Martinelli, Michele, Meylan, Pascal, Mueller, Nicolas J, Müller, Antonia, Müllhaupt, Beat, Passweg, Jakob, Posfay‐Barbe, Klara, Rick, Juliane, Roosnek, Eddy, Rosselet, Anne, Rothlin, Silvia, Ruschitzka, Frank, Schanz, Urs, Schaub, Stefan, Schnyder, Aurelia, Schuurmans, Macé, Seiler, Christian, Sprachta, Jan, Stampf, Susanne, Steinack, Carolin, Stirnimann, Guido, Toso, Christian, Van Delden, Christian, Venetz, Jean‐Pierre, Villard, Jean, Wick, Madeleine, Wilhelm, Markus, Yerly, Patrick, University of Zurich, Swiss Transplant Cohort Study (STCS), Amico, P., Aubert, J.D., Banz, V., Beldi, G., Benden, C., Berger, C., Binet, I., Bochud, P.Y., Branca, S., Bucher, H., Carell, T., Catana, E., Chalandon, Y., de Geest, S., de Rougemont, O., Dickenmann, M., Duchosal, M., Elkrief, L., Fehr, T., Ferrari-Lacraz, S., Garzoni, C., Soccal, P.G., Gaudet, C., Giostra, E., Golshayan, D., Hadaya, K., Halter, J., Hauri, D., Heim, D., Hess, C., Hillinger, S., Hirsch, H.H., Hofbauer, G., Huynh-Do, U., Immer, F., Klaghofer, R., Koller, M., Laesser, B., Laube, G., Lehmann, R., Lovis, C., Majno, P., Manuel, O., Marti, H.P., Martin, P.Y., Martinelli, M., Meylan, P., Mueller, N.J., Müller, A., Müller, T., Müllhaupt, B., Pascual, M., Passweg, J., Posfay-Barbe, K., Rick, J., Roosnek, E., Rosselet, A., Rothlin, S., Ruschitzka, F., Schanz, U., Schaub, S., Schnyder, A., Schuurmans, M., Seiler, C., Sprachta, J., Stampf, S., Steinack, C., Steiger, J., Stirnimann, G., Toso, C., Van Delden, C., Venetz, J.P., Villard, J., Wick, M., Wilhelm, M., and Yerly, P.

Subjects
Male, 10255 Clinic for Thoracic Surgery, Comorbidity, 030230 surgery, Infection and infectious agents/ Viral, Organ transplantation, 10234 Clinic for Infectious Diseases, 0302 clinical medicine, Postoperative Complications, Epidemiology, Immunology and Allergy, Medicine, Pharmacology (medical), Prospective Studies, Prospective cohort study, ddc:616, Infectious disease, education.field_of_study, ddc:618, ddc:617, Incidence, Clinical research/ practice, Middle Aged, 3. Good health, Survival Rate, 10209 Clinic for Cardiology, Female, medicine.symptom, 10178 Clinic for Pneumology, Coronavirus Infections, infectious [Complication], infectious, infection and infectious agents, infection and infectious agents - viral, infectious disease [Aged, Betacoronavirus, Coronavirus Infections/epidemiology, Disease Transmission, Infectious/prevention & control, Follow-Up Studies, Humans, Organ Transplantation/methods, Pandemics, Pneumonia, Viral/epidemiology, Postoperative Complications/epidemiology, Survival Rate/trends, Switzerland/epidemiology, Transplant Recipients, clinical research/ practice, complication], Switzerland, Cohort study, medicine.medical_specialty, Nausea, Population, Pneumonia, Viral, Infection and infectious agents, 610 Medicine & health, Brief Communication, 03 medical and health sciences, Internal medicine, Disease Transmission, Infectious, education, Survival rate, Aged, Transplantation, business.industry, SARS-CoV-2, COVID-19, Organ Transplantation, medicine.disease, 10032 Clinic for Oncology and Hematology, business
Abstract

Immunocompromised patients may be at increased risk for complications of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. However, comprehensive data of SARS‐CoV‐2 infection in solid organ transplant (SOT) recipients are still lacking. We performed a multicenter nationwide observational study within the Swiss Transplant Cohort Study (STCS) to describe the epidemiology, clinical presentation, treatment and outcomes of the first microbiologically documented SARS‐CoV‐2 infection among SOT recipients. Overall, 21 patients were included with a median age of 56 years (10 kidney, 5 liver, 1 pancreas, 1 lung, 1 heart and 3 combined transplantations). The most common presenting symptoms were fever (76%), dry cough (57%), nausea (33%) and diarrhea (33%). Ninety‐five percent and 24% of patients required hospital and ICU admission, respectively, and 19% were intubated. After a median of 33 days of follow‐up, 16 patients were discharged, 3 were still hospitalized and 2 patients died. These data suggest that clinical manifestations of SARS‐CoV‐2 infection in middle‐aged SOT recipients appear to be similar to the general population without an apparent higher rate of complications. These results need to be confirmed in larger cohorts.

Published
2020

30. Management of allergy transfer upon solid organ transplantation

Author

Muller, Yannick D, Vionnet, Julien, Beyeler, Franziska, Eigenmann, Philippe, Caubet, Jean-Christoph, Villard, Jean, Berney, Thierry, Scherer, Kathrin, Spertini, Francois, Fricker, Michael P, Lang, Claudia, Schmid-Grendelmeier, Peter, Benden, Christian, Lombard, Pascale Roux, Aubert, Vincent, Immer, Franz, Pascual, Manuel, Harr, Thomas, Amico, Patrizia, Aubert, John-David, Banz, Vanessa, Beldi, Guido, Berger, Christoph, Binet, Isabelle, Bochud, Pierre-Yves, Branca, Sanda, Bucher, Heiner, Carell, Thierry, Catana, Emmanuelle, Chalandon, Yves, de Geest, Sabina, de Rougemont, Olivier, Dickenmann, Michael, Duchosal, Michel, Elkrief, Laure, Fehr, Thomas, Ferrari-Lacraz, Sylvie, Garzoni, Christian, Soccal, Paola Gasche, Gaudet, Christophe, Giostra, Emiliano, Golshayan, Dela, Hadaya, Karine, Halter, Joerg, Hauri, Dimitri, Heim, Dominik, Hess, Christoph, Hillinger, Sven, Hirsch, Hans H, Hofbauer, Guenther, Huynh-Do, Uyen, Klaghofer, Richard, Koller, Michael, Laesser, Bettina, Laube, Guido, Lehmann, Roger, Lovis, Christian, Majno, Pietro, Manuel, Oriol, Marti, Hans-Peter, Martin, Pierre Yves, Martinelli, Michele, Meylan, Pascal, Morel, Philippe, Mueller, Nicolas J, Mueller, Antonia, Mueller, Thomas, Muellhaupt, Beat, Yerly, Patrick, Passweg, Jakob, Posfay-Barbe, Klara, Rick, Juliane, Roosnek, Eddy, Rosselet, Anne, Rothlin, Silvia, Ruschitzka, Frank, Schanz, Urs, Schaub, Stefan, Schnyder, Aurelia, Seiler, Christian, Sprachta, Jan, Stampf, Susanne, Steiger, Juerg, Stirnimann, Guido, Toso, Christian, Van Delden, Christian, Venetz, Jean-Pierre, Wick, Madeleine, Wilhelm, Markus, Swiss Transplant Cohort Study, Amico, P., Aubert, J.D., Banz, V., Beldi, G., Benden, C., Berger, C., Binet, I., Bochud, P.Y., Branca, S., Bucher, H., Carell, T., Catana, E., Chalandon, Y., de Geest, S., de Rougemont, O., Dickenmann, M., Duchosal, M., Elkrief, L., Fehr, T., Ferrari-Lacraz, S., Garzoni, C., Gasche Soccal, P., Gaudet, C., Giostra, E., Golshayan, D., Hadaya, K., Halter, J., Hauri, D., Heim, D., Hess, C., Hillinger, S., Hirsch, H.H., Hofbauer, G., Huynh-Do, U., Immer, F., Klaghofer, R., Koller, M., Laesser, B., Laube, G., Lehmann, R., Lovis, C., Majno, P., Manuel, O., Marti, H.P., Yves Martin, P., Martinelli, M., Meylan, P., Morel, P., Mueller, N.J., Müller, A., Müller, T., Müllhaupt, B., Pascual, M., Passweg, J., Posfay-Barbe, K., Rick, J., Roosnek, E., Rosselet, A., Rothlin, S., Ruschitzka, F., Schanz, U., Schaub, S., Schnyder, A., Seiler, C., Sprachta, J., Stampf, S., Steiger, J., Stirnimann, G., Toso, C., Van Delden, C., Venetz, J.P., Villard, J., Wick, M., Wilhelm, M., Yerly, P., University of Zurich, Muller, Yannick D, Gasche-Soccal, Paola Marina Alessandra, Posfay Barbe, Klara, and Lovis, Christian

Subjects
Allergy, diagnostic techniques and imaging, IgE, Immunoglobulin E, allergy transfer, anaphylaxis, immunosuppression, management, solid organ transplantation, allergy, business/management, clinical decision-making, clinical research/practice, guidelines, immunoglobulin E, immunosuppression/immune modulation, organ transplantation in general, patient safety, 10255 Clinic for Thoracic Surgery, 2747 Transplantation, medicine.medical_treatment, 030230 surgery, INCREASE, Cohort Studies, 0302 clinical medicine, Solid organ transplantation, Immunology and Allergy, Medicine, 2736 Pharmacology (medical), Pharmacology (medical), LUNG TRANSPLANTATION, ddc:616, Kidney, ddc:618, biology, ddc:617, PEANUT ALLERGY, 10177 Dermatology Clinic, Immunosuppression, practice, Management, clinical decision‐making, medicine.anatomical_structure, B-CELLS, 10209 Clinic for Cardiology, 2723 Immunology and Allergy, 10178 Clinic for Pneumology, Brief Communications, Life Sciences & Biomedicine, Anaphylaxis, medicine.medical_specialty, 610 Medicine & health, Brief Communication, 03 medical and health sciences, Internal medicine, Humans, Peanut Hypersensitivity, Allergy transfer, business, Retrospective Studies, Transplantation, Lung, Science & Technology, immune modulation, business.industry, Organ Transplantation, medicine.disease, clinical research, 10036 Medical Clinic, 10032 Clinic for Oncology and Hematology, biology.protein, ASTHMA, Surgery, IMMUNOGLOBULIN-E
Abstract

Allergy transfer upon solid organ transplantation has been reported in the literature, although only few data are available as to the frequency, significance, and management of these cases. Based on a review of 577 consecutive deceased donors from the Swisstransplant Donor‐Registry, 3 cases (0.5%) of fatal anaphylaxis were identified, 2 because of peanut and 1 of wasp allergy. The sera of all 3 donors and their 10 paired recipients, prospectively collected before and after transplantation for the Swiss Transplant Cohort Study, were retrospectively processed using a commercial protein microarray fluorescent test. As early as 5 days posttransplantation, newly acquired peanut‐specific IgE were transiently detected from 1 donor to 3 recipients, of whom 1 liver and lung recipients developed grade III anaphylaxis. Yet, to define how allergy testing should be performed in transplant recipients and to better understand the impact of immunosuppressive therapy on IgE sensitization, we prospectively studied 5 atopic living‐donor kidney recipients. All pollen‐specific IgE and >90% of skin prick tests remained positive 7 days and 3 months after transplantation, indicating that early diagnosis of donor‐derived IgE sensitization is possible. Importantly, we propose recommendations with respect to safety for recipients undergoing solid‐organ transplantation from donors with a history of fatal anaphylaxis., Based on the Swisstransplant donor registry, the Swiss‐Transplant‐Cohort‐Study, and a prospective analysis on allergy maintenance in atopic recipients, this study makes new recommendations for the management of allergy transfer upon solid organ transplantation, emphasizing the poor effect of immunosuppression on IgE sensitization and the need of early allergological investigation in the donor and respective recipients.

