Epidemiology of Clostridium difficile-associated disease at University Hospital Basel including molecular characterisation of the isolates 2006–2007

A prospective study was conducted during a one-year period between 2006 and 2007 to describe the epidemiology of Clostridium difficile-associated disease (CDAD) at University Hospital Basel, Switzerland (UHBS) and to determine phenotypic and genotypic features of C. difficile strains isolated at the Microbiology Laboratory UHBS including strains from regional non-university hospitals. We prospectively identified 78 CDAD cases at UHBS with an incidence of 2.65/1,000 hospitalised patients or 2.3/10,000 patient-days. Sixteen patients (20.5%) were infected with clindamycin-resistant strains of PCR-ribotype 027 during an outbreak at the geriatric hospital. Among 124 single-patient isolates, 28 (22.6%) were resistant to moxifloxacin and 34 (27.4%) were resistant to clindamycin, but all remained susceptible to metronidazole and vancomycin. Of 102 toxigenic isolates, 19 (18.7%) had an 18-bp deletion in the tcdC gene, eight (7.8%) a 39-bp deletion, and one (1.0%) a 54-bp deletion. Genes for binary toxin were present in 27 (21.8%). PCR-ribotype 027 was associated with older age (median age 83.5 vs. 65.5 years, p < 0.0001) and longer duration of hospitalisation before onset of disease (median 15.5 vs. 9 days, p = 0.014) with a trend towards higher crude mortality, more severe disease, and previous use of macrolides compared to ribotype non-027. Overall, severe disease correlated with use of a nasogastric tube and surprisingly shorter duration of hospitalisation before onset of disease. Today, laboratory-based and epidemiological surveillance systems are required to monitor CDAD cases and emergence of new epidemic strains.     

Risk factors of Clostridium difficile-associated diarrhea in hospitalized adults: Vary by hospitalized duration

BackgroundClostridium difficile is the leading cause of nosocomial infectious diarrhea. Hospitalized patients were at risk of C. difficile-associated diarrhea (CDAD). However the risk factors of CDAD in patients with different hospitalization period are not clear.Material and methodsA prospective investigation was conducted in medical wards of a district hospital in southern Taiwan, from January 2011 to January 2013. We arbitrary divided patients into two groups: hospitalized for at most 14 days and 15–30 days, and analyzed their risk factors for CDAD.ResultsOverall 451 patients were enrolled. The multivariable analysis of 19 (8.0%) patients developing CDAD within 14 days' hospital stay and 216 patients hospitalized for ≤ 14 days without CDAD showed malignancy (odds ratio [OR] 7.15, 95% confidence interval [CI] 1.82–28.09; P = 0.005), prior cephalosporin (OR 10.8, 95% CI 1.3–93.9; P = 0.03) and proton pump inhibitor (PPI; OR 7.1, 95% CI 2.1–24.7; P = 0.002) therapy were independently related to CDAD (Table 3), but hypertension (OR 0.2, 95% CI 0.1–0.7; P = 0.01) was reversely related to CDAD. However, of 9 (4.2%) patients developing CDAD later (15–30 days' hospital stay) and 207 patients with longer hospitalization (15–30 days) but free of CDAD, malignancy (OR 14.0, 95% CI 1.6–124.9; P = 0.02) and underlying diabetes mellitus (OR 20.5, 95% CI 2.9–144.9; P = 0.002) were independent risk factors of CDAD.ConclusionRisk factors for CDAD among hospitalized patients varied by the duration of hospital stay. Intervention strategies to prevent CDAD may be different in terms of hospital stay duration.     

