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.     

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.     

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.     

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.     

5′ Regulatory and 3′ Untranslated Region Polymorphisms of Vitamin D Receptor Gene in South Indian HIV and HIV–TB Patients

Introduction  Vitamin D receptor (VDR) gene polymorphisms in the 5′ regulatory region (Cdx2 and A-1012G), coding region (FokI), and 3′ untranslated region (UTR; BsmI, ApaI, and TaqI) were studied to find out whether these polymorphisms are associated with susceptibility to or protection against HIV-1 and development of tuberculosis (TB) in human immunodeficiency virus (HIV)-1-infected patients. Study Subjects and Methods  The study was carried out in 131 HIV patients without TB (HIV+ TB−) and 113 HIV patients with TB (HIV+ TB+; includes 82 patients with pulmonary TB (HIV+ PTB+) and 31 with extra pulmonary TB), 108 HIV-negative pulmonary TB patients (HIV− PTB+), and 146 healthy controls. Results  Among the 5′ regulatory and coding region polymorphisms, significantly increased frequency of G/A genotype of Cdx-2 was observed in HIV+ TB− group compared to controls (p = 0.012, odds ratio (OR) 1.89 95% confidence interval (CI) 1.14–3.15). In the 3′ UTR genotypes, a decreased frequency of b/b genotype of BsmI in total HIV patients (p = 0.014, OR 0.54 95% CI 0.32–0.89) and increased frequencies of A/A genotype of ApaI in HIV+ TB+ patients (p = 0.041, OR 1.77 95% CI 1.02–3.06) and t/t genotype of TaqI in HIV+ PTB+ patients (p = 0.05, OR 2.32 95% CI 0.99–5.46) were observed compared to controls. Haplotype analysis revealed significantly increased frequencies of 3′ UTR haplotype B-A-t in HIV+ TB+ and HIV+ PTB+ groups (Pc = 0.030, OR 1.75 95% CI 1.14–2.66) and decreased frequencies of b-A-T haplotype in total HIV patients (Pc = 0.012, OR 0.46 95% CI 0.27–0.77), HIV+ TB− (p = 0.031 OR 0.48 95% CI 0.25–0.89), and HIV+ PTB+ groups (Pc = 0.04, OR 0.47 95% CI 0.23–0.89) compared to controls. Conclusions  The results suggest that VDR gene 3′ UTR haplotype b-A-T may be associated with protection against HIV infection while B-A-t haplotype might be associated with susceptibility to development of TB in HIV-1-infected patients.     

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.     

Multiplexed analysis of angiogenesis and lymphangiogenesis factors predicts outcome for non-small cell lung cancer patients

Angiogenesis and lymphangiogenesis are key components of non-small cell lung cancer (NSCLC) tumor growth and metastatic spread; however, the prognostic and predictive role of angiogenic and lymphangiogenic biomarkers remains controversial for NSCLC patients. We assessed VEGF, VEGFC, VEGFD, VEGFR3 protein expression, tumor microvessel, and lymphatic vessel (LmVD) density by immunohistochemistry in 103 NSCLC; biomarkers were analyzed individually as well as multiplexed with each other. No correlations were identified between VEGF, VEGFC, VEGFD, or LmVD and clinical characteristics. VEGFR3 was correlated with VEGFC (p = 0.03), VEGFD (p < 0.0001), and intratumor LmVD (p = 0.03). Tumors that did not express VEGFR3 had a worse prognosis (log rank p = 0.03). VEGF was significantly correlated with survival in adenocarcinomas (log rank p = 0.014) but not in squamous cell carcinomas (log rank p = 0.5). Multivariate Cox regression analysis confirmed the independent prognostic potential of VEGFR3 (hazard ratio (HR) = 0.05; 95% confidence intervals (CI) = 0.008–0.32, p = 0.002) for all patients and VEGF (HR = 8.69, 95% CI = 1.4–53.69, p = 0.02) for adenocarcinomas. When biomarkers were multiplexed, only stage and VEGFC expression were independent predictors of survival for all patients. Weighted expression of VEGFC, VEGFR3, and stage was used to build a prognostic classifier for stage I–IIIA patients; patients in the low risk group had prolonged survival compared with high risk patients (log rank p = 0.02). There was no association between biomarkers and early recurrence or response to treatment. Angiogenic and lymphangiogenic biomarkers studied define subgroups of patients at high risk and may be useful for prognostic stratification of NSCLC patients especially those with early stage disease.     

