Low pre-transplant levels of mannosebinding lectin are associated with viral infections and mortality after haematopoietic allogeneic stem cell transplantation

Background: Mannose-binding lectin (MBL) is a key component of innate immunity. Low serum MBL levels, related to promoter polymorphism and structural variants, have been associated with an increased risk of infection. The aim of this work was to analyse the incidence and severity of infections and mortality in relation to the MBL2 genotype and MBL levels in patients underwent allogeneic haematopoietic stem cell transplantation (Allo-HSCT). Results: This was a prospective cohort study of 72 consecutive patients underwent Allo-HSCT between January 2007 and June 2009 in a tertiary referral centre. Three periods were considered in the patients? follow-up: the early period (0?30 days after Allo-HSCT), the intermediate period (30?100 days after Allo-HSCT) and the late period (> 100 days after Allo-HSCT). A commercial line probe assay for MBL2 genotyping and an ELISA Kit were used to measure MBL levels. A total of 220 episodes of infection were collected in the 72 patients. No association between donor or recipient MBL2 genotype and infection was found. The first episode of infection presented earlier in patients with pre-transplant MBL levels of < 1000 ng/ml (median 6d vs 8d, p = 0.036). MBL levels < 1000 ng/ml in the pre-transplant period (risk ratio (RR) 2.48, 95% CI 1.00?6.13), neutropenic period (0?30 days, RR 3.28, 95% CI 1.53?7.06) and intermediate period (30?100 days, RR 2.37, 95% CI 1.15?4.90) were associated with increased risk of virus infection. No association with bacterial or fungal disease was found. Mortality was associated with pre-transplant MBL levels < 1000 ng/ml (hazard ratio 5.55, 95% CI 1.17?26.30, p = 0.03) but not with MBL2 genotype. Conclusions: Patients who underwent Allo-HSCT with low pre-transplant MBL levels presented the first episode of infection earlier and had an increased risk of viral infections and mortality in the first 6 months post-transplant. Thus, pre-transplant MBL levels would be important in predicting susceptibility to viral infections and mortality and might be considered a biomarker to be included in the pre-transplantation risk assessment.This work was supported by grants from the Fondo de Investigaciones Sanitarias (Ministry of Health of Spain) PI04/0492 to MC Fariñas and Instituto de Investigación Sanitaria Valdecilla (IDIVAL) API 06/01. The content of the paper is solely the responsibility of the authors and does not necessarily represent the official views. The funding body was not involved in the design of the study, collection or analysis of the data, interpretation of the data, or in the writing of the manuscript

Role of age and comorbidities in mortality of patients with infective endocarditis

Purpose: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. Methods: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015. Patients were stratified into three age groups:<65 years, 65 to 80 years, and = 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. Results: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 = 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients =80 years who underwent surgery were significantly lower compared with other age groups (14.3%, 65 years; 20.5%, 65-79 years; 31.3%, =80 years). In-hospital mortality was lower in the <65-year group (20.3%, <65 years;30.1%, 65-79 years;34.7%, =80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%, =80 years; p = 0.003).Independent predictors of mortality were age = 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI = 3 (HR:1.62; 95% CI:1.39–1.88), and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared, the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. Conclusion: There were no differences in the clinical presentation of IE between the groups. Age = 80 years, high comorbidity (measured by CCI), and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Accuracy of different diagnostic tests for early, delayed and late prosthetic joint infection

