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BACKGROUND: Circulating endotoxins could result from bacterial digestive translocation during sepsis, thus contributing to uncontrolled systemic inflammation, leading in turn to organ dysfunction. We addressed this issue in the setting of severe pneumococcal pneumonia. METHODS: Endotoxemia was measured in a clinically relevant rabbit model of ventilated pneumococcal pneumonia and in 110 patients with bacteraemic pneumonia, using a patented mass spectrometry (LC-MS/MS) method for detection of 3-OH fatty acids (C10, C12, C14, C16 and C18), which are molecules bound to the lipid A motif of LPS. RESULTS: Whereas higher levels of systemic inflammation and organ dysfunctions were found, there was no significant difference in lipopolysaccharide concentrations when infected rabbits were compared to non-infected ones, or when patients were compared to healthy volunteers. CONCLUSIONS: Seemingly, endotoxins do not drive the overwhelming inflammation associated with severe forms of pneumococcal pneumonia.
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Endotoxemia , Pneumonia Pneumocócica , Humanos , Animais , Coelhos , Pneumonia Pneumocócica/diagnóstico , Cromatografia Líquida , Espectrometria de Massas em Tandem , Inflamação , Lipopolissacarídeos , EndotoxinasRESUMO
Pneumocystis pneumonia (PcP) remains life-threatening in kidney transplant recipients (KTR). Our study investigated risk factors one-year before PcP. We conducted a monocentric, case-control study including all KTR at the Dijon University Hospital (France) with a diagnosis of PcP between 2005 and 2022 (cases), and matched control KTR with no history of PcP (3 controls/case). Among all 1,135 KTR, 57 cases (5%) and 169 matched-controls were included. PcP was associated with 18% mortality. Compared to controls, cases were older, with a higher immunological risk, and CMV infection was more frequent in the year preceding the occurrence of PcP (23% vs. 4%; p < 0.001). As early as 1 year before PcP, lymphocyte counts were lower and serum creatinine levels were higher in cases, but immunosuppressive regimens were not significantly different. Multivariable analysis identified lymphocyte count, serum creatinine level, being treated by immunosuppressive therapy other than anti-rejection drugs, and CMV infection in the year preceding the time PcP as independently associated with the occurrence of PcP. PcP was associated with an increased risk of subsequent chronic rejection (27% vs. 3%; p = 0.001) and return to dialysis (20% vs. 3%; p = 0.002). The occurrence of CMV infection and a low lymphocyte count could redefine the indications for continuation or reinitiation of anti-Pneumocystis prophylaxis.
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Infecções por Citomegalovirus , Transplante de Rim , Linfopenia , Pneumocystis carinii , Pneumonia por Pneumocystis , Trombocitopenia , Humanos , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/tratamento farmacológico , Estudos de Casos e Controles , Transplante de Rim/efeitos adversos , Creatinina , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/epidemiologia , Fatores de Risco , Linfopenia/complicações , Trombocitopenia/complicações , Transplantados , Estudos RetrospectivosRESUMO
BACKGROUND: Mechanical ventilation for pneumonia may contribute to lung injury due to factors that include mitochondrial dysfunction, and mesenchymal stem cells may attenuate injury. This study hypothesized that mechanical ventilation induces immune and mitochondrial dysfunction, with or without pneumococcal pneumonia, that could be mitigated by mesenchymal stem cells alone or combined with antibiotics. METHODS: Male rabbits underwent protective mechanical ventilation (8 ml/kg tidal volume, 5 cm H2O end-expiratory pressure) or adverse mechanical ventilation (20 ml/kg tidal-volume, zero end-expiratory pressure) or were allowed to breathe spontaneously. The same settings were then repeated during pneumococcal pneumonia. Finally, infected animals during adverse mechanical ventilation received human umbilical cord-derived mesenchymal stem cells (3 × 106/kg, intravenous) and/or ceftaroline (20 mg/kg, intramuscular) or sodium chloride, 4 h after pneumococcal challenge. Twenty-four-hour survival (primary outcome), lung injury, bacterial burden, immune and mitochondrial dysfunction, and lung transcriptomes (secondary outcomes) were assessed. RESULTS: High-pressure adverse