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2.
Artículo en Inglés | MEDLINE | ID: mdl-38083580

RESUMEN

This paper aims to question the sustainability of biomedical engineering practices. The strong sustainability framework is applied to the evaluation and development of medical technologies through the definition of clinical sustainability. A roadmap for developing and evaluating medical technologies in this respect is derived from this framework, as a first step toward a multidisciplinary evaluation tool. On this basis, the current trend towards disposable endoscopes is analyzed and discussed. This highlights the subtle balance between economic, clinical, social, and environmental factors, the lack of evidence at these multiple levels, and the need for multidisciplinarity. This paper concludes with the need to assess all aspects of sustainability and identify and quantify the trade-offs, instead of focusing on one or two key indicators, to have more relevant information in order to make better and more effective decisions. Towards sustainable healthcare, we outline two paths of action: (1) providing evidence that is lacking on the environmental impact of existing or currently developed medical technologies and (2) clarifying the premises and visions underlying our practices.Clinical Relevance- This work provides insights regarding the strong sustainability of medical technologies. This clinical framework may help clinicians and developers in decision-making to reduce indirect negative ecological, social, and health impacts.


Asunto(s)
Equipos Desechables , Endoscopios , Desarrollo Sostenible
3.
Schizophr Bull ; 49(6): 1494-1507, 2023 11 29.
Artículo en Inglés | MEDLINE | ID: mdl-38029279

RESUMEN

BACKGROUND AND HYPOTHESIS: Several studies have shown that spontaneous brain activity, including the total and fractional amplitude of low-frequency fluctuations (LFF) and regional homogeneity (ReHo), is altered in psychosis. Nonetheless, neuroimaging results show a high heterogeneity. For this reason, we gathered the extant literature on spontaneous brain activity in first-episode psychosis (FEP), where the effects of long-term treatment and chronic disease are minimal. STUDY DESIGN: A systematic research was conducted on PubMed, Scopus, and Web of Science to identify studies exploring spontaneous brain activity and local connectivity in FEP estimated using functional magnetic resonance imaging. 20 LFF and 15 ReHo studies were included. Coordinate-Based Activation Likelihood Estimation Meta-Analyses stratified by brain measures, age (adolescent vs adult), and drug-naïve status were performed to identify spatially-convergent alterations in spontaneous brain activity in FEP. STUDY RESULTS: We found a significant increase in LFF in FEP compared to healthy controls (HC) in the right striatum and in ReHo in the left striatum. When pooling together all studies on LFF and ReHo, spontaneous brain activity was increased in the bilateral striatum and superior and middle frontal gyri and decreased in the right precentral gyrus and the right inferior frontal gyrus compared to HC. These results were also replicated in the adult and drug-naïve samples. CONCLUSIONS: Abnormalities in the frontostriatal circuit are present in early psychosis independently of treatment status. Our findings support the view that altered frontostriatal can represent a core neural alteration of the disorder and could be a target of treatment.


Asunto(s)
Mapeo Encefálico , Trastornos Psicóticos , Adulto , Adolescente , Humanos , Mapeo Encefálico/métodos , Encéfalo/patología , Imagen por Resonancia Magnética/métodos , Enfermedad Crónica
4.
J Med Case Rep ; 17(1): 493, 2023 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-38008733

RESUMEN

BACKGROUND: Leptospirosis is known for its pulmonary form characterized by intra-alveolar hemorrhage, exhibiting a high mortality rate. Management by venous-venous extracorporeal membrane oxygenation has been reported in a small number of cases. CASE PRESENTATION: We report herein the case of a 16-year-old Caucasian male who was admitted with rapidly deteriorating respiratory and digestive complaints. He developed severe acute respiratory distress syndrome secondary to disseminated intravascular coagulation and intra-alveolar hemorrhage, requiring initiation of venous-venous extracorporeal membrane oxygenation. Initial infectious and immunological assessments were inconclusive, but repeat serology on the tenth day of admission confirmed a diagnosis of leptospirosis. The patient received multiple transfusions, and upon favorable response to treatment with corticosteroids and antibiotics, he was successfully weaned off venous-venous extracorporeal membrane oxygenation, which was discontinued after 12 days. CONCLUSION: Leptospirosis is a rare cause of severe acute respiratory failure following pulmonary hemorrhage. It is typically diagnosed by serology, with detectable IgM antibodies 5-7 days after the onset of symptoms. We report that early support with respiratory extracorporeal membrane oxygenation favors timely clearance of endobronchial clotting, parenchymal recovery, and prevention of ventilator-induced lung injury. Major hypofibrinogenemia, which did not seem to worsen during extracorporeal membrane oxygenation application, was managed by repeated transfusions. Further studies investigating the pathogenesis of this coagulopathy are required to further optimize the management of this rare and severe complication.


