Author
Fabrice Journe
Other affiliations: Institut Jules Bordet, Free University of Brussels, University of Mons
Bio: Fabrice Journe is an academic researcher from Université libre de Bruxelles. The author has contributed to research in topics: Melanoma & Medicine. The author has an hindex of 28, co-authored 98 publications receiving 3774 citations. Previous affiliations of Fabrice Journe include Institut Jules Bordet & Free University of Brussels.
Papers published on a yearly basis
Papers
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TL;DR: Olfactory and gustatory disorders are prevalent symptoms in European CO VID-19 patients, who may not have nasal symptoms, and the sudden anosmia or ageusia need to be recognized by the international scientific community as important symptoms of the COVID-19 infection.
Abstract: To investigate the occurrence of olfactory and gustatory dysfunctions in patients with laboratory-confirmed COVID-19 infection. Patients with laboratory-confirmed COVID-19 infection were recruited from 12 European hospitals. The following epidemiological and clinical outcomes have been studied: age, sex, ethnicity, comorbidities, and general and otolaryngological symptoms. Patients completed olfactory and gustatory questionnaires based on the smell and taste component of the National Health and Nutrition Examination Survey, and the short version of the Questionnaire of Olfactory Disorders-Negative Statements (sQOD-NS). A total of 417 mild-to-moderate COVID-19 patients completed the study (263 females). The most prevalent general symptoms consisted of cough, myalgia, and loss of appetite. Face pain and nasal obstruction were the most disease-related otolaryngological symptoms. 85.6% and 88.0% of patients reported olfactory and gustatory dysfunctions, respectively. There was a significant association between both disorders (p < 0.001). Olfactory dysfunction (OD) appeared before the other symptoms in 11.8% of cases. The sQO-NS scores were significantly lower in patients with anosmia compared with normosmic or hyposmic individuals (p = 0.001). Among the 18.2% of patients without nasal obstruction or rhinorrhea, 79.7% were hyposmic or anosmic. The early olfactory recovery rate was 44.0%. Females were significantly more affected by olfactory and gustatory dysfunctions than males (p = 0.001). Olfactory and gustatory disorders are prevalent symptoms in European COVID-19 patients, who may not have nasal symptoms. The sudden anosmia or ageusia need to be recognized by the international scientific community as important symptoms of the COVID-19 infection.
2,030 citations
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TL;DR: Using regulatory landscapes and in silico analysis, it is shown that transcriptional reprogramming underlies the distinct cellular states present in melanoma and reveals an essential role for the TEADs, linking it to clinically relevant mechanisms such as invasion and resistance.
Abstract: Transcriptional reprogramming of proliferative melanoma cells into a phenotypically distinct invasive cell subpopulation is a critical event at the origin of metastatic spreading Here we generate transcriptome, open chromatin and histone modification maps of melanoma cultures; and integrate this data with existing transcriptome and DNA methylation profiles from tumour biopsies to gain insight into the mechanisms underlying this key reprogramming event This shows thousands of genomic regulatory regions underlying the proliferative and invasive states, identifying SOX10/MITF and AP-1/TEAD as regulators, respectively Knockdown of TEADs shows a previously unrecognized role in the invasive gene network and establishes a causative link between these transcription factors, cell invasion and sensitivity to MAPK inhibitors Using regulatory landscapes and in silico analysis, we show that transcriptional reprogramming underlies the distinct cellular states present in melanoma Furthermore, it reveals an essential role for the TEADs, linking it to clinically relevant mechanisms such as invasion and resistance
348 citations
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TL;DR: In this article, the authors investigated prevalence and recovery of olfactory dysfunction in COVID-19 patients according to the disease severity and found that the prevalence of OD was significantly higher in mild form (85.9%) compared with moderate-to-critical forms (4.5-6.9%).
