Seasonal trend and clinical presentation of Bacillus cereus bloodstream infection: association with summer and indwelling catheter

Bacillus cereus, an opportunistic pathogen, can cause fatal infection. However, B. cereus bloodstream infections (BSIs) have not been well characterised. From 2008 to 2013, B. cereus isolates from all of the specimens and patients with B. cereus BSIs were identified. Environmental samples were collected to detect B. cereus contamination. We also characterised the clinical presentation of B. cereus BSI through analyses of risk factors for BSI and mortality. A total of 217 clinical B. cereus isolates was detected. Fifty-one patients with nosocomial infections were diagnosed as B. cereus BSI, and 37 had contaminated blood cultures. The number of B. cereus isolates and BSI patients was significantly greater from June to September than from January to April (4.9 vs. 1.5 per month and 1.2 vs. 0.2, respectively). All BSIs were nosocomial and related to central or peripheral vascular catheter. Urinary catheter [odds ratio (OR) 6.93, 95 % confidence interval (CI) 2.40–20.0] was the independent risk factor associated with BSI patients when compared to patients regarded as contaminated. In-hospital mortality among BSI patients was 20 % and was associated with urinary catheter (OR 34.7, 95 % CI 1.89–63.6) and higher Charlson index (OR 1.99, 95 % CI 1.26–3.12). The number of B. cereus isolates and BSI increased during summer. Inpatients with indwelling vascular or urinary catheters should be carefully monitored for potential B. cereus BSIs.     

Time to positivity of blood culture and its prognostic value in bloodstream infection

The purpose of this study was to investigate the relationship between the time to positivity (TTP) of blood cultures and outcome in patients with bloodstream infections (BSIs). Between January 1st, 2011 and December 31st, 2013, the blood cultures of inpatients with BSI or catheter-related BSI were collected at Peking University Third Hospital. The TTP of different isolates was analyzed, and the relationship between the TTP of isolates and outcome of patients with Enterobacter BSI was retrospectively analyzed. We analyzed the TTP of 886 isolates. Escherichia coli has the shortest (11.97?±?10.06 h) and Candida has the longest first TTP (61.62?±?42.77 h). 68.01 % of isolates reached positivity within 24 h and 88.33 % within 48 h. Over 90 % of E. coli isolates reached positivity within 24 h. Over 50 % of Candida isolates reached positivity within 48 h. The TTP differed significantly between cultures that were single or double positive for coagulase-negative staphylococci isolates, Enterobacteriaceae, and Pseudomonas aeruginosa, and between aerobic and anaerobic cultures of E. coli (p?<?0.05). However, the TTP did not differ significantly between coagulase-negative staphylococci (double positivity) and Staphylococcus aureus. The best TTP threshold for prediction of mortality from Enterobacter species BSI was 16.3 h [area under the curve (AUC) 0.730, 95 % confidence interval (CI) 0.557, 0.864, sensitivity 100 %, specificity 44.4 %]. The TTP of clinical isolates may represent a valuable marker of the clinical significance of BSIs. Laboratories and clinics should consider using the TTP to predict the prognosis of patients with BSI by bacteria, including Enterobacter and other species.     

Impact of bloodstream infections on catheter colonization during extracorporeal membrane oxygenation

There are concerns about secondary extracorporeal membrane oxygenation (ECMO) catheter infections in bacteremic patients. We investigated the association between blood stream infection (BSI) and ECMO catheter colonization. From January 2012 to August 2014, 47 adults who received ECMO support were enrolled. The ECMO catheter tip was cultured at the end of the ECMO procedure. The enrolled patients were classified into two groups according to the presence of BSI during ECMO support and analyzed with respect to ECMO catheter colonization. Of 47 cases, BSI during ECMO was identified in 13 patients (27.7 %). ECMO catheter colonization was identified in 6 (46.2 %) patients in the BSI group and 3 (8.8 %) in the non-BSI group. BSI during ECMO support was independently associated with ECMO catheter colonization [odds ratio (OR) 5.55; 95 % confidence interval (CI) 1.00–30.73; p = 0.049]. The organisms colonizing ECMO catheters in the setting of primary BSI were predominantly Gram-positive cocci and Candida species. Acinetobacter baumannii was the most common colonizing pathogen in the setting of secondary BSI. All the organisms colonizing ECMO catheters were multi-drug resistant organisms, including methicillin-resistant S. aureus, Candida glabrata, and carbapenem-resistant A. baumannii. ECMO catheters may become contaminated with multi-drug resistant pathogens in the presence of BSI. Therefore, ECMO should be applied cautiously in septic patients with bacteremia caused by multi-drug resistant pathogens.     

