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.     

Effect of statins on outcomes in immunosuppressed patients with bloodstream infection

Although it has been suggested that statins have a beneficial effect on the outcome of bloodstream infection (BSI) in immunosuppressed patients, prospective studies testing this hypothesis are lacking. We performed an observational analysis of consecutive cancer patients and transplant recipients hospitalized at two tertiary hospitals in Spain (2006–2009). The first episode of BSI occurring in statin users was compared with those occurring in non-statin users. During the study period, 668 consecutive episodes of BSI in 476 immunosuppressed patients were recorded. Underlying diseases were solid tumor (46.2%), hematologic malignancy (35.1%), and transplantation (18.7%). Fifty-nine (12.4%) patients were receiving statins at the onset of BSI. Comparing with statin non-users, patients on statin treatment were older (67.3 vs. 58.7 years; p < 0.001) and had higher frequency of comorbidities (74.6% vs. 40.6%; p < 0.001). There were no significant differences in intensive care unit admission (6.8% vs. 7.7%; p = 1) and overall mortality (15.3% vs. 24%; p = 0.13) between groups. In a multivariate analysis, prior statin use was not associated with increased survival (odds ratio [OR], 0.52; 95% confidence interval [CI], 0.22–1.23; p = 0.14). In conclusion, prior statin use is not associated with increased survival in immunosuppressed patients with BSI. Caution is warranted in attributing beneficial effects to statin use in infections among immunocompromised patients.     

Outcome of hospitalized MDR-TB patients: Israel 2000–2005

MDR-TB has emerged in Israel following an immigrations wave from the Former Soviet Union (FSU) and Ethiopia. The purpose of this study was to outline characteristics and outcome of hospitalized MDR-TB patients. We retrospectively summarized charts of MDR-TB patients hospitalized in the national referral tuberculosis centers from January 2000 to December 2005, and followed them for 2 years. One hundred thirty-two patients were identified with a median age of 40 years and male predominance (77%). The majority of the patients were immigrants from FSU (83%) and Ethiopia (7.6%). They were characterized by alcohol (25.8%) and IV drug abuse (23.5%), presented with advanced disease manifested by hypoalbuminemia (50.8%) and smear positivity (70.5%). Cure was achieved in 50.3% and 30.4% died. Factors independently associated with death were patients’ age (OR = 1.036 for each year, 95%CI 1.0–1.1, p = 0.014), hypoalbuminemia (OR = 2.95, 95%CI 1.1–7.6, p = 0.025), smear positivity at diagnosis (OR = 3.7, 95%CI 1.2–11.4, p = 0.023), alcohol abuse (OR = 4.8, 95%CI 1.7–13.7, p = 0.004) and XDR-TB resistance pattern (OR 8.3, 95%CI 1.5–44.6, p = 0.014). This study brings out the poor prognosis of a highly vulnerable immigration population. Efforts should be focused on earlier diagnosis and treatment in a well controlled hospital environment and to professional support groups to attend to this population’s special needs.     

Incidence and risk factors for newly acquired hepatitis C virus infection among Aboriginal versus non-Aboriginal Canadians in six regions, 1999–2004

The purpose of this study was to compare hepatitis C virus (HCV) incidence and recent patterns of transmission within Aboriginal and non-Aboriginal Canadians. Cases of newly acquired HCV infection (in patients ≥15 years) reported to the Enhanced Hepatitis Strain Surveillance System from six jurisdictions in Canada were analyzed. Information on demographic and clinical characteristics as well as risk factors for HCV infection was collected using standardized questionnaires. Univariate analysis showed Aboriginal patients to be significantly more likely than non-Aboriginal patients to report injection drug use (77.1% vs. 64.0%; p < 0.05), to be female (54.6% vs. 37.6%; p < 0.05), to report high-risk sexual behaviors (48.6% vs. 34.1%, p < 0.05), and to report drug snorting (45.7% vs. 32.7%, p < 0.05). The median age of Aboriginal patients was significantly younger than that of non-Aboriginal patients (31 years [range, 15–71] vs. 34 years [range, 15–81]; p < 0.05). The overall incidence of HCV infection per 100,000 people aged 15 years and older was 18.9 (95% confidence interval [CI] 15.5–23.1) in Aboriginal people and 2.8 (95%CI 2.6–3.1) in non-Aboriginal people. Poisson regression analysis revealed that Aboriginal Canadians were more likely than non-Aboriginal Canadians to develop acute hepatitis C (adjusted rate ratio 5.8, 95%CI 4.7–7.3). An appropriate and effective public health strategy that includes planned and implemented prevention programs in partnership with the Aboriginal community is needed.     