Published
2020

31. The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology

Author

Sylvie Tresson, Sara Mareso, Daniela Campion, Agustín Albillos, Alex Amoros, Hans Van Vlierberghe, Manuel Romero-Gómez, Andrea De Gottardi, Thomas Reiberger, Vicente Arroyo, Boglarka Balogh, Miriam Maschmeier, Marco Pavesi, Javier Martínez, Harald Rupprechter, Sara Montagnese, Alessandra Pohlmann, Minneke J. Coenraad, Pierre Nahon, Agnese Antognoli, Jose Presa Ramos, Christoph Welsch, Alexander L. Gerbes, Pietro Gatti, Richard Moreau, Wim Laleman, Mauro Bernardi, Karen Vagner Danielsen, Laure Elkrief, Christian Jansen, Alexander Zipprich, Lise Lotte Gluud, Paul Horn, Ilaria Giovo, Roland Amathieu, Martina Rizzo, Elisabet Garcia, Joan Clària, Oliviero Riggio, Cristina Sanchez, Rita Garcia, Florian Rainer, Sven Francque, Manuela Merli, Giorgio Maria Saracco, Javier J.M. Fernández, Mária Papp, Martina Gagliardi, Antonella Putignano, Claire Francoz, Debbie L. Shawcross, Manuel Tufoni, Ferran Aguilar, Paola Ponzo, Heinz Zoller, Elsa Solà, Faouzi Saliba, Pavel Strnad, Stefan Zeuzem, Miguel Á. Rodríguez, David Semela, Peter Lykke Eriksen, Anna Curto, Rajiv Jalan, Emanuela Ciraci, Alessandra Brocca, István Altorjay, István Tornai, Edilmar Alvarado-Tapias, Jennifer Lehmann, Rajeshwar P. Mookerjee, Paolo Angeli, Rudolf E. Stauber, Ahmed Elsharkawy, Cristina Solé, Didier Samuel, Daniel Markwardt, Maurizio Baldassarre, Cornelius Engelmann, Cesar Jimenez, Pere Ginès, Frederik Nevens, Osagie Akpata, Germán Soriano, Robert Schierwagen, Eleonora Bertoli, Adam Herber, Jörg Tobiasch Moritz, Michael Praktiknjo, Natalie Van den Ende, William Bernal, Nesrine Amari, Stephen D. Ryder, Ana Clemente, Martin Janicko, Victor Vargas, Mattias Mandorfer, Flemming Bendtsen, Peter Jarcuska, Juan Acevedo, Vish Patel, Esau Moreno, Zsuzsanna Vitális, Tamas Tornai, Rafael Bañares, Christian J. Steib, Christian Trautwein, Thomas Berg, Michael Manns, Paolo Caraceni, Jelte J Schaapman, Carlo Alessandria, Carmine Gambino, Salvatore Piano, Carla Pitarch, Thierry Gustot, Osman Ozdogan, Francois Smits, Henning Grønbæk, Giacomo Zaccherini, Cristina Ripoll, Tony Bruns, Jonel Trebicka, Macarena Simón-Talero, Frank Erhard Uschner, Monica Mesquita, PREDICT STUDY Group, EASL-CLIF Consortium, Trebicka, Jonel, Fernandez, Javier, Papp, Maria, Caraceni, Paolo, Laleman, Wim, Gambino, Carmine, Giovo, Ilaria, Uschner, Frank Erhard, Jimenez, Cesar, Mookerjee, Rajeshwar, Gustot, Thierry, Albillos, Agustin, Banares, Rafael, Janicko, Martin, Steib, Christian, Reiberger, Thomas, Acevedo, Juan, Gatti, Pietro, Bernal, William, Zeuzem, Stefan, Zipprich, Alexander, Piano, Salvatore, Berg, Thomas, Bruns, Tony, Bendtsen, Flemming, Coenraad, Minneke, Merli, Manuela, Stauber, Rudolf, Zoller, Heinz, Ramos, Jose Presa, Sole, Cristina, Soriano, German, de Gottardi, Andrea, Gronbaek, Henning, Saliba, Faouzi, Trautwein, Christian, Ozdogan, Osman Cavit, Francque, Sven, Ryder, Stephen, Nahon, Pierre, Romero-Gomez, Manuel, Van Vlierberghe, Hans, Francoz, Claire, Manns, Michael, Garcia, Elisabet, Tufoni, Manuel, Amoros, Alex, Pavesi, Marco, Sanchez, Cristina, Curto, Anna, Pitarch, Carla, Putignano, Antonella, Moreno, Esau, Shawcross, Debbie, Aguilar, Ferran, Claria, Joan, Ponzo, Paola, Jansen, Christian, Vitalis, Zsuzsanna, Zaccherini, Giacomo, Balogh, Boglarka, Vargas, Victor, Montagnese, Sara, Alessandria, Carlo, Bernardi, Mauro, Gines, Pere, Jalan, Rajiv, Moreau, Richard, Angeli, Paolo, Arroyo, Vicente, Trebicka J., Fernandez J., Papp M., Caraceni P., Laleman W., Gambino C., Giovo I., Uschner F.E., Jimenez C., Mookerjee R., Gustot T., Albillos A., Banares R., Janicko M., Steib C., Reiberger T., Acevedo J., Gatti P., Bernal W., Zeuzem S., Zipprich A., Piano S., Berg T., Bruns T., Bendtsen F., Coenraad M., Merli M., Stauber R., Zoller H., Ramos J.P., Sole C., Soriano G., de Gottardi A., Gronbaek H., Saliba F., Trautwein C., Ozdogan O.C., Francque S., Ryder S., Nahon P., Romero-Gomez M., Van Vlierberghe H., Francoz C., Manns M., Garcia E., Tufoni M., Amoros A., Pavesi M., Sanchez C., Curto A., Pitarch C., Putignano A., Moreno E., Shawcross D., Aguilar F., Claria J., Ponzo P., Jansen C., Vitalis Z., Zaccherini G., Balogh B., Vargas V., Montagnese S., Alessandria C., Bernardi M., Gines P., Jalan R., Moreau R., Angeli P., Arroyo V., Maschmeier M., Semela D., Elkrief L., Elsharkawy A., Tornai T., Tornai I., Altorjay I., Antognoli A., Baldassarre M., Gagliardi M., Bertoli E., Mareso S., Brocca A., Campion D., Saracco G.M., Rizzo M., Lehmann J., Pohlmann A., Praktiknjo M., Schierwagen R., Sola E., Amari N., Rodriguez M., Nevens F., Clemente A., Jarcuska P., Gerbes A., Mandorfer M., Welsch C., Ciraci E., Patel V., Ripoll C., Herber A., Horn P., Danielsen K.V., Gluud L.L., Schaapman J., Riggio O., Rainer F., Moritz J.T., Mesquita M., Alvarado-Tapias E., Akpata O., Lykke Eriksen P., Samuel D., Tresson S., Strnad P., Amathieu R., Simon-Talero M., Smits F., van den Ende N., Martinez J., Garcia R., Markwardt D., Rupprechter H., and Engelmann C.

Subjects
Liver Cirrhosis, Male, CHRONIC LIVER-FAILURE, Cirrhosis, medicine.medical_treatment, Trasplantament hepàtic, Liver transplantation, Chronic liver disease, Severity of Illness Index, Acute complications, Non-elective admission, Outcome, Risk factors, acute complications, Ascites, Medicine and Health Sciences, Prospective Studies, 610 Medicine & health, Hepatic encephalopathy, Mortality rate, Sciences bio-médicales et agricoles, Middle Aged, Prognosis, Europe, Survival Rate, Hepatic cirrhosis, Portal hypertension, Female, medicine.symptom, medicine.medical_specialty, Cirrosi hepàtica, Gastrointestinal hemorrhage, INFLAMMATION, Internal medicine, Hypertension, Portal, SCORE, medicine, Humans, Decompensation, Hepatology, business.industry, MORTALITY, Acute-On-Chronic Liver Failure, Acute complication, Hemorràgia gastrointestinal, medicine.disease, Human medicine, Hepatic transplantation, business, Follow-Up Studies
Abstract

Acute decompensation (AD) of cirrhosis is defined as the acute development of ascites, gastrointestinal hemorrhage, hepatic encephalopathy, infection or any combination thereof, requiring hospitalization. The presence of organ failure(s) in patients with AD defines acute-on-chronic liver failure (ACLF). The PREDICT study is a European, prospective, observational study, designed to characterize the clinical course of AD and to identify predictors of ACLF., info:eu-repo/semantics/published

Published
2020
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32. 2D shear wave liver elastography by aixplorer to detect portal hypertension in cirrhosis: an individual patient data meta-analysis

Author

Sven Franque, Laure Elkrief, Yongsoo Kim, Juan Carlos García-Pagán, Annalisa Berzigotti, Laurent Castera, Giulia Allegretti, Maja Thiele, Horia Stefanescu, Christian Jansen, Pierre-Emmanuel Rautou, Woo Kyoung Jeong, Wim Verlinden, Aleksander Krag, Jonel Trebicka, Fabio Piscaglia, Mads Israelsen, Mie Balle Hugger, Thiele M., Hugger M.B., Kim Y., Rautou P.-E., Elkrief L., Jansen C., Verlinden W., Allegretti G., Israelsen M., Stefanescu H., Piscaglia F., Garcia-Pagan J.C., Franque S., Berzigotti A., Castera L., Jeong W.K., Trebicka J., and Krag A.