Seroprevalence and sources of Toxoplasma infection among indigenous and immigrant pregnant women in Taiwan

Investigation on seroprevalence and risk factors of Toxoplasma gondii infections among indigenous and immigrant pregnant women in Mid-Taiwan showed that anti Taxoplasma-specific IgG antibody counts were significantly higher in indigenes (40.6%) than in immigrants (18.2%), with an odds ratio of OR = 3.34 (95% CI: 1.93–4.80). The titre of Taxoplasma-specific IgG was also significantly higher in indigenes than in immigrants (P < 0.001). Differences of living styles for Toxoplasma infection between the two groups were drinking untreated water (OR = 2.34, 95% CI: 1.36–4.02), consumption of raw/undercooked meats (OR = 10.11 95% CI: 4.92–20.78), especially raw/undercooked pork (P = 0.000), or raw/undercooked viscera (OR = 9.16, 95% CI: 2.97–27.94), contact with cats (OR = 5.69, 95% CI: 2.83–11.47), or soil (OR = 2.55 95% CI: 1.72–3.80). Differences of risk factors for Toxoplasma infection in terms of positive IgG in the two groups were consumption of raw/undercooked meats (P = 0.005) especially raw/undercooked pork (P = 0.004), and contact with cats (P = 0.013) or soil (P = 0.028). It is concluded that seroprevalence of Toxoplasma infection is higher in indigenous pregnant women and related to their living styles. To prevent congenital toxoplasmosis, health education seems required.     

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.     

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.     

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.     

Fungal colonization and/or infection in non-neutropenic critically ill patients: results of the EPCAN observational study

The purpose of this paper is to determine the incidence of fungal colonization and infection in non-neutropenic critically ill patients and to identify factors favoring infection by Candida spp. A total of 1,655 consecutive patients (>18 years of age) admitted for ≥7 days to 73 medical-surgical Spanish intensive care units (ICUs) participated in an observational prospective cohort study. Surveillance samples were obtained once a week. One or more fungi were isolated in different samples in 59.2% of patients, 94.2% of which were Candida spp. There were 864 (52.2%) patients with Candida spp. colonization and 92 (5.5%) with proven Candida infection. In the logistic regression analysis risk factors independently associated with Candida spp. infection were sepsis (odds ratio [OR] = 8.29, 95% confidence interval [CI] 5.07–13.6), multifocal colonization (OR = 3.49, 95% CI 1.74–7.00), surgery (OR = 2.04, 95% CI 1.27–3.30), and the use of total parenteral nutrition (OR = 4.37, 95% CI 2.16–8.33). Patients with Candida spp. infection showed significantly higher in-hospital and intra-ICU mortality rates than those colonized or non-colonized non-infected (P < 0.001). Fungal colonization, mainly due to Candida spp., was documented in nearly 60% of non-neutropenic critically ill patients admitted to the ICU for more than 7 days. Proven candidal infection was diagnosed in 5.5% of cases. Risk factors independently associated with Candida spp. infection were sepsis, multifocal colonization, surgery, and the use of total parenteral nutrition.     

Expression level of the mitotic checkpoint protein and G2–M cell cycle regulators and prognosis in gastrointestinal stromal tumors in the stomach