Risk factors and outcome of levofloxacin-resistant <Emphasis Type="Italic">Elizabethkingia meningoseptica</Emphasis> bacteraemia in adult patients in Taiwan

Elizabethkingia meningoseptica is an emerging nosocomial pathogen associated with high mortality and inherently resistant to many antimicrobial agents. Levofloxacin has been considered as a therapeutic agent based on in vitro susceptibility. We aim to investigate the risk factors and outcomes for levofloxacin-resistant E. meningoseptica bacteraemia. Adult patients with E. meningoseptica bacteraemia were identified retrospectively in a medical centre in Taiwan from January 2011 to July 2015. These strains were identified by the Vitek2 automated system or matrix-assisted laser desorption-ionization time-of-flight mass spectrometry. We compared clinical features and outcomes of patients with levofloxacin-resistant (MIC >2 μg/mL) and levofloxacin-susceptible (MIC ≤2 μg/mL) E. meningoseptica bacteraemia. A total of 93 patients were identified, including 51 (54.8%) with levofloxacin-resistant E. meningoseptica bacteraemia. The APACHE II score (OR, 1.08; 95% CI, 1.02–1.14; p?=?0.008) was the only independent risk factor for levofloxacin-resistant E. meningoseptica bacteraemia. The 14-day mortality for patients with levofloxacin-resistant E. meningoseptica bacteraemia (attributable mortality: 30.7%) was significantly higher than that for patients with the levofloxacin-susceptible strain (56.9% versus 26.2%, p?=?0.003). In the multivariate analysis of risk factors for mortality, appropriate definite antibiotic use was the only factor associated with 14-day survival (OR, 0.11; 95% CI, 0.02–0.55, p?=?0.007). The levofloxacin-resistant strain was borderline significantly associated with mortality (OR, 3.09; 95% CI, 0.88–10.91, p?=?0.079). The early identification of levofloxacin resistance in E. meningoseptica isolates is important to tackle this multi-drug resistance pathogen.     

Previous bloodstream infections due to other pathogens as predictors of carbapenem-resistant <Emphasis Type="Italic">Klebsiella pneumoniae</Emphasis> bacteraemia in colonized patients: results from a retrospective multicentre study

Introduction: the purpose of this retrospective multicenter study was to assess whether the risk of developing bloodstream infections (BSI) due to carbapenem-resistant Klebsiella pneumoniae (CRKP) in colonized patients is influenced by the occurrence of BSI due to other pathogens. Methods: from January 2012 to March 2014, all patients with at least one rectal swab positive for CRKP and at least 30 days of previous hospital stay were included in the study. The primary outcome measure was CRKP BSI, defined as a time-to-event endpoint. The role of potential predictors was evaluated through univariable and multivariable Cox regression analyses, considering previous BSI as a time-dependent variable. Results: during the study period, 353 patients met the inclusion criteria. Thirty-seven developed a CRKP BSI (11%). A higher incidence of CRKP BSI was observed in presence rather than in absence of previous BSI. In the final multivariable model of risk factors for CRKP BSI, multisite colonization (hazard ratio [HR] 13.73, 95% confidence intervals [CI] 3.29–57.32, p?<?0.001), ICU stay (HR 3.14, 95% CI 1.19–8.31, p = 0.021), and previous BSI (p = 0.026, with the overall effect being mainly due to Enterococcus spp. BSI vs absence of BSI, HR 6.62, 95% CI 2.11–20.79) were associated with the development of CRKP BSI, while an inverse association was observed for age (HR 0.98, 95% CI 0.95–1.00, p = 0.027). Conclusions: previous BSI due to other pathogens were associated with an increased risk of CRKP BSI that was independent of other factors in colonized patients with prolonged hospital exposure.     

