Impact of markers of endothelial injury and hypercoagulability on systemic lupus erythematosus.

We have explored the relationship between possible hemostatic changes and clinical manifestation of the systemic lupus erythematosus (SLE) as a function of greater or lesser disease activity according to Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) criteria. Endothelial injury and hypercoagulability were investigated in patients with SLE by measuring thrombomodulin (TM), D-dimer (DDi) and thrombin generation (TG) potential. A total of 90 participants were distributed into three groups: 1) women with SLE presenting with low disease activity (laSLE) (SLEDAI-2K ≤ 4), 2) women with SLE presenting with moderate to high disease activity (mhaSLE) (SLEDAI-2K > 4), and 3) a control group comprising healthy women. Levels of TM and DDi were higher both in the laSLE and mhaSLE groups compared to controls and in mhaSLE compared to the laSLE group. With respect to TG assay, lagtime and endogen thrombin potential, low concentrations of tissue factor provided the best results for discrimination among groups. Analysis of these data allow us to conclude that TM, DDi and TG are potentially useful markers for discriminating patients with very active from those with lower active disease. Higher SLE activity may cause endothelial injury, resulting in higher TG and consequently a hypercoagulability state underlying the picture of thrombosis common in this inflammatory disease.

The maternal 14 bp Ins/Del polymorphism in HLA-G is not associated with preeclampsia risk.

The effect of HLA-G 14 bp Ins/Del polymorphism (rs371194629) on the risk of preeclampsia has been assessed in several populations, yet the results are still conflicting. Lack of power due to small sample sizes is a common cause of inconsistencies in genetic association studies. We aimed to test whether the maternal polymorphism is associated with preeclampsia, eclampsia or HELLP syndrome (acronym for Hemolysis, Elevation of Liver enzymes, Low Platelets). To achieve a statistical power greater than 0.90, a total of 741 women (332 controls, 246 preeclampsia, 57 eclampsia and 106 HELLP) were genotyped for the 14-bp Ins/Del polymorphism. The genetic association with disease status was assessed by Fisher's exact test and odds ratio (OR) estimates using logistic regression model adjusted for maternal age and parity status. Allele and genotype distributions were the same between control and case groups (p > .05). The polymorphism was not associated with the risk of developing preeclampsia [OR = 0.93 (0.72-1.19); p = .541], or eclampsia [OR = 0.90 (0.60-1.38); p = .628] nor HELLP syndrome [OR = 0.92 (0.66-1.28); p = .628]. This well-powered study clearly demonstrates that the maternal HLA-G 14-bp Ins/Del polymorphism is not associated with preeclampsia risk. However, as the offspring genotypes were not evaluated here, we could not rule out the effect of the foetal genotype on the preeclampsia pathogenesis.

Non-alcoholic fatty liver disease in women with polycystic ovary syndrome: systematic review and meta-analysis.

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is an insidious pathologic condition that can manifest from simple steatosis to steatohepatitis (NASH) with potential progression to cirrhosis. Like the polycystic ovary syndrome (PCOS), NAFLD is associated with obesity, diabetes mellitus, insulin resistance and metabolic syndrome. PCOS women have an increased risk of NAFLD, but it is debatable which features of PCOS, either specific (androgen excess) or unspecific (metabolic derangements) affect the NAFLD risk. METHODS: We performed a systematic review and meta-analysis of studies that addressed the association of PCOS and NAFLD. We selected 17 studies published between 2007 and 2017 that included 2734 PCOS patients and 2561 controls of similar age and body mass index (BMI). RESULTS: PCOS patients have increased prevalence of NAFLD (odds ratio 2.54, 95% confidence interval 2.19-2.95). PCOS women with hyperandrogenism (classic phenotype) have a higher prevalence of NAFLD compared to women with PCOS without hyperandrogenism, even after correction for confounding variables. Among women with PCOS, those with NAFLD have higher serum total testosterone (mean difference 0.40 nmol/L, 95% CI 0.29-0.50 nmol/L) and free androgen index (mean difference 4.46, 95% CI 3.53-5.39) than those without NAFLD. The studies that used multivariate analysis controlling for age, BMI, triglycerides, and insulin resistance index confirmed that serum androgens are independent predictors of NAFLD in women with PCOS. CONCLUSION: The prevalence of NAFLD is increased in women with PCOS and the presence of NAFLD is associated with high serum androgen levels, in addition to obesity and insulin resistance.