Asunto(s)
Coagulación Intravascular Diseminada , Oxigenación por Membrana Extracorpórea , Leptospirosis , Enfermedades Pulmonares , Síndrome de Dificultad Respiratoria , Humanos , Masculino , Adolescente , Coagulación Intravascular Diseminada/terapia , Coagulación Intravascular Diseminada/complicaciones , Leptospirosis/complicaciones , Leptospirosis/diagnóstico , Enfermedades Pulmonares/complicaciones , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/terapia , Hemorragia
5.
Intensive Care Med ; 49(10): 1212-1222, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37812242

RESUMEN

PURPOSE: Lower respiratory tract infections (LRTI) are the most frequent infectious complication in patients admitted to the intensive care unit (ICU). We aim to report the clinical characteristics of ICU-admitted patients due to nosocomial LRTI and to describe their microbiology and clinical outcomes. METHODS: A prospective observational study was conducted in 13 countries over two continents from 9th May 2016 until 16th August 2019. Characteristics and outcomes of ventilator-associated pneumonia (VAP), ventilator-associated tracheobronchitis (VAT), ICU hospital-acquired pneumonia (ICU-HAP), HAP that required invasive ventilation (VHAP), and HAP in patients transferred to the ICU without invasive mechanical ventilation were collected. The clinical diagnosis and treatments were per clinical practice and not per protocol. Descriptive statistics were used to compare the study groups. RESULTS: 1060 patients with LRTI (72.5% male sex, median age 64 [50-74] years) were included in the study; 160 (15.1%) developed VAT, 556 (52.5%) VAP, 98 (9.2%) ICU-HAP, 152 (14.3%) HAP, and 94 (8.9%) VHAP. Patients with VHAP had higher serum procalcitonin (PCT) and Sequential Organ Failure Assessment (SOFA) scores. Patients with VAP or VHAP developed acute kidney injury, acute respiratory distress syndrome, multiple organ failure, or septic shock more often. One thousand eight patients had microbiological samples, and 711 (70.5%) had etiological microbiology identified. The most common microorganisms were Pseudomonas aeruginosa (18.4%) and Klebsiella spp (14.4%). In 382 patients (36%), the causative pathogen shows some antimicrobial resistance pattern. ICU, hospital and 28-day mortality were 30.8%, 37.5% and 27.5%, respectively. Patients with VHAP had the highest ICU, in-hospital and 28-day mortality rates. CONCLUSION: VHAP patients presented the highest mortality among those admitted to the ICU. Multidrug-resistant pathogens frequently cause nosocomial LRTI in this multinational cohort study.


Asunto(s)
Infección Hospitalaria , Neumonía Asociada al Ventilador , Infecciones del Sistema Respiratorio , Humanos , Masculino , Persona de Mediana Edad , Femenino , Estudios de Cohortes , Estudios Prospectivos , Infección Hospitalaria/diagnóstico , Infecciones del Sistema Respiratorio/epidemiología , Neumonía Asociada al Ventilador/diagnóstico , Hospitales , Unidades de Cuidados Intensivos
6.
N Engl J Med ; 389(17): 1590-1600, 2023 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-37889107

