A machine learning tool for the diagnosis of SARS-CoV-2 infection from hemogram parameters.

Monocytes and neutrophils play key roles in the cytokine storm triggered by SARS-CoV-2 infection, which changes their conformation and function. These changes are detectable at the cellular and molecular level and may be different to what is observed in other respiratory infections. Here, we applied machine learning (ML) to develop and validate an algorithm to diagnose COVID-19 using blood parameters. In this retrospective single-center study, 49 hemogram parameters from 12,321 patients with clinical suspicion of COVID-19 and tested by RT-PCR (4239 positive and 8082 negative) were analysed. The dataset was randomly divided into training and validation sets. Blood cell parameters and patient age were used to construct the predictive model with the support vector machine (SVM) tool. The model constructed from the training set (5936 patients) achieved an accuracy for diagnosis of SARS-CoV-2 infection of 0.952 (95% CI: 0.875-0.892). Test sensitivity and specificity was 0.868 and 0.899, respectively, with a positive (PPV) and negative (NPV) predictive value of 0.896 and 0.872, respectively (prevalence 0.50). The validation set model (4964 patients) achieved an accuracy of 0.894 (95% CI: 0.883-0.903). Test sensitivity and specificity was 0.8922 and 0.8951, respectively, with a positive (PPV) and negative (NPV) predictive value of 0.817 and 0.94, respectively (prevalence 0.34). The area under the receiver operating characteristic curve was 0.952 for the algorithm performance. This algorithm may allow to rule out COVID-19 diagnosis with 94% of probability. This represents a great advance for early diagnostic orientation and guiding clinical decisions.

Magnetic separation for arsenic and metal recovery from polluted sediments within a circular economy.

Several metals and metalloids (e.g., As, Cd, Cu, Pb, Zn) are toxic at low concentrations, thus their presence in sediments can raise environmental concern. However, these elements can be of economic interest, and several techniques have been used for their recovery and some of them have been widely applied to mining or to industrial soils, but not to sediments. In this work, wet high-intensity magnetic separation (WHIMS) was applied for As, Cd, Cu, Pb and Zn recovery from polluted sediments. A composite sample of 50 kg was taken in the Avilés estuary (Asturias, North Spain) with element concentrations above the legislation limits. Element distribution was assessed using wet-sieving and ICP-MS analysis, revealing that the 125-500 µm grain-size fraction accounts for the 62 w% of the material and that element concentration in this fraction is lower than in the other grain size fractions. Subsequently, WHIMS was applied at three different voltage intensities for the 125-500 µm and <125 µm fractions, revealing excellent recovery ratios, especially for the coarser material. Furthermore, magnetic property measurements coupled to microscopy analysis revealed that the success of the technique derives from concentrating metal-enriched iron oxides particles (ferro- and para-magnetic material) in a mixture of quartz and other minerals (diamagnetic particles). These results indicate the feasibility of the magnetic separation for metal and metalloid recovery from polluted sediments, and thus offer a double benefit of coastal area restoration and valuable material recovery in the context of a circular economy.

Polymorphisms within the ARNT2 and CX3CR1 Genes Are Associated with the Risk of Developing Invasive Aspergillosis.

