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Background. Although recently challenged, systemic inflammatory response syndrome (SIRS) criteria are still commonly used in daily practice to define sepsis. However, several factors in liver cirrhosis may negatively impact its prognostic ability. Goals. To investigate the factors associated with the presence of SIRS, the characteristics of SIRS related to infection, and its prognostic value among patients hospitalized for acute decompensation of cirrhosis. Study. In this cohort study from two tertiary hospitals, 543 patients were followed up, up to 90 days. Data collection, including the prognostic models, was within 48 hours of admission. Results. SIRS was present in 42.7% of the sample and was independently associated with upper gastrointestinal bleeding (UGB), ACLF, infection, and negatively related to beta-blockers. SIRS was associated with mortality in univariate analysis, but not in multiple Cox regression analysis. The Kaplan–Meier survival probability of patients without SIRS was 73.0% and for those with SIRS was 64.7%. The presence of SIRS was not significantly associated with mortality when considering patients with or without infection, separately. Infection in SIRS patients was independently associated with Child-Pugh C and inversely related to UGB. Among subjects with SIRS, mortality was independently related to the presence of infection, ACLF, and Child-Pugh C. Conclusions. SIRS was common in hospitalized patients with cirrhosis and was of no prognostic value, even in the presence of infection.

Introduction and aim: Hepatic encephalopathy (HE) is a frequent complication of cirrhosis, but the clinical and prognostic significance of the progression of mental status in hospitalised cirrhotics is unknown. We aimed to investigate the prognostic significance of serial evaluation of HE in patients hospitalised for acute decompensation (AD) of cirrhosis. Materials and methods: Patients (n = 293) were evaluated for HE (West-Haven criteria) at admission and at day-3 and classified in two groups: (1) Absent or improved HE: HE absent at admission and at day-3, or any improvement at day-3; (2) Unfavourable progression: Development of HE or HE present at admission and stable/worse at day-3. Results: Unfavourable progression of HE was observed in 31% of patients and it was independently associated with previous HE, Child–Pugh C and acute-on-chronic liver failure (ACLF). MELD score and unfavourable progression of HE were independently associated with 90-day mortality. The 90-day Kaplan–Meier survival probability was 91% in patients with MELD

Introduction Adiponectin and resistin levels are increased in patients with cirrhosis, but it prognostic significance is unknown. We sought to investigate the factors associated with adiponectin and resistin levels and its clinical significance in patients with cirrhosis. Materials and methods This was a prospective cohort study that included 122 subjects with cirrhosis who attended an outpatient clinic and were initially evaluated in 2012. Serum adiponectin and resistin levels were measured in samples collected in 2012 (adiponectin and resistin) and 2014 (adiponectin). Thirty healthy subjects served as a control group. Results Higher adiponectin (21.59 μ g/mL vs. 12.52 μg/mL, P l 0.001) and resistin levels (3.83 ng/mL vs. 2.66 ng/mL, P l 0.001) were observed among patients with cirrhosis compared to controls. Patients classified as Child-Pugh B/C had higher adiponectin levels in relation to Child-Pugh A patients. At second measurement, adiponectin levels increased significantly in non-transplant patients and decreased in liver transplant recipients. Univariate Cox analysis showed that among patients with alcoholic liver disease, adiponectin levels were associated with lower transplant-free survival (HR = 1.034, 95% CI 1.006 - 1.062, P = 0.016). The transplant-free survival was significantly lower among patients with alcoholic liver disease and adiponectin ≥ 17 μg/mL (26.55 months, 95% CI 21.40-31.70) as compared to those with levels l 17 μg/mL (33.76 months, 95% CI 30.70-36.82) (P = 0.045). No relationship was found between the levels of resistin and survival. Conclusion Adiponectin but not resistin levels were associated with intensity of liver dysfunction and worse prognosis in patients with alcoholic liver disease, suggesting a potential as a prognostic biomarker.