RESUMEN

BACKGROUND: Passive immunization with plasma collected from convalescent patients has been regularly used to treat coronavirus disease 2019 (Covid-19). Minimal data are available regarding the use of convalescent plasma in patients with Covid-19-induced acute respiratory distress syndrome (ARDS). METHODS: In this open-label trial, we randomly assigned adult patients with Covid-19-induced ARDS who had been receiving invasive mechanical ventilation for less than 5 days in a 1:1 ratio to receive either convalescent plasma with a neutralizing antibody titer of at least 1:320 or standard care alone. Randomization was stratified according to the time from tracheal intubation to inclusion. The primary outcome was death by day 28. RESULTS: A total of 475 patients underwent randomization from September 2020 through March 2022. Overall, 237 patients were assigned to receive convalescent plasma and 238 to receive standard care. Owing to a shortage of convalescent plasma, a neutralizing antibody titer of 1:160 was administered to 17.7% of the patients in the convalescent-plasma group. Glucocorticoids were administered to 466 patients (98.1%). At day 28, mortality was 35.4% in the convalescent-plasma group and 45.0% in the standard-care group (P = 0.03). In a prespecified analysis, this effect was observed mainly in patients who underwent randomization 48 hours or less after the initiation of invasive mechanical ventilation. Serious adverse events did not differ substantially between the two groups. CONCLUSIONS: The administration of plasma collected from convalescent donors with a neutralizing antibody titer of at least 1:160 to patients with Covid-19-induced ARDS within 5 days after the initiation of invasive mechanical ventilation significantly reduced mortality at day 28. This effect was mainly observed in patients who underwent randomization 48 hours or less after ventilation initiation. (Funded by the Belgian Health Care Knowledge Center; ClinicalTrials.gov number, NCT04558476.).


Asunto(s)
Sueroterapia para COVID-19 , COVID-19 , Síndrome de Dificultad Respiratoria , Adulto , Humanos , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/uso terapéutico , COVID-19/complicaciones , COVID-19/inmunología , COVID-19/terapia , Respiración Artificial , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/inmunología , Síndrome de Dificultad Respiratoria/terapia , SARS-CoV-2 , Resultado del Tratamiento
8.
JACC Clin Electrophysiol ; 9(7 Pt 1): 1008-1010, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37438041
10.
Proc Natl Acad Sci U S A ; 120(17): e2217872120, 2023 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-37068225

RESUMEN

Extant terrestrial vertebrates, including birds, have a panoply of symbiotic relationships with many insects and arachnids, such as parasitism or mutualism. Yet, identifying arthropod-vertebrate symbioses in the fossil record has been based largely on indirect evidence; findings of direct association between arthropod guests and dinosaur host remains are exceedingly scarce. Here, we present direct and indirect evidence demonstrating that beetle larvae fed on feathers from an undetermined theropod host (avian or nonavian) 105 million y ago. An exceptional amber assemblage is reported of larval molts (exuviae) intimately associated with plumulaceous feather and other remains, as well as three additional amber pieces preserving isolated conspecific exuviae. Samples were found in the roughly coeval Spanish amber deposits of El Soplao, San Just, and Peñacerrada I. Integration of the morphological, systematic, and taphonomic data shows that the beetle larval exuviae, belonging to three developmental stages, are most consistent with skin/hide beetles (family Dermestidae), an ecologically important group with extant keratophagous species that commonly inhabit bird and mammal nests. These findings show that a symbiotic relationship involving keratophagy comparable to that of beetles and birds in current ecosystems existed between their Early Cretaceous relatives.


Asunto(s)
Escarabajos , Dinosaurios , Animales , Dinosaurios/anatomía & histología , Plumas/anatomía & histología , Simbiosis , Ámbar , Ecosistema , Fósiles , Aves/anatomía & histología , Evolución Biológica , Mamíferos
11.
BMC Anesthesiol ; 23(1): 138, 2023 04 27.
Artículo en Inglés | MEDLINE | ID: mdl-37106345

RESUMEN

BACKGROUND: Despite evidence suggesting a higher risk of barotrauma during COVID-19-related acute respiratory distress syndrome (ARDS) compared to ARDS due to other causes, data are limited about possible associations with patient characteristics, ventilation strategy, and survival. METHODS: This prospective observational multicenter study included consecutive patients with moderate-to-severe COVID-19 ARDS requiring invasive mechanical ventilation and managed at any of 12 centers in France and Belgium between March and December 2020. The primary objective was to determine whether barotrauma was associated with ICU mortality (censored on day 90), and the secondary objective was to identify factors associated with barotrauma. RESULTS: Of 586 patients, 48 (8.2%) experienced barotrauma, including 35 with pneumothorax, 23 with pneumomediastinum, 1 with pneumoperitoneum, and 6 with subcutaneous emphysema. Median time from mechanical ventilation initiation to barotrauma detection was 3 [0-17] days. All patients received protective ventilation and nearly half (23/48) were in volume-controlled mode. Barotrauma was associated with higher hospital mortality (P < 0.001) even after adjustment on age, sex, comorbidities, PaO2/FiO2 at intubation, plateau pressure at intubation, and center (P < 0.05). The group with barotrauma had a lower mean body mass index (28.6 ± 5.8 vs. 30.3 ± 5.9, P = 0.03) and a higher proportion of patients given corticosteroids (87.5% vs. 63.4%, P = 0.001). CONCLUSION: Barotrauma during mechanical ventilation for COVID-19 ARDS was associated with higher hospital mortality.