The biological behavior of gastrointestinal stromal tumors (GISTs) ranges from benign to malignant, and the risk of an adverse outcome is correlated with the location of the primary tumor, tumor size, and mitotic counts. Cell cycle regulators are potentially associated with the tumorigenesis and progression of GISTs. Checkpoint with forkhead and ring finger (CHFR) functions as an important checkpoint protein in the early to mid-prophase to regulate mitosis. In this study, we evaluated the expression of CHFR and several cell cycle regulators, including cyclin A, cyclin B1, cdc2, and cdk2, by immunohistochemical staining in 53 cases of primary gastric GISTs, and compared the immunohistochemical results with the clinicopathological factors or the GIST risk grades as modified by Miettinen et al. Of the 53 cases, 18 (34%) showed decreased nuclear CHFR expression. Decreased CHFR expression was correlated with higher mitotic counts [>5/50 high-power fields (HPFs)] (p = 0.039) and a high-risk grade (p = 0.0475), but not with expression of other cell cycle regulators. Higher cyclin A labeling index (LI, >1.5%), cyclin B1 LI (>0.25%), cdc2 LI (>1.16%), Ki-67 LI (>4.9%), mitotic counts (>5/50 HPF) and high-risk grade were each associated with shorter disease-free survival (p = 0.0017, p = 0.003, p = 0.0471, p = 0.002, p < 0.001, and p = 0.0017, respectively). Our results suggest that modified risk grade and increased expression of G2–M regulators such as cyclin A, cyclin B1, and cdc2 are useful for predicting the biological behavior of gastric GISTs. In addition, decreased CHFR expression may play a role in increased proliferative activity of higher grade GISTs.     

Investigations on the biology, epidemiology, pathology, and control of Tunga penetrans in Brazil: VII. The importance of animal reservoirs for human infestation

In Brazil tungiasis is endemic in many resource-poor communities, where various domestic and sylvatic animals act as reservoirs for this zoonosis. To determine the role of animal reservoirs in human tungiasis, a cross-sectional study was performed in a traditional fishing community in northeast Brazil. The human and the animal populations were examined for the presence of embedded sand fleas and the prevalence and the intensity of infestation were correlated. The overall prevalence of tungiasis in humans was 39% (95% CI 34–43%). Of six mammal species present in the village, only cats and dogs were found infested. The prevalence in these animals was 59% (95% CI 50–68%). In households, where infested pet animals were present, a higher percentage of household members had tungiasis (42% [95% CI 30–53%] versus 27% [20–33%], p = 0.02), and the intensity of the infestation was higher (six lesions versus two lesions, p = 0.01). The intensity of infestation in animals correlated with the intensity of infestation in humans (rho = 0.3, p = 0.02). Living in a household with an infested dog or cat led to a 1.6-fold (95% CI 1.1–2.3, p = 0.015) increase in the odds for the presence of tungiasis in household members in the bivariate analysis and remained a significant risk factor in the multivariate regression analysis. The study shows that in this impoverished community tungiasis is highly prevalent in humans and domestic animals. In particular, it underlines the importance to include animals in control operation aiming at the reduction of disease occurrence in the human population.     

Expression of pERK and pAKT in human astrocytomas: correlation with IDH1-R132H presence,vascular endothelial growth factor,microvascular characteristics and clinical outcome

Although pERK and pAKT are reportedly activated in various neoplasms, little information is available about their significance in astrocytomas. Paraffin-embedded tissue from 82 patients with diffuse infiltrating astrocytomas (grades II to IV) was investigated for the association of pERK and pAKT activation with clinicopathological features, vascular endothelial growth factor (VEGF), isocitrate dehydrogenase 1 and microvascular parameters. Nuclear pERK labelling index (LI) increased with increasing cytoplasmic pERK LI and nuclear and cytoplasmic pAKT LI (p = 0.0019, p = 0.0260 and p = 0.0012, respectively). Accordingly, cytoplasmic pERK increased with increasing levels of nuclear (p = 0.0001) and marginally with cytoplasmic pAKT LI (p = 0.0526). Nuclear and cytoplasmic pERK LI and nuclear pAKT LI were positively correlated with tumour histological grade (p = 0.0040, p = 0.0238 for pERK and p = 0.0004 for pAKT, respectively). VEGF expression was correlated with nuclear pERK (p = 0.0099) and nuclear pAKT LI (p = 0.0002). Interestingly, pERK cytoplasmic LI increased with microvessel calibre (p = 0.0287), whereas pAKT nuclear LI was marginally related to microvessel density (p = 0.0685). The presence of IDH1-R132H was related only to histological grade and lower microvessel calibre. Multivariate survival analysis in the entire cohort selected cytoplasmic pAKT LI (p = 0.045), histological grade, microvessel calibre (p = 0.028), patients' age, gender and surgical excision as independent predictors of survival. Moreover, in glioblastomas, pERK nuclear LI emerged as a favourable prognosticator in the presence of IDH1-R132H. pERK and pAKT in astrocytomas are interrelated and associated with tumour grade and angiogenesis. Moreover, the importance of cytoplasmic pAKT immunoexpression in patients' prognosis and nuclear pERK immunoexpression in glioblastomas is confirmed.     