Risk factors for Clostridium difficile-associated diarrhea on an adult hematology-oncology ward

Nosocomial diarrhea caused by Clostridium difficile causes significant morbidity and mortality in an increasing proportion of hospitalized patients annually. This case-control study of patients admitted to the hematology-oncology ward of a tertiary academic medical center over a 2-year period demonstrates that patients with Clostridium difficile-associated diarrhea (CDAD) were 22 times more likely than ward-matched controls with diarrhea to have received any antibiotic either during hospitalization or in the month preceding admission (p < 0.005), and they were nearly three times as likely as controls to have received a cephalosporin during the same period (p < 0.005). Diarrhea among lung cancer patients was approximately three times more likely to be caused by this organism than to be due to other causes (p = 0.04). A trend towards CDAD patients receiving higher numbers of different antibiotics during hospitalization (3.3 vs. 2.6, 95%CI −1.42–0.02, p = 0.06) was noted. Administration of interleukin-2 either during hospitalization or in the 30 days preceding admission was seven times more likely to have occurred in CDAD cases (p = 0.04), raising the question of whether or not this agent increases risk.     

Predictors of mortality in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia: the role of empiric antibiotic therapy

The objective of this study was to evaluate prognostic factors and the influence of different empiric antibiotic therapies on outcome and mortality in a cohort of 100 inpatients with bacteraemia (84 cases nosocomial) caused by methicillin-resistant Staphylococcus aureus (MRSA). Patients were investigated by means of a standard protocol at a 944-bed hospital in the years 2000–2004. Empiric antibiotic therapies included vancomycin (n = 49), teicoplanin (n = 20), linezolid (n = 17), other antibiotics active in vitro (n = 7), and inactive antibiotics (n = 7). Overall mortality was 40% (12% among linezolid-treated patients; 46.3% among glycopeptide-treated patients). In bivariate analyses, the following factors were statistically associated with higher mortality: rapidly fatal underlying disease, altered mental status, metabolic acidosis, and acute severe clinical condition at the onset of bacteraemia; development of complications (septic shock, renal failure, and disseminated intravascular coagulopathy); empiric monotherapy with glycopeptides (vs combination therapy with an aminoglycoside); and inadequate empiric treatment. Empiric therapy with linezolid was associated with lower mortality. In multivariate analysis, risk factors associated with higher mortality included acute severity of illness (OR 7.49; 95%CI 1.19–25.3) and altered mental status (OR 4.83; 95%CI 1.22–19.15) at onset, complications (OR 3.42; 95%CI 1.02–17.46), and inappropriate empiric treatment (OR 7.6; 95%CI 1.87–31.14). In multivariate analysis limited to patients who received empiric therapy with either linezolid (n = 17) or glycopeptides (n = 69), linezolid was associated with greater rates of survival (OR 7.7; 95%CI 1.1–53) and microbiological eradication (OR 11.76; 95%CI 1.46–90.9) but not with fewer complications (OR 0.71; 95%CI 0.16–3.25). In conclusion, the main prognostic factors associated with mortality in patients with MRSA bacteraemia are complications, acute severe clinical condition at onset, and inappropriate empiric treatment. Empiric therapy with linezolid was associated with greater survival and more successful microbiological eradication but did not reduce complications.     

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.     

Compliance with recommendations and clinical outcomes for formal and informal infectious disease specialist consultations

The purpose of this study was to compare compliance with recommendations and clinical outcomes between formal and informal infectious disease specialist consultations. Six hundred twenty-seven consecutive adult inpatients who received an infectious disease consultation in a university-affiliated hospital were included. After adjusting for quintile of propensity score, we compared compliance with the consultant’s recommendations and clinical outcomes for 443 (70.7%) and 184 (29.3%) formal and informal consultations. Informal and formal consultations were associated with comparable levels of compliance with recommendations for antimicrobial treatment (86.5% vs 88.9%; adjusted odds ratio [aOR], 0.63; 95% confidence interval, 0.34–1.14; P = 0.13) and diagnostic or monitoring tests (72.6% vs 72.0%; aOR, 0.91 [0.53–1.57]; P = 0.73). The rates of early clinical improvement (58.2% vs 58.6%; aOR, 1.11 [0.70–1.74]; P = 0.66), subsequent consultation (34.2% vs 36.3%; aOR, 0.80 [0.53–1.21]; P = 0.29), in-hospital mortality (4.9% vs 8.4%; aOR, 0.55 [0.24–1.24]; P = 0.15), and the median length of stay (23 vs 20 days; aOR of discharge, 0.90 [0.74–1.10]; P = 0.30) did not differ depending on the type of consultation. This study provides observational evidence that informal consultations result in levels of compliance with recommendations comparable to formal consultations, without compromising patient safety. Further study is needed to refine the criteria for requesting or providing informal rather than formal consultations.     