Invasive aspergillosis (IA) is a life-threatening infection that affects an increasing number of patients undergoing chemotherapy or allo-transplantation, and recent studies have shown that genetic factors contribute to disease susceptibility. In this two-stage, population-based, case-control study, we evaluated whether 7 potentially functional single nucleotide polymorphisms (SNPs) within the ARNT2 and CX3CR1 genes influence the risk of IA in high-risk hematological patients. We genotyped selected SNPs in a cohort of 500 hematological patients (103 of those had been diagnosed with proven or probable IA), and we evaluated their association with the risk of developing IA. The association of the most interesting markers of IA risk was then validated in a replication population, including 474 subjects (94 IA and 380 non-IA patients). Functional experiments were also performed to confirm the biological relevance of the most interesting markers. The meta-analysis of both populations showed that carriers of the ARNT2rs1374213G, CX3CR1rs7631529A, and CX3CR1rs9823718G alleles (where the RefSeq identifier appears as a subscript) had a significantly increased risk of developing IA according to a log-additive model (P value from the meta-analysis [PMeta] = 9.8 · 10-5, PMeta = 1.5 · 10-4, and PMeta =7.9 · 10-5, respectively). Haplotype analysis also confirmed the association of the CX3CR1 haplotype with AG CGG with an increased risk of IA (P = 4.0 · 10-4). Mechanistically, we observed that monocyte-derived macrophages (MDM) from subjects carrying the ARNTR2rs1374213G allele or the GG genotype showed a significantly impaired fungicidal activity but that MDM from carriers of the ARNT2rs1374213G and CX3CR1rs9823718G or CX3CR1rs7631529A alleles had deregulated immune responses to Aspergillus conidia. These results, together with those from expression quantitative trait locus (eQTL) data browsers showing a strong correlation of the CX3CR1rs9823718G allele with lower levels of CX3CR1 mRNA in whole peripheral blood (P = 2.46 · 10-7) and primary monocytes (P = 4.31 · 10-7), highlight the role of the ARNT2 and CX3CR1 loci in modulating and predicting IA risk and provide new insights into the host immune mechanisms involved in IA development.

Ventilator-associated pneumonia by methicillin-susceptible Staphylococcus aureus: do minimum inhibitory concentrations to vancomycin and daptomycin matter?

The use of vancomycin minimum inhibitory concentration (MIC) as an outcome predictor in patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia has become an important topic for debate in the last few years. Given these previous results, we decided to investigate whether MICs to vancomycin or daptomycin had any effect on the evolution of patients with ventilator-associated pneumonia (VAP) due to MSSA. An observational, retrospective, multicenter study was conducted among patients with MSSA VAP. We analyzed the relationship between vancomycin and daptomycin MICs and early clinical response (72 h), 30-day mortality, intensive care unit (ICU) length of stay (LOS), and duration on mechanical ventilation. Univariate and multivariate analyses were performed. Sixty-six patients from 12 centers were included. Twenty-six patients (39%) had an infection due to MSSA strains with a vancomycin MIC ≥1.5 µg/mL. Daptomycin MIC was determined in 58 patients, of whom 17 (29%) had an MIC ≥1.0 µg/mL. Ten patients (15%) did not respond to first-line treatment. Only daptomycin MIC ≥1.0 µg/mL had a significant association [odds ratio (OR): 30.00; 95% confidence interval (CI): 2.91-60.41] with early treatment failure. The 30-day mortality was 12% (n = 8). Any variable was associated with mortality in the multivariate analysis. None of the variables studied were associated with ICU LOS or duration on mechanical ventilation. In patients with MSSA VAP, vancomycin MIC does not influence the response to antibiotic treatment or the 30-day mortality. Daptomycin MIC was directly related to early treatment failure.

Pathogen-related factors affecting outcome of catheter-related bacteremia due to methicillin-susceptible Staphylococcus aureus in a Spanish multicenter study.

Even with appropriate clinical management, complicated methicillin-susceptible Staphylococcus aureus (MSSA) catheter-related bacteremia (CRB) is frequent. We investigated the influence of molecular characteristics of MSSA strains on the risk of complicated bacteremia (CB) in MSSA-CRB. A multicenter prospective study was conducted in Spain between 2011 and 2014 on MSSA-CRB. Optimized protocol-guided clinical management was required. CB included endocarditis, septic thrombophlebitis, persistent bacteremia and/or end-organ hematogenous spread. Molecular typing, agr functionality and DNA microarray analysis of virulence factors were performed in all MSSA isolates. Out of 83 MSSA-CRB episodes included, 26 (31.3%) developed CB. MSSA isolates belonged to 16 clonal complexes (CCs), with CC30 (32.5%), CC5 (15.7%) and CC45 (13.3) being the most common. Comparison between MSSA isolates in episodes with or without CB revealed no differences regarding agr type and functionality. However, our results showed that CC15 and the presence of genes like cna, chp and cap8 were associated with the development of CB. The multivariate analysis highlighted that the presence of cna (Hazard ratio 2.9; 95% CI 1.14-7.6) was associated with the development of CB. Our results suggest that particular CCs and specific genes may influence the outcome of MSSA-CRB.