Introduction and aim. New criteria for acute kidney injury (AKI) in cirrhosis have been proposed, but its prognostic significance is unclear. This study aims to evaluate the prognostic significance of the AKI criteria in cirrhotic patients hospitalized for acute decompensation.Material and methods. This is a prospective cohort study. AKI was defined as an increase in creatinine (Cr) levels ≥ 0.3 mg/dL in 48 h or ≥ 50% of the basal value in the last 7d. AKI was divided into stages 1 (elevation: < 2x basal), 2 (2 or 3x), and 3 (> 3x).Results. In this study, 227 patients aged 53.9 ± 11.5 years were included, of whom 37% had AKI (28% AKI1, 5% AKI2, and 4% AKI3). Thirty percent of the patients died or were transplanted within 90 days from causes related to the presence of ascites at hospital admission and higher values of Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) scores, but not to the presence of AKI. In a regression analysis conducted to assess the effect of the final Cr level in patients with AKI, 90-day mortality was associated with ascites, higher CLIF-SOFA score, and AKI with final Cr level ≥ 1.5 mg/dL. The patients with AKI with Cr levels ≥ 1.5 mg/dL showed lower transplant-free survival rates than those without AKI, and those with AKI1 with final Cr level < 1.5 mg/dL.Conclusions. Early AKI was frequent and associated with 90-day mortality or transplantation only when the final Cr level was ≥ 1.5 mg/dL. Distinct approaches are needed for patients with AKI1 according to final Cr.

Introduction. Adiponectin and resistin levels are increased in patients with cirrhosis, but it prognostic significance is unknown. We sought to investigate the factors associated with adiponectin and resistin levels and its clinical significance in patients with cirrhosis.Materials and methods. This was a prospective cohort study that included 122 subjects with cirrhosis who attended an outpatient clinic and were initially evaluated in 2012. Serum adiponectin and resistin levels were measured in samples collected in 2012 (adiponectin and resistin) and 2014 (adiponectin). Thirty healthy subjects served as a control group.Results. Higher adiponectin (21.59 μg/mL vs. 12.52 μg/mL, P < 0.001) and resistin levels (3.83 ng/mL vs. 2.66 ng/mL, P < 0.001) were observed among patients with cirrhosis compared to controls. Patients classified as Child-Pugh B/C had higher adiponectin levels in relation to ChildPugh A patients. At second measurement, adiponectin levels increased significantly in non-transplant patients and decreased in liver transplant recipients. Univariate Cox analysis showed that among patients with alcoholic liver disease, adiponectin levels were associated with lower transplant-free survival (HR = 1.034, 95% CI 1.006 - 1.062, P = 0.016). The transplant-free survival was significantly lower among patients with alcoholic liver disease and adiponectin ≥ 17 μg/mL (26.55 months, 95% CI 21.40-31.70) as compared to those with levels < 17 μg/mL (33.76 months, 95% CI 30.70-36.82) (P = 0.045). No relationship was found between the levels of resistin and survival.Conclusion. Adiponectin but not resistin levels were associated with intensity of liver dysfunction and worse prognosis in patients with alcoholic liver disease, suggesting a potential as a prognostic biomarker.

Introduction Although both pro- and anti-inflammatory circulating cytokines are known to be elevated in liver cirrhosis, its clinical significance is not completely recognized. Our aim was to evaluate the prognostic significance of circulating cytokines interleukin (IL)-6, IL-17 and IL-10 in different stages of cirrhosis. Methods This prospective study included two cohorts: (1) stable cirrhosis attended in the Outpatient Clinic (n = 118), and (2) subjects hospitalized for acute decompensation (AD) (n = 130). Thirty healthy subjects served as control group. Results Patients with cirrhosis exhibited higher levels of cytokines as compared to controls. In stable cirrhosis, during a median follow-up of 17 months, liver-related events occurred in 26 patients. Higher IL-10 levels and Child-Pugh B/C were independently associated with reduced event-free survival. In AD cohort, death after 90 days of follow-up occurred in 39 patients and was independently associated with ascites, higher IL-6 and model for end-stage liver disease. IL-6 levels also showed higher AUROC than CRP for predicting bacterial infection in the AD cohort (0.831 ± 0.043 vs. 0.763 ± 0.048, respectively). IL-17 decreased at third day of hospitalization only in patients who progressed to death. Higher IL-6 levels were observed in acute-on-chronic liver failure (ACLF) patients even in the absence of bacterial infection whereas IL-10 was higher only in subjects with infection-related ACLF. Higher IL-10 and IL-17 levels were associated with progression to death in ACLF. Conclusions The pattern of immune response seems to vary according to the phase of cirrhosis and is related to prognosis, from stable disease to ACLF.