Abstract: OBJECTIVE: To investigate prevalence and recovery of olfactory dysfunction (OD) in COVID-19 patients according to the disease severity. METHODS: From 22 March to 3 June 2020, 2581 COVID-19 patients were identified from 18 European hospitals. Epidemiological and clinical data were extracted at baseline and within the 2-month post-infection. RESULTS: The prevalence of OD was significantly higher in mild form (85.9%) compared with moderate-to-critical forms (4.5-6.9%; P = 0.001). Of the 1916 patients with OD, 1363 completed the evaluations (71.1%). A total of 328 patients (24.1%) did not subjectively recover olfaction 60 days after the onset of the dysfunction. The mean duration of self-reported OD was 21.6 ± 17.9 days. Objective olfactory evaluations identified hyposmia/anosmia in 54.7% and 36.6% of mild and moderate-to-critical forms, respectively (P = 0.001). At 60 days and 6 months, 15.3% and 4.7% of anosmic/hyposmic patients did not objectively recover olfaction, respectively. The higher baseline severity of objective olfactory evaluations was strongly predictive of persistent OD (P < 0.001). CONCLUSION: OD is more prevalent in mild COVID-19 forms than in moderate-to-critical forms. OD disappeared in 95% of patients regarding objective olfactory evaluations at 6 months.
147 citations
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TL;DR: To investigate olfactory dysfunction in patients with mild coronavirus disease 2019 (COVID‐19) through patient‐reported outcome questionnaires and objective psychophysical testing.
Abstract: Objective: To investigate olfactory dysfunction (OD) in patients with mild coronavirus disease 2019 (COVID-19) through patient-reported outcome questionnaires and objective psychophysical testing. Methods: COVID-19 patients with self-reported sudden-onset OD were recruited. Epidemiological and clinical data were collected. Nasal complaints were evaluated with the sinonasal outcome-22. Subjective olfactory and gustatory status was evaluated with the National Health and Nutrition Examination Survey. Objective OD was evaluated using psychophysical tests. Results: Eighty-six patients completed the study. The most common symptoms were fatigue (72.9%), headache (60.0%), nasal obstruction (58.6%), and postnasal drip (48.6%). Total loss of smell was self-reported by 61.4% of patients. Objective olfactory testings identified 41 anosmic (47.7%), 12 hyposmic (14.0%), and 33 normosmic (38.3%) patients. There was no correlation between the objective test results and subjective reports of nasal obstruction or postnasal drip. Conclusion: A significant proportion of COVID-19 patients reporting OD do not have OD on objective testing.
122 citations
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TL;DR: To investigate the therapeutic benefit of proton pump inhibitors (PPIs) over placebo in patients with laryngopharyngeal reflux and to analyze the epidemiological factors of heterogeneity in the literature.
Abstract: Objectives To investigate the therapeutic benefit of proton pump inhibitors (PPIs) over placebo in patients with laryngopharyngeal reflux (LPR) and to analyze the epidemiological factors of heterogeneity in the literature. Methods An electronic literature search was conducted to identify articles published between 1990 and 2018 about clinical trials describing the efficiency of medical treatment(s) on LPR. First, a meta-analysis of placebo randomized controlled trials (RCTs) comparing PPIs versus placebo was conducted according to diet. The heterogeneity, response to PPIs, and evolution of clinical scores were analyzed for aggregate results. Second, a systematic review of diagnosis methods, clinical outcome of treatment, and therapeutic regimens was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Results The search identified 1,140 relevant publications, of which 72 studies met the inclusion criteria for a total of 5,781 patients. Ten RCTs were included in the meta-analysis. The combined relative risk was 1.31 in favor of PPIs and increased to 1.42 when patients did not receive diet recommendations. Randomized controlled trials were characterized by a significant heterogeneity due to discrepancies in clinical therapeutic outcomes, diagnosis methods (lack of gold standard diagnostic tools), and therapeutic scheme. The epidemiological analysis of all articles supports the existence of these discrepancies in the entire literature. In particular, many symptoms and signs commonly encountered in LPR are not assessed in the treatment effectiveness. The lack of diagnosis precision and variability of inclusion criteria particularly create bias in all reported and included articles. Conclusion This meta-analysis supports a mild superiority of PPIs over placebo and the importance of diet as additional treatment but demonstrates the heterogeneity between studies, limiting the elaboration of clear conclusions. International recommendations are proposed for the development of future trials. Laryngoscope, 129:1174-1187, 2019.
102 citations
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TL;DR: This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19, the novel severe acute respiratory syndrome coronavirus 2 pandemic that has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease.