Prevalence of heterophyiosis in Tilapia fish and humans in Northern Egypt

A total of 100 Tilapia fish samples were collected from brackish water (n = 50) and fresh water (n = 50) resources, Northern Egypt, and examined for heterophyid encysted metacercariae (EMC) during the period from August 2007 to July 2008. The overall prevalence of infection was 32%; 22% for brackish water fish and 42% for fresh water fish. Significant differences in parasite occurrence among body regions were found, with muscles of the tail and caudal third being highly affected (93.4%) followed by middle third (84.3%) and anterior third (75%), while the head region had the lowest infection (21.9%). The prevalence was highest in summer season (46.4%) followed by spring (37.5%) and autumn (27.3%), and was lowest in winter (15.4%). The prevalence of infection decreased as fish size increased. Adult heterophyids, Heterophyes heterophyes, Heterophyes aequalis, Pygidiopsis genata, Haplorchis yokogawai, and Ascocotyle (Phagicola) ascolonga were recovered from EMC-feed puppies. Eggs of heterophyid type were detected in 10 (13.3%) out of 75 human stool specimens from local residents. An association exists between being a female (odd ratio [OR] 1.59 and 95% confidence interval [CI] 0.42–6.04), a fisherman (OR 1.39 [95% CI 0.26–7.48]), a housewife (OR 1.24 [95% CI 0.29–6.28]), 15–45 years old (OR 2.22 [95% CI 0.58–8.53]), or aged 5–14 years (OR 1.29 [95% CI 0.30–5.58]) and heterophyid infection. Measures should be implemented to reduce the risk of transmission of heterophyids to human and fish-eating animals.     

Short- and long-term outcome of HIV-infected patients admitted to the intensive care unit

The purpose of this investigation was to analyse the impact of the availability of highly active antiretroviral therapy (HAART) on the long-term outcome of human immunodeficiency virus (HIV)-infected patients admitted to the intensive care unit (ICU). A retrospective cohort study of HIV-infected patients admitted to the ICU was undertaken. Outcomes in the pre-HAART era (1990–June 1996), early- (July 1996–2002), and recent-HAART (2003–2008) periods and total HAART era (July 1996–2008) were analysed and compared with those reported of the general population. A total of 127 ICU admissions were included. The 1-year mortality decreased from 71% in the pre-HAART era to 50% in the recent-HAART period (p = 0.06). The 5-year mortality decreased from 87% in the pre-HAART era to 59% in the early-HAART period (p = 0.005). Independent predictors of 1-year mortality in the HAART era were age (odds ratio [OR] = 1.16 [95% confidence interval [CI] = 1.06–1.27]), APACHE II score > 20 (6.04 [1.25–29.22]) and mechanical ventilation (40.01 [3.01–532.65]). The 5-year survival after hospitalisation was 80% and in the range of the reported survival of non-HIV-infected patients (83.7%). Predictors of 1-year mortality for HIV patients admitted to the ICU in the HAART era were all non-HIV-related. Short- and long-term outcome has improved since the introduction of HAART and is comparable to the outcome data in non-HIV-infected ICU patients.     

C-reactive protein and nitric oxide levels in ischemic stroke and its subtypes: correlation with clinical outcome