Context: IGF-I serum levels are suppressed in cirrhosis, but its prognostic significance is unknown.Objectives: To investigate the prognostic value of IGF-I in patients admitted for acute decompensation of cirrhosis.Materials and methods: Cohort study that included 103 patients. IGF-I was measured by enzyme-linked immunosorbent assay (ELISA).Results: Ninety-day mortality was 26.2% and it was independently associated with MELD, age and IGF-I. The Kaplan–Meier survival probability at 90 days was 94.3% in patients with IGF-I ≥13 ng/mL and 63.2% for patients with IGF-I

SETTING Information about the sputum cells of pulmonary tuberculosis (PTB) patients is scarce. The analysis of sputum cells using optical microscopy (OM) is a well-established method, but it has some serious limitations. OBJECTIVE To establish a new flow cytometry (FC) protocol for the leucocyte evaluation of sputum samples from PTB patients. DESIGN A new FC protocol using 0.1% dithiothreitol and 0.5% paraformaldehyde was developed to fluidise sputum samples and kill Mycobacterium tuberculosis, respectively, to allow the analysis of sputum samples collected from TB patients. The protocol was validated by comparing it with OM, and the cellularity of 30 sputum samples from patients with PTB was evaluated. RESULTS The comparison between leucocyte subsets analysed using OM and FC showed agreement. Immunophenotyping of leucocytes from sputum samples showed that neutrophils (95.7%) comprised the largest proportion of sputum cells, followed by monocytes/macrophages (2.6%) and lymphocytes (1.6%). Among the total T-lymphocytes (100%), 12.3% were T-helper cells, 24.1% were cytotoxic T-cells and 62.9% were gamma/delta T; none of the T lymphocytes had the CD4+/CD8+ phenotype. CONCLUSION FC is a useful method for evaluating the different subtypes of leucocytes present in the sputum samples of PTB patients.

The leaves of the neotropical dioecious shrub Hedyosmum brasiliense (HB) are employed popularly as a sedative, aphrodisiac and as a substitute for green tea. The aim of this work was to study the composition of the hot tea infusion from the fresh leaves of HB, comparing its androecious or gynoecious parts, including the isolation and identification of new secondary metabolites. The characterization of the HB tea infusion was achieved by means of UHPLC–ESI(±)-HRMS and the isolation of its secondary metabolites was done through FCPC and MPLC. Both female and male plant extracts presented similar chemical profiles, with rosmarinic acid (RA) as the main compound. The FCPC analysis led to a one-step isolation of RA 97% pure. A new sesquiterpene lactone (1-α-acetoxyeudesma-3,7(11)–dien–8,12–olide) is reported herein for the first time. The additional compounds isolated and characterized by NMR and LC–MS are isorinic acid, a glycosylated flavonol, two neolignans reported for the first time for HB and three other sesquiterpene lactones which were previously isolated from the ethanol extract. Neither the extract nor its major constituent (RA) exhibited in-vitro antimycobacterial activity.

Introduction. Lower 25-hydroxyvitamin D [25(OH)D] levels have been observed in cirrhotic patients and have been related to disease severity. However, most previous studies included patients with very advanced disease, lacking an adequate control for other variables that could interfere with vitamin D levels. We sought to investigate the prevalence of hypovitaminosis D and the factors related to its occurrence. Material and methods. This cross-sectional study included 133 cirrhotic patients and 30 healthy controls. Bivariate and multivariate analyses were performed to determine factors associated with 25(OH)D levels below the lower tertile. Thirty patients who had been recently hospitalized were compared in two time points. Results. Mean 25(OH)D levels were 32.34 ± 11.38 in controls and 27.03 ± 6.22 ng/mL in patients (P = 0.018). 25(OH)D levels were < 30 ng/mL in 69.9% and < 20 ng/mL in 14.3% of the sample. Levels of 25(OH)D below the lower tertile (< 24 ng/mL) were independently associated with higher triceps skinfold and non-Caucasian race. Parathyroid hormone above the reference value (65 pg/mL) was found in 24.6% of patients without association with 25(OH)D or severity of liver disease. Significantly lower levels of 25(OH)D were found at the time of acute decompensation of cirrhosis. Conclusions. In conclusion, hypovitaminosis D was prevalent in cirrhotics and it was associated with adiposity and non-Caucasian race in stable patients with relatively well preserved liver function. However, significantly lower levels were observed during admission for acute decompensation suggesting an impact of systemic inflammation or liver dysfunction on 25(OH)D levels.