mechanical ventilation reduced the survival of infected animals (0%; 0 of 7) compared with spontaneous breathing (100%; 7 of 7) and protective mechanical ventilation (86%; 6 of 7; both P < 0.001), with higher lung pathology scores (median [interquartile ranges], 5.5 [4.5 to 7.0] vs. 12.6 [12.0 to 14.0]; P = 0.046), interleukin-8 lung concentrations (106 [54 to 316] vs. 804 [753 to 868] pg/g of lung; P = 0.012), and alveolar mitochondrial DNA release (0.33 [0.28 to 0.36] vs. 0.98 [0.76 to 1.21] ng/µl; P < 0.001) compared with infected spontaneously breathing animals. Survival (0%; 0 of 7; control group) was improved by mesenchymal stem cells (57%; 4 of 7; P = 0.001) or ceftaroline alone (57%; 4 of 7; P < 0.001) and improved even more with a combination treatment (86%; 6 of 7; P < 0.001). Mesenchymal stem cells reduced lung pathology score (8.5 [7.0 to 10.5] vs. 12.6 [12.0 to 14.0]; P = 0.043) and alveolar mitochondrial DNA release (0.39 (0.34 to 0.65) vs. 0.98 (0.76 to 1.21) ng/µl; P = 0.025). Mesenchymal stem cells combined with ceftaroline reduced interleukin-8 lung concentrations (665 [595 to 795] vs. 804 [753 to 868] pg/g of lung; P = 0.007) compared to ceftaroline alone. CONCLUSIONS: In this preclinical study, mesenchymal stem cells improved the outcome of rabbits with pneumonia and high-pressure mechanical ventilation by correcting immune and mitochondrial dysfunction and when combined with the antibiotic ceftaroline was synergistic in mitigating lung inflammation.
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Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Imunidade Celular/fisiologia , Mitocôndrias/imunologia , Pneumonia Pneumocócica/imunologia , Pneumonia Pneumocócica/terapia , Respiração Artificial/efeitos adversos , Animais , Masculino , Células-Tronco Mesenquimais/fisiologia , Mitocôndrias/metabolismo , Pneumonia Pneumocócica/metabolismo , Estudos Prospectivos , Coelhos , Distribuição AleatóriaRESUMO
INTRODUCTION: Obesity is commonly reported in COVID-19 patients and is associated with poorer outcomes. It is suggested that leptin could be the missing link between obesity and severe COVID-19. Our study aimed to unravel the link between adipokines, COVID-19 status, immune response, and outcomes in severe pneumonia. METHODS: In this prospective observational single-center study, 63 immunocompetent patients with severe pneumonia (36 non-COVID-19 and 27 COVID-19) were enrolled, most required intensive care. Clinical and biological characteristics (glucose metabolism, plasma adipokines, and cytokine concentrations) and outcomes were compared. RESULTS: At similar baseline severity, COVID-19 patients required mechanical ventilation for significantly longer than non-COVID-19 patients (p = 0.0049). Plasma concentrations of leptin and adiponectin were respectively positively and negatively correlated with BMI and glucose metabolism (glycemia and insulinemia), but not significantly different between the two groups. Leptin levels were negatively correlated with IL-1ß and IL-6, but the adipokines were not correlated with most other inflammatory mediators, baseline severity (SOFA score), or the duration of mechanical ventilation. CONCLUSION: Adipokine levels were correlated with BMI but not with most inflammatory mediators, severity, or outcomes in severe pneumonia, regardless of the origin. The link between obesity, dysregulated immune response, and life-threatening COVID-19 requires further investigation. CLINICAL TRIAL: ClinicalTrials.gov: NCT03505281.
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Adipocinas/imunologia , COVID-19/imunologia , Obesidade/complicações , Adipocinas/sangue , Adiponectina , Idoso , Citocinas , Feminino , Humanos , Imunidade , Leptina , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
During an epidemic period, we compared patients hospitalized for initial suspicion of COVID-19 but for whom an alternative diagnosis was finally retained (n = 152) with those who had COVID-19 (n = 222). Most common diagnoses were another infectious disease and heart failure. COVID-19-negative patients were more often active smokers had less often cough, fever, and digestive symptoms, as compared to the 222 COVID-19-positive patients. They had higher median neutrophil and lymphocyte counts and lower CRP level. In multivariate analysis, no current smoking, neurocognitive disorder, myalgia, and fibrinogen ≥4g/L were independently associated with a final diagnosis of COVID-19.