Asunto(s)
Barotrauma , COVID-19 , Síndrome de Dificultad Respiratoria , Humanos , Estudios Retrospectivos , Estudios Prospectivos , COVID-19/terapia , COVID-19/complicaciones , Respiración Artificial/efectos adversos , Barotrauma/epidemiología , Barotrauma/etiología
12.
Ann Intensive Care ; 13(1): 29, 2023 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-37072645

RESUMEN

BACKGROUND: Immune checkpoint inhibitors (ICI) have revolutionized the management of cancer. They can induce immune-related adverse events (irAE) leading to intensive care unit (ICU) admission. We aimed to describe irAEs for ICU admissions in solid cancer patients treated with ICIs. METHODS: This prospective multicenter study was conducted in France and Belgium. Adult patients with solid tumor and treated with systemic ICIs within the last 6 months, requiring non-programmed ICU admission were included. Patients admitted for microbiologically documented sepsis were excluded. Imputability of irAEs in ICU admissions was described according to the WHO-UMC classification system at ICU admission and at ICU discharge. The use of immunosuppressant treatment was reported. RESULTS: 115 patients were eligible. Solid tumor was mainly lung cancer (n = 76, 66%) and melanoma (n = 18, 16%). They were mainly treated with an anti-PD-(L)1 alone (n = 110, 96%). Main ICU admission reasons were acute respiratory failure (n = 66, 57%), colitis (n = 14, 13%), and cardiovascular disease (n = 13, 11%). ICU admission was considered "likely" associated with irAE for 48% (n = 55) of patients. Factors independently associated with irAE were a good ECOG performance status (PS) (ECOG-PS of 0 or 1 vs. ECOG-PS of 2-3, odds ratio [OR] = 6.34, 95% confidence interval [95% CI] 2.13-18.90, and OR = 3.66, 95% CI 1.33-10.03, respectively), and a history of irAE (OR = 3.28, 95% CI 1.19-9.01). Steroids were prescribed for 41/55 (75%) patients with ICU admission "likely" related to irAE. Three patients were subsequently treated with immunosuppressants. CONCLUSION: IrAEs accounted for half of ICU admissions in cancer patients receiving ICIs. They could be treated with steroids. Identifying the imputability of irAEs in ICU admissions remains a challenge.

14.
Crit Care ; 27(1): 6, 2023 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-36609390

RESUMEN

OBJECTIVES: The occurrence of mediastinitis after cardiac surgery remains a rare and severe complication associated with poor outcomes. Whereas bacterial mediastinitis have been largely described, little is known about their fungal etiologies. We report incidence, characteristics and outcome of post-cardiac surgery fungal mediastinitis. METHODS: Multicenter retrospective study among 10 intensive care units (ICU) in France and Belgium of proven cases of fungal mediastinitis after cardiac surgery (2009-2019). RESULTS: Among 73,688 cardiac surgery procedures, 40 patients developed fungal mediastinitis. Five were supported with left ventricular assist device and five with veno-arterial extracorporeal membrane oxygenation before initial surgery. Twelve patients received prior heart transplantation. Interval between initial surgery and mediastinitis was 38 [17-61] days. Only half of the patients showed local signs of infection. Septic shock was uncommon at diagnosis (12.5%). Forty-three fungal strains were identified: Candida spp. (34 patients), Trichosporon spp. (5 patients) and Aspergillus spp. (4 patients). Hospital mortality was 58%. Survivors were younger (59 [43-65] vs. 65 [61-73] yo; p = 0.013), had lower body mass index (24 [20-26] vs. 30 [24-32] kg/m2; p = 0.028) and lower Simplified Acute Physiology Score II score at ICU admission (37 [28-40] vs. 54 [34-61]; p = 0.012). CONCLUSION: Fungal mediastinitis is a very rare complication after cardiac surgery, associated with a high mortality rate. This entity should be suspected in patients with a smoldering infectious postoperative course, especially those supported with short- or long-term invasive cardiac support devices, or following heart transplantation.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Mediastinitis , Humanos , Estudios Retrospectivos , Mediastinitis/epidemiología , Mediastinitis/microbiología , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Procedimientos Quirúrgicos Cardíacos/métodos , Candida , Bélgica
15.
Intensive Care Med ; 48(9): 1185-1196, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35978137