Should Asymptomatic Bacteriuria Be Systematically Treated in Kidney Transplant Recipients? Results From a Randomized Controlled Trial.

The indication for antimicrobial treatment of asymptomatic bacteriuria (AB) after kidney transplantation (KT) remains controversial. Between January 2011 and December 2013, 112 KT recipients that developed one episode or more of AB beyond the second month after transplantation were included in this open-label trial. Participants were randomized (1:1 ratio) to the treatment group (systematic antimicrobial therapy for all episodes of AB occurring ≤24 mo after transplantation [53 patients]) or control group (no antimicrobial therapy [59 patients]). Systematic screening for AB was performed similarly in both groups. The primary outcome was the occurrence of acute pyelonephritis at 24-mo follow-up. Secondary outcomes included lower urinary tract infection, acute rejection, Clostridium difficile infection, colonization or infection by multidrug-resistant bacteria, graft function and all-cause mortality. There were no differences in the primary outcome in the intention-to-treat population (7.5% [4 of 53] in the treatment group vs. 8.4% [5 of 59] in the control group; odds ratio [OR] 0.88, 95% confidence interval [CI] 0.22-3.47) or the per-protocol population (3.8% [1 of 26] in the treatment group vs. 8.0% [4 of 50] in the control group; OR 0.46, 95% CI 0.05-4.34). Moreover, we found no differences in any of the secondary outcomes. In conclusion, systematic screening and treatment of AB beyond the second month after transplantation provided no apparent benefit among KT recipients (NCT02373085).

Infectious Complications Following Small Bowel Transplantation.

Microbiological spectrum and outcome of infectious complications following small bowel transplantation (SBT) have not been thoroughly characterized. We performed a retrospective analysis of all patients undergoing SBT from 2004 to 2013 in Spain. Sixty-nine patients underwent a total of 87 SBT procedures (65 pediatric, 22 adult). The median follow-up was 867 days. Overall, 81 transplant patients (93.1%) developed 263 episodes of infection (incidence rate: 2.81 episodes per 1000 transplant-days), with no significant differences between adult and pediatric populations. Most infections were bacterial (47.5%). Despite universal prophylaxis, 22 transplant patients (25.3%) developed cytomegalovirus disease, mainly in the form of enteritis. Specifically, 54 episodes of opportunistic infection (OI) occurred in 35 transplant patients. Infection was the major cause of mortality (17 of 24 deaths). Multivariate analysis identified retransplantation (hazard ratio [HR]: 2.21; 95% confidence interval [CI]: 1.02-4.80; p = 0.046) and posttransplant renal replacement therapy (RRT; HR: 4.19; 95% CI: 1.40-12.60; p = 0.011) as risk factors for OI. RRT was also a risk factor for invasive fungal disease (IFD; HR: 24.90; 95% CI: 5.35-115.91; p < 0.001). In conclusion, infection is the most frequent complication and the leading cause of death following SBT. Posttransplant RRT and retransplantation identify those recipients at high risk for developing OI and IFD.

Clinical Presentation and Determinants of Mortality of Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: A Multinational Cohort Study.

