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We performed an observational study to investigate intensive care unit incidence, risk factors, and outcomes of coronavirus disease-associated pulmonary aspergillosis (CAPA). We found 10%-15% CAPA incidence among 823 patients in 2 cohorts. Several factors were independently associated with CAPA in 1 cohort and mortality rates were 43%-52%.We performed an observational study to investigate intensive care unit incidence, risk factors, and outcomes of coronavirus disease-associated pulmonary aspergillosis (CAPA). We found 10%-15% CAPA incidence among 823 patients in 2 cohorts. Several factors were independently associated with CAPA in 1 cohort and mortality rates were 43%-52%.

Although hepatocellular carcinoma (HCC) is one of the most common malignancies and constitutes the third leading cause of cancer-related deaths, the underlying molecular mechanisms are not fully understood. In the present study, we demonstrate for the first time that hepatocytes express signalling lymphocytic activation molecule family member 3 (SLAMF3/CD229) but not other SLAMF members. We provide evidence to show that SLAMF3 is involved in the control of hepatocyte proliferation and in hepatocellular carcinogenesis. SLAMF3 expression is significantly lower in primary human HCC samples and HCC cell lines than in human healthy primary hepatocytes. In HCC cell lines, the restoration of high levels of SLAMF3 expression inhibited cell proliferation and migration and enhanced apoptosis. Furthermore, SLAMF3 expression was associated with inhibition of HCC xenograft progression in the nude mouse model. The restoration of SLAMF3 expression levels also decreased the phosphorylation of MAPK ERK1/2, JNK and mTOR. In samples from resected HCC patients, SLAMF3 expression levels were significantly lower in tumorous tissues than in peritumoral tissues. Our results identify SLAMF3 as a specific marker of normal hepatocytes and provide evidence for its potential role in the control of proliferation of HCC cells.

Background Recent multicenter studies identified COVID-19 as a risk factor for invasive pulmonary aspergillosis (IPA). However, no large multicenter study has compared the incidence of IPA between COVID-19 and influenza patients. Objectives To determine the incidence of putative IPA in critically ill SARS-CoV-2 patients, compared with influenza patients. Methods This study was a planned ancillary analysis of the coVAPid multicenter retrospective European cohort. Consecutive adult patients requiring invasive mechanical ventilation for > 48 h for SARS-CoV-2 pneumonia or influenza pneumonia were included. The 28-day cumulative incidence of putative IPA, based on Blot definition, was the primary outcome. IPA incidence was estimated using the Kalbfleisch and Prentice method, considering extubation (dead or alive) within 28 days as competing event. Results A total of 1047 patients were included (566 in the SARS-CoV-2 group and 481 in the influenza group). The incidence of putative IPA was lower in SARS-CoV-2 pneumonia group (14, 2.5%) than in influenza pneumonia group (29, 6%), adjusted cause-specific hazard ratio (cHR) 3.29 (95% CI 1.53–7.02, p  = 0.0006). When putative IPA and Aspergillus respiratory tract colonization were combined, the incidence was also significantly lower in the SARS-CoV-2 group, as compared to influenza group (4.1% vs. 10.2%), adjusted cHR 3.21 (95% CI 1.88–5.46, p  < 0.0001). In the whole study population, putative IPA was associated with significant increase in 28-day mortality rate, and length of ICU stay, compared with colonized patients, or those with no IPA or Aspergillus colonization. Conclusions Overall, the incidence of putative IPA was low. Its incidence was significantly lower in patients with SARS-CoV-2 pneumonia than in those with influenza pneumonia. Clinical trial registration The study was registered at ClinicalTrials.gov, number NCT04359693 .

Pre‐BCR acts as a critical checkpoint in B cell development. However, its signalling cascade still remains indistinctly characterised in human. We investigated pre‐BCR signalling pathway to examine its regulation in normal primary pre‐B lymphocytes and pre‐B cell lines. In cell lines, early signalling events occurring after pre‐BCR stimulation include phosphorylation of Lyn, Blk and Syk together with ZAP70, Btk, Vav, PLC‐γ2 and various adaptor proteins, such as BLNK, LAB, LAT and SLP‐76. Further downstream, these molecules induced activation of the PI3K/AKT and MAP‐kinase resulting in an augmentation of canonical NF‐κB pathways and cFos/AP1 activation. PI3K and MAPK exerted opposing effects on the pre‐BCR‐induced activation of the canonical NF‐κB and c‐Fos/AP1 pathways. Immediate nuclear export of FoxO3A and delayed import of IRF4 were additional events observed after pre‐BCR crosslinking in primary cells. Pre‐BCR‐induced down‐regulation of Rag1, Rag2, E2A and Pax5 transcripts occurred in a PI3K‐dependent manner. Finally we bring evidence that pre‐BCR stimulation or co stimulation with CD19 enhances cell cycle signal. PI3K and MAPK exerted opposing effects on the pre‐BCR‐induced activation of the canonical NF‐κB and c‐Fos/AP1 pathways. In addition, pre‐BCR‐induced down‐regulation of Rag1, Rag2, E2A and Pax5 transcripts occurred in a PI3K‐dependent manner.