Seroprevalence of antibodies against bacterial pathogens in sheep from Equatorial Guinea.

Equatorial Guinea (EG) is a country in Central Africa with typical tropical weather. Sheep are an important source of food in EG, but the absence of information regarding infectious diseases that affect the native flocks of small ruminants is a concern. The country is currently implementing several new practices in the sheep industry associated with the importation of sheep from other countries. This study aimed to evaluate the seroprevalence of bacterial infections that are important to the sheep industry in EG sheep flocks. The detection of specific antibodies for the four agents studied was performed using enzyme-linked immunosorbent assay in 1,002 serum samples from EG sheep. The results showed a true prevalence of 13.37% for antibodies against Corynebacterium pseudotuberculosis, 0.59% for Brucella ovis, 19.89% for Chlamydophila abortus and 0.79% for Mycoplasma agalactiae in animals from production flocks. Among a group of 35 samples from isolated native animals, 47.56% were seropositive for antibodies against C. pseudotuberculosis, 42.84% for B. ovis, 54.28% for C. abortus and 11.35% for M. agalactiae. These results comprise the first report of the prevalence of infectious diseases in sheep in EG. They highlight the importance of adopting adequate measures to prevent infection by bacteria endemic to EG native flocks during the development of the sheep industry in the country.

La Guinée équatoriale est un pays d'Afrique centrale au climat typiquement tropical. Les moutons constituent une source importante d'aliments pour le pays, ce qui rend particulièrement alarmante l'absence d'informations concernant les maladies infectieuses affectant le cheptel autochtone de petits ruminants. Le pays met actuellement en place de nouvelles pratiques d'élevage ovin, en lien avec l'importation de moutons d'autres pays. La présente étude avait pour objet d'évaluer la prévalence sérologique de quelques infections bactériennes majeures pour le secteur de l'élevage dans le cheptel ovin de la Guinée équatoriale. Pour les besoins de l'étude, 1 002 échantillons de sérum prélevés de moutons autochtones ont été soumis à une épreuve immuno-enzymatique pour la détection d'anticorps spécifiques dirigés contre quatre agents bactériens. La prévalence réelle de moutons issus de troupeaux d'élevage possédant des anticorps vis-à-vis de chacune des bactéries recherchées s'est élevée à 13,37 % pour Corynebacterium pseudotuberculosis, à 0,59 % pour Brucella ovis, à 19,89 % pour Chlamydophila abortus et à 0,79 % pour Mycoplasma agalactiae. Dans un groupe de 35 prélèvements issus d'animaux isolés autochtones, le taux d'échantillons positifs était de 47,56 % pour C. pseudotuberculosis, de 42,84 % pour B. ovis, de 54,28 % pour C. abortus et de 11,35 % pour M. agalactiae. Ces résultats constituent le premier rapport sur la prévalence des maladies infectieuses chez le mouton en Guinée équatoriale. Ils soulignent l'importance d'adopter des mesures appropriées afin de prévenir les infections dues à des bactéries endémiques dans le cheptel autochtone de la Guinée équatoriale, à un moment où ce pays cherche à développer l'élevage ovin.