A retrospective study of 230 consecutive patients hospitalized for presumed travel-related illness (2000–2006)

A good knowledge of morbidity profiles among ill-returned travelers is necessary in order to guide their management. We reviewed the medical charts of 230 patients hospitalized in one infectious diseases department in France for presumed travel-related illnesses. The male-to-female ratio was 1.6 and the median age was 33 years (interquartile range [IQR], 25–50). Most patients (70.9%) were returning from sub-Saharan Africa. The median duration of travel was 28 days (IQR, 15–60) and the median time from return of travel to hospitalization was 13 days (IQR, 7–21). Malaria was the most frequent diagnosis (49.1%), which was especially encountered in patients returning from sub-Saharan Africa (95.6%), without adequate chemoprophylaxis (78.2%). Imported diseases at risk of secondary transmission were also diagnosed, including pulmonary tuberculosis (n = 8), viral hepatitis (n = 8), typhoid fever (n = 6), human immunodeficiency virus (HIV) (six new diagnosis), non-typhoid salmonellosis (n = 5), severe acute respiratory syndrome, and Crimean-Congo hemorrhagic fever. This study underlines the need to maintain tropical expertise for infectious diseases physicians, even in Europe.     

Relation between Epstein-Barr virus and multiple sclerosis: analytic study of scientific production

Numerous studies have been carried out to determine whether infection by the Epstein-Barr virus (EBV) can be considered as a risk factor for multiple sclerosis (MS). This work is a meta-analysis of case–control observational studies published before January 2009 aimed at assessing the degree of association between EBV and MS infections. A Medline electronic database search was carried out using “Epstein-Barr virus” and “multiple sclerosis” as keywords, from which we selected 30 published studies that met our methodology criteria. We found an association between MS and an exposure to EBV, studied by determining the anti-VCA IgG antibodies (odds ratio [OR] = 5.5; 95% confidence interval [CI] = 3.37–8.81; p < 0.0001), anti-complex EBNA IgG (OR = 5.4; 95% CI = 2.94–9.76; p < 0.0001) and anti-EBNA-1 IgG (OR = 12.1; 95% CI = 3.13–46.89; p < 0.0001). No significant association could be found when studying anti-EA IgG (OR = 1.3; 95% CI = 0.68–2.35; p = 0.457), EBV DNA in serum (OR = 1.8; 95% CI = 0.99–3.36; p = 0.051) and DNA in brain tissues and in cerebrospinal fluid (CSF) (OR = 0.9; 95% CI = 0.38–2.01; p = 0.768). This meta-analysis detected an association between infection by EBV and MS through the investigation of antibodies, mainly anti-EBNA-1, anti-complex EBNA and anti-VCA IgG.     

Clinical predictive values of extended-spectrum beta-lactamase carriage in patients admitted to medical wards

We aimed to reassess, through clinical items, populations at risk for extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) carriage at admission to hospital and to assess the risk of further positive clinical culture of ESBL-E among carriers. We performed a 5-month cohort study in a medicine ward of a 500-bed university teaching hospital in the Parisian area of France. All admitted patients were prospectively enrolled for rectal swabbing and clinical data collection, including bacterial infection at admission and during stay. Variables associated with ESBL-E carriage were identified by univariate and multivariate analysis. Five hundred patients were included. The prevalence of ESBL-E was 6.6% (33/500) upon admission. Only previous carriage of multidrug-resistant bacteria (MDRB) was associated with carriage (odds ratio [OR]: 17.7, 95% confidence interval (CI) 5.8–54.2, p < 0.001), yet, the positive predictive value (PPV) was not higher than 50%. When prior MDRB carriage was not considered in the multivariate analysis, only prior antibiotic consumption was found to be associated with carriage at admission (OR: 2.2 [1.1–4.5], p = 0.02). Two patients had ESBL-E infection at admission, yet, no patient became infected with ESBL-E during their stay. The clinical prediction of ESBL carriage at admission in our wards was found to be poorly efficient for assessing the at-risk population.     