The prognostic factors and optimal therapy for invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT) remain poorly studied. We included in this multinational retrospective study 112 recipients diagnosed with probable (75.0% of cases) or proven (25.0%) IPA between 2000 and 2013. The median interval from transplantation to diagnosis was 230 days. Cough, fever, and expectoration were the most common symptoms at presentation. Bilateral pulmonary involvement was observed in 63.6% of cases. Positivity rates for the galactomannan assay in serum and bronchoalveolar lavage samples were 61.3% and 57.1%, respectively. Aspergillus fumigatus was the most commonly identified species. Six- and 12-week survival rates were 68.8% and 60.7%, respectively, and 22.1% of survivors experienced graft loss. Occurrence of IPA within the first 6 months (hazard ratio [HR]: 2.29; p-value = 0.027) and bilateral involvement at diagnosis (HR: 3.00; p-value = 0.017) were independent predictors for 6-week all-cause mortality, whereas the initial use of a voriconazole-based regimen showed a protective effect (HR: 0.34; p-value = 0.007). The administration of antifungal combination therapy had no apparent impact on outcome. In conclusion, IPA entails a dismal prognosis among KT recipients. Maintaining a low clinical suspicion threshold is key to achieve a prompt diagnosis and to initiate voriconazole therapy.

Risk Factors Associated With Early Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: Results From a Multinational Matched Case-Control Study.

Risk factors for invasive pulmonary aspergillosis (IPA) after kidney transplantation have been poorly explored. We performed a multinational case-control study that included 51 kidney transplant (KT) recipients diagnosed with early (first 180 posttransplant days) IPA at 19 institutions between 2000 and 2013. Control recipients were matched (1:1 ratio) by center and date of transplantation. Overall mortality among cases was 60.8%, and 25.0% of living recipients experienced graft loss. Pretransplant diagnosis of chronic pulmonary obstructive disease (COPD; odds ratio [OR]: 9.96; 95% confidence interval [CI]: 1.09-90.58; p = 0.041) and delayed graft function (OR: 3.40; 95% CI: 1.08-10.73; p = 0.037) were identified as independent risk factors for IPA among those variables already available in the immediate peritransplant period. The development of bloodstream infection (OR: 18.76; 95% CI: 1.04-339.37; p = 0.047) and acute graft rejection (OR: 40.73, 95% CI: 3.63-456.98; p = 0.003) within the 3 mo prior to the diagnosis of IPA acted as risk factors during the subsequent period. In conclusion, pretransplant COPD, impaired graft function and the occurrence of serious posttransplant infections may be useful to identify KT recipients at the highest risk of early IPA. Future studies should explore the potential benefit of antimold prophylaxis in this group.

Propensity Score Analysis of the Role of Initial Antifungal Therapy in the Outcome of Candida glabrata Bloodstream Infections.

Candida glabrata isolates have reduced in vitro susceptibility to azoles, which raises concerns about the clinical effectiveness of fluconazole for treating bloodstream infection (BSI) by this Candida species. We aimed to evaluate whether the choice of initial antifungal treatment (fluconazole versus echinocandins or liposomal amphotericin B [L-AmB]-based regimens) has an impact on the outcome of C. glabrata BSI. We analyzed data from a prospective, multicenter, population-based surveillance program on candidemia conducted in 5 metropolitan areas of Spain (May 2010 to April 2011). Adult patients with an episode of C. glabrata BSI were included. The main outcomes were 14-day mortality and treatment failure (14-day mortality and/or persistent C. glabrata BSI for ≥48 h despite antifungal initiation). The impact of using fluconazole as initial antifungal treatment on the patients' prognosis was assessed by logistic regression analysis with the addition of a propensity score approach. A total of 94 patients with C. glabrata BSI were identified. Of these, 34 had received fluconazole and 35 had received an echinocandin/L-AmB-based regimen. Patients in the echinocandin/L-AmB group had poorer baseline clinical status than did those in the fluconazole group. Patients in the fluconazole group were more frequently (55.9% versus 28.6%) and much earlier (median time, 3 versus 7 days) switched to another antifungal regimen. Overall, 14-day mortality was 13% (9/69) and treatment failure 34.8% (24/69), with no significant differences between the groups. On multivariate analysis, after adjusting for baseline characteristics by propensity score, fluconazole use was not associated with an unfavorable evolution (adjusted odds ratio [OR] for 14-day mortality, 1.16, with 95% confidence interval [CI] of 0.22 to 6.17; adjusted OR for treatment failure, 0.83, with 95% CI of 0.27 to 2.61). In conclusion, initial fluconazole treatment was not associated with a poorer outcome than that obtained with echinocandins/L-AmB regimens in patients with C. glabrata BSI. (This study has been registered at ClinicalTrials.gov under registration no. NCT01236261.).