Guinea Ecuatorial es un país centroafricano con un clima tropical típico, en el que las ovejas constituyen una importante fuente de alimento. Por ello es preocupante la ausencia de información sobre las enfermedades infecciosas que afectan a los rebaños autóctonos de pequeños rumiantes. El país está implantando ahora una serie de nuevos procedimientos en el sector ovino, vinculados a la importación de ovejas de otros países. Los autores describen un estudio encaminado a evaluar la seroprevalencia en los rebaños de ovejas del país de infecciones bacterianas de importancia para el sector. Para detectar anticuerpos específicos contra los cuatro agentes estudiados se aplicó la técnica del ensayo inmunoenzimático a 1 002 muestras de suero de ovejas autóctonas. Los resultados pusieron de manifiesto una prevalencia real de anticuerpos contra Corynebacterium pseudotuberculosis del 13,37%, del 0,59% contra Brucella ovis, del 19,89% contra Chlamydophila abortus y del 0,79% contra Mycoplasma agalactiae en ejemplares pertenecientes a rebaños productivos. De un grupo de 35 muestras procedentes de animales autóctonos aislados, un 47,56% resultaron seropositivas para los anticuerpos contra C. pseudotuberculosis, un 42,84% en el caso de B. ovis, un 54,28% en el de C. abortus y un 11,35% en el de M. agalactiae. Estos resultados, que constituyen el primer informe sobre la prevalencia de enfermedades infecciosas en las ovejas de Guinea Ecuatorial, demuestran la importancia de instituir medidas adecuadas para prevenir la infección por bacterias endémicas de los rebaños autóctonos de Guinea Ecuatorial en un momento en que la industria ovina del país está en pleno crecimiento.

Prevalence of food allergy in infants and pre-schoolers in Brazil.

BACKGROUND: Food allergy is an increasing problem in public health, especially in childhood. Its incidence has increased in the last decade. Despite this, estimates of the actual incidence and prevalence are uncertain. The aim of this study was to estimate the prevalence of food allergy in infants and pre-schoolers. METHODS: The parents of 3897 children completed questionnaires on the occurrence of any reaction to food. Children with parentally reported reactions were selected for further examination including a clinical interview, physical examination, allergic tests, and if necessary, oral food challenge to conclude the diagnosis of FA. RESULTS: The estimated prevalence of allergy in children aged 4-59 months was 0.61%, being, 1.9% in infants and 0.4% in pre-schoolers. Among the 604 patients physicians evaluated with parent-reported FA, 24 (4%) had a confirmed diagnosis of food allergy, and 580 (96%) were excluded in the remaining. Of these, approximately half (51/52.6%) of 97 infants and (128/48%) of 487 pre-schoolers already performed the diet exclusion suspected food for a period of time. CONCLUSION: This study shows that high overall prevalence of parental belief of current food allergy however the same was not observed in the in physician-diagnosed food allergy. The prevalence of food allergy was lower than that observed in the literature. This study alerts health professionals to the risk entailed by overestimation of cases of food allergy and unnecessary dietary exclusion, which may result in impairment in growth and development of children, especially in their first years of life.

Fish composition and species richness in eastern South American coastal lagoons: additional support for the freshwater ecoregions of the world.

The relationships between fish composition, connectivity and morphometry of 103 lagoons in nine freshwater ecoregions (FEOW) between 2·83° S and 37·64° S were evaluated in order to detect possible congruence between the gradient of species richness and similarities of assemblage composition. Most lagoons included in the study were <2 km(2) , with a maximum of 3975 km(2) in surface area. Combined surface area of all lagoons included in the study was 5411 km(2) . Number of species varied locally from one to 76. A multiple regression revealed that latitude, attributes of morphometry and connectivity, and sampling effort explained a large amount of variability in species richness. Lagoon area was a good predictor of species richness except in low latitude ecoregions, where lagoons are typically small-sized and not affected by marine immigrants, and where non-native fish species accounted for a significant portion of species richness. Relationships between species and area in small-sized lagoons (<2 km(2) ) is highly similar to the expected number in each ecoregion, with systems located between 18·27° S and 30·15° S attaining higher levels of species richness. Similarities in species composition within the primary, secondary and peripheral or marine divisions revealed strong continental biogeographic patterns only for species less tolerant or intolerant to salinity. Further support for the FEOW scheme in the eastern border of South America is therefore provided, and now includes ecotonal systems inhabited simultaneously by freshwater and marine species of fishes.

Effect of calcium, bicarbonate, and albumin on capacitation-related events in equine sperm.