RESUMEN

PURPOSE: Management and outcomes of pregnant women with coronavirus disease 2019 (COVID-19) admitted to intensive care unit (ICU) remain to be investigated. METHODS: A retrospective multicenter study conducted in 32 ICUs in France, Belgium and Switzerland. Maternal management as well as maternal and neonatal outcomes were reported. RESULTS: Among the 187 pregnant women with COVID-19 (33 ± 6 years old and 28 ± 7 weeks' gestation), 76 (41%) were obese, 12 (6%) had diabetes mellitus and 66 (35%) had pregnancy-related complications. Standard oxygenation, high-flow nasal oxygen therapy (HFNO) and non-invasive ventilation (NIV) were used as the only oxygenation technique in 41 (22%), 55 (29%) and 18 (10%) patients, respectively, and 73 (39%) were intubated. Overall, 72 (39%) patients required several oxygenation techniques and 15 (8%) required venovenous extracorporeal membrane oxygenation. Corticosteroids and tocilizumab were administered in 157 (84%) and 25 (13%) patients, respectively. Awake prone positioning or prone positioning was performed in 49 (26%) patients. In multivariate analysis, risk factors for intubation were obesity (cause-specific hazard ratio (CSH) 2.00, 95% CI (1.05-3.80), p = 0.03), term of pregnancy (CSH 1.07, 95% CI (1.02-1.10), per + 1 week gestation, p = 0.01), extent of computed tomography (CT) scan abnormalities > 50% (CSH 2.69, 95% CI (1.30-5.60), p < 0.01) and NIV use (CSH 2.06, 95% CI (1.09-3.90), p = 0.03). Delivery was required during ICU stay in 70 (37%) patients, mainly due to maternal respiratory worsening, and improved the driving pressure and oxygenation. Maternal and fetal/neonatal mortality rates were 1% and 4%, respectively. The rate of maternal and/or neonatal complications increased with the invasiveness of maternal respiratory support. CONCLUSION: In ICU, corticosteroids, tocilizumab and prone positioning were used in few pregnant women with COVID-19. Over a third of patients were intubated and delivery improved the driving pressure.


Asunto(s)
COVID-19 , Complicaciones Infecciosas del Embarazo , Adulto , COVID-19/complicaciones , COVID-19/terapia , Femenino , Humanos , Recién Nacido , Unidades de Cuidados Intensivos , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/terapia , Mujeres Embarazadas , SARS-CoV-2
16.
Crit Care ; 26(1): 183, 2022 06 18.
Artículo en Inglés | MEDLINE | ID: mdl-35717241

RESUMEN

BACKGROUND: Clarithromycin may act as immune-regulating treatment in sepsis and acute respiratory dysfunction syndrome. However, clinical evidence remains inconclusive. We aimed to evaluate whether clarithromycin improves 28-day mortality among patients with sepsis, respiratory and multiple organ dysfunction syndrome. METHODS: We conducted a multicenter, randomized, clinical trial in patients with sepsis. Participants with ratio of partial oxygen pressure to fraction of inspired oxygen less than 200 and more than 3 SOFA points from systems other than the respiratory function were enrolled between December 2017 and September 2019. Patients were randomized to receive 1 gr of clarithromycin or placebo intravenously once daily for 4 consecutive days. The primary endpoint was 28-day all-cause mortality. Secondary outcomes were 90-day mortality; sepsis response (defined as at least 25% decrease in SOFA score by day 7); sepsis recurrence; and differences in peripheral blood cell populations and leukocyte transcriptomics. RESULTS: Fifty-five patients were allocated to each arm. By day 28, 27 (49.1%) patients in the clarithromycin and 25 (45.5%) in the placebo group died (risk difference 3.6% [95% confidence interval (CI) - 15.7 to 22.7]; P = 0.703, adjusted OR 1.03 [95%CI 0.35-3.06]; P = 0.959). There were no statistical differences in 90-day mortality and sepsis response. Clarithromycin was associated with lower incidence of sepsis recurrence (OR 0.21 [95%CI 0.06-0.68]; P = 0.012); significant increase in monocyte HLA-DR expression; expansion of non-classical monocytes; and upregulation of genes involved in cholesterol homeostasis. Serious and non-serious adverse events were equally distributed. CONCLUSIONS: Clarithromycin did not reduce mortality among patients with sepsis with respiratory and multiple organ dysfunction. Clarithromycin was associated with lower sepsis recurrence, possibly through a mechanism of immune restoration. Clinical trial registration clinicaltrials.gov identifier NCT03345992 registered 17 November 2017; EudraCT 2017-001056-55.