Evaluation of three rapid assays for detection of Clostridium difficile toxin A and toxin B in stool specimens

Diagnosis of Clostridium difficile-associated disease continues to be difficult for clinical microbiology laboratories. The aim of this study was to evaluate the performance of three enzyme immunoassays for detection of C. difficile toxins A and B: the recently marketed rapid enzyme immunoassay Ridascreen Clostridium difficile Toxin A/B (R-Biopharm, Darmstadt, Germany) and two established enzyme immunoassays, the C. difficile Tox A/B II Assay (TechLab, Blacksburg, VA, USA) and the ProSpecT C. difficile Toxin A/B Microplate Assay (Remel, Lenexa, KS, USA). Stool specimens (n = 383) from patients with a clinical diagnosis of antibiotic-associated diarrhea were examined by these three enzyme immunoassays and were additionally cultured for C. difficile on selective agar. Samples giving discordant enzyme immunoassay results underwent confirmatory testing by tissue culture cytotoxin B assay and by PCR for toxin A (tcdA) and toxin B (tcdB) genes from C. difficile. Using the criteria adopted for this study, 60 (15.7%) samples tested positive for toxins A and/or B. Sensitivity and specificity of the enzyme immunoassays were, respectively, 88.3 and 100% for the TechLab enzyme immunoassay, 91.7 and 100% for the R-Biopharm enzyme immunoassay, and 93.3 and 100% for the Remel enzyme immunoassay. The differences between these results are statistically not significant (p > 0.05). The results show that all three enzyme immunoassays are acceptable tests for the detection of C. difficile toxins A and B directly in fecal specimens or in toxigenic cultures.     

Clostridium difficile infection in Polish pediatric outpatients with inflammatory bowel disease

The prevalence of Clostridium difficile infection (CDI) in pediatric patients with inflammatory bowel disease (IBD) is still not sufficiently recognized. We assessed the prevalence of CDI and recurrences in outpatients with IBD. In addition, the influence of IBD therapy on CDI and antimicrobial susceptibility of the potentially causative C. difficile strains was assessed. This was a prospective, single-center, observational study. All specimens were obtained between January 2005 and January 2007 from the IBD outpatient service and screened for C. difficile and its toxins. C. difficile isolates were genotyped by PCR ribotyping. Diagnosis of Crohn’s disease (CD) and ulcerative colitis (UC) was based on Porto criteria. Severity of disease was assessed using the Hyams scale (for Crohn’s disease) and the Truelove–Witts scale (for ulcerative colitis). One hundred and forty-three fecal samples from 58 pediatric IBD patients (21 with Crohn’s disease and 37 with ulcerative colitis) were screened. The risk of C. difficile infection was 60% and was independent of disease type (CD or UC) (χ2 = 2.5821, df = 3, p = 0.4606). About 17% of pediatric IBD patients experienced a recurrence of CDI. All C. difficile strains were susceptible to metronidazole, vancomycin and rifampin. A high prevalence of C. difficile infection and recurrences in pediatric outpatients with IBD was observed, independent of disease type. There was no significant correlation between C. difficile infection and IBD therapy. PCR ribotyping revealed C. difficile re-infection and relapses during episodes of IBD in pediatric outpatients.     

Major depressive disorder during pregnancy and emotional attachment to the fetus

While there is good evidence that depression negatively impacts mother-to-infant emotional attachment in the postpartum period, the impact of depression in pregnancy on maternal emotions and cognitions about the fetus (often termed “maternal–fetal attachment” or MFA) is unclear. This study compared MFA scores from women meeting clinical criteria for Major Depressive Disorder (MDD) with scores from nondepressed women. Participants were 161 women enrolled at 23–36 weeks gestation, of whom 65 met criteria for MDD via the Structured Clinical Interview for the DSM-IV-TR during their second and/or third trimesters. Cranley’s Maternal Fetal Attachment Scale was administered at 26 and 36 weeks gestation. Generalized linear modeling was used to assess the effect of MDD, anxiety, and antidepressant use on MFA. MDD was negatively related to MFA (LR) = 4.58, df = 1, p < 0.04). Neither anxiety (LR = 0.22, p < 0.64), nor antidepressant use (LR = 0.20, df = 1, p < 0.66) were related to MFA. Depression severity was negatively related to MFAS scores (B = −0.005, SE = .002, p < 0.0012) when including the interaction of MDD group and HRSD scores in the model. This study is the first to demonstrate that clinically defined MDD during pregnancy negatively impacts MFA, suggesting that the basis for poor mother-to-infant attachment in postpartum MDD may have roots in pregnancy.     