Repeatable methods for IVF have not been established in the horse, reflecting the failure of standard capacitating media to induce changes required for fertilization capacity in equine sperm. One important step in capacitation is membrane cholesterol efflux, which in other species is triggered by cholesterol oxidation and is typically enhanced using albumin as a sterol acceptor. We incubated equine sperm in the presence of calcium, BSA, and bicarbonate, alone or in combination. Bicarbonate induced an increase in reactive oxygen species (ROS) that was abolished by the addition of calcium or BSA. Bicarbonate induced protein tyrosine phosphorylation (PY), even in the presence of calcium or BSA. Incubation at high pH enhanced PY but did not increase ROS production. Notably, no combination of these factors was associated with significant cholesterol efflux, as assessed by fluorescent quantitative cholesterol assay and confirmed by filipin staining. By contrast, sperm treated with methyl-ß-cyclodextrin showed a significant reduction in cholesterol levels, but no significant increase in PY or ROS. Presence of BSA increased sperm binding to bovine zonae pellucidae in all three stallions. These results show that presence of serum albumin is not associated with a reduction in membrane cholesterol levels in equine sperm, highlighting the failure of equine sperm to exhibit core capacitation-related changes in a standard capacitating medium. These data indicate an atypical relationship among cholesterol efflux, ROS production, and PY in equine sperm. Our findings may help to elucidate factors affecting failure of equine IVF under standard conditions.

A randomised controlled trial of periconal eye blockade with or without ultrasound guidance.

We randomly allocated 129 participants with normal eyes to periconal blockade with (n = 69) or without (n = 60) ultrasound guidance before cataract surgery. There was no difference in the rates of complication, 1/69 and 0/60, respectively, p = 1.0. The rate of intraconal needle placement was 1/69 with ultrasound and 12/60 without ultrasound, a relative risk (95% CI) of 0.07 (0.01-0.55), p < 0.0001.

Polymyxin use as a risk factor for colonization or infection with polymyxin-resistant Acinetobacter baumannii after liver transplantation.

INTRODUCTION: Acinetobacter baumannii is a leading agent of healthcare-associated infection. The objective of this study was to evaluate cases of colonization or infection with polymyxin-resistant A. baumannii (PRAB) in liver transplant recipients and to identify the risk factors for the acquisition of PRAB. METHODS: We evaluated all patients undergoing liver transplantation (LT) between January and November of 2011. The exclusion criterion was death within the first 72 h after transplant. Patients were screened for PRAB through weekly rectal and inguinal swabs during their stay in the intensive care unit (ICU) and at ICU discharge. Patients who came from other hospitals or had been treated in the emergency room for >72 h were screened at ICU admission. The minimum inhibitory concentrations (MICs) for polymyxins were determined by broth microdilution, and clonality was determined by pulsed-field gel electrophoresis. The stepwise logistic regression was used to identify risk factors related to acquisition of PRAB, and Cox forward regression used to identify risk factors for 60-day mortality. RESULTS: We evaluated 65 patients submitted to LT, among whom PRAB was isolated in 7, 4 of whom developed infection. The MICs for polymyxin E ranged from 16 to 128 mg/mL. All patients with PRAB required dialysis. The median time of polymyxin use before PRAB isolation was 21 days. These 4 included 1 case of primary bloodstream infection (BSI), which was treated with the carbapenem-polymyxin combination; 1 case of surgical site infection, which was treated with gentamicin, polymyxin, ampicillin-sulbactam, and tigecycline; and 2 cases of pneumonia, treated with the combination of carbapenem-polymyxin. In the case of BSI and in 1 of the cases of pneumonia, the treatment was considered successful. Mortality was 71% among the cases, compared with 33% among the non-cases. CONCLUSION: In the final model of the survival analysis, PRAB colonization or infection after LT was independently associated with mortality. One predominant clone was identified. The only risk factor identified in the multivariate analysis was polymyxin use. PRAB was an agent with high mortality, and the most important risk factor associated with colonization or infection for such bacterium was polymyxin use.

Effect of breeding activity on the microflora of the external genitalia and in the semen of stallions, and the relationship between micro-organisms on the skin and on the external genitalia.

