Expression of paired basic amino acid-cleaving enzyme 4 (PACE4) correlated with prognosis in non-small cell lung cancer (NSCLC) patients

Background

Paired basic amino acid-cleaving enzyme 4 (PACE4) was shown to enhance tumor cells proliferation and invasive. This study provides the first investigation of PACE4 expression in non-small cell lung cancer (NSCLC) and the correlation with clinicopathologic features, prognostic indicators of 172 cases.

Methods

Quantitative real-time PCR (RT-PCR) and immunofluorescence (IF) were applied to detect PACE4 expression in NSCLC and 16HBE cell lines, then 172 consecutive NSCLC and 15 normal lung tissues were studied through immunohistochemistry (IHC). The association between PACE4 expression and clinicopathological parameters was evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of PACE4 expression on survival.

Results

PACE4 expression in NSCLC were significantly higher than normal lung cell and tissues (P<0.05). PACE4 had cytoplasmic expression and was observed in 111 of the 172 (64.5%) NSCLC patients. Clinicopathologically, PACE4 expression was significantly associated with lymph node metastasis (N stage) (P=0.007), and clinical stage (P=0.024). Multivariable analysis confirmed that PACE4 expression increased the hazard of death after adjusting for other clinicopathological factors [hazards ratio (HR): 1.584; 95% confidence interval (CI): 1.167-2.151; P<0.001]. Overall survival (OS) was significantly prolonged in PACE4 negative group when compared with PACE4 positive group (5-year survival rates, 23.1% vs. 54.5%, log-rank test, χ²=17.717, P<0.001), as was disease-free survival (DFS) (5-year survival rates, 23.4% vs. 55.4%, log-rank test, χ²=20.486, P<0.001).

Conclusions

Our results suggest that positive expression of PACE4 is an independent factor for NSCLC patients and it might serve as a potential prognostic biomarker for patients with NSCLC.     

Prognostic value of FLT3 mutations in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy

Background

Fms-like tyrosine kinase-3 (FLT3) gene mutations are frequent in acute promyelocytic leukemia but their prognostic value is not well established.

Design and Methods

We evaluated FLT3-internal tandem duplication and FLT3-D835 mutations in patients treated with all-trans retinoic acid and anthracycline-based chemotherapy enrolled in two subsequent trials of the Programa de Estudio y Tratamiento de las Hemopatías Malignas (PETHEMA) and Hemato-Oncologie voor Volwassenen Nederland (HOVON) groups between 1996 and 2005.

Results

FLT3-internal tandem duplication and FLT3-D835 mutation status was available for 306 (41%) and 213 (29%) patients, respectively. Sixty-eight (22%) and 20 (9%) patients had internal tandem duplication and D835 mutations, respectively. Internal tandem duplication was correlated with higher white blood cell and blast counts, lactate dehydrogenase, relapse-risk score, fever, hemorrhage, coagulopathy, BCR3 isoform, M3 variant subtype, and expression of CD2, CD34, human leukocyte antigen-DR, and CD11b surface antigens. The FLT3-D835 mutation was not significantly associated with any clinical or biological characteristic. Univariate analysis showed higher relapse and lower survival rates in patients with a FLT3-internal tandem duplication, while no impact was observed in relation to FLT3-D835. The prognostic value of the FLT3-internal tandem duplication was not retained in the multivariate analysis.

Conclusions

FLT3-internal tandem duplication mutations are associated with several hematologic features in acute promyelocytic leukemia, in particular with high white blood cell counts, but we were unable to demonstrate an independent prognostic value in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based regimens.     

Helicobacter pylori Infection Enhances Gastric Mucosal Inflammation in Individuals Carrying the 260-T Allele of the CD14 Gene

Background/Aims

We aim to evaluate the association between promoter polymorphism of the clusters of differentiation 14 (CD14) gene and Helicobacter pylori-induced gastric mucosal inflammation in a healthy Korean population.