Multi-drug-resistant gram-negative bacterial infection in surgical patients hospitalized in the ICU: a cohort study

We sought to identify risk factors for postoperative infections, caused by multi-drug-resistant gram-negative bacteria (MDR-GNB) in surgical patients. This was a retrospective cohort study among patients hospitalized in the intensive care unit (ICU) for more than 5 days, following general surgical operations. Comparison of patients who developed infection caused by MDR-GNB with the remainder of the cohort showed that every minute of operative time, use of special treatments during hospitalization (antineoplastic, immunosuppressive or immunomodulating therapies), every day of metronidazole, and every day of carbapenems use, increased patients’ odds to acquire an infection caused by MDR-GNB by 0.7%, 8.9 times, 9%, and 9%, respectively [OR (95% CI): 1.007 (1.003–1.011), p = 0.001; 8.9 (1.8–17.3), p = 0.004; 1.09 (1.04–1.18), p = 0.039; 1.09 (1.01–1.18), p = 0.023, respectively]. The above were adjusted in the multivariable analysis for the confounder of time distribution of infections caused by MDR-GNB. Finally, the secondary comparison, with patients that did not develop any infection, showed that patients who had received antibiotics, within 3 months prior to admission, had 3.8 times higher odds to acquire an infection caused by MDR-GNB [OR (95% CI): 3.8 (1.07–13.2), p = 0.002]. This study depicts certain, potentially modifiable, risk factors for postoperative infections in patients hospitalized in the ICU for more than 5 days.     

Relationship Between Eosinophilia and Levels of Chemokines (CCL5 and CCL11) and IL-5 in Bronchoalveolar Lavage Fluid of Patients With Mustard Gas-Induced Pulmonary Fibrosis

Objective Therefore, this study was designed to analyze the bronchoalveolar lavage (BAL) fluid concentrations of IL-5, RANTES (CCL5) and eotaxin (CCL11) and also to examine the relationship between the percentage and absolute number of the BAL eosinophils and these measured chemokines in patients with sulfur mustard (SM) gas-induced pulmonary fibrosis (PF). Patients Fifteen veterans with mustard gas-induced PF and 14 normal veterans as control group. Intervention Pulmonary function tests, tests for D_LCO, computed tomography scans of the chest, analyses of BAL fluids for RANTES (CCL5), eotaxin (CCL11), and IL-5 were performed in all cases. Results Eosinophilic alveolitis was the predominant feature (p < 0.0001). There were significant differences in CCL5, CCL11, and IL-5 levels of BAL fluid between patients with PF and controls (p < 0.0001, p < 0.0001, and p = 0.001, respectively). The concentrations of CCL5 and CCL11 showed positive correlations with percentage (r = 0.57 and p = 0.03; r = 0.52 and p = 0.04, respectively) and absolute counts (r = 0.54 and p = 0.04, r = 0.53 and p = 0.04, respectively) of BAL eosinophils. There were significant positive correlations between the concentrations of IL-5 and the proportion and total cell number of eosinophils in BAL (r = 0.67 and p = 0.01; r = 0.59 and p = 0.02, respectively) too. Conclusion A significant correlation between BAL CCL5, CCL11, and IL-5 levels and eosinophils in patients with pulmonary fibrosis due to SM gas inhalation has been demonstrated, suggesting that these C–C chemokines and IL-5 contribute to the recruitment of eosinophils cells in the lung in these victims.     

The epidemiology of extraintestinal non-typhoid Salmonella in Israel: the effects of patients’ age and sex

Extraintestinal disease occurs in 5–8% of non-typhoid Salmonella enterica (NTS) infections and is more likely to be associated with hospitalization and death. The study examined the epidemiology of extraintestinal NTS infections in Israel and the possible effects of patients’ age and sex. NTS isolates passively submitted to the National Salmonella Reference Center during 1996–2006 were the source for the study cohort. Poisson regression models were used to assess incidence trends over the study years and to evaluate the effects of patients’ age and sex on the incidence of extraintestinal NTS manifestations. A total of 36,822 stool and 1,415 (3.7%) patient-unique NTS isolates from blood (74.1%), urine (18.3%), and other sources (3.7%) were studied. Serotypes Enteritidis, Virchow, and Typhimurium accounted for 66.3% of the isolates. Analysis showed a highly significant quadratic (U-shaped) relationship between patients’ age and the incidence of extraintestinal isolation (p < 0.001), with increasing risk in the two extremes of age. Differences between the incidence of blood and urine sources were significant in patients <10 and ≥60 years old (relative risk [RR] = 5.88, 95% confidence interval [CI] 3.36–10.30, p < 0.001 and RR = 1.66, 95% CI 1.09–2.53, p = 0.017, respectively). Males ≥60 years of age were more likely than females of the same age to have bacteremia (RR = 1.90, 95% CI 1.39–2.61, p > 0.001) and less likely to have urinary NTS isolation (RR = 0.50, 95% CI 0.28–0.89, p = 0.018). Serotype Virchow had the highest incidence in patients <10 years of age, while serotype Enteritidis had the highest incidence in patients ≥60 years old. The study revealed a complex effect of patients’ age and sex on the epidemiology of extraintestinal NTS manifestations.     