A possible role of breeding activities in the composition of the microbial population in stallions' external genitalia (EG) and the relationship between micro-organisms colonizing the skin of the abdomen and the ones colonizing the EG have not been studied. In experiment 1, EG microbiological samples were collected from 41 stallions used for both natural cover and semen collection (BST) and from 18 non-breeding stallions (NBST). A higher (p < 0.05) frequency of isolation of potentially pathogenic species was found for BST. Age did not influence number of micro-organism species isolated both in BST and NBST. In experiment 2, the microbial content of the EG and semen was compared in 23 BST. Most micro-organisms isolated from the EG were present in semen, albeit with a numerically lower prevalence. In 7 stallions, six microbial species isolated from semen were absent from the EG cultures, suggesting contamination by the operator. In experiment 3, a numerically higher number of micro-organism species was isolated from the EG of 31 stallions, than from their skin of the ventral abdomen in contact with the penis or from the skin of the thorax. With the sole exception of Escherichia coli, potentially pathogenic bacteria were only isolated from the EG but not from the skin. Results suggest that breeding activity increased the number of species colonizing the EG; most species isolated from the EG were also found in semen even if with a lower frequency, and additional semen contamination seemed to occur during its manipulation. Many micro-organism species of the skin were also isolated from the penis, but independently of being or not in contact with the penis, skin did not seem to provide an adequate environment for the growth of potentially pathogenic bacteria that were isolated from EG, with the sole exception for E. coli.

Infection rate and risk factors associated with infections related to external ventricular drain.

OBJECTIVE: To describe incidence rates and risk factors associated with external ventricular drain (EVD)-related infections at a tertiary Brazilian teaching hospital. METHODS: The patient cohort consisted of all patients at a major teaching hospital in Brazil with an EVD during the period 1 April 2007 to 30 June 2008 (15 months). Patients were followed up for 30 days after catheter removal. According to the Center for Diseases Control and Prevention criteria for meningitis/ventriculitis, all of the central nervous system (CNS) infections that occurred during this period could be considered to be meningitis or ventriculitis related to EVD placement. Infection rates were calculated using different denominators, such as (1) per patient (incidence), (2) per procedure, and (3) per 1,000 catheter-days (drain-associated infection rate). Patient demographic data, medical history of underlying diseases, antibiotic prophylaxis usage, American Society of Anesthesiologists Score classification, duration of surgery and hospitalization, length of time the EVD was in place, and overall mortality were evaluated during the study period. A logistic regression model was developed to identify factors associated with infection. RESULTS: A total of 119 patients, 130 EVD procedures, and 839 catheter-days were evaluated. The incidence of infection was 18.3%, the infection rate was 16.9% per procedure, and the drain-associated infection rate was 22.4 per 1,000 catheter-days; 77% of the infections were caused by Gram-negative micro-organisms. Only 75% of patients received antibiotic prophylaxis. The infection rate increased with length of the hospital stay. The length of time the catheter was in place was the only independent risk factor associated with infection (p = 0.0369). CONCLUSION: The incidence of EVD-related infections is high in our hospital, Gram-negative micro-organisms were the most frequent causal agents identified and length of time that the catheter was in place contributed to the infection rate.

Chronic Aerobic Training at Different Volumes in the Modulation of Macrophage Function and in vivo Infection of BALB/c Mice by Leishmania major.

Physical inactivity is one of the main causes of chronic diseases; however, strenuous exercise can induce immunosuppression. Several studies suggest that moderate amounts of exercise lead to a Th1 response, favoring the resolution of infections caused by intracellular microorganisms, while high volumes of exercise tend to direct the response to Th2, favoring infection by them. Leishmaniasis is a parasitic disease promoted by parasites of the Leishmania genus, with clinical manifestations that vary according to the species of the parasite and the immune response of the host. The experimental Leishmania major-BALB/C mouse model provides a good model for the resistance (Th1 response) or susceptibility (Th2 response) that determines the progression of this infection. The aim of this study was to evaluate the effect of aerobic training at different volumes on modulation of in vitro macrophage infection by L. major, as well as to assess the effect of high volume (HV) aerobic training on the development of L. major in vivo in BALB/c mice. Uninfected animals were submitted to various exercise volumes: none (SED), light (LV), moderate (MV), high (HV), very high (VHV), and tapering (TAP). The macrophages of these animals were infected by L. major and the LV and MV groups showed a decrease in the infection factor, while the VHV showed an increase in the infection factor, when treated with LPS. The cytokine concentration pattern measured in the supernatants of these macrophages suggested a predominant Th1 response profile in the LV and MV groups, while the Th2 profile predominated in the VHV and TAP groups. Groups of BALB/C mice infected with L. major were subjected to high volume (iHV) or non-periodized high volume (iNPHV) exercise or kept sedentary (iSED). The exercised animals suffered a significant increase in injuries caused by the parasites. The animals in the group submitted to high volume exercise (iHV) showed visceralization of the infection. These data strongly suggest that a very high volume of aerobic training increased the susceptibility of BALB/C mice to L. major infection, while moderate distribution of training loads promoted immunological balance, better controlling the infection by this parasite.