Significance of the isolation of Staphylococcus aureus from a central venous catheter tip in the absence of concomitant bacteremia: a clinical approach.

The optimal approach following the isolation of Staphylococcus aureus from an intravascular catheter tip in the absence of concomitant bacteremia remains unclear. We aimed to determine the rate of delayed complications in these patients. We performed a retrospective observational study (during the period 2002-2012) including patients with a catheter tip culture yielding S. aureus. Patients were followed up for ≥6 months. The primary endpoint was the occurrence of delayed staphylococcal complications (either bacteremia and/or metastatic distant infections). A total of 113 patients were included (75 % male, median age 61 years): 46 and 67 with negative and positive blood cultures, respectively. We found a lower rate of delayed staphylococcal complications in cases with no bacteremia within 48 h since catheter removal than in cases of confirmed S. aureus catheter-related bacteremia (0.0 % vs. 25.4 %; p-value < 0.001). In the group without bacteremia, there was a subgroup of 15 patients (32.6 %) who did not receive antimicrobial treatment. Again, delayed complications occurred less commonly in this subgroup of patients without bacteremia (0.0 % vs. 25.4 %; p-value = 0.033). In contrast to patients with S. aureus catheter-related bacteremia, no delayed infectious complications were observed in patients with an isolated catheter tip culture yielding S. aureus and negative blood cultures within 48 h of catheter removal. Futures studies are needed to assess if the therapeutic approach could be different for this group of patients.

Post-transplant monitoring of NK cell counts as a simple approach to predict the occurrence of opportunistic infection in liver transplant recipients.

BACKGROUND: Monitoring of peripheral blood lymphocyte subpopulation (PBLS) counts might be useful for estimating the risk of infection after liver transplantation (LT). METHODS: We prospectively measured total lymphocyte and PBLS counts at baseline and post-transplant months 1 and 6 in 92 LT recipients. PBLS were enumerated by single-platform 6-color flow cytometry technology. Areas under receiver operating characteristic (ROC) curves were used to evaluate the accuracy of different PBLS for predicting cytomegalovirus (CMV) disease and overall opportunistic infection (OI). Adjusted hazard ratios (aHRs) for both outcomes were estimated by Cox regression. RESULTS: After a median follow-up of 730.0 days, 29 patients (31.5%) developed 38 episodes of OI (including 22 episodes of CMV disease). The counts of CD3(+) , CD4(+) , and CD8(+) T cells, and CD56(+) CD16(+) natural killer (NK) cells at month 1 were significantly lower in patients subsequently developing OI. The NK cell count was the best predictive parameter (area under ROC curve for predicting CMV disease: 0.78; P-value = 0.001). Patients with an NK cell count <0.050 × 10(3) cells/µL had higher cumulative incidences of CMV disease (P-value = 0.001) and overall OI (P-value <0.001). In the multivariate models, an NK cell count <0.050 × 10(3) cells/µL at month 1 post transplantation remained as an independent risk factor for CMV disease (aHR: 5.54; P-value = 0.003) and overall OI (aHR: 7.56; P-value <0.001). CONCLUSION: Post-transplant kinetics of NK cell counts may be used as a simple and affordable proxy to the cell-mediated immunity status in LT recipients and to their associated risk of OI.