Subjects
Liver Cirrhosis, medicine.medical_specialty, Cirrhosis, Cirrosi hepàtica, Portal venous pressure, Subgroup analysis, Aixplorer, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Ascites, Hypertension, Portal, medicine, Humans, Malalties cròniques, Hepatology, medicine.diagnostic_test, business.industry, Decompensated liver disease, medicine.disease, Portal Pressure, 3. Good health, compensated advanced chronic liver disease, Liver, Hepatic cirrhosis, 030220 oncology & carcinogenesis, Meta-analysis, Chronic diseases, Portal hypertension, Elasticity Imaging Techniques, 030211 gastroenterology & hepatology, supersonic shear imagine, Elastography, liver vein catheterization, Human medicine, medicine.symptom, Varices, business
Abstract

Background & Aims: Liver stiffness measured with 2-dimensional shear wave elastography by Supersonic Imagine (2DSWE-SSI) is well-established for fibrosis diagnostics, but non-conclusive for portal hypertension. Methods: We performed an individual patient data meta-analysis of 2DSWE-SSI to identify clinically significant portal hypertension (CSPH), severe portal hypertension and large varices in cirrhosis patients, using hepatic venous pressure gradient and upper endoscopy as reference. We used meta-analytical integration of diagnostic accuracies with optimized rule-out (sensitivity-90%) and rule-in (specificity-90%) cut-offs. Results: Five studies from seven centres shared data on 519 patients. After exclusion, we included 328 patients. Eighty-nine (27%) were compensated and 286 (87%) had CSPH. 2DSWE-SSI&nbsp

Published
2020
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33. Non-invasive diagnosis and follow-up of vascular liver diseases

Author

Isabelle Ollivier-Hourmand, Christophe Bureau, Marie Decraecker, Aurélie Plessier, Nathalie Ganne-Carrié, Valérie Vilgrain, M. Bourlière, Maxime Ronot, Laure Elkrief, Pierre-Emmanuel Rautou, Victor de Lédinghen, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de référence des Maladies Vasculaires du Foie [Paris] (FILFOIE), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Saint-Joseph [Marseille], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Avicenne [AP-HP], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), École pratique des hautes études (EPHE), and Malbec, Odile

Subjects
Liver Cirrhosis, medicine.medical_specialty, Hepatology, medicine.diagnostic_test, business.industry, [SDV]Life Sciences [q-bio], Biopsy, Liver Diseases, Non invasive, Gastroenterology, MEDLINE, [SDV] Life Sciences [q-bio], Liver, Liver biopsy, Medicine, Elasticity Imaging Techniques, Humans, Radiology, Abnormality, business, Follow-Up Studies
Abstract

International audience; Vascular disorders of the liver are rare diseases, some of which are diagnosed mainly with non-invasive tests and others by liver biopsy. Non-invasive methods can be used to diagnose and monitor these diseases. However, their evaluation needs to be performed by expert centers. Liver biopsy is needed each time there is an unexplained abnormality.

Published
2021
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34. Prolonged SARS-CoV-2 RNA virus shedding and lymphopenia are hallmarks of COVID-19 in cancer patients with poor prognosis

Author

Goubet, Anne-Gaëlle, Dubuisson, Agathe, Geraud, Arthur, Danlos, François-Xavier, Terrisse, Safae, Silva, Carolina Alves Costa, Drubay, Damien, Touri, Lea, Picard, Marion, Mazzenga, Marine, Silvin, Aymeric, Dunsmore, Garett, Haddad, Yacine, Pizzato, Eugenie, Ly, Pierre, Flament, Caroline, Melenotte, Cléa, Solary, Eric, Fontenay, Michaela, Garcia, Gabriel, Balleyguier, Corinne, Lassau, Nathalie, Maeurer, Markus, Grajeda-Iglesias, Claudia, Nirmalathasan, Nitharsshini, Aprahamian, Fanny, Durand, Sylvère, Kepp, Oliver, Ferrere, Gladys, Thelemaque, Cassandra, Lahmar, Imran, Fahrner, Jean-Eudes, Meziani, Lydia, Ahmed-Belkacem, Abdelhakim, Saïdani, Nadia, La Scola, Bernard, Raoult, Didier, Gentile, Stéphanie, Cortaredona, Sébastien, Ippolito, Giuseppe, Lelouvier, Benjamin, Roulet, Alain, Andre, Fabrice, Barlesi, Fabrice, Soria, Jean-Charles, Pradon, Caroline, Gallois, Emmanuelle, Pommeret, Fanny, Colomba, Emeline, Ginhoux, Florent, Kazandjian, Suzanne, Elkrief, Arielle, Routy, Bertrand, Miyara, Makoto, Gorochov, Guy, Deutsch, Eric, Albiges, Laurence, Stoclin, Annabelle, Gachot, Bertrand, Florin, Anne, Merad, Mansouria, Scotte, Florian, Assaad, Souad, Kroemer, Guido, Blay, Jean-Yves, Marabelle, Aurélien, Griscelli, Frank, Zitvogel, Laurence, Derosa, Lisa, Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Saclay, Institut Gustave Roussy (IGR), Oncostat (U1018 (Équipe 2)), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay (BIOMAPS), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Champalimaud Centre for the Unknown [Lisbon], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Radiothérapie Moléculaire et Innovation Thérapeutique (RaMo-IT), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Intercommunal de Cornouaille (CHIC), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), National Institute for Infectious Diseases 'Lazzaro Spallanzani', Vaiomer, Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), E-institute of Shanghai University Immunology Division, Shanghai University, Duke-NUS Medical School [Singapore], McGill University Health Center [Montreal] (MUHC), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, UNICANCER, Université Paris Cité (UPCité), Karolinska Institutet [Stockholm], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Chinese Academy of Medical Sciences [Suzhou, Chine] (CAMS), Modèles de Cellules Souches Malignes et Thérapeutiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, National Infrastructure INGESTEM, Université Paris Sud, A-GG was supported by Fondation pour la Recherche Médicale (FRM). LD has received support by the Philanthropia Fondation Gustave Roussy. The Gustave Roussy sponsored clinical study on COVID-19 (ONCOVID, NCT NCT04341207 has been supported by the Fondation Gustave Roussy, the Dassault family, Malakoff Humanis, Agnès b., Izipizi, Ralph Lauren and Sanofi). LZ and GK were supported by RHU Torino Lumière (ANR-16-RHUS-0008), ONCOBIOME H2020 network, the Seerave Foundation, the Ligue contre le Cancer (équipe labelisée), Agence Nationale de la Recherche (ANR)—Projets blancs, ANR under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases, Association pour la recherche sur le cancer (ARC), Cancéropôle Ile-de-France, FRM, a donation by Elior, the European Research Council (ERC), Fondation Carrefour, High-end Foreign Expert Program in China (GDW20171100085 and GDW20181100051), Institut National du Cancer (INCa), Inserm (HTE), Institut Universitaire de France, LeDucq Foundation, the LabEx Immuno-Oncology, the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE), CARE network (directed by Prof. Mariette, Kremlin Bicêtre AP-HP), and the SIRIC Cancer Research and Personalized Medicine (CARPEM). GI was supported by Italian Ministry of Health (grants Ricerca CorrenteLinea 1, 1 'Infezioni Emergenti e Riemergenti', projects COVID-2020-12371675 and COVID‐2020‐12371817). MMy and GG were supported by ANR Flash COVID-19 program and ARS-CoV-2 Program of the Faculty of Medicine from Sorbonne University ICOViD programs (PI: GG)., ANR-16-RHUS-0008,LUMIERE,LUMIERE(2016), European Project: 825410,ONCOBIOME, École pratique des hautes études (EPHE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), COMBE, Isabelle, LUMIERE - - LUMIERE2016 - ANR-16-RHUS-0008 - RHUS - VALID, European Union’s Horizon 2020 research and innovation programme under grant agreement. - ONCOBIOME - 825410 - INCOMING, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Oncostat team [Villejuif], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Unité BioMaps (BIOMAPS), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université de Paris (UP), Department of Radiology, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut de Recherche Biomédicale des Armées (IRBA)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), and Université Paris Cité (UPC)

Subjects
Adult, DNA, Bacterial, Male, Time Factors, Adolescent, Article, Cohort Studies, Young Adult, Prognostic markers, Medical research, Enterobacteriaceae, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Lymphopenia, Nasopharynx, Neoplasms, Humans, Pandemics, Aged, Aged, 80 and over, SARS-CoV-2, COVID-19, Middle Aged, Prognosis, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Virus Shedding, Interferon Type I, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, RNA, Viral, Female, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Micrococcaceae
Abstract

International audience; Patients with cancer are at higher risk of severe coronavirus infectious disease 2019 (COVID-19), but the mechanisms underlying virus–host interactions during cancer therapies remain elusive. When comparing nasopharyngeal swabs from cancer and noncancer patients for RT-qPCR cycle thresholds measuring acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 1063 patients (58% with cancer), we found that malignant disease favors the magnitude and duration of viral RNA shedding concomitant with prolonged serum elevations of type 1 IFN that anticorrelated with anti-RBD IgG antibodies. Cancer patients with a prolonged SARS-CoV-2 RNA detection exhibited the typical immunopathology of severe COVID-19 at the early phase of infection including circulation of immature neutrophils, depletion of nonconventional monocytes, and a general lymphopenia that, however, was accompanied by a rise in plasmablasts, activated follicular T-helper cells, and non-naive Granzyme B + FasL + , Eomes high TCF-1 high , PD-1 + CD8 + Tc1 cells. Virus-induced lymphopenia worsened cancer-associated lymphocyte loss, and low lymphocyte counts correlated with chronic SARS-CoV-2 RNA shedding, COVID-19 severity, and a higher risk of cancer-related death in the first and second surge of the pandemic. Lymphocyte loss correlated with significant changes in metabolites from the polyamine and biliary salt pathways as well as increased blood DNA from Enterobacteriaceae and Micrococcaceae gut family members in long-term viral carriers. We surmise that cancer therapies may exacerbate the paradoxical association between lymphopenia and COVID-19-related immunopathology, and that the prevention of COVID-19-induced lymphocyte loss may reduce cancer-associated death.

Published
2021
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35. The negative impact of antibiotics on outcomes in cancer patients treated with immunotherapy: a new independent prognostic factor?