Abstract: Importance The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19. Observations SARS-CoV-2 is spread primarily via respiratory droplets during close face-to-face contact. Infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. The average time from exposure to symptom onset is 5 days, and 97.5% of people who develop symptoms do so within 11.5 days. The most common symptoms are fever, dry cough, and shortness of breath. Radiographic and laboratory abnormalities, such as lymphopenia and elevated lactate dehydrogenase, are common, but nonspecific. Diagnosis is made by detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing, although false-negative test results may occur in up to 20% to 67% of patients; however, this is dependent on the quality and timing of testing. Manifestations of COVID-19 include asymptomatic carriers and fulminant disease characterized by sepsis and acute respiratory failure. Approximately 5% of patients with COVID-19, and 20% of those hospitalized, experience severe symptoms necessitating intensive care. More than 75% of patients hospitalized with COVID-19 require supplemental oxygen. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care (21.6% vs 24.6%; age-adjusted rate ratio, 0.83 [95% CI, 0.74-0.92]) and that remdesivir improves time to recovery (hospital discharge or no supplemental oxygen requirement) from 15 to 11 days. In a randomized trial of 103 patients with COVID-19, convalescent plasma did not shorten time to recovery. Ongoing trials are testing antiviral therapies, immune modulators, and anticoagulants. The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%. At least 120 SARS-CoV-2 vaccines are under development. Until an effective vaccine is available, the primary methods to reduce spread are face masks, social distancing, and contact tracing. Monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies. Conclusions and Relevance As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions.
3,371 citations
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TL;DR: The extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 are reviewed to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.
Abstract: Although COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here we review the extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.
2,113 citations
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University of KwaZulu-Natal1, University of Massachusetts Medical School2, Ragon Institute of MGH, MIT and Harvard3, Harvard University4, Broad Institute5, Massachusetts Institute of Technology6, Boston Children's Hospital7, Aix-Marseille University8, Centre national de la recherche scientifique9, Vanderbilt University Medical Center10, Brigham and Women's Hospital11, University of California, Berkeley12, University of Washington13, Fred Hutchinson Cancer Research Center14, Seattle Children's15, University of Pittsburgh16, University of Sheffield17, United States Department of Veterans Affairs18, University College London19, Scripps Research Institute20
TL;DR: The data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection.
1,911 citations
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01 Jan 2011
TL;DR: Firm evidence is provided for Foxp3+CD25+CD4+ Treg cells as an indispensable cellular constituent of the normal immune system for establishing and maintaining immunologic self-tolerance and immune homeostasis.
Abstract: Despite the skepticism that once prevailed among immunologists, it is now widely accepted that the normal immune system harbors a T-cell population, called regulatory T cells (Treg cells), specialized for immune suppression. It was first shown that depletion of a T-cell subpopulation from normal rodents produced autoimmune disease. Search for a molecular marker specific for such autoimmune-preventive Treg cells has revealed that the majority, if not all, of them constitutively express the CD25 molecule as depletion of CD25+CD4+ T cells spontaneously evokes autoimmune disease in otherwise normal rodents. The expression of CD25 by Treg cells has made it possible to delineate their developmental pathways, in particular their thymic development, and establish simple in vitro assay for assessing their suppressive activity. The marker and the in vitro assay have helped to identify human Treg cells with similar functional and phenotypic characteristics. Recent efforts have shown that natural Treg cells specifically express the transcription factor Foxp3 and that mutations of the Foxp3 gene produce a variety of immunological diseases in humans and rodents. Specific expression of Foxp3 in natural Treg cells has enabled their functional and developmental characterization by genetic approach. These studies altogether have provided firm evidence for Foxp3+CD25+CD4+ Treg cells as an indispensable cellular constituent of the normal immune system for establishing and maintaining immunologic self-tolerance and immune homeostasis. Treg cells are now within the scope of clinical use to treat immunological diseases and control physiological and pathological immune responses.
1,745 citations
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TL;DR: Results suggest that modulation of FXR activity and BA metabolism may open new attractive pharmacological approaches for the treatment of the metabolic syndrome and type 2 diabetes.
Abstract: The incidence of the metabolic syndrome has taken epidemic proportions in the past decades, contributing to an increased risk of cardiovascular disease and diabetes. The metabolic syndrome can be d...
1,376 citations