Reduced pro-inflammatory responses to <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> bloodstream infection and low prevalence of enterotoxin genes in isolates from patients on haemodialysis

Patients with end-stage renal failure undergo regular haemodialysis (HD) and often develop episodes of Staphylococcus aureus bloodstream infection (BSI), which can re-occur. However, clinically, patients on HD, with S. aureus BSI, respond well to treatment, rarely developing overt signs of sepsis. We investigated the contributions of bacterial virulence and cytokine responses to the clinical course of S. aureus BSI in HD and non-HD patients. Seventy patients were recruited, including 27 (38.6 %) patients on HD. Isolates were spa-typed and virulence and antimicrobial resistance gene carriage was investigated using DNA microarray analysis. Four inflammatory cytokines, IL-6, RANTES, GROγ and leptin, were measured in patient plasma on the day of diagnosis and after 7 days. There was no significant difference in the prevalence of genotypes or antimicrobial resistance genes in S. aureus isolates from HD compared to non-HD patients. The enterotoxin gene cluster (containing staphylococcal enterotoxins seg, sei, sem, sen, seo and seu) was significantly less prevalent among BSI isolates from HD patients compared to non-HD patients. Comparing inflammatory cytokine response to S. aureus BSI in HD patients to non-HD patients, IL-6 and GROγ were significantly lower (p?=?0.021 and p?=?0.001, respectively) in HD patients compared to other patients on the day of diagnosis and RANTES levels were significantly lower (p?=?0.025) in HD patients on day 7 following diagnosis. Lowered cytokine responses in HD patients and a reduced potential for super-antigen production by infecting isolates may partly explain the favourable clinical responses to episodes of S. aureus BSI in HD patients that we noted clinically.     

Incidence and antimicrobial resistance trends in bloodstream infections caused by ESKAPE and <Emphasis Type="Italic">Escherichia coli</Emphasis> at a large teaching hospital in Rome,a 9-year analysis (2007–2015)

The proportion of antimicrobial resistance (AMR) among the ESKAPE and Escherichia coli (ESKAPEEc) pathogens causing bloodstream infection (BSI) increased worldwide. We described longitudinal trends in ESKAPEEc BSI and AMR over 9 years (2007–2015) at a large teaching hospital in Italy. Of 9720 unique BSI episodes, 6002 (61.7%) were caused by ESKAPEEc pathogens. The majority of these episodes (4374; 72.9%) were hospital-onset infections. The most frequent pathogen was E. coli (32.8%), followed by Staphylococcus aureus (20.6%), Klebsiella pneumoniae (16.1%), and Pseudomonas aeruginosa (11.6%). There was a significant increase of hospital-onset K. pneumoniae (from 2.3 to 5.0 per 10,000 patient-days; P =?0.001) and community-onset E. coli (from 3.3 to 9. 1 per 10,000 emergency admissions; P =?0.04) BSIs. Among hospital-onset BSIs, increases of extended-spectrum β-lactamase (ESBL)-producing E. coli (from 25.4 to 35.2%, P?= 0.006), carbapenemase-producing K. pneumoniae (from 4.2 to 51.6%, P <?0.001), and methicillin-resistant S. aureus (from 33.9 to 44.4%, P <?0.001) BSIs were observed between the 2007–2009 and 2010–2012 study periods. In contrast, a decrease of BSIs caused by P. aeruginosa resistant to ceftazidime (from 45.5 to 28.2%, P <?0.001), ciprofloxacin (from 46 to 36.3%, P =?0.05), and meropenem (from 55 to 39.9%, P =?0.03) was observed through all 9 years of the study period. Among community-onset BSIs, increases of BSIs caused by ESBL-producing E. coli (from 28.6 to 42.2%, P =?0.002) and carbapenemase-producing K. pneumoniae (from 0 to 17.6%) were observed between the 2007–2009 and 2010–2012 study periods. Our findings show increased rates of BSI and relative AMR for specific pathogen-health care setting combinations, and call for continued active surveillance and infection control policies.     

Interleukin-28B TT genotype is frequently found in patients with hepatitis C virus cirrhosis but does not influence hepatocarcinogenesis

Persistent hepatitis C virus (HCV) infection is associated with progressive hepatic fibrosis and ultimately hepatocellular carcinoma. The interleukin-28B (IL28B) rs12979860 polymorphism is associated with fibrosis progression in chronic HCV infection. IL28B encodes interferon-λ, which has both antiviral and anti-proliferative properties. This study aimed to determine whether IL28B rs12979860 polymorphism is also associated with development of hepatocellular carcinoma both in chronic HCV infection and in non-viral-related cirrhosis. Real-time polymerase chain reaction and melting curve analyses were used to genotype 311 patients who underwent liver transplantation for HCV cirrhosis (n = 202) or alcoholic cirrhosis (n = 109). HCV patients were older (p = 0.012) and less likely males (p < 0.001) than patients with alcoholic cirrhosis. IL28B rs12979860 TT genotype [OR 6.08, 95 % CI 2.11–17.53; p < 0.001] and T allele carriage (CT + TT; OR 2.3, CI 95 % 1.42–3.72; p = 0.001) were more frequent among HCV patients and, among them, more common in patients infected with HCV genotype 1 (CT + TT; OR 1.79, CI 95 % 1.03–3.09; p = 0.009). Incidence of hepatocellular carcinoma was higher in HCV cirrhosis (OR 2.7, CI 95 % 1.5–4.7; p < 0.001), with no differences according to HCV genotype. IL28B genotype distribution was similar among patients with or without hepatocellular carcinoma, in both HCV patients regardless viral genotype (p = 0.84) and alcoholic patients (p = 0.91). Multivariate analysis showed that older age (OR 1.06, CI 95 % 1.02–1.1; p = 0.003) and male gender (OR 2.49, CI 95 % 1.24–5; p = 0.01) were independent risk factors for hepatocellular carcinoma in HCV patients. In summary, the current study did not find a significant association between IL28B rs12979860 polymorphism and hepatocarcinogenesis.     