Background: Despite the circulating levels of PTX3 were related to the severity of various diseases, there are no studies investigating its role in patients with liver cirrhosis. We aimed to study PTX3 levels in patients with liver cirrhosis. Material and methods: A prospective cohort study included 130 patients hospitalized for acute decompensation of liver cirrhosis, 29 stable cirrhotic outpatients and 32 healthy controls evaluated in a tertiary hospital in Southern Brasil. Results: The median PTX3 level was significantly higher in stable cirrhotic patients compared to controls (2.6 vs. 1.1 ng/mL; p < 0.001), hospitalized cirrhotic patients compared to controls (3.8 vs. 1.1 ng/mL; p < 0.001), and hospitalized cirrhotic patients compared to stable cirrhotic patients (3.8 vs. 2.6 ng/ mL; p = 0.001). A positive correlation was found between PTX3 and serum creatinine (r = 0.220; p = 0.012), Chronic Liver Failure -Sequential Organ Failure Assessment score (CLIF-SOFA) (r = 0.220; p = 0.010), MELD (r = 0.279; p = 0.001) and Child-Pugh score (r = 0.224; p = 0.010). Significantly higher levels of PTX3 were observed in patients on admission with ACLF (8.9 vs. 3.1 ng/mL; p < 0.001) and MELD score ≥ 20 (6.6 vs. 3.4 ng/mL; p = 0.002). Death within 90 days occurred in 30.8% of patients and was associated with higher levels of PTX3 (5.3 vs. 3.4 ng/mL; p = 0.009). The probability of Kaplan-Meier survival was 77.0% in patients with PTX-3 < 5.3 ng mL (upper tercile) and 53.5% in those with PTX3 ≥ 5.3 ng/mL (p = 0.002). Conclusion: These results indicate the potential for use of PTX3 as an inflammatory biomarker for the prognosis of patients with hepatic cirrhosis.

Background Tuberculosis (TB) control programs face the challenges of decreasing incidence, mortality rates, and drug resistance while increasing treatment adherence. The Brazilian TB control program recommended the decentralization of patient care as a strategy for combating the disease. This study evaluated the performance of this policy in an area with high default rates, comparing epidemiological and operational indicators between two similar municipalities. Methods This study analyzed epidemiological and operational indicators on new cases of pulmonary tuberculosis reported in the Brazilian Notifiable Diseases Information System between 2006 and 2015. In addition, to characterize differences between the populations of the two studied municipalities, a prospective cohort study was conducted between 2014 and 2015, in which patients with new cases of culture-confirmed pulmonary tuberculosis were interviewed and monitored until the disease outcome. A descriptive analysis, the chi-square test, and a Poisson regression model were employed to compare TB treatment outcomes and health care indicators between the municipalities. Results Two thousand three hundred nine cases were evaluated, of which 207 patients were interviewed. Over the 2006–2015 period, TB incidence per 100,000 population in the municipality with decentralized care was significantly higher (39%, 95% CI 27–49%) in comparison to that of the municipality with centralized care. TB treatment default rate (45%, 95% CI 12–90%) was also higher in the municipality with decentralized care. During the two-year follow-up, significant differences were found between patients in centralized care and those in decentralized care regarding treatment success (84.5 vs. 66.1%), treatment default (10.7 vs. 25.8%), illicit drug use (27.7 vs. 45.9%), and homelessness (3.6 vs. 12.9%). The operational indicators revealed that the proportion of control smear tests, medical imaging, and HIV tests were all significantly higher in the centralized care. However, a significantly higher proportion of patients started treatment in the early stages of the disease in the municipality with decentralized care. Conclusions These data showed a low success rate in TB treatment in both municipalities. Decentralization of TB care, alone, did not improve the main epidemiological and operational indicators related to disease control when compared to centralized care. Full implementation of strategies already recommended is needed to improve TB treatment success rates.