Abstract Background A combination of laboratory, histopathological and microbiological tests for diagnosis of prosthetic joint infection (PJI) have been strongly recommended. This study aims to characterize the accuracy of individual or group tests, such as culture of sonicate fluid, synovial fluid and peri-implant tissue, C-reactive protein (CRP) and histopathology for detection of early, delayed and late PJI. Methods A prospective study of patients undergoing hip or knee arthroplasty from February 2009 to February 2014 was performed in a Spanish tertiary health care hospital. The diagnostic accuracy of the different methods was evaluated constructing receiver-operating-characteristic (ROC) curve areas. Results One hundred thirty consecutive patients were included: 18 (13.8%) early PJI, 35 (27%) delayed PJI and 77 (59.2%) late PJI. For individual parameters, the area under the ROC curve for peri-implant tissue culture was larger for early (0.917) than for delayed (0.829) and late PJI (0.778), p = 0.033. There was a significantly larger difference for ROC area in the synovial fluid culture for delayed (0.803) than for early (0.781) and late infections (0.679), p = 0.039. The comparison of the areas under the ROC curves for the two microbiological tests showed that sonicate fluid was significantly different from peri-implant tissue in delayed (0.951 vs 0.829, p = 0.005) and late PJI (0.901 vs 0.778, p = 0.000). The conjunction of preoperative parameters, synovial fluid culture and CRP, improved the accuracy for late PJI (p = 0.01). The conjunction of histopathology and sonicate fluid culture increased the area under ROC curve of sonication in early (0.917 vs 1.000); p = 0.06 and late cases (0.901 vs 0.999); p < 0.001. Conclusion For early PJI, sonicate fluid and peri-implant tissue cultures achieve the same best sensitivity. For delayed and late PJI, sonicate fluid culture is the most sensitive individual diagnostic method. By combining histopathology and peri-implant tissue, all early, 97% of delayed and 94.8% of late cases are diagnosed. The conjunction of histopathology and sonicate fluid culture yields a sensitivity of 100% for all types of infection

Light and strong SiC networks

The directional freezing of microfiber suspensions is used to assemble highly porous (porosities ranging between 92% and 98%) SiC networks. These networks exhibit a unique hierarchical architecture in which thin layers with honeycomb‐like structure and internal strut length in the order of 1–10 μm in size are aligned with an interlayer spacing ranging between 15 and 50 μm. The resulting structures exhibit strengths (up to 3 MPa) and stiffness (up to 0.3 GPa) that are higher than aerogels of similar density and comparable to other ceramic microlattices fabricated by vapor deposition. Furthermore, this wet processing technique allows the fabrication of large‐size samples that are stable at high temperature, with acoustic impedance that can be manipulated over one order of magnitude (0.03–0.3 MRayl), electrically conductive and with very low thermal conductivity. The approach can be extended to other ceramic materials and opens new opportunities for the fabrication of ultralight structures with unique mechanical and functional properties in practical dimensions

Immunometabolic actions of trabectedin and lurbinectedin on human macrophages: relevance for their anti-tumor activity

In recent years, the central role of cell bioenergetics in regulating immune cell function and fate has been recognized, giving rise to the interest in immunometabolism, an area of research focused on the interaction between metabolic regulation and immune function. Thus, early metabolic changes associated with the polarization of macrophages into pro-inflammatory or pro- resolving cells under different stimuli have been characterized. Tumor-associated macrophages are among the most abundant cells in the tumor microenvironment; however, it exists an unmet need to study the effect of chemotherapeutics on macrophage immunometabolism. Here, we use a systems biology approach that integrates transcriptomics and metabolomics to unveil the immunometabolic effects of trabectedin (TRB) and lurbinectedin (LUR), two DNA-binding agents with proven antitumor activity. Our results show that TRB and LUR activate human macrophages toward a pro-inflammatory phenotype by inducing a specific metabolic rewiring program that includes ROS production, changes in the mitochondrial inner membrane potential, increased pentose phosphate pathway, lactate release, tricarboxylic acids (TCA) cycle, serine and methylglyoxal pathways in human macrophages. Glutamine, aspartate, histidine, and proline intracellular levels are also decreased, whereas oxygen consumption is reduced. The observed immunometabolic changes explain additional antitumor activities of these compounds and open new avenues to design therapeutic interventions that specifically target the immunometabolic landscape in the treatment of cancer