Asunto(s)
Claritromicina , Sepsis , Administración Intravenosa , Claritromicina/farmacología , Claritromicina/uso terapéutico , Humanos , Insuficiencia Multiorgánica/complicaciones , Insuficiencia Multiorgánica/tratamiento farmacológico , Oxígeno/uso terapéutico , Sepsis/complicaciones
17.
Curr Opin Insect Sci ; 51: 100915, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35364331

RESUMEN

The study of terrestrial arthopod fossils preserved with microscopic fidelity in amber and as permineralized replicas has been revolutionized by CT scanning. Fine preservation facilitates phylogenetic interpretation of fossils, but molecular divergence-time models still commonly use insufficient fossil calibrations, skewing estimates away from the direct (i.e. fossil, morphological) evidence. Interactions among terrestrial arthropods (predation, parasitoidism; phoresy, social symbionts) are briefly reviewed from the fossil record. Predation is the oldest and most widespread, originating with arachnids since probably the Silurian. The first phoretic arthropods were probably mites (Acari). Parasitoidism extends to the early Jurassic ~200 mya, with four main episodes proposed by [1•]. 100-myo Burmese amber, the most diverse Cretaceous paleobiota, is unique for our understanding of insect eusociality and interrelationships among terrestrial arthropods. Eusocial insect colonies are ecological sinks for thousands of symbiont species; ages of the major eusocial groups and some of their nest symbionts are discussed. Fossilized arthropod interrelationships in Miocene Dominican amber are presented as visual exemplars.


Asunto(s)
Ámbar , Artrópodos , Animales , Evolución Biológica , Fósiles , Insectos , Filogenia
18.
JCI Insight ; 7(9)2022 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-35380990

RESUMEN

Severe COVID-19 disease is associated with dysregulation of the myeloid compartment during acute infection. Survivors frequently experience long-lasting sequelae, but little is known about the eventual persistence of this immune alteration. Herein, we evaluated TLR-induced cytokine responses in a cohort of mild to critical patients during acute or convalescent phases (n = 97). In the acute phase, we observed impaired cytokine production by monocytes in the patients with the most severe COVID-19. This capacity was globally restored in convalescent patients. However, we observed increased responsiveness to TLR1/2 ligation in patients who recovered from severe disease, indicating that these cells display distinct functional properties at the different stages of the disease. In patients with acute severe COVID-19, we identified a specific transcriptomic and epigenomic state in monocytes that can account for their functional refractoriness. The molecular profile of monocytes from recovering patients was distinct and characterized by increased chromatin accessibility at activating protein 1 (AP1) and MAF loci. These results demonstrate that severe COVID-19 infection has a profound impact on the differentiation status and function of circulating monocytes, during both the acute and the convalescent phases, in a completely distinct manner. This could have important implications for our understanding of short- and long-term COVID-19-related morbidity.


Asunto(s)
COVID-19 , Citocinas/metabolismo , Progresión de la Enfermedad , Humanos , Monocitos/metabolismo , SARS-CoV-2
19.
Front Immunol ; 13: 769839, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35422799