Author

L. Zitvogel, Arielle Elkrief, Lisa Derosa, Bertrand Routy, and Guido Kroemer

Subjects
0301 basic medicine, Oncology, Prognostic factor, medicine.medical_specialty, Standard of care, medicine.drug_class, medicine.medical_treatment, Antibiotics, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, Neoplasms, Internal medicine, medicine, Humans, Microbiome, Surrogate endpoint, business.industry, Cancer, Hematology, Immunotherapy, Prognosis, medicine.disease, Anti-Bacterial Agents, Gastrointestinal Microbiome, Survival Rate, 030104 developmental biology, 030220 oncology & carcinogenesis, Dysbiosis, business
Abstract

Immune-checkpoint inhibitors (ICI) now represent the standard of care for several cancer types. In pre-clinical models, absence of an intact gut microbiome negatively impacted ICI efficacy and these findings permitted to unravel the importance of the commensal microbiota in immuno-oncology. Recently, multiple clinical studies including more than 1800 patients in aggregate demonstrated the negative predictive impact of treatments with broad-spectrum antibiotics (ATB) on cancer patients receiving ICI. Altogether, these results have led to the hypothesis that ATB-induced dysbiosis might influence the clinical response through the modulation of the gut microbiome. Controversy still remains, as ATB treatment might simply constitute a surrogate marker of unfit or immunodeficient patients. In this review, we summarize recent publications addressing the impact of the gut microbiome on ICI efficacy, discuss currently available data on the effect of ATB administered in different time-frames respect to ICI initiation, and finally, evoke the therapeutic implications of these findings.

Published
2019
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36. Porto-sinusoidal vascular disease: proposal and description of a novel entity

Author

De Gottardi, A, Rautou, PE, Schouten, Joanne, Rubbia-Brandt, L, Leebeek, Frank, Trebicka, J, Darwish Murad, Sarwa, Vilgrain, V, Hernandez-Gea, V, Nery, F, Plessier, A, Berzigotti, A, Bioulac-Sage, P, Primignani, M, Seinela, D, Elkrief, L, Bedossa, P, Willa, D, Garcia-Pagan, JC, Jakob, B, Cazals-Hatem, D, Alonso, C, Erasmus MC other, Hematology, and Gastroenterology & Hepatology

Subjects
Pathology, medicine.medical_specialty, Cirrhosis, ddc:616.07, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Incomplete septal cirrhosis, Venules, 600 Technology, Hypertension, Portal, medicine, Humans, Vascular Diseases, 610 Medicine & health, ddc:617, Hepatology, medicine.diagnostic_test, Portal Vein, Vascular disease, business.industry, Gastroenterology, medicine.disease, Capillaries, Portal vein thrombosis, Portal System, 030220 oncology & carcinogenesis, Liver biopsy, Portal hypertension, 030211 gastroenterology & hepatology, business, Nodular regenerative hyperplasia
Abstract

Portal hypertension in the absence of portal vein thrombosis and without cirrhosis, but with mild or moderate alterations of liver histology (eg, obliterative venopathy, nodular regenerative hyperplasia, or incomplete septal cirrhosis) is being increasingly recognised. Owing to the heterogeneity of causes and histological findings, a substantial number of terms have been used to describe such idiopathic non-cirrhotic portal hypertension. Patients with the same clinical and histological features exist, but without portal hypertension at the time of diagnosis. Therefore, improved criteria are needed to define this form of liver disease. Here, we propose the term porto-sinusoidal vascular disease, since all lesions found involve the portal venules or sinusoids. The definition of this entity is based on the characteristic absence of cirrhosis with or without signs of portal hypertension or histological lesions. The presence of known causes of liver disease does not rule out porto-sinusoidal vascular disease, but specific causes of vascular liver disease are excluded from its definition. The diagnosis of porto-sinusoidal vascular disease is based on liver biopsy and might include signs specific for portal hypertension with normal or mildly elevated liver stiffness values and no complete portal vein thrombosis. We provide simple diagnostic criteria, because agreement on a uniform nomenclature is an essential requirement for future collaborative studies.

Published
2019
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37. Reasons for delay in timely administration of adjuvant chemotherapy for patients with stage III colon cancer: a multicentre cohort study from the McGill University Department of Oncology

Author

Arielle Elkrief, Sender Liberman, Adrian Langleben, Allaa Ali, Thierry Alcindor, Olga Aleynikova, Caroline Rousseau, Genevieve Redstone, Luca A. Petruccelli, Carol-Ann Vasilevsky, Doneal Thomas, Dawn Anderson, Petr Kavan, Gabriela Ghitulescu, Myriam Fernandez, and Richard Dalfen

Subjects
Oncology, medicine.medical_specialty, Medicine (General), Universities, Leadership and Management, Adjuvant chemotherapy, time-to-treatment, process mapping, Medical Oncology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, R5-920, Chart review, Internal medicine, medicine, Humans, 030212 general & internal medicine, General hospital, Original Research, Neoplasm Staging, Retrospective Studies, Surgical complication, Proportional hazards model, business.industry, 030503 health policy & services, Health Policy, Public Health, Environmental and Occupational Health, Cancer, medicine.disease, Stage III Colon Cancer, outpatients, interruptions, Chemotherapy, Adjuvant, Colonic Neoplasms, 0305 other medical science, business, clinical practice guidelines, Cohort study
Abstract

PurposeAdjuvant chemotherapy within 56 or 84 days following curative resection is globally accepted as the standard of care for stage III colon cancer as it has been associated with improved overall survival. Initiation of adjuvant chemotherapy within this time frame is therefore recommended by clinical practice guidelines, including the European Society for Medical Oncology. The objective of this study was to evaluate adherence to these clinical practice guidelines for patients with stage III colon cancer across the Rossy Cancer Network (RCN); a partnership of McGill University’s Faculty of Medicine, McGill University Health Centre, Jewish General Hospital and St Mary’s Hospital Center.Patients and methods187 patients who had been diagnosed with stage III colon cancer and received adjuvant chemotherapy within the RCN partner hospitals from 2012 to 2015 were included. Patient and treatment information was retrospectively determined by chart review. Χ2 and Wilcoxon rank-sum tests were used to measure associations and a multivariate Cox regression model was used to determine risk factors contributing to delays in administration of adjuvant chemotherapy.ResultsThe median turnaround time between surgery and adjuvant chemotherapy was 69 days. Importantly, only 27% of patients met the 56-day target, and 71% met the 84-day target. Increasing age, having more than one surgical complication and being diagnosed between 2013–2014 and 2014–2015 reduced the likelihood that patients met these targets. Furthermore, delays were observed at most intervals from surgery to first adjuvant chemotherapy treatment.ConclusionOur study found that within these academic hospital settings, 27% of patients met the 56-day target, and 71% met the 84-day target. Delays were associated with hospital, surgeon and patient-related factors. Initiatives in quality improvement are needed in order to improve adherence to recommended treatment guidelines for prompt administration of adjuvant chemotherapy for stage III colon cancer.

Published
2021

38. Association of Clinical Factors and Recent Anti-Cancer Therapy with COVID-19 Severity among Patients with Cancer: A Report from the COVID-19 and Cancer Consortium

Author

Deepak Ravindranathan, T. S. Bekaii-Saab, Minh-Phuong Huynh-Le, Stephanie Berg, David Gill, C. Hennessy, Shuchi Gulati, Zhuoer Xie, Keith Stockerl-Goldstein, Ang Li, Clarke A. Low, D. Y. Reuben, Emily Hsu, Sharad Goyal, Petros Grivas, Chih-Yuan Hsu, D. J. Hausrath, Jessica Hawley, Harry Menon, Huili Zhu, A. Jayaraj, Barry Dixon, Rachel P. Rosovsky, Benjamin French, L. Tachiki, A. J. Piper-Vallillo, Dimitrios Farmakiotis, Daniel Kwon, Susan Halabi, Thorvardur R. Halfdanarson, Gary H. Lyman, Astha Thakkar, Arturo Loaiza-Bonilla, A. Fazio, Sumit A. Shah, Mehmet Asim Bilen, Michael A. Thompson, X. Li, Suki Subbiah, Matthias Weiss, Catherine Curran, E. Tadesse, Christopher McNair, Matthew Puc, Prakash Peddi, Corrie A. Painter, Ali Raza Khaki, Donna R. Rivera, Maryam B. Lustberg, Eric H. Bernicker, Vadim S. Koshkin, A. Nizam, M. Streckfuss, Alice Zhou, Aakash Desai, Sunny R K Singh, John M. Nakayama, Leslie A. Fecher, Samuel M. Rubinstein, Gd L. Lopes, Philip E. Lammers, Yu Shyr, Jaymin M. Patel, J. Crowell, Sanjay Mishra, Anup Kasi, Donald C. Vinh, Leyre Zubiri, Jeremy L. Warner, Nathan A. Pennell, V. Mico, Rana R. McKay, Amit Verma, M. E. Reeves, Daniel W. Bowles, Cathleen Park, Jared D. Acoba, David D. Chism, Gayathri Nagaraj, Matthew D. Galsky, Arielle Elkrief, M. Smits, Kripa Patel, N. L. Nock, Chinmay Jani, Clara Hwang, Mansi R. Shah, Angelo Cabal, Eric B. Durbin, Brian I. Rini, Peter Paul Yu, Tian Zhang, Dimpy P. Shah, M. Salazar, Shilpa Gupta, Lori J. Rosenstein, Christopher R. Friese, Gary K. Schwartz, Andrew Schmidt, Daniel Blake Flora, Justin Shaya, P. Bindal, D. Mundt, Julie Fu, Matthew D Tucker, Trisha Wise-Draper, Toni K. Choueiri, Deborah B. Doroshow, Rohit Bishnoi, E. Wulff-Burchfield, Balazs Halmos, Chintan Shah, Babar Bashir, Solange Peters, Nathaniel Bouganim, Paolo Caimi, Ruben A. Mesa, Maheen Z. Abidi, Daniel G. Stover, Nicole M. Kuderer, Michael Glover, Jia Wu, Punita Grover, Shirish M. Gadgeel, E. S. Nakasone, Douglas B. Johnson, Hina Khan, and Ziad Bakouny

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, medicine.medical_treatment, Laboratory measurements, Disease, neoplasm, law.invention, Cancer, 03 medical and health sciences, COVID-19 Testing, 0302 clinical medicine, law, Neoplasms, Internal medicine, medicine, Humans, Outcomes, Pandemics, Etoposide, Aged, Chemotherapy, SARS-CoV-2, business.industry, COVID-19, Hematology, medicine.disease, Intensive care unit, Clinical trial, 030104 developmental biology, Oncology, Anti-cancer therapy, 030220 oncology & carcinogenesis, Cohort, SARS-CoV2, Absolute neutrophil count, Female, Original Article, business, medicine.drug
Abstract

BACKGROUND: Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies. PATIENTS AND METHODS: Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients). RESULTS: A total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality. CONCLUSIONS: Clinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies. CLINICAL TRIAL IDENTIFIER: NCT04354701.