Factors Associated with Nosocomial Diarrhea and Clostridium difficile-Associated Disease on the Adult Wards of an Urban Tertiary Care Hospital

 A prospective survey of the adult inpatient population of an urban tertiary care hospital was conducted to determine factors associated with the development of nosocomial diarrhea and the acquisition of Clostridium difficile-associated disease. During the 3-month survey, 98 patients with nosocomial diarrhea were enrolled, and 38 controls were recruited. The controls were patients without diarrhea lying in beds adjacent to the affected patients. Factors significantly associated with nosocomial diarrhea were the administration of a special diet (P=0.02) and receipt of a greater number of different antibiotics (P=0.02). Among the 98 patients with diarrhea, Clostridium difficile toxin B was identified in the stool of 13. Factors found to be associated with the presence of toxin B as compared to other causes of nosocomial diarrhea were a greater number of individual antibiotics used during hospitalization (P=0.02) and receipt of a cephalosporin (P=0.03) or, more specifically, a third-generation cephalosporin (P=0.02). Among patients with nosocomial diarrhea, those who had toxin in their stool had a significantly higher total antibiotic burden (expressed as antibiotic days) than those with diarrhea due to other causes (P=0.01).     

Clostridium difficile infection in an endemic setting in the Netherlands

The purpose of this investigation was to study risk factors for Clostridium difficile infection (CDI) in an endemic setting. In a 34-month prospective case–control study, we compared the risk factors and clinical characteristics of all consecutively diagnosed hospitalised CDI patients (n = 93) with those of patients without diarrhoea (n = 76) and patients with non-CDI diarrhoea (n = 64). The incidence of CDI was 17.5 per 10,000 hospital admissions. C. difficile polymerase chain reaction (PCR) ribotype 014 was the most frequently found type (15.9%), followed by types 078 (12.7%) and 015 (7.9%). Independent risk factors for endemic CDI were the use of second-generation cephalosporins, previous hospital admission and previous stay at the intensive care unit (ICU). The use of third-generation cephalosporins was a risk factor for diarrhoea in general. We found no association of CDI with the use of fluoroquinolones or proton pump inhibitors (PPIs). The overall 30-day mortality among CDI patients, patients without diarrhoea and patients with non-CDI diarrhoea was 7.5%, 0% and 1.6%, respectively. In this endemic setting, risk factors for CDI differed from those in outbreak situations. Some risk factors that have been ascribed to CDI earlier were, in this study, not specific for CDI, but for diarrhoea in general. The 30-day mortality among CDI patients was relatively high.     

Prognostic value of procalcitonin in <Emphasis Type="Italic">Legionella</Emphasis> pneumonia