RESUMEN

The new pandemic virus SARS-CoV-2 is characterized by uncontrolled hyper-inflammation in severe cases. As the IL-22/IL-22R1 axis was reported to be involved in inflammation during viral infections, we characterized the expression of IL-22 receptor1, IL-22 and IL-22 binding protein in COVID-19 patients. Blood samples were collected from 19 non-severe and 14 severe patients on the day they presented (D0), at D14, and six months later, and from 6 non-infected controls. The IL-22R1 expression was characterized by flow cytometry. Results were related to HLA-DR expression of myeloid cells, to plasma concentrations of different cytokines and chemokines and NK cells and T lymphocytes functions characterized by their IFN-γ, IL-22, IL-17A, granzyme B and perforin content. The numbers of IL-22R1+ classical, intermediate, and non-classical monocytes and the proportions of IL-22R1+ plasmacytoid DC (pDC), myeloid DC1 and DC2 (mDC1, mDC2) were higher in patients than controls at D0. The proportions of IL-22R1+ classical and intermediate monocytes, and pDC and mDC2 remained high for six months. High proportions of IL-22R1+ non-classical monocytes and mDC2 displayed HLA-DRhigh expression and were thus activated. Multivariate analysis for all IL-22R1+ myeloid cells discriminated the severity of the disease (AUC=0.9023). However, correlation analysis between IL-22R1+ cell subsets and plasma chemokine concentrations suggested pro-inflammatory effects of some subsets and protective effects of others. The numbers of IL-22R1+ classical monocytes and pDC were positively correlated with pro-inflammatory chemokines MCP-1 and IP-10 in severe infections, whereas IL-22R1+ intermediate monocytes were negatively correlated with IL-6, IFN-α and CRP in non-severe infections. Moreover, in the absence of in vitro stimulation, NK and CD4+ T cells produced IFN-γ and IL-22, and CD4+ and CD8+ T cells produced IL-17A. CD4+ T lymphocytes also expressed IL-22R1, the density of its expression defining two different functional subsets. In conclusion, we provide the first evidence that SARS-CoV-2 infection is characterized by an abnormal expression of IL22R1 on blood myeloid cells and CD4+ T lymphocytes. Our results suggest that the involvement of the IL-22R1/IL-22 axis could be protective at the beginning of SARS-CoV-2 infection but could shift to a detrimental response over time.


Asunto(s)
COVID-19 , Linfocitos T CD8-positivos , Quimiocinas/metabolismo , Antígenos HLA-DR/metabolismo , Humanos , Inflamación/metabolismo , Interleucina-17/metabolismo , Receptores de Interleucina , SARS-CoV-2
20.
Chest ; 161(6): 1475-1484, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35063450

RESUMEN

BACKGROUND: The characteristics and outcomes of adult patients with respiratory syncytial virus (RSV) infection who require ICU admission are poorly defined. Although several studies in adults with RSV infection have been published in recent years, they did not focus specifically on patients with critical illness. RESEARCH QUESTION: What are the characteristics and outcomes of adult patients in the ICU with RSV infection and how do they compare with those of patients in the ICU with influenza infection? STUDY DESIGN AND METHODS: This retrospective, multicenter study in France and Belgium (17 sites) compared the characteristics and outcomes of adult patients in the ICU with RSV infection vs those with influenza infection between November 2011 and April 2018. Each patient with RSV infection was matched by institution and date of diagnosis with a patient with influenza infection. In-hospital mortality was compared between the two groups, with adjustment for prognostic factors in a multivariate model (sex, age, main underlying conditions, and concurrent bloodstream infection). RESULTS: Data from 618 patients (309 with RSV infection and 309 with influenza infection) were analyzed. Patients with RSV infection were significantly more likely to have an underlying chronic respiratory condition (60.2% vs 40.1%; P < .001) and to be immunocompromised (35% vs 26.2%; P = .02) than patients with influenza infection. Several differences in clinical signs and biological data at diagnosis were found between the groups. In-hospital mortality was not significantly different between the two groups (23.9% in the RSV group vs 25.6% in the influenza group; P = .63), even after adjustment for prognostic factors in a multivariate model. INTERPRETATION: Adult patients in the ICU with RSV infection differ from adult patients in the ICU with influenza in terms of comorbidities and characteristics at diagnosis. RSV infection was associated with high in-hospital mortality, approaching 25%. In multivariate analysis, RSV infection was associated with a similar odds of in-hospital death compared with influenza infection.


Asunto(s)
Gripe Humana , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Adulto , Estudios de Cohortes , Mortalidad Hospitalaria , Hospitalización , Humanos , Gripe Humana/complicaciones , Gripe Humana/diagnóstico , Gripe Humana/epidemiología , Unidades de Cuidados Intensivos , Infecciones por Virus Sincitial Respiratorio/complicaciones , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Infecciones por Virus Sincitial Respiratorio/epidemiología , Estudios Retrospectivos
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