<Emphasis Type="Italic">Mycoplasma pneumoniae</Emphasis> infection in primary care investigated by real-time PCR in England and Wales

Real-time PCR was employed to detect a conserved region of the P1 cytadhesin gene of Mycoplasma pneumoniae in combined nose and throat swabs collected from patients attending GP surgeries during 2005–2009 with symptoms of respiratory tract infection (RTI). Samples were collected as part of an annual winter epidemiological and virological linked study in England and Wales. A total of 3,987 samples were tested, 65 (1.7%, 95%CI 1.3–2.1) had detectable M. pneumoniae DNA. Positive patients were detected of both gender, aged from 9 months to 78 years, who had clinical signs of upper RTI, fever and/or myalgia, an influenza-like illness to lower RTI. Mixed infections were identified in four cases, two with influenza A H1, one with H3 and one with influenza B. Children aged 5–14 years were more likely to have detectable M. pneumoniae in samples than all other age groups (Fishers p = 0.03), attributed to the 2005–2006 season in which 6.0% (12/200, 95%CI 3.4–10.3) of 5–14 year olds had detectable M. pneumoniae in comparison to 2.2% in 2006–2007 (3/141 95%CI 0.5–6.4), 2.2% in 2007–2008 (2/89 95%CI 0.1–8.3) and 0% in 2008-2009 (0/151 95%CI 0–2.9).     

<Emphasis Type="Italic">Stenotrophomonas maltophilia</Emphasis> pneumonia in cancer patients without traditional risk factors for infection, 1997–2004

In order to elucidate the spectrum of Stenotrophomonas maltophilia pneumonia in cancer patients without traditional risk factors, 44 cancer patients (cases) with S. maltophilia pneumonia in whom S. maltophilia pneumonia risk factors were not present were compared with two S. maltophilia pneumonia risk groups (controls) including 43 neutropenic non-intensive care unit (ICU) and 21 non-neutropenic ICU patients. The case and control patients had similar demographic and underlying clinical characteristics. Compared with case patients with S. maltophilia pneumonia, neutropenic patients had higher exposure to carbapenem antibiotics (58 vs. 41%; p < 0.03), more frequent hematologic malignancy (95 vs. 64%; p < 0.0003), and they presented with concurrent bacteremia more often (23 vs. 0%; p < 0.0005). Patients with S. maltophilia pneumonia in the ICU needed vasopressor therapy more frequently than cases (62 vs. 5%; p < 0.0001). Hospital-acquired S. maltophilia pneumonia was more common among controls than cases (98 vs. 61%; p < 0.000002). Among the cases, 15 (34%) received outpatient oral antimicrobial therapy, while 29 were hospitalized and eight (28%) were subsequently admitted to the ICU. The mean duration of ICU stay, even among these eight patients (19 ± 40 days), was comparable to that of patients with neutropenia (23 ± 26 days) and those who developed S. maltophilia pneumonia during their ICU stay (34 ± 22 days; p = 0.46). The overall infection-associated mortality in the 108 patients with S. maltophilia pneumonia was 25%. Twenty percent of patients without traditional risk factors for S. maltophilia pneumonia died due to progressive infection. In a multivariate logistic regression analysis, only admission to the ICU predicted death (odds ratio 33; 95% confidence interval, 4.51–241.2; p < 0.0006). The results of this study indicate S. maltophilia pneumonia is a serious infection even in non-neutropenic, non-ICU patients with cancer. This work was presented in part at the 15th European Congress of Clinical Microbiology and Infectious Diseases, Copenhagen, Denmark, April 2–5, 2005 (abstract no P1374) and at the 45th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington D.C., December 16–19, 2005 (abstract no K-1535).     