The diagnostic reliability and prognostic implications of procalcitonin (PCT) (ng/ml) on admission in patients with community-acquired pneumonia (CAP) due to Legionella pneumophila are unknown. We retrospectively analysed PCT values in 29 patients with microbiologically proven Legionella-CAP admitted to the University Hospital Basel, Switzerland, between 2002 and 2007 and compared them to other markers of infection, namely, C-reactive protein (CRP) (mg/l) and leukocyte count (10⁹/l), and two prognostic severity assessment scores (PSI and CURB65). Laboratory analysis demonstrated that PCT values on admission were >0.1 in over 93%, >0.25 in over 86%, and >0.5 in over 82% of patients with Legionella-CAP. Patients with adverse medical outcomes (59%, n = 17) including need for ICU admission (55%, n = 16) and/or inhospital mortality (14%, n = 4) had significantly higher median PCT values on admission (4.27 [IQR 2.46–9.48] vs 0.97 [IQR 0.29–2.44], p = 0.01), while the PSI (124 [IQR 81–147] vs 94 [IQR 75–116], p = 0.19), the CURB65 (2 [IQR 1–2] vs 1 [1–3], p = 0.47), CRP values (282 [IQR 218–343], p = 0.28 vs 201 [IQR 147–279], p = 0.28), and leukocyte counts (12 [IQR 10–21] vs 12 [IQR 9–15], p = 0.58) were similar. In receiver operating curves, PCT concentrations on admission had a higher prognostic accuracy to predict adverse outcomes (AUC 0.78 [95%CI 0.61–96]) as compared to the PSI (0.64 [95%CI 0.43–0.86], p = 0.23), the CURB65 (0.58 [95%CI 0.36–0.79], p = 0.21), CRP (0.61 [95%CI 0.39–0.84], p = 0.19), and leukocyte count (0.57 [95%CI 0.35–0.78], p = 0.12). Kaplan-Meier curves demonstrated that patients with initial PCT values above the optimal cut-off of 1.5 had a significantly higher risk of death and/or ICU admission (log rank p = 0.003) during the hospital stay. In patients with CAP due to Legionella, PCT levels on admission might be an interesting predictor for adverse medical outcomes. Jeannine Haeuptle, Roya Zaborsky, and Rico Fiumefreddo contributed equally to this article.     

LYVE-1 upregulation and lymphatic invasion correlate with adverse prognostic factors and lymph node metastasis in neuroblastoma

Neuroblastoma (NB) accounts for 15% of all childhood cancer deaths. The majority of patients have widespread lymphatic and/or haematogenous metastases at diagnosis, but lymphangiogenesis has not been well documented. Sixty-seven NBs were immunostained for the lymphatic endothelial marker, LYVE-1, and the lymphatic density (LD) and lymphatic invasion (LI), were counted in LYVE-1-expressing lymphatics. LYVE-1-stained lymphatic vessels and LI were present in 26/67 (39%) and 14/67 (21%) of the NBs, respectively. Central LD (CLD) and LI were higher in NBs from stage 4 (p = 0.012, p = 0.004, respectively), high-risk group (p = 0.030, p = 0.002), NBs with high mitosis karyorrhexis index (MKI) (p = 0.011, p = 0.005), unfavourable histology group (p = 0.040, p = 0.017) and distant lymph node metastasis (LNM) (p < 0.001 for each). Marginal LD (MLD) was higher in patients with LNM (p < 0.001). CLD and MLD correlated with LI (p < 0.001 each). Total LYVE-1 protein levels, quantified by a sensitive enzyme-linked immunosorbent assay (n = 55), were also higher in NBs from patients with stage 4 disease (p = 0.046), high-risk group (p = 0.028), MYCN-amplified NBs (p = 0.034) and LNM (p = 0.038). Kaplan–Meier analysis showed that the presence of CLD was associated with both worse OS at 5 years (77% [95% CI: 62–87%] versus 60% [95% CI: 32–80%], p = 0.062) and EFS (74% [95% CI: 58–85%] versus 43% [95% CI: 15–69%], p = 0.070) and LI with OS (71% [95% CI: 57–81%] versus 56% [95% CI: 26–78%], p = 0.055). Significant upregulation of LYVE-1 and the presence of LI in patients with stage 4 and high-risk disease, MYCN-amplification and LNM suggests that LYVE-1 may have value as predictors of outcome.     