Methods

The study population consisted of 267 healthy subjects who visited our hospital for free nationwide gastric cancer screening. Promoter polymorphism at -260 C/T of the CD14 gene was determined by polymerase chain reaction and restriction fragment length polymorphism analysis. The severity of gastric mucosal inflammation was estimated by a gastritis score based on the sum of the values of the grade and activity of the gastritis. Expression of soluble CD14 (sCD14) was assessed by quantitative sandwich ELISA.

Results

CD14 polymorphism was not associated with H. pylori infection. There were no significant differences in gastritis scores among the genotype subgroups, but subjects carrying the CD14 -260 CT/TT genotype had significantly higher sCD14 levels than those carrying the CC genotype. Subjects with the 260-T allele of the CD14 gene and H. pylori infection had significantly higher sCD14 levels than those with the same genotype but without infection.

Conclusions

In individuals with the T allele at the -260 site of the promoter region of the CD14 gene, H. pylori infection accentuates gastric mucosal inflammation.     

Expression of the Transmembrane Glycoprotein CD44s Is Potentially an Independent Predictor of Recurrence in Hepatocellular Carcinoma

Background/Aims

Cluster differentiation 44 standard isoform (CD44s) is a transmembrane glycoprotein. CD44s is a known prognostic factor in various cancers, due to its involvement in tumor cell growth, invasion and metastasis. Its prognostic role, however, is debated because it can be a positive or negative prognostic factor depending on tumor type and is still an ambiguous prognostic indicator in other cancers, especially hepatocellular carcinoma (HCC). We investigated the relationship between CD44s expression and survival in HCC patients.

Methods

A total of 260 HCC samples were collected to generate a tissue microarray. Staining of the arrays with a primary mouse CD44s monoclonal antibody was followed by evaluation of the relationship between CD44s expression and tumor differentiation. The effect of CD44s expression on patient survival was analyzed.

Results

CD44s protein expression correlated with histological grade (most and worst Edmondson grade) of the HCC (p=0.029 and p=0.039, respectively) and adversely affected the disease free survival period based on univariate and multivariate analyses (p=0.038 and p=0.077, respectively).

Conclusions

High CD44s protein expression correlates with shorter disease free survival and poorly differentiated HCC. CD44s-targeted therapy may be efficacious for HCC treatment in the future.     

Comparison of the prognostic accuracy of the sixth and seventh editions of the TNM classification for intrahepatic cholangiocarcinoma

Background

The seventh TNM edition introduced a new, specific staging structure for intrahepatic cholangiocarcinoma (IHC).

Objective

To compare the accuracy of the sixth and the new seventh edition to predict survival after hepatectomy for IHC.

Methods

In all, 434 consecutive patients who underwent hepatectomy at 16 tertiary-care centres (1990–2008) were identified. End points were overall (OS) and recurrence-free survival (RFS) for both T cohorts and stage strata.

Results

After a median follow-up of 32.4 months, 3- and 5-year OS and RFS estimates were 47.1% and 32.9%, and 26.5% and 19.1%, respectively. Overall, both the editions were statistically significant discriminators of OS and RFS (P < 0.05). However, the survival curves of the new T2a and T2b cohorts appear superimposed. Conversely, the old T2 and T3 cohorts accurately stratify patients into distinct prognostic groups (P < 0.01). The seventh edition does not show monotonicity of gradients (the T4 category demonstrates significantly better OS and RFS compared with T2 patients). The seventh edition stage I and II are significantly different whereas the old stage I and II were not.

Conclusions

The new seventh edition of the AJCC/UICC Staging System proved to be adequate although further studies are need to confirm its superiority compared with the previous edition.     

Prognostic value of FGFR1 gene copy number in patients with non-small cell lung cancer: a meta-analysis

Background

A number of studies have investigated the relationship between fibroblast growth factor receptor1 (FGFR1) gene copy number and survival in non-small cell lung cancer (NSCLC) patients. However, conclusions reported by different parties seem to be inconsistent, especially regarding the differences among different histopathologic subtypes. To derive a more precise estimate of the prognostic significance of FGFR1 gene copy number, we have reviewed published studies and carried out a meta-analysis.