Patterns and trends of pediatric bloodstream infections: a 7-year surveillance study

We characterize the epidemiology of pediatric bloodstream infections (BSIs) in Switzerland. We analyzed pathogen distribution and resistance patterns in monomicrobial and polymicrobial BSIs in children from 2008 to 2014 using data from the Swiss antibiotic resistance centre (ANRESIS). A confirmatory statistical analysis was performed comparing pathogens and resistance across 20 acute care hospitals. We identified 3,067 bacteremia episodes, of which 1,823 (59 %) were considered true BSI episodes. Overall, S. aureus (16.5 %, 300) was the most frequent pathogen, followed by E. coli (15.1 %, 276), coagulase-negative staphylococci (CoNS, 12.9 %, 235), S. pneumoniae (11.1 %, 202) and non-E. coli Enterobacteriaceae (8.7 %, 159). S. aureus and E. coli showed similar frequencies in all of the variables analyzed (e.g., hospital acquisition, hospital type, medical specialty). The proportion of these microorganisms did not change over time, resistance rates remained low (4.3 % methicillin resistance in S. aureus; 7.3 % third-/fourth-generation cephalosporin resistance in E. coli), and no significant resistance trends were observed. We observed a 50 % increase of CoNS BSIs from 2008 (9.8 %, 27) to 2014 (15.2 %, 46, p value for trend?=?0.03). S. pneumoniae decreased from 17.5 % (48) to 6.6 % (20) during that timeframe (p for trend?=?0.007). S. aureus and E. coli remained the most significant pathogens among pediatric BSIs in Switzerland, exhibiting low resistance rates. CoNS accounted for a greater proportion of BSIs over time. The decrease in bacteremic pneumococcal infections can likely be attributed to the introduction of the 13-valent conjugate vaccine in 2011.     

Blood stream infection is associated with cerebrovascular accident in patients with left ventricular assist device: a systematic review and meta-analysis

Cerebrovascular accident (CVA) is one of the major complications and a leading cause of death in patients with a left ventricular assist device (LVAD). Multiple studies of have shown that patients with blood stream infection (BSI) are more likely to develop CVA compared to patients without BSI. However, there is no meta-analysis to confirm this association. Studies were systematically acquired from MEDLINE and EMBASE electronic databases. Included studies assessed patients with heart failure requiring LVAD and reported the number of patients who had BSI post LVAD, incidence of ischemic CVA, hemorrhagic CVA, or any CVA. Pooled effect size was calculated with a random-effect model, weighted for the inverse of variance. Heterogeneity was assessed with I². Six studies were analyzed. Participants with LVAD who developed BSI were more likely to have a CVA compared to participants without BSI (RR 3.43, 95% CI 2.49–4.72, I²?=?0). In four studies, there was an association between BSI and increased incidence of hemorrhagic CVA post LVAD (RR 5.28, 95% CI 2.65–10.53) with minimal heterogeneity (I²?=?30%). In three studies, participants with BSI were more likely to develop ischemic CVA (RR 2.18, 95% CI 1.23–3.84) compared to patients without BSI. This meta-analysis suggested that there maybe an association between blood stream infection and cerebrovascular accident in patients with LVAD.     