Role of laboratory variables in differentiating SARS-coronavirus from other causes of community-acquired pneumonia within the first 72 h of hospitalization

The Centers for Disease Control and Prevention (CDC) recommend that SARS-coronavirus (SARS-CoV) testing be considered in epidemiologically high-risk patients hospitalized with community-acquired pneumonia (CAP) if no alternative diagnosis is identified after 72 h. The aim of this study was to identify routine laboratory variables that might indicate the need for SARS-CoV testing. Routine hematological/biochemical variables in patients with laboratory-confirmed SARS (2003) were compared with those in consecutive patients hospitalized June–December 2004 with radiologically confirmed CAP. Stepwise logistic regression analyses were performed to identify discriminating variables at baseline and by day 3 of hospitalization. Nasopharyngeal aspiration and antigen detection for influenza virus and respiratory syncytial virus using an immunofluorescence assay (IFA) were routinely performed in patients with CAP. Altogether, 181 patients with CAP (who remained undiagnosed by IFA) and 303 patients with SARS were studied. The mean intervals from symptom onset to admission were 3.1 and 2.8 days, respectively (p > 0.05). The etiological agent of CAP was identified retrospectively in only 39% of cases, the majority being bacterial pathogens. At baseline, age and absolute neutrophil count (ANC) were the only independent discriminating variables (p < 0.0001). Using a value of <4.4 × 10⁹/l as the cutoff for ANC, the sensitivity and specificity of ANC for discriminating SARS were 64 and 95%, respectively (AUC 0.90). By day 3 of hospitalization, age (p < 0.0001), change in ANC (p = 0.0003), and change in bilirubin (p = 0.0065) were discriminating variables. A model combining age <65 years, a change in ANC of >−3 × 10⁹/l, and a change in bilirubin of ≥0 mmol/l had a sensitivity of 43% and a specificity of 95% for SARS (AUC 0.90). There are only a few laboratory features (including lymphopenia) that clearly discriminate SARS from other causes of CAP. Nevertheless, when evaluating epidemiologically high-risk patients with CAP and no immediate alternative diagnosis, a low ANC on presentation along with poor clinical and laboratory responses after 72 h of antibiotic treatment may raise the index of suspicion for SARS and indicate a need to perform SARS-CoV testing.     

Factors influencing the clinical outcome of methicillin-resistant Staphylococcus aureus bacteraemia

Methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia is associated with high mortality due to a combination of host, pathogen and therapy related factors. This was a retrospective exploratory study to evaluate host, pathogen and therapy related factors influencing the clinical outcome of MRSA bacteraemia in a UK teaching hospital setting. Of the 38 consecutive episodes of MRSA bacteraemia over a 1-year period, 16 of 38 (40%) patients died at 1 month and 21/38 (55%) died at 6 months. Univariate analysis revealed age (p < 0.006), mean serum vancomycin level (p < 0.035), agr group I (p < 0.036) and set4-var2_11 gene (p < 0.036) at 1 month; and age (p < 0.004) and set4-var2_11 gene (p < 0.002) at 6 months as significant factors. However, there was no association between first trough vancomycin concentration and outcome at 1 month. Multivariate survival analysis from time of admission showed, for each one year increase in age, a patient is 1.121 (95% CI 1.006–1.250, p < 0.007) times more likely to die at any particular point in time, and patients with a mean serum vancomycin level of <10 mg/L, the odds ratio of adverse outcome is 16.129 (95% CI 2.398–111.111) compared to patients with a mean serum level >10 mg/L. A variety of host, pathogen, and therapy related factors influence the clinical outcome of MRSA bacteraemia.     

Randomized Controlled Clinical Trial of Blood Glucose Awareness Training (BGAT III) in Switzerland and Germany

Although both diabetes and the efficacy of medical management are international issues, psycho-educational interventions might be culturally bound. Blood Glucose Awareness Training (BGAT) is a psycho-educational program for patients with type 1 diabetes mellitus. It is focused on improving recognition and management of extreme blood glucose levels, and is the best documented American psycho-educational program for this purpose. A randomized controlled clinical trial of BGAT's long-term benefits in a non-American setting has been lacking. One hundred and eleven adults with type 1 diabetes mellitus from Switzerland and Germany participated. After a 6 months baseline assessment, subjects were randomly assigned to receive either 2 months of BGAT (n = 56) or a physician-guided self-help control intervention (n = 55). BGAT improved recognition of low (p = 0.008), high (p = .03), and overall blood glucose (p = 0.001), and reduced frequency of severe hypoglycemia (p = 0.04), without compromising metabolic control. BGAT reduced both the external locus of control (p < 0.02) and fear of hypoglycemia (p < 0.02). BGAT was efficacious in reducing adverse clinical events and achieving clinically desirable goals in a European, as well as American setting.     