Progressive increase of resistance in Enterobacteriaceae urinary isolates from kidney transplant recipients over the past decade: narrowing of the therapeutic options.

BACKGROUND: Antibiotic resistance is an emerging phenomenon in kidney transplantation (KT). METHODS: We compared species distribution and antimicrobial susceptibility patterns in 1052 isolates from urine cultures obtained in 2 different cohorts of kidney transplant recipients in a single center (Cohort A: 189 patients undergoing KT between January 2002 and December 2004 [336 isolates]; Cohort B: 115 patients undergoing KT between January 2011 and December 2013 [716 isolates]). RESULTS: Asymptomatic bacteriuria accounted for most of the isolates (86.9% in Cohort A and 92.3% in Cohort B). Klebsiella pneumoniae (9.5% vs. 15.6%), Pseudomonas aeruginosa (1.8% vs. 7.9%), and Enterobacter cloacae (0.6% vs. 3.1%) were significantly more common in Cohort B. The isolation of K. pneumoniae in Cohort B was associated with the occurrence of acute pyelonephritis (9.8% of all K. pneumoniae isolates vs. 2.8% of the remaining uropathogens; P = 0.001). Non-susceptibility rates among Enterobacteriaceae in Cohort B were higher for every class of antibiotics (P ≤ 0.003) with the exception of fosfomycin. Compared to Cohort A, significant increases were seen in isolates from Cohort B for multidrug-resistant (MDR) (43.9% vs. 67.8%, respectively; P = 0.001), extended-spectrum beta-lactamase (ESBL)-producing (6.6% vs. 26.1%; P = 0.001), and carbapenemase-producing Enterobacteriaceae strains (0.0% vs. 5.0%; P = 0.001). Such differences were mostly attributable to K. pneumoniae (as 54.5% and 13.4% of isolates in Cohort B were ESBL-producing and carbapenemase-producing, respectively). MDR isolates were responsible for 69.1% of episodes of symptomatic urinary tract infection in Cohort B. CONCLUSION: The increase in resistance rates among Enterobacteriaceae uropathogens is significant and may have an effect on KT programs.

Detection of Epstein-Barr virus DNAemia after lung transplantation and its potential relationship with the development of post-transplant complications.

BACKGROUND: Recent studies suggest that Epstein-Barr virus DNAemia (EBVd) may act as a surrogate marker of post-transplant immunosuppression. This hypothesis has not been tested so far in lung transplant (LT) recipients. METHODS: We included 63 patients undergoing lung transplantation at our center between October 2008 and May 2013. Whole blood EBVd was systematically assessed by real-time polymerase chain reaction assay on a quarterly basis. The occurrence of late complications (overall and opportunistic infection [OI] and chronic lung allograft dysfunction [CLAD]) was analyzed according to the detection of EBVd within the first 6 months post transplantation. RESULTS: Any EBVd was detected in 30 (47.6%) patients. Peak EBVd was higher in patients with late overall infection (2.23 vs. 1.73 log10 copies/mL; P = 0.026) and late OI (2.39 vs. 1.74 log10 copies/mL; P = 0.004). The areas under receiver operating characteristic curves for predicting both events were 0.806 and 0.871 respectively. The presence of an EBVd ≥2 log10 copies/mL during the first 6 months post transplantation was associated with a higher risk of late OI (adjusted hazard ratio [aHR] 7.92; 95% confidence interval [CI] 2.10-29.85; P = 0.002). Patients with detectable EBVd during the first 6 months also had lower CLAD-free survival (P = 0.035), although this association did not remain statistically significant in the multivariate analysis (aHR 1.26; 95% CI 0.87-5.29; P = 0.099). CONCLUSIONS: Although preliminary in nature, our results suggest that the detection of EBVd within the first 6 months after transplantation is associated with the subsequent occurrence of late OI in LT recipients.

Polymorphisms in Host Immunity-Modulating Genes and Risk of Invasive Aspergillosis: Results from the AspBIOmics Consortium.