Clinical significance and outcome of <Emphasis Type="Italic">Aeromonas</Emphasis> spp. infections among 204 adult patients

The objectives of this investigation were to analyze the clinical patterns, risk groups, prognostic factors, and mortality of infections caused by Aeromonas spp. This was a retrospective study of adult patients with Aeromonas spp. isolates attended at the Hospital del Mar in Barcelona, Spain, between January 2006 and December 2012. Epidemiological data, antimicrobial susceptibility, clinical patterns, underlying illnesses, type of infection, admission to the intensive care unit (ICU), number of episodes, coinfection, antimicrobial therapy, and evolution were analyzed. A total of 221 clinical samples from 204 patients were positive for Aeromonas spp. The mean age of the patients was 67.6 years. The main clinical form of presentation was gastrointestinal (78.4%). Malignancy was the main risk group in 69 (33.8%) patients, and 48 (23.5%) were previously healthy. Twenty-one patients (10.3%) were admitted to the ICU. Infections were acquired in the hospital in 52.5% of the patients, and 28.9% were polymicrobial. The overall mortality (after 1 year of follow-up from the first positive culture) was 26.5%. Univariate analysis identified an association between increased mortality and the following variables: age ≥80 years, hospitalization, admission to the ICU, malignancy, extraintestinal infection, and appropriate antimicrobial therapy. In the multivariate analysis, age ≥80 years [odds ratio (OR), 4.37 [95% confidence interval (CI), 1.68–11.35; p?=?0.002]], admission to the ICU (OR, 6.59 [95% CI, 2.17–19.99; p?=?0.001]), and malignancy (OR, 3.62 [95% CI, 1.32–9.90; p?=?0.012]) were significantly associated with mortality. Aeromonas infections are mainly gastrointestinal. The 1-year follow-up mortality rate was high. Old age (age?≥80 years), admission to the ICU, and malignancy were identified as independent risk factors for mortality.     

Risk factors and clinical outcomes for carbapenem-resistant <Emphasis Type="Italic">Enterobacteriaceae</Emphasis> nosocomial infections

This study was aimed to determine the risk factors of Carbapenem-resistant Enterobacteriaceae (CRE) nosocomial infections and assess the clinical outcomes. A case-case–control design was used to compare two groups of case patients with control patients from March 2010 to November 2014 in China. Risk factors for the acquisition of CRE infections and clinical outcomes were analyzed by univariable and multivariable analysis. A total of 94 patients with CRE infections, 93 patients with Carbapenem-susceptible Enterobacteriaceae (CSE) infections, and 93 patients with organisms other than Enterobacteriaceae infections were enrolled in this study. Fifty-five isolates were detected as the carbapenemase gene. KPC-2 was the most common carbapenemase (65.5 %, 36/55), followed by NDM-1 (16.4 %, 9/55), IMP-4 (14.5 %, 8/55), NDM-5 (1.8 %, 1/55), and NDM-7 (1.8 %, 1/55). Multivariable analysis implicated previous use of third or fourth generation cephalosporins (odds ratio [OR], 4.557; 95 % confidence interval [CI], 1.971–10.539; P?<?0.001) and carbapenems (OR, 4.058; 95 % CI, 1.753-9.397; P?=?0.001) as independent risk factors associated with CRE infection. The in-hospital mortality of the CRE group was 57.4 %. In the population of CRE infection, presence of central venous catheters (OR, 4.464; 95 % CI, 1.332–14.925; P?=?0.015) and receipt of immunosuppressors (OR, 7.246; 95 % CI, 1.217–43.478; P?=?0.030) were independent risk factors for mortality. Appropriate definitive treatment (OR, 0.339; 95 % CI, 0.120–0.954; P?=?0.040) was a protective factor for in-hospital death of CRE infection. Kaplan–Meier curves of the CRE group had the shortest survival time compared with the other two groups. Survival time of patients infected with Enterobacteriaceae with a high meropenem MIC (≥8 mg/L) was shorter than that of patients with a low meropenem MIC (2,4, and?≤?1 mg/L). In conclusion, CRE nosocomial infections are associated with prior exposure to third or fourth generation cephalosporins and carbapenems. Patients infected with CRE had poor outcome and high mortality, especially high meropenem MIC (≥8 mg/L). Appropriate definitive treatment to CRE infections in the patient is essential.     