Published
2021

39. Clinical impact of COVID-19 on patients with cancer treated with immune checkpoint inhibition

Author

Paolo A. Ascierto, Serigne Lo, Carlo Tondini, Richard D. Carvajal, Karijn P M Suijkerbuijk, Kerry L. Reynolds, Jessica S.W. Borgers, Jeremy Lupu, Christian U. Blank, Séverine Roy, Christian Posch, Michael Erdmann, Mario Mandalà, Ines Pires da Silva, Matteo S. Carlino, Maria Grazia Vitale, Tim Cooksley, F. Stephen Hodi, Megan H. Trager, Carola Berking, Leyre Zubiri, Laura Pala, Sharon Nahm, Dirk Schadendorf, Paola Queirolo, Alon Vaisman, Neha Papneja, Paul Lorigan, Joanna Mangana, Aljosja Rogiers, Alexander M. Menzies, Thiago Pimentel Muniz, Caroline Robert, Ryan J. Sullivan, John B. A. G. Haanen, Marcus O. Butler, Reinhard Dummer, Peter Bowling, Wilson H. Miller, Osama E. Rahma, Arielle Elkrief, Samuel D. Saibil, Chiara Tentori, Joseph M. Grimes, Michael Manos, Lisa Zimmer, Georgina V. Long, April A.N. Rose, and Axel Hauschild

Subjects
Male, 0301 basic medicine, Cancer Research, viruses, Medizin, law.invention, Cohort Studies, 0302 clinical medicine, law, Neoplasms, Immunology and Allergy, Immune Checkpoint Inhibitors, RC254-282, Cause of death, Aged, 80 and over, Clinical/Translational Cancer Immunotherapy, education.field_of_study, Manchester Cancer Research Centre, Mortality rate, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, virus diseases, Middle Aged, Intensive care unit, ddc, Oncology, 030220 oncology & carcinogenesis, Molecular Medicine, Female, immunotherapy, Adult, medicine.medical_specialty, Immunology, Population, macromolecular substances, 03 medical and health sciences, Internal medicine, Intensive care, medicine, Humans, ddc:610, Ticilimumab, Risk factor, education, Aged, Retrospective Studies, Pharmacology, SARS-CoV-2, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, COVID-19, Cancer, biochemical phenomena, metabolism, and nutrition, medicine.disease, Coronavirus, 030104 developmental biology, nervous system, business
Abstract

BackgroundPatients with cancer who are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more likely to develop severe illness and die compared with those without cancer. The impact of immune checkpoint inhibition (ICI) on the severity of COVID-19 illness is unknown. The aim of this study was to investigate whether ICI confers an additional risk for severe COVID-19 in patients with cancer.MethodsWe analyzed data from 110 patients with laboratory-confirmed SARS-CoV-2 while on treatment with ICI without chemotherapy in 19 hospitals in North America, Europe and Australia. The primary objective was to describe the clinical course and to identify factors associated with hospital and intensive care (ICU) admission and mortality.FindingsThirty-five (32%) patients were admitted to hospital and 18 (16%) died. All patients who died had advanced cancer, and only four were admitted to ICU. COVID-19 was the primary cause of death in 8 (7%) patients. Factors independently associated with an increased risk for hospital admission were ECOG ≥2 (OR 39.25, 95% CI 4.17 to 369.2, p=0.0013), treatment with combination ICI (OR 5.68, 95% CI 1.58 to 20.36, p=0.0273) and presence of COVID-19 symptoms (OR 5.30, 95% CI 1.57 to 17.89, p=0.0073). Seventy-six (73%) patients interrupted ICI due to SARS-CoV-2 infection, 43 (57%) of whom had resumed at data cut-off.InterpretationCOVID-19–related mortality in the ICI-treated population does not appear to be higher than previously published mortality rates for patients with cancer. Inpatient mortality of patients with cancer treated with ICI was high in comparison with previously reported rates for hospitalized patients with cancer and was due to COVID-19 in almost half of the cases. We identified factors associated with adverse outcomes in ICI-treated patients with COVID-19.

Published
2021
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40. Cannabis Use Is Inversely Associated with Overweight and Obesity in Hepatitis B Virus-Infected Patients (ANRS CO22 Hepather Cohort)

Author

Barré, Tangui, Pol, Stanislas, Ramier, Clémence, Di Beo, Vincent, Carrat, Fabrice, Bureau, Morgane, Bourlière, Marc, Dorival, Céline, Serfaty, Lawrence, Asselah, Tarik, Boursier, Jérôme, Marcellin, Fabienne, Carrieri, Patrizia, Fontaine, Hélène, Protopopescu, Camelia, Alric, Laurent, Bonnet, Delphine, Payssan-Sicart, Virginie, Pomes, Chloe, Zoulim, Fabien, Maynard, Marianne, Bai, Roxane, Hucault, Lucie, Bailly, François, Raffi, François, Billaud, Eric, Boutoille, David, Lefebvre, Maeva, André-Garnier, Elisabeth, Cales, Paul, Hubert, Isabelle, Lannes, Adrien, Lunel, Françoise, Boyer, Nathalie, Giuily, Nathalie, Castelnau, Corinne, Scoazec, Giovanna, Rousseaud, Emilie, Vallet-Pichard, Anaïs, Sogni, Philippe, Ledinghen, Victor De, Foucher, Juliette, Hiriart, Jean-Baptiste, M'Bouyou, Jancell, Irlès-Depé, Marie, Si Ahmed, Si Nafa, Oules, Valérie, Tran, Albert, Anty, Rodolphe, Gelsi, Eve, Truchi, Régine, Thabut, Dominique, Hammeche, Saloua, Moussali, Joseph, Causse, Xavier, Dieuleveult, Barbara De, Ouarani, Brahim, Labarrière, Damien, Ganne, Nathalie, Grando-Lemaire, Véronique, Nahon, Pierre, Brulé, Séverine, Ulker, Betul, Guyader, Dominique, Jezequel, Caroline, Brener, Audrey, Laligant, Anne, Rabot, Aline, Renard, Isabelle, Habersetzer, François, Baumert, Thomas, Doffoel, Michel, Mutter, Catherine, Simo-Noumbissie, Pauline, Razi, Esma, Bronowicki, Jean-Pierre, Barraud, Hélène, Bensenane, Mouni, Nani, Abdelbasset, Hassani-Nani, Sarah, Bernard, Marie-Albertine, Pageaux, Georges-Philippe, Larrey, Dominique, Meszaros, Magda, Metivier, Sophie, Bureau, Christophe, Morales, Thibault, Peron, Jean Marie, Robic, Marie Angèle, Decaens, Thomas, Faure, Marine, Froissart, Bruno, Hilleret, Marie-Noelle, Zarski, Jean-Pierre, Riachi, Ghassan, Goria, Odile, Paris, Fatima, Montialoux, Hélène, Leroy, Vincent, Amaddeo, Giuliana, Varaut, Anne, Simoes, Mélanie, Amzal, Rachida, Chazouillières, Olivier, Andreani, Tony, Angoulevant, Bénédicte, Chevance, Azeline, Samuel, Didier, Antonini, Teresa, Coilly, Audrey, Duclos Vallée, Jean-Charles, Tateo, Mariagrazia, Abergel, Armand, Reymond, Maud, Brigitte, Chanteranne, Benjamin, Buchard, Muti, Léon, Geist, Claire, Conroy, Guillaume, Riffault, Raphaëlle, Rosa, Isabelle, Barrault, Camille, Costes, Laurent, Hagège, Hervé, Loustaud-Ratti, Véronique, Carrier, Paul, Debette-Gratien, Maryline, Mathurin, Philippe, Lassailly, Guillaume, Lemaitre, Elise, Canva, Valérie, Dharancy, Sébastien, Louvet, Alexandre, Minello, Anne, Latournerie, Marianne, Bardou, Marc, Mouillot, Thomas, d'Alteroche, Louis, Barbereau, Didier, Nicolas, Charlotte, Elkrief, Laure, Jaillais, Anaïs, Gournay, Jérôme, Chevalier, Caroline, Archambeaud, Isabelle, Habes, Sarah, Portal, Isabelle, Gelu-Simeon, Moana, Saillard, Eric, Lafrance, Marie-Josée, Catherine, Lucie, Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), ESIM - Déterminants Sociaux de la Santé et du Recours aux Soins (DS3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépato-gastro-entérologie, Assistance Publique - Hôpitaux de Marseille (APHM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital de Hautepierre [Strasbourg], Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), and BOURGEAIS, Véronique

Subjects
Hepatitis B virus, medicine.medical_specialty, Cirrhosis, [SDV]Life Sciences [q-bio], Aucun, Overweight, medicine.disease_cause, Virus, 03 medical and health sciences, Hepatitis B, Chronic, 0302 clinical medicine, Internal medicine, medicine, Humans, Pharmacology (medical), Obesity, ComputingMilieux_MISCELLANEOUS, Cannabis, 030304 developmental biology, Pharmacology, 0303 health sciences, biology, Cannabinoids, business.industry, Liver Neoplasms, Hepatitis B, biology.organism_classification, medicine.disease, digestive system diseases, 3. Good health, [SDV] Life Sciences [q-bio], Complementary and alternative medicine, Hepatocellular carcinoma, Cohort, cannabis, obesity, overweight, socioeconomic status, 030211 gastroenterology & hepatology, medicine.symptom, business
Abstract

International audience; Background: Chronic hepatitis B virus (HBV) infection may evolve into cirrhosis and hepatocellular carcinoma, and this progression may be accelerated by specific risk factors, including overweight and obesity. Although evidence for a protective effect of cannabis use on elevated body weight has been found for other populations, no data are available for HBV-infected patients.Aims: We aimed to identify risk factors (including cannabis use) for overweight and obesity in patients with HBV chronic infection.Methods: Using baseline data from the French ANRS CO22 Hepather cohort, we performed two separate analyses, one using “central obesity” (based on waist circumference) and the other “overweight” and “obesity” (based on body mass index) as outcomes. Logistic and multinomial regressions were used to model central obesity and overweight/obesity, respectively.Results: Among the 3706 patients in the study population, 50.8% had central obesity, 34.7% overweight, and 14.4% obesity. After multivariable adjustment, current cannabis use was associated with a 59% lower risk of central obesity compared with no lifetime use (adjusted odds ratio [95% CI]: 0.41 [0.24 to 0.70]). It was also associated with a 54% and 84% lower risk of overweight (adjusted relative risk ratio [95% CI]: 0.46 [0.27 to 0.76]) and obesity (0.16 [0.04 to 0.67]), respectively.Conclusions: Cannabis use was associated with lower risks of overweight and obesity in patients with HBV chronic infection. Future studies should test whether these potential benefits of cannabis and cannabinoid use translate into reduced liver disease progression in this high-risk population.