Recent studies suggest that immune-modulating single-nucleotide polymorphisms (SNPs) influence the risk of developing cancer-related infections. Here, we evaluated whether 36 SNPs within 14 immune-related genes are associated with the risk of invasive aspergillosis (IA) and whether genotyping of these variants might improve disease risk prediction. We conducted a case-control association study of 781 immunocompromised patients, 149 of whom were diagnosed with IA. Association analysis showed that the IL4Rrs2107356 and IL8rs2227307 SNPs (using dbSNP numbering) were associated with an increased risk of IA (IL4Rrs2107356 odds ratio [OR], 1.92; 95% confidence interval [CI], 1.20 to 3.09; IL8rs2227307 OR, 1.73; 95% CI, 1.06 to 2.81), whereas the IL12Brs3212227 and IFNγrs2069705 variants were significantly associated with a decreased risk of developing the infection (IL12Brs3212227 OR, 0.60; 95% CI, 0.38 to 0.96; IFNγrs2069705 OR, 0.63; 95% CI, 0.41 to 0.97). An allogeneic hematopoietic stem cell transplantation (allo-HSCT)-stratified analysis revealed that the effect observed for the IL4Rrs2107356 and IFNγrs2069705 SNPs was stronger in allo-HSCT (IL4Rrs2107356 OR, 5.63; 95% CI, 1.20 to 3.09; IFNγrs2069705 OR, 0.24; 95% CI, 0.10 to 0.59) than in non-HSCT patients, suggesting that the presence of these SNPs renders patients more vulnerable to infection, especially under severe and prolonged immunosuppressive conditions. Importantly, in vitro studies revealed that carriers of the IFNγrs2069705C allele showed a significantly increased macrophage-mediated neutralization of fungal conidia (P = 0.0003) and, under stimulation conditions, produced higher levels of gamma interferon (IFNγ) mRNA (P = 0.049) and IFNγ and tumor necrosis factor alpha (TNF-α) cytokines (P value for 96 h of treatment with lipopolysaccharide [PLPS-96 h], 0.057; P value for 96 h of treatment with phytohemagglutinin [PPHA-96 h], 0.036; PLPS+PHA-96 h = 0.030; PPHA-72 h = 0.045; PLPS+PHA-72 h = 0.018; PLPS-96 h = 0.058; PLPS+PHA-96 h = 0.0058). Finally, we also observed that the addition of SNPs significantly associated with IA to a model including clinical variables led to a substantial improvement in the discriminatory ability to predict disease (area under the concentration-time curve [AUC] of 0.659 versus AUC of 0.564; P-2 log likehood ratio test = 5.2 · 10(-4) and P50.000 permutation test = 9.34 · 10(-5)). These findings suggest that the IFNγrs2069705 SNP influences the risk of IA and that predictive models built with IFNγ, IL8, IL12p70, and VEGFA variants can used to predict disease risk and to implement risk-adapted prophylaxis or diagnostic strategies.

Association between individual and combined SNPs in genes related to innate immunity and incidence of CMV infection in seropositive kidney transplant recipients.

In this study, we assessed the association between single-nucleotide polymorphisms (SNPs) in seven candidate genes involved in orchestrating the immune response against cytomegalovirus (CMV) and the 12-month incidence of CMV infection in 315 CMV-seropositive kidney transplant (KT) recipients. Patients were managed either by antiviral prophylaxis or preemptive therapy. CMV infection occurred in 140 patients (44.4%), including 13 episodes of disease. After adjusting for various clinical covariates, patients harboring T-allele genotypes of interleukin-28B (IL28B) (rs12979860) SNP had lower incidence of CMV infection (adjusted hazard ratio [aHR]: 0.66; 95% confidence interval [CI]: 0.46-0.96; p-value = 0.029). In the analysis restricted to patients not receiving prophylaxis, carriers of the TT genotype of toll-like receptor 9 (TLR9) (rs5743836) SNP had lower incidence of infection (aHR: 0.61; 95% CI: 0.38-0.96; p-value = 0.035), whereas the GG genotype of dendritic cell-specific ICAM 3-grabbing nonintegrin (DC-SIGN) (rs735240) SNP exerted the opposite effect (aHR: 1.86; 95% CI: 1.18-2.94; p-value = 0.008). An independent association was found between the number of unfavorable SNP genotypes carried by the patient and the incidence of CMV infection. In conclusion, specific SNPs in IL28B, TLR9 and DC-SIGN genes may play a role in modulating the susceptibility to CMV infection in CMV-seropositive KT recipients.