Studies in different populations have shown that ischemic stroke can trigger an acute phase response resulting in a rise of plasma concentration of C-reactive protein (CRP). However, there are very limited studies on CRP and first ischemic stroke divided into subtypes. High levels of CRP may also be associated with poor outcome. The present study was taken up to investigate the prognostic value of CRP within 24 h of onset of ischemic stroke. Five hundred and eighty one patients with first stroke and 575 age- and sex-matched healthy controls were involved in the study. High-sensitivity C-reactive protein (hsCRP) levels were estimated, and follow-up interviews were conducted with patients at 3, 6, and 12 months post-event to determine stroke outcome. In addition to this plasma, NO _x (nitrate and nitrite) was measured to detect the serum NO (an important biomarker of inflammation and oxidative stress) levels in ischemic stroke patients and controls. The relationship between CRP value and poor outcome (>2 on modified Rankin Scale Score and <5 on an extended Glasgow outcome scale) was studied. There was a significant association between elevated levels of CRP and NO with the disease. A stepwise multiple logistic regression analysis confirmed these findings after adjustment for potential confounders [adjusted odds ratio = 2.890, 95% CI (1.603–5.011) with p < 0.01 and adjusted odds ratio = 2.364, 95% CI (1.312–3.998) with p < 0.01 for hsCRP and NO, respectively]. After adjustment of potential confounders, patients with high CRP levels had a significant increased risk of poor outcome [adjusted odds ratio = 3.50, 95% CI (1.312–6.365) and p < 0.001]. Elevated levels of hsCRP associated significantly with all stroke subtypes classified according to Trial of ORG 10172 in Acute Stroke Treatment classification except for lacunar stroke and stroke of other determined etiology. In conclusion, hsCRP and NO levels predict the incidence of ischemic stroke and hsCRP is an independent prognostic factor of poor outcome at 3 months.     

Risk factors for multidrug-resistant tuberculosis in a tuberculosis unit in Madrid,Spain

The setting for this retrospective cohort study was a specialised tuberculosis unit in Madrid, Spain. The objective was to describe the risk factors for multidrug-resistant tuberculosis (MDR-TB). The medical records of all patients admitted to the unit were reviewed retrospectively to identify factors associated with multidrug resistance. Patients with positive culture for M. tuberculosis and with available drug-susceptibility tests were included. The variables assessed were age, gender, country of origin, homelessness, alcohol consumption, intravenous drug use, methadone substitution therapy, contact with a tuberculosis patient, sputum smear, site of disease, previous tuberculosis treatment, HIV infection, history of imprisonment, diabetes mellitus and chronic obstructive pulmonary disease. Thirty patients with MDR-TB and 666 patients with non-MDR-TB were included from the years 1997 to 2006. The only factors associated with MDR-TB in multivariate analysis were previous tuberculosis treatment (OR: 3.44; 95% CI: 1.58–7.50; p = 0.003), age group 45–64 years (OR: 3.24; 95% CI: 1.34–7.81; p = 0.009) and alcohol abuse (OR: 0.12; 95% CI: 0.03 to 0.55; p = 0.003). In our study, patients who had had previous treatment for tuberculosis, who were 45–64 years of age or who had no history of alcohol abuse were more likely to have MDR-TB.     

Obesity-dependent association of TNF-LTA locus with type 2 diabetes in North Indians

Six common genetic variants (rs2229094, rs1041981, rs1800630, rs1800629, rs361525, and rs1800610) in the TNF-LTA locus encoding the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and lymphotoxin-α have been shown to be associated with various metabolic traits including susceptibility to type 2 diabetes, metabolic syndrome, insulin resistance, and increased body mass index (BMI) in Caucasians from different geographic locations and have yielded mixed results. We tested for the association of these variants with type 2 diabetes in North Indians by studying 2,115 participants comprising of 1,073 type 2 diabetes patients and 1,042 controls. We report the association of a promoter region variant of TNF: rs1800630 and non-synonymous LTA variant: rs2229094 with type 2 diabetes [OR = 0.83 (95% CI 0.72–0.95), P = 0.005 and OR = 0.86 (95% CI 0.75–0.98), P = 0.02, respectively]. Although these associations were BMI-dependent, no interactive effect of BMI and variants on type 2 diabetes was detectable. Further, the haplotype carrying all the six major alleles conferred susceptibility to type 2 diabetes [OR = 1.23 (95% CI 1.06–1.42), P = 0.005; P _permuted = 0.02], with the effect much enhanced in non-obese subjects [OR = 1.45 (95% CI 1.19–1.78), P = 2 × 10⁻⁴: P _permuted = 3 × 10⁻⁴]. The minor allele of rs2229094 was associated with lower hsCRP, BMI, and waist circumference (WC), while the minor allele of rs1800630 showed association with lower BMI and WC (all P < 0.01). This is the first report demonstrating association of rs1800630 and rs2229094 with type 2 diabetes in any population, suggesting an important role of the TNF-LTA locus in type 2 diabetes in North Indians.