Paradoxical response to carbonic anhydrase inhibitors in patients with intraretinal cystoid spaces.

Background: Intraretinal cystoid spaces (IRCS) are fluid-filled spaces seen in some retinal dystrophies and often treated with carbonic anhydrase inhibitors. The purpose of this study is to report an unexpected bilateral improvement in the IRCS after discontinuation of therapy. Material and Methods: We identified from our records 23 patients with retinal dystrophy and IRCS who had been treated with topical and/or oral carbonic anhydrase inhibitors. All subjects had regular follow-up with OCT and previous genetic testing. Results: We identified four (17%) patients who experienced a bilateral and symmetrical paradoxical improvement in IRCS size and visual acuity after discontinuation of carbonic anhydrase inhibitors. Two were mutations in RS1, one in CLN3 and another in NR2E3. All patients were followed for at least three years (range 39-63 months). None had systemic abnormalities. Conclusions: Patients with IRCS may exhibit a paradoxical response after discontinuation of carbonic anhydrase inhibitors. Although the pathophysiology of these phenomena is unclear, stopping treatment may be an option in patients who cease to improve or get worse on treatment.

Differences for T-Cell Subtypes in Aspiration Biopsies of Patients With Kidney Transplant Under Polyclonal and Monoclonal Immunosuppressive Treatments.

Thymoglobulin, or antithymocyte globulin (ATG), and anti-interleukin 2α (IL-2α) chain receptor antibody (IL-2αRAb) achieve comparable good results in kidney transplantation notwithstanding different actions on immune cells. Previously, we reported the usefulness of flow cytometry (FC) analysis of lymphocyte subsets present in peripheral blood sample (PBL) and fine-needle aspiration biopsies (FNABs) for clinical surveillance, as, FC reaches very high predictive positive values for acute rejection diagnosis. Now we report an FC study on 2 kidney transplantation (KT) groups under ATG (n = 19) and IL-2αRAb (n = 24) treatment. Both groups were further treated with calcineurin inhibitors mycophenolate mofetil (MMF) and prednisone. PBL and FNAB samples were collected on day 7 post-KT, stained for several T- and B-lymphocyte subsets, and acquired using FACScan. Statistical analysis were done by Mann-Whitney U test. FNAB results showed a significant downregulation by ATG of CD3 (P < .001), CD4 (P = .009), CD4CD29 (P = .003), and CD2 (P ≤ .001) and significant upregulation of death receptor (DR) (P = .03), CD3CD69 (P < .001), and CD3CD25 (P < .0001) as compared to groups treated with IL-2αRAb. For PBL, the same trend was seen for CD3, CD4, CD2, CD3CD25, CD3CD69, CD4CD29, and DR plus a downregulation of CD45RO (P = .001) and an upregulation of CD4CD45RA (P < .0001) in IL-2αRAb. This study shows that among stable KTs, ATG as compared to IL-2αRAb induces a significant downregulation of a subset of T-memory (CD4CD29) cells but an upregulation of antigen-experienced cells (CD45RO). Further, ATG decreases CD2, CD3, CD4, and naïve (CD45RA) and stimulates T cells as translated by CD3CD69 and DR. As it should be expected from an IL-2αRAb agent, CD25 cells were virtually eliminated.

Species distribution and antifungal susceptibility of 358 Trichosporon clinical isolates collected in 24 medical centres.