Cannabis and bipolar disorder: does quitting cannabis use during manic/mixed episode improve clinical/functional outcomes?

OBJECTIVE: To examine whether bipolar disorder patients who stop cannabis use during a manic/mixed episode have better clinical and functional outcomes than continued use or never use. METHOD: Data from the European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM), a 2-year prospective observational study in adults with a manic/mixed episode of bipolar disorder, was used. Three cannabis use groups were: current use (between 12-week and 24-month visits); no current but previous use (during first 12 weeks); and never use. Associations between cannabis use and outcomes were analyzed using regression models. RESULTS: Of 1922 patients analyzed, 6.9% were current users, 4.6% previous users, and 88.5% never users. Clinical outcomes differed between groups (P<0.019): previous users had highest rates of remission (68.1%) and recovery (38.7%), and lowest rates of recurrence (42.1%) and relapse (29.8%). Logistic regression showed previous users had similar outcomes to never users (all P>0.05), whereas current users had lower recovery (P=0.004) and remission (P=0.014), higher recurrence (P=0.014), greater work impairment (P=0.016), and were more likely not to be living with partner (P=0.006) than never users. CONCLUSION: Bipolar patients who stop using cannabis during manic/mixed episode have similar clinical and functional outcomes to never users, while continued use is associated with higher risk of recurrence and poorer functioning.

Mycobacterium abscessus pulmonary infection complicated with vertebral osteomyelitis in a heart transplant recipient: case report and literature review.

Infections produced by Mycobacterium abscessus are emerging in immunosuppressed patients, such as solid organ transplant recipients. We report the first case, to our knowledge, of a vertebral osteomyelitis caused by M. abscessus in a heart transplant recipient, and review the risk factors, manifestations, and therapeutic approaches to this uncommon disease.

Impact of squalene-based adjuvanted influenza vaccination on graft outcome in kidney transplant recipients.

BACKGROUND: Safety concerns have been raised about the use of adjuvanted vaccines after kidney transplantation. METHODS: We retrospectively analyzed 65 kidney transplant (KT) recipients who received ≥1 dose of influenza vaccine (pandemic or seasonal) during the 2009-2010 campaign. Participants were classified into 2 groups: those who received a squalene-based AS03- or MF59-adjuvanted vaccine ("adjuvanted vaccination" [AV] group, n = 37) and those who exclusively received non-adjuvanted vaccines ("non-adjuvanted vaccination" [NAV] group, n = 28). Primary outcomes included occurrence of biopsy-proven acute graft rejection (BPAR) and graft function at months 6 and 12 after vaccination. Patients were followed up until graft loss, death, or October 2010. RESULTS: Four episodes of BPAR occurred during post-vaccination follow-up, with no differences between the AV and NAV groups, in terms of cumulative incidence (5.4% vs. 7.1%, respectively; P = 0.581), incidence rate (0.22 vs. 0.18 episodes per 1000 transplant-days; P = 0.950), or occurrence of severe episodes (T-cell-mediated BPAR of grade ≥2a) (2.7% vs. 3.6%; P = 0.680). No between-group differences were seen in graft function after vaccination. CONCLUSION: Adjuvanted influenza vaccination in KT recipients seems to be safe regarding graft outcome.