Published
2021
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41. Epidemiology and Effects of Bacterial Infections in Patients With Cirrhosis Worldwide

Author

Florence Wong, Luis Colombato, Giacomo Zaccherini, Dong Joon Kim, Rita de Cassia Ribeiro Barea, Adrià Juanola, Aleksander Krag, Julio Vorobioff, Javier Romaní Fernández, Jae Seok Hwang, Richard Moreau, Salvatore Piano, Gustavo Romero, Juan Pablo Roblero, Adrián Gadano, Gustavo Navarro, Rakhi Maiwall, Cosmas A. Rinaldi Lesmana, E.L. Yoon, Virendra Singh, M. Marino, Shiv Kumar Sarin, Carlos Brodersen, Carlo Alessandria, François Durand, Victor Vargas, Carmine Gambino, Ji Won Park, Pramod Kumar, Sophie Restellini, M. V. Maevskaya, Nikolaos Pyrsopoulos, Eduardo Fassio, Marcos Girala, Macarena Simón-Talero, Tony Bruns, Paolo Caraceni, Vikas Gautam, Laure Elkrief, Tae Hee Lee, Manuela Merli, Hyoung Su Kim, Tae Hun Kim, Preetam Nath, Ki Tae Suk, Elza Cotrim Soares, Xavier Verhelst, Tiago Sevá-Pereira, Paolo Angeli, C. Toledo, Sebastián Marciano, Barbara Lattanzi, Robert A. de Man, Annette Dam Fialla, Gisela Pinero, Sung Eun Kim, Nicolas M. Intagliata, Hans Van Vlierberghe, Pere Ginès, Kalyan Ram Bhamidimarri, Liane Rabinowich, Do Seon Song, Shivaram Prasad Singh, Michele Bartoletti, Alexander L. Gerbes, Marco Sacco, Laurentius A. Lesmana, Sang Gyune Kim, Jeong Han Kim, Sun Young Yim, Thomas D. Boyer, Piano, Salvatore, Singh, Virendra, Caraceni, Paolo, Maiwall, Rakhi, Alessandria, Carlo, Fernandez, Javier, Soares, Elza Cotrim, Kim, Dong Joon, Kim, Sung Eun, Marino, Monica, Vorobioff, Julio, de Cassia Ribeiro Barea, Rita, Merli, Manuela, Elkrief, Laure, Vargas, Victor, Krag, Aleksander, Singh, Shivaram Prasad, Lesmana, Laurentius Adrianto, Toledo, Claudio, Marciano, Sebastian, Verhelst, Xavier, Wong, Florence, Intagliata, Nicola, Rabinowich, Liane, Colombato, Lui, Kim, Sang Gyune, Gerbes, Alexander, Durand, Francoi, Roblero, Juan Pablo, Bhamidimarri, Kalyan Ram, Boyer, Thomas D, Maevskaya, Marina, Fassio, Eduardo, Kim, Hyoung Su, Hwang, Jae Seok, Gines, Pere, Gadano, Adrian, Sarin, Shiv Kumar, Angeli, Paolo, and Gastroenterology & Hepatology

Subjects
Liver Cirrhosis, Male, 0301 basic medicine, Time Factors, Cirrhosis, Cross-sectional study, medicine.medical_treatment, Resistance, Antibiotics, Drug Resistance, GLOBAL, resistance, sepsis, stewardship, Liver Cirrhosis/epidemiology, Liver transplantation, Global Health, 0302 clinical medicine, Risk Factors, Drug Resistance, Multiple, Bacterial, Epidemiology, Prevalence, Hospital Mortality, Prospective Studies, Incidence (epidemiology), Global, Sepsis, Stewardship, Adult, Aged, Anti-Bacterial Agents, Bacterial Infections, Cross-Sectional Studies, Female, Humans, Liver Transplantation, Middle Aged, Mycoses, Prognosis, Bacterial, Gastroenterology, sepsi, 030211 gastroenterology & hepatology, Multiple, medicine.medical_specialty, medicine.drug_class, 03 medical and health sciences, Spontaneous bacterial peritonitis, Internal medicine, medicine, Hepatology, business.industry, medicine.disease, Anti-Bacterial Agents/therapeutic use, 030104 developmental biology, Mycoses/epidemiology, business, Bacterial Infections/epidemiology
Abstract

Background & Aims: Bacterial infections are common and life-threatening in patients with cirrhosis. Little is known about the epidemiology of bacterial infections in different regions. We performed a multicenter prospective intercontinental study to assess the prevalence and outcomes of bacterial and fungal infections in patients with cirrhosis. Methods: We collected data from 1302 hospitalized patients with cirrhosis and bacterial or fungal infections at 46 centers (15 in Asia, 15 in Europe, 11 in South America, and 5 in North America) from October 2015 through September 2016. We obtained demographic, clinical, microbiology, and treatment data at time of diagnosis of infection and during hospitalization. Patients were followed until death, liver transplantation, or discharge. Results: The global prevalence of multidrug-resistant (MDR) bacteria was 34% (95% confidence interval 31%–37%). The prevalence of MDR bacteria differed significantly among geographic areas, with the greatest prevalence in Asia. Independent risk factors for infection with MDR bacteria were infection in Asia (particularly in India), use of antibiotics in the 3 months before hospitalization, prior health care exposure, and site of infection. Infections caused by MDR bacteria were associated with a lower rate of resolution of infection, a higher incidence of shock and new organ failures, and higher in-hospital mortality than those caused by non-MDR bacteria. Administration of adequate empirical antibiotic treatment was independently associated with improved in-hospital and 28-day survival. Conclusions: In a worldwide study of hospitalized patients, we found a high prevalence of infection with MDR bacteria in patients with cirrhosis. Differences in the prevalence of MDR bacterial infections in different global regions indicate the need for different empirical antibiotic strategies in different continents and countries. While we await new antibiotics, effort should be made to decrease the spread of MDR bacteria in patients with cirrhosis.

Published
2019
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42. A Systematic Framework to Rapidly Obtain Data on Patients with Cancer and COVID-19: CCC19 Governance, Protocol, and Quality Assurance

Author

Sarah Wall, Babar Bashir, Toni K. Choueiri, Salvatore Del Prete, Grace Shaw, Solange Peters, Catherine Curran, Navid Hafez, Nathaniel Bouganim, Sarah Nagle, Julie Tsu-Yu Wu, Jared D. Acoba, Vaibhav Kumar, Gabrielle Bouchard, Lisa Weissmann, Hagen F. Kennecke, Tian Zhang, Manmeet Ahluwalia, Sanjay Goel, Samuel M. Rubinstein, Daruka Mahadevan, Elizabeth A. Griffiths, Destry J. Elms, Michael J. Gurley, Arturo Loaiza-Bonilla, Suki Subbiah, Gilberto Lopes, Lisa Tachiki, David M. Aboulafia, Kent Hoskins, Daniel W. Bowles, Sandeep H. Mashru, Matthew Puc, Prakash Peddi, Nathan A. Pennell, Stephen V. Liu, Justin F. Gainor, Ali Raza Khaki, Rebecca L. Zon, Matthew D Tucker, Amanda Nizam, Bryan A. Faller, Deborah B. Doroshow, Nitin Ohri, Brian I. Rini, Abdul-Hai Mansoor, Sachin R. Jhawar, George D. Demetri, Catherine Stratton, Eliezer M. Van Allen, Praveen Vikas, Alvaro G. Menendez, Amelie G. Ramirez, Jonathan M. Loree, Divaya Bhutani, Clarke A. Low, Anju Nohria, Melissa K. Accordino, Rohit Bishnoi, Pamela C Egan, Rachel P. Rosovsky, Julie C. Fu, Fiona Busser, Orestis A. Panagiotou, Aditya Bardia, Peter Paul Yu, Susan Van Loon, Genevieve M. Boland, Douglas B. Johnson, Anup Kasi, Barbara Logan, Alice Zhou, Matthew D. Galsky, Arielle Elkrief, Mary Salazar, Rosemary Zacks, Carmen C. Solorzano, Andrew Schmidt, Paolo Caimi, Zhuoer Xie, Michael T. Schweizer, Briana Barrow McCollough, Jessica K. Altman, Christopher McNair, Cassandra Hennessy, Angelo Cabal, Qamar Ul Zaman, Alex Cheng, Keith Stockerl-Goldstein, John C. Leighton, Joshua D. Palmer, Scott J. Dawsey, Deepak Ravindranathan, Jonathan Riess, Miriam Santos Dutra, Daniel Blake Flora, Aakash Desai, Rana R. McKay, Ruben A. Mesa, Maheen Z. Abidi, Cathleen Park, Jill S. Barnholtz-Sloan, Erin Cook, Trisha Wise-Draper, Shannon K. McWeeney, Donald C. Vinh, Clara Hwang, Stephanie Berg, Leyre Zubiri, Daniel G. Stover, Michelle Marcum, Sarah Mushtaq, Wilhelmina D. Cabalona, Eyob Tadesse, Kanishka G. Patel, Ryan Monahan, Ziad Bakouny, Pankil Shah, David Gill, Terence Duane Rhodes, Marc A. Rovito, Chih-Yuan Hsu, Elizabeth T. Loggers, Shilpa Gupta, Susie Owenby, Benjamin A. Gartrell, David D. Chism, Neeta K. Venepalli, Punita Grover, Adam J. Olszewski, Sonya A. Reid, Firas Wehbe, Omar Butt, Emily Hsu, Poorva Bindal, Paul L. Weinstein, Jessica Hawley, Tanya M. Wildes, Subha Madhavan, Claire Hoppenot, Margaret E. Gatti-Mays, Huili Zhu, Michael Glover, Rawad Elias, Elizabeth S. Nakasone, Heather H. Nelson, Gerald Batist, Gary H. Lyman, John F. Deeken, Michael H. Bar, Pamela Bohachek, Benjamin French, Mark A. Lewis, Daniel J. Hausrath, Mary F. Mulcahy, X. Li, David A. Slosky, Michael J. Wagner, Nicole Williams, Hina Khan, Grace Glace, Jessica M. Clement, Pier Vitale Nuzzo, Petros Grivas, Brett A. Schroeder, Tanios Bekaii-Saab, John M. Nakayama, Vasil Mico, Young Soo Rho, Chaim Miller, Amit Verma, Kaitlin M. Kelleher, Elwyn C. Cabebe, William A. Wood, Elizabeth J. Davis, Anne H. Angevine, Cristiano Ferrario, Shaveta Vinayak, Jerome J. Graber, Monika Joshi, Danielle A. Shafer, Mary M. Pasquinelli, Mark Bonnen, Shirish M. Gadgeel, Balazs Halmos, Lucy L. Wang, Dawn L. Hershman, Sana Z. Mahmood, Dimpy P. Shah, Maryam B. Lustberg, Albert C. Yeh, Eric H. Bernicker, Mitrianna Streckfuss, Leslie A. Fecher, Clement Pillainayagam, Karen Stauffer, Gayathri Nagaraj, Dimitrios Farmakiotis, Elizabeth Marie Wulff-Burchfield, Chintan Shah, Sibel Blau, Ryan H. Nguyen, Lane R. Rosen, Robert L. Rice, Mark E. Dailey, Melanie J. Clark, Goetz Kloecker, Alicia K. Morgans, Cameron Rink, Umit Topaloglu, Mark A. Fiala, Saif I. Alimohamed, Gary K. Schwartz, Jessica Yasmine Islam, Bertrand Routy, James L. Chen, Oscar K. Serrano, Chinmay Jani, Shuchi Gulati, K.M. Lo, Alokkumar Jha, Anthony P. Gulati, Lori J. Rosenstein, Roy S. Herbst, Matthias Weiss, Justin Shaya, Philip E. Lammers, Irene S. Yu, Syed A. Ahmad, Salma K. Jabbour, Erin A. Gillaspie, Irma Hoyo-Ulloa, Jordan Kharofa, Jean M. Connors, Daniel Mundt, Christopher R. Friese, Ryan C. Lynch, Mansi R. Shah, Howard Zaren, M. Wasif Saif, Gerald Gantt, Lawrence E. Feldman, Jian Campian, Daniel Y. Reuben, Sanjay G. Revankar, Merry Jennifer Markham, Melissa Smits, Patricia LoRusso, Thorvardur R. Halfdanarson, Christine Pilar, Eric B. Durbin, Blanche Mavromatis, Yu Shyr, Jaymin M. Patel, Candice Schwartz, Ang Li, Antonio Giordano, Amit Kulkarni, Joerg Rathmann, Harry Menon, Amro Elshoury, Mahir Khan, Theresa M. Carducci, Susan Halabi, Sumit A. Shah, Jeremy L. Warner, Mehmet Asim Bilen, Kerry L. Reynolds, Michael A. Thompson, Ahmad Daher, Lidia Schapira, Eneida R. Nemecek, Sanjay Mishra, Jamie Stratton, Karen Vega-Luna, Tyler Masters, Corrie A. Painter, Archana Ajmera, Jorge A. Garcia, Wenxin Xu, Christopher Lemmon, and Jeanna Knoble