OBJECTIVES: To provide species distribution and antifungal susceptibility profiles of 358 Trichosporon clinical isolates collected from 24 tertiary-care hospitals. METHODS: Species identification was performed by sequencing the IGS1 region of rDNA. Antifungal susceptibility testing for amphotericin B, fluconazole, voriconazole and posaconazole followed the Clinical and Laboratory Standards Institute reference method. Tentative epidemiologic cutoff values (97.5% ECVs) of antifungals for Trichosporon asahii were also calculated. RESULTS: Isolates were cultured mostly from urine (155/358, 43.3%) and blood (82/358, 23%) samples. Trichosporon asahii was the most common species (273/358, 76.3%), followed by T. inkin (35/358, 9.7%). Isolation of non-T. asahii species increased substantially over the last 11 years [11/77 (14.2%) from 1997 to 2007 vs. 74/281, (26.3%) from 2008 to 2018, p0.03]. Antifungal susceptibility testing showed high amphotericin B minimum inhibitory concentrations against Trichosporon isolates, with higher values for T. faecale. The ECV for amphotericin B and T. asahii was set at 4 µg/mL. Among the triazole derivatives, fluconazole was the least active drug. The ECVs for fluconazole and posaconazole against T. asahii were set at 8 and 0.5 µg/mL, respectively. Voriconazole showed the strongest in vitro activity against the Trichosporon isolates; its ECV for T. asahii was set at 0.25 µg/mL after 48 hours' incubation. CONCLUSIONS: Trichosporon species diversity has increased over the years in human samples, and antifungal susceptibility profiles were species specific. Trichosporon asahii antifungal ECVs were proposed, which may be helpful to guide antifungal therapy.

Evaluation of potential biomarkers for the diagnosis and monitoring of Systemic Lupus Erythematosus using the Cytometric Beads Array (CBA).

BACKGROUND: Systemic Lupus Erythematosus (SLE) is an autoimmune, multisystemic disease. Currently diagnosis depends on complex criteria developed by the American College of Rheumatology. Moreover, the lack of specific biomarkers also challenges the diagnosis. METHODS: Inflammatory biomarkers such as IL-8, IP-10, MIG, MIP-1α and RANTES were measured in serum samples from SLE patients and subjects in control groups (patients with other autoimmune diseases and healthy individuals). Forty-six SLE patients (22 patients with low activity, SLEDAI-2 K ≤ 4, 24 patients with moderate/high activity, SLEDAI-2 K > 4), 42 patients with other autoimmune diseases (OAD group), and 8 healthy volunteers participated in this study. RESULTS: MIG (p < .001) and RANTES (p < .001) concentrations in SLE patients and healthy controls, and IP-10 concentrations in SLE patients with different disease activities (low activity, p < .01, moderate/high activity, p < .05) differed significantly. IL-8 (p < .001) and MIP-1α (p < .001) concentrations in SLE patients differed from those in patients from the OAD group. IL-8 (p < .05), IP-10 (p < .01), MIG (p < .05), MIP-1α (p < .001), and RANTES (p < .05) were correlated with SLE activity; their concentrations in SLE patients with low and moderate/high activity differed significantly. CONCLUSIONS: Given the findings of this study, one can envision the possibility of future use of some of these cytokines to assist in the screening of SLE patients, or even in monitoring disease activity.

Natural killer cell subpopulations in putative resistant individuals and patients with active Mycobacterium tuberculosis infection.

Herein, we intended to perform flow-cytometric analyses of peripheral blood NK-cell subsets in patients with active tuberculosis (TB) and those putative resistant subjects displaying positive tuberculin skin test (TST+) and compared with TST- healthy controls. Our findings demonstrated distinct phenotypic features in TST+ as compared with TB. While lower values of NK-cells with increased frequency of CD3-CD16+ CD56- and CD3-CD16-CD56+ subsets besides lower frequency of CD3-CD16+ CD56+ NK-cells was observed in TST+, unaltered levels of NK-cells with increased levels of CD3-CD16+ CD56- NK-cells with lower frequency of CD3-CD16+ CD56+ NK-cells was found in TB. Additional analysis highlighted a shift towards increased levels of CD3-CD16-/+CD56bright NK-cells as the hallmark of TST+, whereas unaltered frequency was observed in TB. Increased levels of CD3+CD56+ cells were observed in both TST+ and TB. Further focusing on the monocyte/NK-cell network, we have reported that enhanced frequency of CD14+ CD16+ monocytes particularly observed in TST+. Outstanding were the distinct correlation profiles observed between CD3-CD16-CD56+ NK-cells and CD3+ CD56+ cells CD14+ CD16+ monocytes for TST+ and TB. These data suggested that high levels of CD3-CD16-CD56+ NK-cells aside CD14+ CD16+ monocytes as well as non-concurrent increment of CD3+ CD56+ cells, may be involved in protective mechanisms in putative tuberculosis-resistant individuals. On the other hand, the basal levels of macrophage-like monocytes despite its positive correlation with increased levels of CD3+ CD56+ cells may count for the lack of the protective immunity in patients with active tuberculosis. Further studies focusing on the cytokine profiling of peripheral blood innate immunity cells before and after chemotherapeutic treatment are currently under evaluation.