Methods

The meta-analysis was conducted in accordance with PRISMA guidelines. The required data for estimation of individual hazard ratios (HRs) for survival were extracted from the publications and an overall HR was calculated.

Results

We identified 6 eligible studies, all dealing with NSCLC. The global quality score ranged 32.5-80%, with a median of 53.33%. For FGFR1 amplification in three studies including differed according to histological type, the overall RR was 0.86 which 95% confidence interval (CI) was 0.75 to 0.99 and P value was 0.048. Combined HR for the six evaluable studies was 1.17 (95% CI: 0.95 to 1.43). In the subgroup of squamous cell lung cancer (SQCC), the combined HR was 1.24 (95% CI: 0.89 to 1.73). For the Asian populations’ studies, the combined HR was 1.67 (95% CI: 1.1 to 2.52).

Conclusions

FGFR1 amplification significantly was more frequent in SQCC. FGFR1 was not associated with poorer survival in patients with NSCLC. Furthermore studies will be needed in terms of survival implications.     

Phytochemical screening and antioxidant capacity of the aerial parts of Thymelaea hirsuta L.

Objective

To assess antioxidant activities of different aerial parts of Thymelaea hirsuta (T. hirsuta) from west Algeria, and to search for new sources of safe and inexpensive antioxidants.

Methods

Samples of leaves, stems and flowers from T. hirsuta were tested for total phenolic content, flavonoids content, and evaluation its total antioxidant activity, were done using the spectrophotometric analyses.

Results

Results of preliminary phytochemical screening of leaf, flower and stem of T. hirsuta revealed the presence of tannins, alkaloids, steroids, saponins, coumarins, reducteurs compound and anthraquinones. The total phenolics and flavonoids were estimated. The aqueous extracts of the aerial parts of T. hirsuta showed potent in vitro antioxydant activities using various models viz, DPPH scavenging assay, ferric reducing antioxidant power (FRAP) and ABTS radical scavenging activity.

Conclusions

On the basis of the results obtained, T. hirsuta extracts are rich sources of natural antioxidants appears to be an alternative to synthetic antioxidants and this justifies its therapeutic usage.     

Investigating the key membrane protein changes during in vitro erythropoiesis of protein 4.2 (?) cells (mutations Chartres 1 and 2)

Background

Protein 4.2 deficiency caused by mutations in the EPB42 gene results in hereditary spherocytosis with characteristic alterations of CD47, CD44 and RhAG. We decided to investigate at which stage of erythropoiesis these hallmarks of protein 4.2 deficiency arise in a novel protein 4.2 patient and whether they cause disruption to the band 3 macrocomplex.

Design and Methods

We used immunoprecipitations and detergent extractability to assess the strength of protein associations within the band 3 macrocomplex and with the cytoskeleton in erythrocytes. Patient erythroblasts were cultured from peripheral blood mononuclear cells to study the effects of protein 4.2 deficiency during erythropoiesis.

Results

We report a patient with two novel mutations in EPB42 resulting in complete protein 4.2 deficiency. Immunoprecipitations revealed a weakened ankyrin-1-band 3 interaction in erythrocytes resulting in increased band 3 detergent extractability. CD44 abundance and its association with the cytoskeleton were increased. Erythroblast differentiation revealed that protein 4.2 and band 3 appear simultaneously and associate early in differentiation. Protein 4.2 deficiency results in lower CD47, higher CD44 expression and increased RhAG glycosylation starting from the basophilic stage. The normal downregulation of CD44 expression was not seen during protein 4.2(−) erythroblast differentiation. Knockdown of CD47 did not increase CD44 expression, arguing against a direct reciprocal relationship.

Conclusions

We have established that the characteristic changes caused by protein 4.2 deficiency occur early during erythropoiesis. We postulate that weakening of the ankyrin-1-band 3 association during protein 4.2 deficiency is compensated, in part, by increased CD44-cytoskeleton binding.     

Correlation between group behavior and quorum sensing in Pseudomonas aeruginosa isolated from patients with hospital-acquired pneumonia

Background

This study investigated the correlation between the expression of the Las and Rhl quorum-sensing (QS) systems and the communal behavior (motility, biofilm formation, and pyocyanin production) of Pseudomonas aeruginosa (P. aeruginosa) isolated from patients with hospital-acquired pneumonia.