Pulmonary cryptococcosis in patients without HIV infection: factors associated with disseminated disease

Cryptococcus neoformans is an uncommonly recognized cause of pneumonia in HIV-negative patients. Because of its propensity to disseminate to the meninges and other sites, a lumbar puncture is recommended for patients with pulmonary cryptococcosis, regardless of other risk factors. This study explored clinical and laboratory features to help predict which patients had pulmonary disease alone versus those who had pulmonary plus extrapulmonary disease. A retrospective chart review at 15 medical centers was performed from 1990 to 2000 of all HIV-negative patients who had pulmonary cryptococcosis. Demographic, clinical, radiographic, and laboratory features were evaluated to determine factors that differentiated those patients who had extrapulmonary disease. Among 166 patients who had pulmonary cryptococcosis, 122 had pulmonary infection only and 44 had pulmonary plus extrapulmonary (disseminated) disease. A negative serum cryptococcal antigen titer was more common in patients with pulmonary disease alone (p < 0.01). Multivariate analysis demonstrated that patients who had disseminated disease were more likely than those who only had pulmonary disease to have cirrhosis (p = 0.049), headache (p < 0.001), weight loss (p = 0.003), fever (p = 0.035), altered mental status (p < 0.001), and to be receiving high-dose corticosteroids (p = 0.008). In this large cohort of HIV-negative patients with pulmonary cryptococcosis, there were easily distinguished clinical and laboratory features among patients with pulmonary disease alone versus those with pulmonary plus extrapulmonary disease. These findings may be helpful in the evaluation of HIV-negative patients with pulmonary cryptococcosis with regard to the need for lumbar puncture or to search for disseminated disease.     

Subacute Inflammatory Activation in Subjects with Acute Coronary Syndrome and Left Ventricular Dysfunction

Several lines of evidence indicate that increased inflammatory cytokine levels can be used for risk prediction in patients with acute coronary syndrome (ACS). This study therefore aimed to evaluate correlations between levels of soluble interleukin (IL)-2 receptor (sIL-2r), IL-6, and IL-8 and in-hospital incidence of acute heart failure (AHF) and left ventricular (LV) systolic dysfunction in the subacute phase of ACS. In 48 consecutive patients with ACS, circulating levels of sIL-2r, IL-6, and IL-8 were ascertained 72–96 h after onset of symptoms. Clinical data, LV function, and in-hospital incidence of AHF were also evaluated. IL-8 levels were significantly higher in patients with pulmonary edema (1,829 ± 2,496 vs 456 ± 624 pg/ml, p < 0.05); sIL-2r, IL-6, and IL-8 levels were increased proportionally to Killip class (r = 0.35, p < 0.05; r = 0.48, r = 0.47, p < 0.01) and in patients with LV ejection fraction (LVEF) < 30%. Levels of sIL-2r were inversely related to LVEF in subjects with acute myocardial infarction (r = −0.51, p < 0.05). Soluble IL-2r and IL-8 levels were related to mitral regurgitation severity (r = 0.34, p < 0.05; r = 0.37, p < 0.05). Levels of sIL-2 were proportional to LV end-diastolic diameter (r = 0.49, p < 0.001) and LV end-systolic diameter (r = 0.58, p < 0.001). Number of cytokines with circulating values above upper level of normal was significantly correlated with Killip class and LVEF (r = 0.40, r = −0.38, p < 0.05). sIL-2r, IL-6, and IL-8 are increased in patients with ACS and systolic dysfunction or AHF. These data suggest that inflammatory cytokine activity detectable in peripheral blood may be useful in identifying subjects with a worse clinical course.     