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COVID-19/diagnóstico , Adulto , Idoso , COVID-19/terapia , COVID-19/virologia , Hospitalização , Humanos , Masculino , Pacientes/estatística & dados numéricos , Estudos Retrospectivos , SARS-CoV-2/fisiologiaRESUMO
BACKGROUND: Although immune modulation is a promising therapeutic avenue in coronavirus disease 2019 (COVID-19), the most relevant targets remain to be found. COVID-19 has peculiar characteristics and outcomes, suggesting a unique immunopathogenesis. METHODS: Thirty-six immunocompetent non-COVID-19 and 27 COVID-19 patients with severe pneumonia were prospectively enrolled in a single center, most requiring intensive care. Clinical and biological characteristics (including T cell phenotype and function and plasma concentrations of 30 cytokines) and outcomes were compared. RESULTS: At similar baseline respiratory severity, COVID-19 patients required mechanical ventilation for significantly longer than non-COVID-19 patients (15 [7-22] vs. 4 (0-15) days; p = 0.0049). COVID-19 patients had lower levels of most classical inflammatory cytokines (G-CSF, CCL20, IL-1ß, IL-2, IL-6, IL-8, IL-15, TNF-α, TGF-ß), but higher plasma concentrations of CXCL10, GM-CSF and CCL5, compared to non-COVID-19 patients. COVID-19 patients displayed similar T-cell exhaustion to non-COVID-19 patients, but with a more unbalanced inflammatory/anti-inflammatory cytokine response (IL-6/IL-10 and TNF-α/IL-10 ratios). Principal component analysis identified two main patterns, with a clear distinction between non-COVID-19 and COVID-19 patients. Multivariate regression analysis confirmed that GM-CSF, CXCL10 and IL-10 levels were independently associated with the duration of mechanical ventilation. CONCLUSION: We identified a unique cytokine response, with higher plasma GM-CSF and CXCL10 in COVID-19 patients that were independently associated with the longer duration of mechanical ventilation. These cytokines could represent the dysregulated immune response in severe COVID-19, as well as promising therapeutic targets. ClinicalTrials.gov: NCT03505281.
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COVID-19/diagnóstico , COVID-19/imunologia , Imunidade Inata/fisiologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Idoso , Idoso de 80 Anos ou mais , COVID-19/mortalidade , COVID-19/terapia , Cuidados Críticos , Feminino , França/epidemiologia , Humanos , Imunofenotipagem , Ativação Linfocitária/fisiologia , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Prognóstico , Respiração Artificial , SARS-CoV-2/fisiologia , Índice de Gravidade de DoençaRESUMO
BACKGROUND: COVID-19-related ARDS has unique features when compared with ARDS from other origins, suggesting a distinctive inflammatory pathogenesis. Data regarding the host response within the lung are sparse. The objective is to compare alveolar and systemic inflammation response patterns, mitochondrial alarmin release, and outcomes according to ARDS etiology (i.e., COVID-19 vs. non-COVID-19). METHODS: Bronchoalveolar lavage fluid and plasma were obtained from 7 control, 7 non-COVID-19 ARDS, and 14 COVID-19 ARDS patients. Clinical data, plasma, and epithelial lining fluid (ELF) concentrations of 45 inflammatory mediators and cell-free mitochondrial DNA were measured and compared. RESULTS: COVID-19 ARDS patients required mechanical ventilation (MV) for significantly longer, even after adjustment for potential confounders. There was a trend toward higher concentrations of plasma CCL5, CXCL2, CXCL10, CD40 ligand, IL-10, and GM-CSF, and ELF concentrations of CXCL1, CXCL10, granzyme B, TRAIL, and EGF in the COVID-19 ARDS group compared with the non-COVID-19 ARDS group. Plasma and ELF CXCL10 concentrations were independently associated with the number of ventilator-free days, without correlation between ELF CXCL-10 and viral load. Mitochondrial DNA plasma and ELF concentrations were elevated in all ARDS patients, with no differences between the two groups. ELF concentrations of mitochondrial DNA were correlated with alveolar cell counts, as well as IL-8 and IL-1ß concentrations. CONCLUSION: CXCL10 could be one key mediator involved in the dysregulated immune response. It should be evaluated as a candidate biomarker that may predict the duration of MV in COVID-19 ARDS patients. Targeting the CXCL10-CXCR3 axis could also be considered as a new therapeutic approach. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03955887.