Prospective study in critically ill non-neutropenic patients: diagnostic potential of (1,3)-β-D-glucan assay and circulating galactomannan for the diagnosis of invasive fungal disease

Diagnosis of invasive fungal disease (IFD) in patients under intensive care is challenging. Circulating biomarkers, (1,3)-β-D-glucan (BG) and galactomannan (GM), were prospectively assessed in 98 critically ill patients at risk of IFD. There were 11 cases of invasive aspergillosis (IA; 4 proven and 7 probable), 9 cases of proven invasive candidiasis (IC), 1 case of mixed proven IC and probable IA, 1 case of proven zygomycosis, and 1 case of mixed mycelial proven IFD. In all IA cases there was no significant difference when the area under the receiver operating characteristic curve (AUC) of GM (0.873 [95%CI, 0.75–0.99]) and BG (0.856 [95% CI, 0.71–0.99]) were compared (p = 0.871). The AUC for BG in IC and for the rest of the IFD cases was 0.605 (95% CI, 0.39–0.82) and 0.768 (95% CI, 0.63–0.90) respectively. Positive BG (40%) predated blood culture (n = 3) and abdominal pus (n = 1) a mean of 3.25 days before Candida was grown. In patients with IFD caused by molds, BG appeared a mean of 5.65 days before culture results. For the diagnosis of patients at risk of IC, BG has shown a high NPV (94.5%), with positive results also predating blood cultures in 30% of patients. In conclusion, early BG results permit a timely initiation of antifungal therapy in patients at risk of IFD.     

Clinical outcomes of bacteremic pneumococcal infections in an area with high resistance

In a retrospective study designed to gather information in a region with high antimicrobial resistance, the outcomes of 216 episodes of laboratory-confirmed pneumococcal bacteremia treated in Hong Kong between 1995 and 2001 were assessed. The patients had a mean age (±standard deviation) of 40±33.7 years. In all patients, the clinical diagnosis was confirmed by isolation of Streptococcus pneumoniae from blood (n=216), cerebrospinal fluid (n=7) and/or other sterile sites (n=12). Penicillin nonsusceptibility was found in 37.5% of the isolates (20.8% intermediate and 16.7% resistant). Penicillin nonsusceptibility was not a risk factor for inpatient mortality (p=0.7), nor did it affect duration of fever (p=0.4), requirement for intensive care unit admission (p=0.4) or development of suppurative complications (p=0.2). Advanced age (OR 11.3, 95%CI 4.5–28.2, p<0.01), critical illness (OR 11.3, 95%CI 4.5–28.2, p<0.001) and discordant therapy (OR 4.3, 95%CI 1.7–10.9, p<0.002) involving agents with poor anti-pneumococcal activity (but not penicillins and broad-spectrum β-lactam agents) were significantly associated with mortality.     

Impact of multi-drug-resistant <Emphasis Type="Italic">Acinetobacter baumannii</Emphasis> on clinical outcomes

We conducted a retrospective matched cohort study to examine the impact of isolation of multi-drug-resistant (MDR) Acinetobacter baumannii on patient outcomes. Cases from whom MDR A. baumannii was isolated in a clinical culture (n = 118) were compared with controls from whom MDR A. baumannii was not isolated (n = 118). Cases and controls were matched according to ward, calendar month of hospitalization, and duration of hospitalization before culture. The following outcomes were compared in multivariable analysis: in-hospital mortality, length of stay, need for mechanical ventilation, and functional status at discharge. MDR A. baumannii was determined to be a pathogen in 72% of cases. In 36% of cases, the patient died, versus 21% of controls (odds ratio [OR] 2.21, 95% confidence interval [CI] 1.17–4.16, P = 0.014). Median length of stay for surviving cases was 17 days, versus 11 for surviving controls (multiplicative effect 1.55, 95% CI 0.99–2.44, P = 0.057). Fifty-two percent of cases required mechanical ventilation, versus 25% of controls (OR 3.72, 95% CI 1.91–7.25, P<0.001); 60% of surviving cases were discharged with reduced functional status, versus 38% of controls (OR 4.4, 95% CI 1.66–11.61, P = 0.003). In multivariable analysis, clinical isolation of MDR A. baumannii remained a significant predictor of mortality (OR 6.23, 95% CI 1.31–29.5, P = 0.021), need for mechanical ventilation (OR 7.34, 95% CI 2.24–24.0, P<0.001), and reduced functional status on discharge (OR 7.93, 95% CI 1.1–56.85, P = 0.039). Thus, MDR A. baumannii acquisition is associated with severe adverse outcomes, including increased mortality, need for mechanical ventilation, and reduced functional status.     