We performed an observational study to investigate intensive care unit incidence, risk factors, and outcomes of coronavirus disease–associated pulmonary aspergillosis (CAPA). We found 10%–15% CAPA incidence among 823 patients in 2 cohorts. Several factors were independently associated with CAPA in 1 cohort and mortality rates were 43%–52%.

We performed an observational study to investigate intensive care unit incidence, risk factors, and outcomes of coronavirus disease-associated pulmonary aspergillosis (CAPA). We found 10%-15% CAPA incidence among 823 patients in 2 cohorts. Several factors were independently associated with CAPA in 1 cohort and mortality rates were 43%-52%.

Although hepatocellular carcinoma (HCC) is one of the most common malignancies and constitutes the third leading cause of cancer-related deaths, the underlying molecular mechanisms are not fully understood. In the present study, we demonstrate for the first time that hepatocytes express signalling lymphocytic activation molecule family member 3 (SLAMF3/CD229) but not other SLAMF members. We provide evidence to show that SLAMF3 is involved in the control of hepatocyte proliferation and in hepatocellular carcinogenesis. SLAMF3 expression is significantly lower in primary human HCC samples and HCC cell lines than in human healthy primary hepatocytes. In HCC cell lines, the restoration of high levels of SLAMF3 expression inhibited cell proliferation and migration and enhanced apoptosis. Furthermore, SLAMF3 expression was associated with inhibition of HCC xenograft progression in the nude mouse model. The restoration of SLAMF3 expression levels also decreased the phosphorylation of MAPK ERK1/2, JNK and mTOR. In samples from resected HCC patients, SLAMF3 expression levels were significantly lower in tumorous tissues than in peritumoral tissues. Our results identify SLAMF3 as a specific marker of normal hepatocytes and provide evidence for its potential role in the control of proliferation of HCC cells.

Background Mannose-binding lectin (MBL) plays an important role in the innate immune response. In addition to activating the complement, MBL can induce cytokine production and contribute to a deleterious inflammatory response with severe A(H1N1)pdm09 virus infection. Our aim was to determine if serum MBL levels correlate with the risk of mortality in intensive care units (ICU) patients with A(H1N1)pdm09 infection. Methods Prospective observational study was performed in ICU patients with acute respiratory distress syndrome due to influenza A(H1N1)pdm09 virus. Demographic characteristics and severity indices were recorded at ICU admission. MBL was assayed from blood drawn at influenza diagnosis within 24–48 h following the ICU admission. Outcomes were compared according to MBL levels. Results are expressed as median and interquartile range. Results Serum MBL levels were studied in 27 patients (age: 56 [IQR 29] years) with severe A(H1N1)pdm09 infection and in 70 healthy controls. Median admission SAPSII and SOFA scores were 49 [IQR 26] and 12 [IQR 5], respectively. Mortality rate after a 30-day was 37%. MBL was significantly higher in non-survivors (3741 [IQR 2336] ng/ml) vs survivors (215 [IQR 1307] ng/ml), p  = 0.006, as well as control group (1814 [IQR 2250] ng/ml), p  = 0.01. In contrast, MBL levels in survivors group were significantly lower than the controls group (215 [IQR 1307] ng/ml vs. 1814 [IQR 2250] ng/ml, p  = 0.005). MBL cut-off > 1870 ng/ml had a sensitivity of 80% and a specificity of 88.2% for mortality [AUC = 0.82 (95% CI 0.63–0.94)]. Kaplan–Meier analysis demonstrated a strong association between MBL levels and mortality (log-rank 7.8, p  = 0.005). MBL > 1870 ng/ml was independently associated with mortality (HR = 8.7, 95% CI 1.2–29.1, p  = 0.007). Conclusions This study shows that baseline MBL > 1870 ng/ml is associated with higher mortality in ICU patients with severe A(H1N1)pdm09 infection.

Pre‐BCR acts as a critical checkpoint in B cell development. However, its signalling cascade still remains indistinctly characterised in human. We investigated pre‐BCR signalling pathway to examine its regulation in normal primary pre‐B lymphocytes and pre‐B cell lines. In cell lines, early signalling events occurring after pre‐BCR stimulation include phosphorylation of Lyn, Blk and Syk together with ZAP70, Btk, Vav, PLC‐γ2 and various adaptor proteins, such as BLNK, LAB, LAT and SLP‐76. Further downstream, these molecules induced activation of the PI3K/AKT and MAP‐kinase resulting in an augmentation of canonical NF‐κB pathways and cFos/AP1 activation. PI3K and MAPK exerted opposing effects on the pre‐BCR‐induced activation of the canonical NF‐κB and c‐Fos/AP1 pathways. Immediate nuclear export of FoxO3A and delayed import of IRF4 were additional events observed after pre‐BCR crosslinking in primary cells. Pre‐BCR‐induced down‐regulation of Rag1, Rag2, E2A and Pax5 transcripts occurred in a PI3K‐dependent manner. Finally we bring evidence that pre‐BCR stimulation or co stimulation with CD19 enhances cell cycle signal.