Correlation between status of epidermal growth factor receptor mutation and distant metastases of lung adenocarcinoma upon initial diagnosis based on 1063 patients in China

The study aimed to explore the correlations between status of epidermal growth factor receptor (EGFR) mutations and distant metastases. A total of 1063 patients with lung adenocarcinoma indentified with status of EGFR mutations from August 2010 to May 2015 at Shanxi Cancer Hospital were enrolled. 456 patients were confirmed with EGFR mutations. The associations among EGFR mutations, clinical factors, and distant metastases at initial diagnosis were evaluated. Patients harboring EGFR mutation were more likely to be female (P < 0.001), with no smoking history (P < 0.001), brain metastases (P = 0.029), and higher ECOG performance scores (P = 0.025). The correlation between EGFR mutation status and distant metastases showed statistical significance both in univariate (P = 0.022) and in multivariate analysis (OR 1.573, 95 % CI 1.202–2.059, P = 0.001) especially in brain metastases (OR 1.675, 95 % CI 1.132–2.479, P = 0.010) and lung metastases (OR 1.571, 59 % CI 1.101–2.243 P = 0.013). Furthermore, the 19del mutations showed associations with brain metastases (OR 1.586, 95 % CI 1.028–2.447, P = 0.037), and lung metastases (OR 1.587, 95 % CI 1.065–2.346, P = 0.023). The exon 21 point mutations showed statistically significant differences in liver metastases (OR 1.987, 95 % CI 1.094–3.067, P = 0.024). In conclusion, the EGFR mutations in lung adenocarcinoma patients were independently correlated with distant metastases. Subgroup analyses showed that patients harboring 19del mutations presented different distant metastases compared with those harboring 21 point mutaions.     

Community-acquired <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> bloodstream infection: a classification that should not falsely reassure the clinician

Pseudomonas aeruginosa bloodstream infection (BSI) is predominantly acquired in the hospital setting. Community-onset infection is less common. Differences in epidemiology, clinical features, microbiological factors and BSI outcomes led to the separation of bacterial community-onset BSI into the categories of healthcare-associated infection (HCAI) and community-acquired infection (CAI). Community-acquired P. aeruginosa BSI epidemiology is not well defined in the literature. In addition, it is also not clear if the same factors separate CAI and HCAI BSI caused by P. aeruginosa alone. A retrospective multicentre cohort study was performed looking at P. aeruginosa BSI from January 2008 to January 2011. Strict definitions for HCAI and CAI were applied. Extensive epidemiological, clinical and outcome data were obtained. Thirty-four CAI episodes and 156 HCAI episodes were analysed. The CAI group could be characterised into seven distinct categories based on comorbidities and clinically suspected source of infection. A pre-morbidly healthy group could not be identified. On multivariate analysis, the presence of a rheumatological or a gastrointestinal comorbidity were significantly associated with CAI. There was no significant difference in length of stay or rates of mortality between HCAI or CAI. The clinician should not be falsely reassured regarding outcome by the diagnosis of a community-acquired P. aeruginosa BSI.     

The relevance of Tim-3 polymorphisms and F protein to the outcomes of HCV infection

Hepatitis C virus (HCV) is one of the major causes of liver inflammation. The aim of this study was to investigate the associations of T-cell immunoglobulin and mucin domain-3 (Tim-3) polymorphisms and the alternate reading frame protein (F protein) with the outcomes of HCV infection. Three single-nucleotide polymorphisms (SNPs; rs10053538, rs12186731, and rs13170556) of Tim-3 were genotyped in this study, which included 203 healthy controls, 558 hepatitis C anti-F-positive patients, and 163 hepatitis C anti-F-negative patients. The results revealed that the rs12186731 CT and rs13170556 TC and CC genotypes were significantly less frequent in the anti-F-positive patients [odds ratio (OR)?=?0.54, 95 % confidence interval (CI)?=?0.35–0.83, p?=?0.005; OR?=?0.26, 95 % CI?=?0.18–0.39, p?<?0.001; and OR?=?0.19, 95 % CI?=?0.10–0.35, p?<?0.001, respectively), and the rs13170556 TC genotype was more frequent in the chronic HCV (CHC) patients (OR?=?1.70, 95 % CI?=?1.20–2.40, p?=?0.002). The combined analysis of the rs12186731 CT and rs13170556 TC/CC genotypes revealed a locus-dosage protective effect in the anti-F-positive patients (OR?=?0.22, 95 % CI?=?0.14–0.33, p _trend?<?0.001). Stratified analyses revealed that the frequencies of the rs12186731 (CT?+?TT) genotypes were significantly lower in the older (OR?=?0.31, 95 % CI?=?0.15–0.65, p?=?0.002) and female (OR?=?0.30, 95 % CI?=?0.17–0.52, p?<?0.001) subgroups, and rs13170556 (TC?+?CC) genotypes exhibited the same effect in all subgroups (all p?<?0.001) in the anti-F antibody generations. Moreover, the rs13170556 (TC?+?CC) genotypes were significantly more frequent in the younger (OR?=?1.86, 95 % CI?=?1.18–2.94, p?=?0.007) and female (OR?=?2.38, 95 % CI?=?1.48–3.83, p?<?0.001) subgroups of CHC patients. These findings suggest that the rs12186731 CT and rs13170556 TC/CC genotypes of Tim-3 provide potential protective effects with the F protein in the outcomes of HCV infection and that these effects are related to sex and age.     