Infectious endocarditis in patients with cirrhosis of the liver: a model of infection in the frail patient

The purposes of this paper was to discover whether cirrhosis is a predisposing cause of infectious endocarditis (IE) and to determine the microbiology, prognosis and the role of cardiac surgery on mortality. A review of cases of IE at a university-affiliated hospital over a period of 10 years was conducted. Thirty-one (9.8%) patients among 316 cases of IE had hepatic cirrhosis. Valve disorders were present in 62.2% of cirrhotic patients and infection occurred on the aortic (48%) and mitral valves (45%). Endocarditis was hospital-acquired in 14 (45%) and 11 (17.7%) cirrhotic patients and controls, respectively (odds ratio [OR] 3.82; 95% confidence interval [CI]: 1.46–9.99; p = 0.005). Staphylococcus aureus was the most common causative microorganism, but β-hemolytic streptococci were most frequently isolated in cirrhotic patients (OR 8.75; 95% CI: 1.7–45.2; p = 0.001). Renal failure was more frequent in patients with cirrhosis (OR 8.23; 95% CI: 3.06–22.2; p = 0.001). Cirrhotic patients had a higher mortality (51% vs. 17.7%; OR 4.95; 95% CI: 1.89–12.91; p = 0.001) associated with the severity of liver disease. Valve replacement was performed less frequently in cirrhotic patients (56.2% vs. 92%) and the operative mortality was extremely high in patients at stages B and C. Hepatic cirrhosis is a frequent comorbid condition in patients with endocarditis. Due to the presence of severe hepatic dysfunction, cardiac surgery is not undertaken even when indicated and mortality is high in stages B and C. Endocarditis is a serious hazard for hospitalized cirrhotic patients.     

Warfarin therapy and incidence of cerebrovascular complications in left-sided native valve endocarditis

Anticoagulant therapy has been anticipated to increase the risk of cerebrovascular complications (CVC) in native valve endocarditis (NVE). This study investigates the relationship between ongoing oral anticoagulant therapy and the incidence of symptomatic CVC in left-sided NVE. In a prospective cohort study, the CVC incidence was compared between NVE patients with and without ongoing warfarin. Among 587 NVE episodes, 48 (8%) occurred in patients on warfarin. A symptomatic CVC was seen in 144 (25%) patients, with only three on warfarin. CVC were significantly less frequent in patients on warfarin (6% vs. 26%, odds ratio [OR] 0.20, 95% confidence interval [CI] 0.06–0.6, p = 0.006). No increase in haemorrhagic lesions was detected in patients on warfarin. Staphylococcus aureus aetiology (adjusted OR [aOR] 6.3, 95% CI 3.8–10.4) and vegetation length (aOR 1.04, 96% CI 1.01–1.07) were risk factors for CVC, while warfarin on admission (aOR 0.26, 95% CI 0.07–0.94), history of congestive heart failure (adjusted OR 0.22, 95% CI 0.1–0.52) and previous endocarditis (aOR 0.1, 95% CI 0.01–0.79) correlated with lower CVC frequency.     

Usefulness of Route of Transmission, Absolute CD8+ T-Cell Counts, and Levels of Serum Tumor Necrosis Factor Alpha as Predictors of Survival of HIV-1-Infected Patients with Very Low CD4+ T-Cell Counts

 Potential cofactors of survival in HIV-1-infected patients with CD4+ T-cell counts of ≤100 cells/μl were investigated. All 132 patients with CD4+ T-cell counts of ≤100 cells/μl were selected from 416 patients included in an antiretroviral therapy cohort (1989–1999). Fifty of 54 deaths were due to AIDS. There were significant associations (P<0.05) between survival and CD8+ T-cell counts, clinical AIDS stage, risk group, and antiretroviral drug regimen after baseline, but only the use of protease inhibitors had an independent effect on survival (hazard ratio [HR], 0.096; 95% confidence interval [95%CI], 0.094–0.097). A substudy restricted to the cohort of 108 patients never exposed to PIs detected independent associations between survival and CD8+ T-cell counts (P=0.0016), experience with antiretroviral therapy before baseline (HR, 2.52; 95%CI, 1.31–4.82), sexual risk group for HIV infection (HR, 3.7; 95%CI, 1.92–7.12), and levels of serum tumor necrosis factor alpha (P=0.02). This study confirms that the use of PI-containing antiretroviral regimens strongly predicts survival of HIV-1-infected patients with very low CD4+ T-cell counts. When the study was restricted to patients never exposed to PIs, the parenteral route of disease transmission, high absolute CD8+ T-cell counts, and low serum levels of tumor necrosis factor alpha were independent predictors of survival in extremely advanced HIV-1 disease.