To investigate the prognostic significance of insulin-like growth factor-binding protein 3 (IGFBP-3) in patients with cirrhosis.Prospective study that included two cohorts: outpatients with stable cirrhosis (n = 138) and patients hospitalized for acute decompensation (n = 189). Development of complications, mortality or liver transplantation was assessed by periodical phone calls and during outpatient visits. The cohort of stable cirrhosis also underwent clinical and laboratory evaluation yearly (2013 and 2014) in predefined study visits. In patients with stable cirrhosis, IGFBP-3 levels were measured at baseline (2012) and at second re-evaluation (2014). In hospitalized subjects, IGFBP-3 levels were measured in serum samples collected in the first and in the third day after admission and stored at -80 °C. IGFBP-3 levels were measured by immunochemiluminescence.IGFBP-3 levels were lower in hospitalized patients as compared to outpatients (0.94 mcg/mL vs 1.69 mcg/mL, P0.001) and increased after liver transplantation (3.81 mcg/mL vs 1.33 mcg/mL, P = 0.008). During the follow-up of the stable cohort, 17 patients died and 11 received liver transplantation. Bivariate analysis showed that death or transplant was associated with lower IGFBP-3 levels (1.44 mcg/mL vs 1.74 mcg/mL, P = 0.027). The Kaplan-Meier transplant-free survival probability was 88.6% in patients with IGFBP-3 ≥ 1.67 mcg/mL and 72.1% for those with IGFBP31.67 mcg/mL (P = 0.015). In the hospitalized cohort, 30-d mortality was 24.3% and was independently associated with creatinine, INR, SpO2/FiO2 ratio and IGFBP-3 levels in the logistic regression. The 90-d transplant-free survival probability was 80.4% in patients with IGFBP-3 ≥ 0.86 mcg/mL and 56.1% for those with IGFBP30.86 mcg/mL (P0.001).Lower IGFBP-3 levels were associated with worse outcomes in patients with cirrhosis, and might represent a promising prognostic tool that can be incorporated in clinical practice.

BACKGROUND Tuberculosis (TB), one of the major airborne infectious bacterial diseases, remains an important health problem worldwide. It is estimated that there are 1700 new cases per year in Santa Catarina State, Brazil. OBJECTIVE To improve polymerase chain reaction (PCR) sensitivity in detecting Mycobacterium tuberculosis in sputum samples. METHODS This study proposed the use of glass beads as a modification of the routine protocol for sputum preparation used in the Laboratory of Molecular Biology and Mycobacteria at the Federal University of Santa Catarina, Florianopolis, Brazil. The study comprised 120 sputum samples, 60 of which were treated with the routine protocol, while 60 were treated with the modified protocol using glass beads. RESULTS Samples treated with the routine protocol had a sensitivity of 56.7% (95%CI 44.1-69.2) in 16S rRNA PCR and 81.7% (95%CI 71.9-91.5) in insertion sequence (IS) 6110 PCR, compared with culture. Samples treated with the modified protocol had a sensitivity of 73.3% (95%CI 62.1-84.5) in 16S rRNA PCR and 100% in IS6110 PCR. CONCLUSION The modified protocol using glass beads greatly improved mycobacterial detection in sputum samples compared with the routine protocol.

It is estimated that one third of the world population is infected with Mycobacterium tuberculosis, resulting in 2 million deaths annually. More than 8 million new cases of tuberculosis (TB) are registered per year worldwide, and Brazil ranks 19th among the top 23 countries with the highest rates of TB. The determining factors for the control of this disease include early detection, appropriate therapy and measures for avoiding transmission. The conventional diagnoses (smear and microorganism culture) have time limitations for implementation and operation, since the result may take up to 60 days to be released. Therefore, early detection is critical for blocking the chain of TB transmission. Mycobacterial diseases caused by nontuberculous mycobacteria are also having a major impact due to increased outbreaks of surgical infections. Thereby, the rapid and specific identification of microorganisms is important for the diagnosis, which will determine the type of treatment (treatment according to species). Knowledge of etiologic agents of mycobacterial diseases, as well as sensitive and specific diagnosis allows proper treatment by blocking the chain of TB transmission and controlling nontuberculous mycobacteria outbreaks.