Community-acquired <Emphasis Type="Italic">Clostridium difficile</Emphasis> infection in Serbian pediatric population

Carriage of Clostridium (C.) difficile in the intestinum of children, as well as its role in the disease (diarrhea) onset, is still controversial. The aim of this study is to investigate the community-acquired Clostridium difficile infection (CA-CDI) in Serbian pediatric population and to describe the basic clinical characteristics and risk factors for CA-CDI occurrence in Serbian pediatric population. The data obtained from 63 Serbian pediatric patients with CA-CDI and from control group of 126 children with community-acquired diarrhea, whose stool specimens were negative for C. difficile and toxins A/B, were mutually compared. In the current work, we found that children with CA-CDI display a significantly less severe disease clinical presentation than children with diarrheas of other origin. Lethal outcome was noted in two cases, but in children with severe underlying diseases (Crohn’s disease and leukemia). By using the multivariate statistical regression model, the following statistically significant risk factors for community-acquired C. difficile-associated diarrhea development were determined: previous application of laxatives (OR?=?0.199, CI 0.55–0.79, p?=?0.015), general antibiotic use during the previous 2 months (OR?=?0.05, CI 0.02–0.17, p?<?0.001), and specifically the use of penicillins (OR?=?0.112, CI 0.04–0.31, p?<?0.0001) and cephalosporins (OR?=?0.16, CI 40.06–0.44, p?<?0.0001). Antibiotics from the groups of cephalosporins and penicillins were found to be the most important independent risk factors. Laxative application plays a significant role in the community-acquired Clostridium difficile infections in children, with mechanisms that are not completely understood.     

The effects of <Emphasis Type="Italic">SP110</Emphasis>’s associated genes on fresh cavitary pulmonary tuberculosis in Han Chinese population

SP110 is a promising anti-Mycobacterium tuberculosis (MTB) gene. To investigate the effects of SP110 and its associated genes, i.e., MYBBP1A and RELA, on pathological progression of MTB infection, an association study with 424 patients of fresh pulmonary tuberculosis (PTB) and 424 healthy controls was performed. Moreover, classification and regression tree and multifactor dimensionality reduction were employed to explore the effects of gene–gene interactions on cavitary PTB. The results indicated that both the heterozygous genotype GC and homozygous genotype CC in rs3809849 had significant effects on the risk of PTB (OR 1.42, 95 % CI 1.06–1.92, p 0.019; OR 1.55, 95 % CI 1.04–2.33, p = 0.033, respectively), and heterozygous genotype CT in rs9061 also had similar effects (OR 1.43, 95 % CI 1.07–1.90, p = 0.014). The rs3809849 and rs9905742 in MYBBP1A were also significantly associated with cavitary PTB (p = 0.00046 and 0.039, respectively), while rs9061 in SP110 had no such association (p = 0.06931) except its significant association with non-cavitary PTB (p = 0.0093). The interaction of MYBBP1A and RELA had significant effect on cavitary PTB (OR 4.24, 95 % CI 1.44–12.49, p = 0.005). These suggest that MYBBP1A instead of SP110 may be a genetic risk factor for cavitary PTB and play important effects on its whole progress.     

Pathological and prognostic significance of matrix metalloproteinase-2 expression in ovarian cancer: a meta-analysis