Cognitive Behavioral Therapy Techniques for Distress and Pain in Breast Cancer Patients: A Meta-Analysis

This meta-analysis is the first to examine cognitive behavioral therapy (CBT) techniques for distress and pain specifically in breast cancer patients. Twenty studies that used CBT techniques with breast cancer patients were identified and effect sizes were calculated to determine (1) whether CBT techniques have a significant impact on distress and pain, (2) if individual or group treatments are more effective, (3) whether severity of cancer diagnosis influences distress and pain outcomes, and, (4) if there is a relationship between CBT technique efficacy for distress and pain. Results revealed effect sizes of d = 0.31 for distress (p < 0.05) and .49 for pain (p < 0.05), indicating that 62 and 69% of breast cancer patients in the CBT techniques treatment groups had less distress and less pain (respectively) relative to the control groups. Studies with individual treatment approaches had significantly larger effects compared to studies that employed group approaches for distress (p = 0.04), but not for pain (p > 0.05). There were no significant differences in effects between those with or without metastases (p > 0.05). The correlation between effect sizes for distress and pain was not significant (p = 0.07). Overall, the results support the use of CBT techniques administered individually to manage distress and pain in breast cancer patients. However, more well-designed studies are needed.     

The correlation between Clostridium-difficile infection and human gut concentrations of Bacteroidetes phylum and clostridial species

We aimed to assess differences in bacterial intensities of Bacteroidetes phylum and different clostridial species in the human intestines with respect to C. difficile infection. Patients with a stool assay for C. difficile toxin were identified via the microbiology laboratory in our institute. Bacterial populations were quantified from stool samples of four groups of patients: Group I—patients with C. difficile associated diarrhea (CDAD); Group II—asymptomatic C. difficile carriers; Group III—patients with non-C. difficile diarrhea; Group IV—patients with no diarrhea and negative stool samples for the C. difficile toxin (control group). Stool was examined for three genes—C. difficile toxin A gene, 16S rRNA gene from Clostridium thermocellum representing other clostridial species, and 16S rRNA gene from Bacteroides fragilis representing the Bacteroidetes phylum. Fifty-nine patients underwent analysis of the stool (CDAD group 14, carriers group 14, non-C. difficile diarrhea group 16, control group 15). C. difficile concentration was highest in the CDAD group, followed by the carriers group. Higher concentrations of both clostridial species and Bacteriodetes were observed in the control and non-C. difficile diarrhea groups compared to the CDAD and carriers groups. We demonstrated an inverse association between infection with C. difficile and the abundance of Bacteroidetes phylum and other clostridial species in human intestines. Studies with larger samples and broader diagnostic procedures are needed in order to better explore and understand this association.     

Characteristics of <Emphasis Type="Italic">Streptococcus bovis</Emphasis> endocarditis and its differences with <Emphasis Type="Italic">Streptococcus viridans</Emphasis> endocarditis

The purpose of this study was to evaluate the characteristics of infective endocarditis (IE) caused by S. bovis and compare them to those caused by streptococci of the viridans group (SVG). A prospective study was undertaken considering 55 consecutive cases of IE due to S. bovis and 41 to SVG over 18 years. The study was divided into two periods (1988–1996 and 1997–2005). S. bovis caused 24% of the IE in our centre and constituted the main aetiology for this disease, showing an increase of 358% during the second period studied. Biotype I was responsible for 94.5% of cases and there was a high degree of association with colon tumours (53%). Over the period of the study, 107 patients admitted to our hospital had bacteraemia caused by S. bovis and 310 patients had bacteraemia caused by SVG. In the first group, 55 (51%) were endocarditis cases, but only 41 (13%) of the patients with SVG bacteraemia had endocarditis (p < 0.0001). The distinguishing features of endocarditis caused by S. bovis in comparison with those caused by SGV were: a greater increase in cases during the 2nd period studied (from 12 to 43 vs. from 19 to 22, p < 0.01), a higher percentage of males (93% vs. 71%, p < 0.004), patients significantly older (median age 66 vs. 58.5, p < 0.004), less predisposing cardiopathy (42% vs. 76%, p < 0.0009), more bivalvular involvement (42% vs. 22%, p < 0.04), more spondylitis (9% vs. 0%, p < 0.04), a higher association with colonic tumours (53% vs. 5%, p < 0.0001), and a higher percentage of antibiotic resistance: erythromycin 66% vs. 19%, p < 0.0001; clindamycin 67% vs. 11%, p < 0.0001; cotrimoxazole 77% vs. 30.5%, p < 0.0001, respectively. IE due to S. bovis is an emergent disease in our environment, presenting different characteristics to those produced by SVG.