Epidemiology, risk factors and outcomes of multi-drug-resistant bloodstream infections in haematopoietic stem cell transplant recipients: importance of previous gut colonization.

BACKGROUND: Bloodstream infections (BSI) are a major complication in the early phase of a haematopoietic stem cell transplant (HSCT). AIM: To describe the incidence and risk factors for BSI occurring in the pre-engraftment phase of HSCT, and its impact on mortality. METHODS: Clinical variables of 232 HSCT patients were analysed retrospectively between 2014 and 2015. Univariate Cox regression analyses were performed to test the association between each covariate and the outcome. Covariates with P < 0.10 on univariate analysis were included in a multiple Cox regression analysis using a backward elimination method. FINDINGS: The cumulative incidence of BSI was 25.4%, mainly caused by Gram-negative bacteria (GNB) (55.2%). Approximately 40.5% of the patients had gut colonization by multi-drug-resistant (MDR) bacteria (vancomycin-resistant enterococcus and carbapenem-resistant GNB). Among patients colonized by MDR GNB, 20% developed an overt BSI due to MDR bacteria with the same pattern of sensitivity. Of the 13 deaths related to infection, 10 were patients with BSI caused by MDR GNB. The independent risk factors for BSI were gut colonization by MDR bacteria including GNB (P < 0.001) and duration of neutropenia >10 days (P = 0.005), and those associated with BSI caused by MDR bacteria were age >62 years (P = 0.03), use of total parenteral nutrition (TPN) (P < 0.001) and previous gut colonization by MDR GNB (P = 0.002). CONCLUSIONS: Previous gut colonization by MDR was an independent risk factor for BSI, together with TPN and age, and had an impact on outcome. These findings suggest that gut decolonization may be a potential strategy to prevent BSI.

Vancomycin-resistant enterococci isolates colonizing and infecting haematology patients: clonality, and virulence and resistance profile.

BACKGROUND: Vancomycin-resistant enterococci (VRE) are an important agent of colonization and infection in haematology patients. However, the role of virulence on VRE colonization and infection is controversial. AIM: To characterize the lineage, virulence and resistance profile of VRE infection and colonization isolates; as well as their impact on outcome of haematology patients using a regression logistic model. METHODS: Eighty-six isolates (80 Enterococcus faecium and six E. faecalis) from 76 patients were evaluated. Polymerase chain reaction for resistance and virulence genes, and pulsed-field gel electrophoresis and whole genome sequencing of the major clusters, were performed. Bivariate and multivariate analyses were carried out to evaluate the role of virulence genes on outcome. FINDINGS: All isolates harboured the vanA gene. Regarding the virulence genes, 96.5% of isolates were positive for esp, 69.8% for gelE and asa1 genes. VRE infection isolates were more virulent than colonization isolates and harboured more often the gelE gene (P = 0.008). Infections caused by VRE carrying asa1 gene resulted more frequently in death (P = 0.004), but only the predominant clone remained as protector in the multivariate model. The E. faecium strains were assigned to seven STs (ST78, ST412, ST478, ST792, ST896, ST987, ST963) that belonged to CC17. The E. faecalis sequenced belonged to ST9 (CC9). CONCLUSION: E. faecium was predominant, and infection isolates were more virulent than colonization isolates and harboured more often the gene gelE. Infections caused by VRE carrying the asa1 gene appeared to be associated with a fatal outcome.