Matrix metalloproteinase-2 (MMP-2) has been linked with tumor invasion and metastasis. However, the role of MMP-2 expression in ovarian cancer remains controversial. By searching the PubMed, Embase, Wanfang, and China National Knowledge Infrastructure databases, we conducted a meta-analysis to evaluate the pathological and prognostic significance of MMP-2 in ovarian cancer. Studies were pooled, and the odds ratio (OR) and its corresponding 95 % confidence interval (CI) were calculated. Version 11.0 STATA software was used for statistical analysis. Twenty-seven relevant articles were included for this meta-analysis study. The expression of MMP-2 in cancer tissue was significantly higher than that in benign or normal ovarian tissue [cancer vs. benign, OR 10.09 (95 % CI 6.95–14.64); P < 0.001; cancer vs. normal, OR 30.48 (95 % CI 17.19–54.05); P < 0.001; benign vs. normal, OR 1.88 (95 % CI 1.08–3.29); P = 0.025]. The expression of MMP-2 in stage III–IV or lymph node metastasis was significantly higher than that in stage I–II or that without metastasis, respectively [OR 5.83 (95 % CI 4.32–7.85); P < 0.001; OR 7.20 (95 % CI 4.75–10.91); P < 0.001]. MMP-2 was associated with histological types and grade of ovarian cancer [serous vs. mucinous, OR 1.67 (95 % CI 1.17–2.39); P = 0.004; grade 3 vs. 1, 2, OR 3.23 (95 % CI 2.29–4.55); P < 0.001]. However, the age of patients was not associated with MMP-2 expression [OR 1.25 (95 % CI 0.61–2.58); P = 0.546]. In conclusion, MMP-2 is related to the malignant degree, FIGO stage, histological types and grade, and lymph node metastasis of ovarian cancer. It may play a significant role in clinical guidelines for the treatment and prognostic evaluation.     

Initial antifungal strategy does not correlate with mortality in patients with candidemia

The incidence of Candida bloodstream infections (BSIs) has increased over time, especially in medical wards. The objective of this study was to evaluate the impact of different antifungal treatment strategies on 30-day mortality in patients with Candida BSI not admitted to intensive care units (ICUs) at disease onset. This prospective, monocentric, cohort study was conducted at an 1100-bed university hospital in Rome, Italy, where an infectious disease consultation team was implemented. All cases of Candida BSIs observed in adult patients from November 2012 to April 2014 were included. Patients were grouped according to the initial antifungal strategy: fluconazole, echinocandin, or liposomal amphotericin B. Cox regression analysis was used to identify risk factors significantly associated with 15-day and 30-day mortality. During the study period, 130 patients with candidemia were observed (58 % with C. albicans, 7 % with C. glabrata, and 23 % with C. parapsilosis). The first antifungal drug was fluconazole for 40 % of patients, echinocandin for 57.0 %, and liposomal amphotericin B for 4 %. During follow-up, 33 % of patients died. The cumulative mortality 30 days after the candidemia episode was 30.8 % and was similar among groups. In the Cox regression analysis, clinical presentation was the only independent factor associated with 15-day mortality, and Acute Physiology and Chronic Health Evaluation (APACHE) II score and clinical presentation were the independent factors associated with 30-day mortality. No differences in 15-day and 30-day mortality were observed between patients with and without C. albicans candidemia. In patients with candidemia admitted to medical or surgical wards, clinical severity but not the initial antifungal strategy were significantly correlated with mortality.     

Clinicopathological and prognostic significance of Nestin expression in patients with non-small cell lung cancer: a systematic review and meta-analysis

Latest evidence indicates that Nestin expression may be associated with the high malignancy and poor prognosis of non-small cell lung cancer (NSCLC), but a relevant consensus has not been reached until now. Therefore, we conducted this meta-analysis to evaluate the clinicopathological and prognostic significance of Nestin expression in patients with NSCLC. We searched PubMed, EMBASE and the Web of Science for eligible full-text articles. Odds ratio (OR) and hazard ratio (HR) with 95 % confidence interval (95 % CI) severed as the summarized statistics. Q-test and I ²-statistic were applied to evaluate the heterogeneity, and sensitivity analysis was conducted for adjustments. Publication bias was detected by Begg’s test and Egger’s test. Finally, eight eligible articles with 834 NSCLC cases were included. Nestin expression was found to be significantly associated with the unfavorable outcomes of differentiation degree (OR: 2.47; 95 % CI 1.61–3.79; P < 0.001), lymphatic metastasis (OR: 2.45; 95 % CI 1.41–4.25; P = 0.001), TNM stage (OR: 1.73; 95 % CI 1.07–2.79; P = 0.025) and tumor size (OR: 2.68; 95 % CI 1.20–5.98; P = 0.016), but not associated with gender, age, smoking status and NSCLC subtypes. Nestin expression could significantly predict the lower overall survival of NSCLC (HR: 2.41; 95 % CI 1.72–3.38; P < 0.001). The prognostic value of Nestin remained statistically reliable in the subgroups stratified by statistical analysis, patients’ origins and follow-up periods, but not significant in patients with squamous cell carcinoma. In conclusion, Nestin expression may be an independent predictor for the poor prognosis and clinicopathological characteristics of NSCLC. Further studies are necessary to validate our discoveries.