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Quimiocina CXCL10/metabolismo , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Respiração Artificial/estatística & dados numéricos , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/terapia , Adulto , Idoso , COVID-19 , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Prospectivos , Fatores de TempoRESUMO
An overall reduction in the incidence of AIDS and a change in the spectrum of lung disease have been noticed in persons living with HIV (PLHIV). Our aim was to provide an epidemiological update regarding the prevalence of lung diseases in PLHIV hospitalised in France.We analysed the prevalence of lung disease in PLHIV hospitalised in France from 2007 to 2013, from the French nationwide hospital medical information database, and assessed the association between HIV and incident noninfectious disease over 4â years of follow-up.A total of 52â091 PLHIV were hospitalised in France between 2007 and 2013. Among PLHIV hospitalised with lung disease, noninfectious lung diseases increased significantly from 45.6% to 54.7% between 2007 and 2013, whereas the proportion of patients with at least one infectious lung disease decreased significantly. In 2010, 10â067 prevalent hospitalised PLHIV were compared with 8â244â682 hospitalised non-PLHIV. In 30-49-year-old patients, HIV infection was associated with chronic obstructive pulmonary disease (COPD), chronic respiratory failure, emphysema, lung fibrosis and pulmonary arterial hypertension (PAH) even after adjustment for smoking.The emergence of noninfectious lung disease, in particular COPD, emphysema, lung fibrosis, PAH and chronic respiratory disease, in PLHIV would justify mass screening in this population.
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Infecções por HIV/complicações , Hospitalização/tendências , Pneumopatias/epidemiologia , Doenças não Transmissíveis/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fumar/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Streptococcus pyogenes can colonize genitourinary tract, but it is a rare cause of salpingitis. CASE REPORT: We report a case of bilateral salpingitis due to Streptococcus pyogenes in a 34-year-old woman using an intra-uterine device and which occurred following a family history of recurrent S. pyogenes infections. We review 12 other cases reported in the literature, and discuss the pathophysiological mechanisms of this potentially life-threatening disease. CONCLUSION: It is important to take into account consider Streptococcus pyogenes as a cause of acute salpingitis in the context of recent intra-familial Streptococcus pyogenes infections.
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Salpingite/diagnóstico , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/diagnóstico , Streptococcus pyogenes/isolamento & purificação , Adolescente , Adulto , Feminino , Humanos , Dispositivos Intrauterinos , Recidiva , Salpingite/tratamento farmacológico , Salpingite/microbiologia , Infecções Estreptocócicas/tratamento farmacológico , Adulto JovemAssuntos
COVID-19 , Síndrome do Desconforto Respiratório , Humanos , Intubação Intratraqueal , SARS-CoV-2 , Carga ViralRESUMO
Invasive fungal infections are severe infections and constantly rising in developed countries. Indeed, advances in hematology, oncology, transplantation and intensive care medicine, are responsible for a longer and deeper immunodepression, in patients which are increasingly older. Only HIV-associated cryptococcosis and Pneumocystis pneumonia are decreasing, in countries where HAART are available and have been able to restore immunity. An increase in the antifungal therapies exposure lead to the emergence of less susceptible species/isolates to usual treatments, and other fungi (Mucorales, Scedosporium, Fusarium). However, in developing countries where access to HAART is limited, cryptococcosis remains a major public health. To a lesser degree, some endemic mycoses are on the rise.
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Terapia de Imunossupressão , Micoses/diagnóstico , Micoses/epidemiologia , Aspergilose/diagnóstico , Aspergilose/epidemiologia , Candidíase/diagnóstico , Candidíase/epidemiologia , Criptococose/diagnóstico , Criptococose/epidemiologia , Cryptococcus neoformans/isolamento & purificação , Países em Desenvolvimento/estatística & dados numéricos , França/epidemiologia , Saúde Global/estatística & dados numéricos , Humanos , Incidência , Mucormicose/diagnóstico , Mucormicose/epidemiologia , Micoses/microbiologia , Micoses/mortalidade , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/epidemiologia , Taxa de SobrevidaRESUMO
Significant changes were observed in the lung imaging of hospitalised COVID-19 patients from 2020 to 2023, with the emergence of more signs of co-infection https://bit.ly/3TaQlJ2.
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Our study aimed to compare children under 5 years hospitalized with respiratory syncytial virus in prepandemic and late-pandemic periods. We included 209 children at the Dijon University Hospital (France). We observed a nearly 3-fold increase in the number of cases in the late period, with older children, but less frequently requiring intensive care. These observations could help prepare a new pandemic.
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COVID-19 , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Criança , Humanos , Lactente , Pré-Escolar , Adolescente , Infecções por Vírus Respiratório Sincicial/epidemiologia , Pandemias , COVID-19/epidemiologia , Cuidados CríticosRESUMO
Among 15 strains of Listeria monocytogenes tested, a synergy between amoxicillin and ceftriaxone was observed in 14 (93%) according to minimal inhibitory concentration strips and 12 (80%) per the checkerboard methods, as well as for 2 of the 3 strains tested by the time-killing curve. This association may be an alternative treatment for listeriosis in the future.