Subjects
0301 basic medicine, Cancer Research, Quality management, MEDLINE, 03 medical and health sciences, COVID-19 Testing, 0302 clinical medicine, Neoplasms, Pandemic, medicine, Electronic Health Records, Humans, Protocol (science), SARS-CoV-2, business.industry, Corporate governance, COVID-19, Cancer, Cell Biology, medicine.disease, Quality Improvement, Data Accuracy, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Scale (social sciences), Commentary, Business, Medical emergency, Quality assurance
Abstract

When the COVID-19 pandemic began, formal frameworks to collect data about affected patients were lacking. The COVID-19 and Cancer Consortium (CCC19) was formed to collect granular data on patients with cancer and COVID-19 at scale and as rapidly as possible. CCC19 has grown from five initial institutions to 125 institutions with >400 collaborators. More than 5,000 cases with complete baseline data have been accrued. Future directions include increased electronic health record integration for direct data ingestion, expansion to additional domestic and international sites, more intentional patient involvement, and granular analyses of still-unanswered questions related to cancer subtypes and treatments.

Published
2020
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43. Evolution and phenotypic characterization of whole HBV genome in compliant patients experiencing unexplained entecavir treatment failure

Author

Denys Brand, Laure Elkrief, Morgan Maugey, Pascal Potier, Alain Moreau, Catherine Gaudy-Graffin, Louis d’Alteroche, Clément Lier, Sandrine Lefeuvre, Emmanuelle Roch, Benjamin Combe, Lynda Handala, and Julien Marlet

Subjects
0301 basic medicine, Adult, Male, Hepatitis B virus, Guanine, 030106 microbiology, Drug resistance, Genome, Viral, Genome, Antiviral Agents, Deep sequencing, 03 medical and health sciences, symbols.namesake, Virology, Drug Resistance, Viral, medicine, Humans, Treatment Failure, Selection, Genetic, Aged, Pharmacology, Sanger sequencing, business.industry, Entecavir, Hepatitis B, medicine.disease, Resistance mutation, Phenotype, 3. Good health, 030104 developmental biology, Mutation, symbols, Patient Compliance, Female, business, medicine.drug
Abstract

Entecavir treatment failure can be observed in compliant patients despite an absence of detectable resistance mutations by Pol/RT Sanger sequencing. We hypothesized that these unexplained treatment failures could rely on other mechanisms of viral resistance, especially on mutations selected outside of the Pol/RT domain. Partial virological response to entecavir was observed in three patients treated with immunosuppressive drugs, without selection of Pol/RT resistance mutations. Mutations selected in the whole HBV genome during entecavir treatment and potentially associated with resistance were searched for using deep sequencing and characterized using a phenotypic resistance assay. Mutations Q206K (pre-core/core), Q120K (pre-S1/pre-S2, T-cell epitope) and A300E (spacer domain) were selected during entecavir treatment in patient #1 but were not associated with an increased level of resistance to entecavir or an increase in HBV replication capacity. Core promoter mutations T1753G, A1762T and G1764A were present as major mutations before and after treatment in patient #1. HBs Ag immune escape mutations were present as major mutations before and after treatment in patients #2 (sK122R, sT126I, sP127S and sG145R) and #3 (sM133I). We demonstrated that PVR to entecavir does not require selection of any resistance mutation in the whole HBV genome. Our results demonstrate that major mutations can be selected outside of the Pol/RT domain before or during entecavir treatment. These mutations could contribute to entecavir treatment failure by other mechanisms than an increased level of resistance.

Published
2020

44. Changes in Lung Cancer Treatment as a Result of the Coronavirus Disease 2019 Pandemic

Author

Arielle Elkrief, Nathaniel Bouganim, and Suzanne Kazandjian

Subjects
Adult, Male, Cancer Research, 2019-20 coronavirus outbreak, Lung Neoplasms, Time Factors, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Medical Oncology, Carcinoma, Non-Small-Cell Lung, Pandemic, Research Letter, medicine, Humans, Prospective Studies, skin and connective tissue diseases, Lung cancer, Aged, Aged, 80 and over, business.industry, COVID-19, General Medicine, Middle Aged, Prognosis, medicine.disease, Small Cell Lung Carcinoma, Virology, Oncology, Female, sense organs, business, Delivery of Health Care
Abstract

This prospective observational study assesses changes in treatment plans for patients with lung cancer and qualifies the types of changes observed as a direct result of the coronavirus disease 2019 pandemic.

Published
2020
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45. Physiologic colonic uptake of

Author

Lena, Cvetkovic, Claudine, Régis, Corentin, Richard, Lisa, Derosa, Antoine, Leblond, Julie, Malo, Meriem, Messaoudene, Antoine, Desilets, Wiam, Belkaid, Arielle, Elkrief, Bertrand, Routy, and Daniel, Juneau

Subjects
Lung Neoplasms, Colon, Fluorodeoxyglucose F18, Carcinoma, Non-Small-Cell Lung, Positron Emission Tomography Computed Tomography, Humans, Prognosis, Immune Checkpoint Inhibitors, Gastrointestinal Microbiome
Abstract

Immune checkpoint inhibitors (ICI) represent the backbone treatment for advanced non-small cell lung cancer (NSCLC). Emerging data suggest that increased gut microbiome diversity is associated with favorable response to ICI and that antibiotic-induced dysbiosis is associated with deleterious outcomes.Seventy-one patients with advanced NSCLC who underwent a PET/CT prior to ICI were identified. Blinded colonic contouring was performed for each colon segment and patients were stratified according to the median of the average colon SUVThe high colon SUVLower colon physiologic

Published
2020

46. High mortality among hospital-acquired COVID-19 infection in patients with cancer: A multicentre observational cohort study

Author

Kevin Jao, Wilson H. Miller, Neha Papneja, Nathalie Daaboul, Catherine Groleau, Stephane Doucet, Antoine Desilets, Jonathan M. Loree, Caroline Letendre, Thai Hoa Tran, Eric Bhang, Corentin Richard, Layla Shbat, Erin Cook, Bertrand Routy, Julie Malo, Nathaniel Bouganim, Donald C. Vinh, Lena Cvetkovic, Arielle Elkrief, Wiam Belkaid, Yahia A. Lakehal, and Gerald Batist

Subjects
0301 basic medicine, Male, Cancer Research, Multivariate analysis, Cohort Studies, 0302 clinical medicine, Risk Factors, Neoplasms, Medicine, hospital-acquired, Young adult, Child, Aged, 80 and over, education.field_of_study, Incidence (epidemiology), Hazard ratio, Middle Aged, Prognosis, Hospitals, Survival Rate, Oncology, 030220 oncology & carcinogenesis, Child, Preschool, Female, Coronavirus Infections, Cohort study, Adult, medicine.medical_specialty, Canada, Adolescent, Population, Pneumonia, Viral, Article, 03 medical and health sciences, Betacoronavirus, Young Adult, Internal medicine, cancer, Humans, Mortality, education, Survival rate, Pandemics, Aged, business.industry, SARS-CoV-2, Cancer, COVID-19, nosocomial, medicine.disease, 030104 developmental biology, business
Abstract

Introduction Studies suggest that patients with cancer are more likely to experience severe outcomes from COVID-19. Therefore, cancer centers have undertaken efforts to care for patients with cancer in COVID-free units. Nevertheless, the frequency and relevance of nosocomial transmission of COVID-19 in patients with cancer remain unknown. The goal of this study was to determine the incidence and impact of hospital-acquired COVID-19 in this population and identify predictive factors for COVID-19 severity in patients with cancer. Methods Patients with cancer and a laboratory-confirmed diagnosis of COVID-19 were prospectively identified using provincial registries and hospital databases between March 3rd and May 23rd, 2020 in the provinces of Quebec and British Columbia in Canada. Patient’s baseline characteristics including age, sex, comorbidities, cancer type, and type of anti-cancer treatment were collected. The exposure of interest was incidence of hospital-acquired infection defined by diagnosis of SARS-CoV-2 ≥ 5 days after hospital admission for COVID-unrelated cause. Co-primary outcomes were death or composite outcomes of severe illness from COVID-19 such as hospitalization, supplemental oxygen, intensive-care unit (ICU) admission and/or mechanical ventilation. Results A total of 252 patients (N=249 adult, and N=3 pediatric) with COVID-19 and cancer were identified, and the majority were residents of Quebec (N=233). One-hundred-and-six patients (42.1%) received active anti-cancer treatment in the last 3 months prior to COVID-19 diagnosis. During a median follow-up of 25 days, 33 (13.1%) required admission to the ICU, and 71 (28.2%) died. Forty-seven (19.1%) had a diagnosis of hospital-acquired COVID-19. Median overall survival was shorter in those with hospital-acquired infection, compared to a contemporary community-acquired population (27 days vs unreached, HR 2.3, 95% CI 1.2-4.4, p=0.0006). Multivariate analysis demonstrated that hospital-acquired COVID-19, age, ECOG status, and advanced stage of cancer were independently associated with death. Interpretation Our study demonstrates a high rate of nosocomial transmission of COVID-19, associated with increased mortality in both univariate and multivariate analysis in the cancer population, reinforcing the importance of treating patients with cancer in COVID-free units. We also validated that age and advanced cancer were negative predictive factors for COVID-19 severity in patients with cancer., Highlights • We found a high rate of nosocomial transmission of COVID-19 in patients with cancer. • Nosocomial COVID-19 increased mortality compared to community-acquired infection. • Nosocomial COVID-19, age, ECOG, and stage were independently associated with death. • COVID-free units and infection control procedures are required to protect patients.

Published
2020

47. Combined treatment of refractory ascites with an alfapump® plus hernia repair in the same surgical session: A retrospective, multicentre, European pilot study in cirrhotic patients

Author

L. Elkrief, D. Valla, Eric Nguyen-Khac, D. Pricope, Laurent Spahr, F. Storni, R. Sarba, J.-M. Regimbeau, Charles Sabbagh, A. DeGottardi, Safi Dokmak, W. Staszewicz, CHU Amiens-Picardie, Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 (GRAP), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA-CESTA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), CHU Pontchaillou [Rennes], Simplification des soins chez les patients complexes - UR UPJV 7518 (SSPC), and Université de Picardie Jules Verne (UPJV)

Subjects
Liver Cirrhosis, medicine.medical_specialty, Cirrhosis, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Pilot Projects, law.invention, Randomized controlled trial, law, Ascites, Paracentesis, Medicine, Humans, Hernia, 610 Medicine & health, Herniorrhaphy, Retrospective Studies, medicine.diagnostic_test, business.industry, Standard treatment, General Medicine, medicine.disease, Hernia repair, Surgery, Concomitant, medicine.symptom, business
Abstract

International audience; Introduction: The treatment of symptomatic hernia in cirrhotic patients with refractory ascites is critical but challenging. The objective of this study was to assess the feasibility and safety of the implantation of alfapump (R) combined with concomitant hernia repair in cirrhotic patients with refractory ascites. Methods: Using data from six European centres, we retrospectively compared patients treated with alfapump (R) system implantation and concomitant hernia repair [the combined treatment group (CT group, n = 12)] or with intermittent paracentesis hernia repair [the standard treatment group (ST group, n = 26)]. Some patients of the ST group had hernia repair in an elective setting (STel group) and others in emergency (STem group). The endpoints were requirement of peritoneal drainage, the rate of infectious complications, the in-hospital mortality, the length of stay, paracentesis-free survival. Results: Postoperatively, none of the patients in the CT group and 21 patients (80%) in the ST group underwent peritoneal drainage for the evacuation of ascites fluid (P < 0.0001). The overall incidence of infectious complications was not different between groups but there were fewer infections in the CT group than in the STem group (33% vs. 81%; P = 0.01). There was no difference for in-hospital mortality. The length of stay was shorter in the CT group (P = 0.03). Paracentesis-free survival was significantly better (P = 0.0003) in the CT group than in the ST group. Conclusion: Implantation of alfapump combined with concomitant hernia repair seems feasible and safe in cirrhotic patients; however, larger and randomized study are required. (C) 2020 Published by Elsevier Masson SAS.

Published
2020
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48. The role of the gut microbiome on radiation therapy efficacy and gastrointestinal complications: A systematic review

Author

Houda Bahig, David Pasquier, Marion Tonneau, Mathias Chamaillard, Bertrand Routy, Arielle Elkrief, and Thomas Paz Del Socorro

Subjects
medicine.medical_treatment, Rectum, Gut flora, Bioinformatics, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Immune system, Neoplasms, medicine, Mucositis, Humans, Radiology, Nuclear Medicine and imaging, Intestinal Mucosa, Adverse effect, Stomatitis, biology, business.industry, Hematology, Immunotherapy, biology.organism_classification, medicine.disease, Gastrointestinal Microbiome, Radiation therapy, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, business, Adjuvant
Abstract

Radiation therapy (RT) is an essential component of therapy either curative or palliative armamentarium in oncology, but its efficacy varies considerably among patients through many extrinsic and intrinsic mechanisms of the tumour, which are beginning to be better understood. Recent studies have shown that the gut microbiome represents a key factor in the modulation of the systemic immune response and consequently on patients' outcome. Moreover, the emergence of biomarkers that are derived from the gut microbiota has fuelled the development of adjuvant strategies for patients treated with immunotherapy in combination or not with RT. Despite progress in development of more precise radiotherapy techniques, almost all patients undergoing RT to the abdomen, pelvis, or rectum develop acute adverse events as a consequence of several dose-limiting parameters such as the location of irradiation that may subsequently damage normal tissue including the intestinal epithelium. Several lines of evidence in preclinical models identified that vancomycin improves RT-induced gastrointestinal toxicities such as diarrhea and oral mucositis. In order to gain further insight into this rapidly evolving field, we have systematically reviewed the studies that have described how the gut microbiome may directly or indirectly modulate RT efficacy and its gastro-intestinal toxicities. Lastly, we outline current knowledge gaps and discuss potentially more satisfactory therapeutic options to restore the functionality of the gut microbiome of patients treated with RT.

Published
2020

49. Erratum: Therapeutic landscape of metastatic non-small-cell lung cancer in Canada in 2020

Author

Elkrief, A., Joubert, P., Florescu, M., Tehfe, M., Blais, N., and Routy, B.

Subjects
Canada, Lung Neoplasms, Article Doi, small cell, History, 21st Century, landscape of metastatic, cell lung, Therapeutic Landscape, Carcinoma, Non-Small-Cell Lung, Humans, 10.3747/co.27.5953, Immunotherapy, Neoplasm Metastasis, Erratum
Abstract

Lung cancer is the most commonly diagnosed cancer in Canada and remains associated with high mortality. Nevertheless, recent advances in the fields of immuno-oncology and precision medicine have led to significant improvements in clinical outcome in metastatic non-small-cell lung cancer (nsclc). Those improvements were facilitated by a greater understanding of the biologic classification of nsclc, which catalyzed discoveries of novel therapies. Here, we present a comprehensive review of the recent avalanche of practice-changing trials in metastatic nsclc, and we offer an approach to the management of this disease from a Canadian perspective. We begin with an overview of the pathologic and molecular characterization of metastatic nsclc. Next, we review the indications for currently approved immune checkpoint inhibitors, and we provide an approach to the management of disease with a driver mutation. Finally, we address future avenues in both diagnostics and therapeutics for patients with advanced and metastatic nsclc.

Published
2020
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50. The Gut Microbiome Associates with Immune Checkpoint Inhibition Outcomes in Patients with Advanced Non-Small Cell Lung Cancer

Author

Taiki Hakozaki, Safae Terrisse, Yusuke Okuma, Iris Mimpen, Laurence Zitvogel, Bertrand Routy, Lisa Derosa, Arielle Elkrief, Corentin Richard, Myriam Benlaifaoui, and Yukio Hosomi

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, medicine.medical_specialty, Lung Neoplasms, medicine.drug_class, Immunology, Antibiotics, 03 medical and health sciences, 0302 clinical medicine, Immune system, Internal medicine, Carcinoma, Non-Small-Cell Lung, medicine, Clinical endpoint, Humans, Prospective Studies, Adverse effect, Lung cancer, Immune Checkpoint Inhibitors, Aged, biology, business.industry, medicine.disease, Survival Analysis, Immune checkpoint, Gastrointestinal Microbiome, 030104 developmental biology, Treatment Outcome, 030220 oncology & carcinogenesis, biology.protein, Female, Antibody, business, Ruminococcaceae
Abstract

The gut microbiome (GM) plays an important role in shaping systemic immune responses and influences immune checkpoint inhibitor (ICI) efficacy. Antibiotics worsen clinical outcomes in patients receiving ICI. However, whether GM profiling and baseline antibiotic can be a biomarker of ICI efficacy in advanced non–small cell lung cancer (NSCLC) remains unknown. We prospectively collected baseline (pre-ICI) fecal samples and clinical data of 70 Japanese patients suffering from advanced NSCLC and treated them with anti–PD-1/PD-L1 antibodies as a first-line or treatment-refractory therapy. We performed 16S rRNA V3–V4 sequencing of gene amplicons of fecal samples, and bacteria diversity and differential abundance analysis was performed. The clinical endpoints were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAE). ORR was 34%, and median PFS and OS were 5.2 and 16.2 months, respectively. Patients who received pre-ICI antibiotic had lower alpha diversity at baseline and underrepresentation of Ruminococcaceae UCG 13 and Agathobacter. When analyzing antibiotic-free patients, alpha diversity correlated with OS. In addition, Ruminococcaceae UCG 13 and Agathobacter were enriched in patients with favorable ORR and PFS >6 months. Ruminococcaceae UCG 13 was enriched in patients with OS >12 months. GM differences were observed between patients who experienced low- versus high-grade irAE. We demonstrated the negative influence of antibiotic on the GM composition and identified the bacteria repertoire in patients experiencing favorable responses to ICI. See articles by Tomita et al., p. 1236, and Peng et al., p. 1251

Published
2020

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