Methods

We analyzed 138 P. aeruginosa isolates from 48 patients (30 men and 18 women; age 68.18±15.08 years). P. aeruginosa clinical isolates were assessed for Las and Rhl gene expression and bacterial motility, biofilm formation, and pyocyanin production.

Results

P. aeruginosa swimming, twitching, and swarming motility positively correlated with the expression of LasI, LasR, and RhlI (P<0.05) but not with that of RhlR (P>0.05). At all analyzed time points, a significant positive correlation was found between biofilm formation and the expression of LasI, LasR (P<0.01), and RhlI (P<0.05 for day 1, P<0.01 for days 7 and 14), whereas RhlR expression positively correlated with biofilm formation only on day 14 (P<0.05). On days 1 and 7, positive correlation was observed between pyocyanin production and the levels of LasI and RhlI (P<0.05). In bacterial clearance cases, the expression of QS-related genes and the group behavior of the pathogen did not correlate (P>0.05). However, in cases of persistent P. aeruginosa infection, the changes in LasI and LasR gene expression were positively correlated with those in bacterial motility (P<0.05), and the changes in LasI, LasR, RhlI, and RhlR expression showed a significant positive association with those in biofilm formation (P<0.01).

Conclusions

In patients with hospital-acquired pneumonia, the expression of the Las and Rhl QS genes was associated with bacterial motility, biofilm formation, and pyocyanin production, suggesting an involvement of the QS genes in the clearance of pathogenic P. aeruginosa in patients.     

ATM gene alterations in chronic lymphocytic leukemia patients induce a distinct gene expression profile and predict disease progression

Background

The genetic characterization of chronic lymphocytic leukemia cells correlates with the behavior, progression and response to treatment of the disease.

Design and Methods

Our aim was to investigate the role of ATM gene alterations, their biological consequences and their value in predicting disease progression. The ATM gene was analyzed by denaturing high performance liquid chromatography and multiplex ligation probe amplification in a series of patients at diagnosis. The results were correlated with immunoglobulin gene mutations, cytogenetic abnormalities, ZAP-70 and CD38 expression, TP53 mutations, gene expression profile and treatment-free interval.

Results

Mutational screening of the ATM gene identified point mutations in 8/57 cases (14%). Multiplex ligation probe amplification analysis identified six patients with 11q deletion: all of them had at least 20% of deleted cells, analyzed by fluorescent in situ hybridization. Overall, ATM point mutations and deletions were detected in 14/57 (24.6%) cases at presentation, representing the most common unfavorable genetic anomalies in chronic lymphocytic leukemia, also in stage A patients. Patients with deleted or mutated ATM had a significantly shorter treatment-free interval compared to patients without ATM alterations. ATM-mutated cases had a peculiar gene expression profile characterized by the deregulation of genes involved in apoptosis and DNA repair. Finally, definition of the structure of the ATM-mutated protein led to a hypothesis that functional abnormalities are responsible for the unfavorable clinical course of patients carrying these point mutations.

Conclusions

ATM alterations are present at diagnosis in about 25% of individuals with chronic lymphocytic leukemia; these alterations are associated with a peculiar gene expression pattern and a shorter treatment-free interval.     

Eosinophilia: A poor predictor of Strongyloides infection in refugees

BACKGROUND:

Canada resettles 10,000 to 12,000 refugees annually. Despite this being a highly vulnerable population, there are little Canadian data on subclinical tropical diseases harboured in this population over the past 20 years.

OBJECTIVES:

To determine the seroprevalence and predictors of Strongyloides infection in refugees arriving in Edmonton, Alberta.

METHODS:

A retrospective chart review of all refugees seen at the New Canadians Clinic between March 2009 and April 2010 was performed. Demographic, symptom and physical examination data were collected from the charts. Laboratory results were obtained from the electronic laboratory records.

RESULTS:

A total of 350 subjects were studied. The overall seroprevalence of strongyloidiasis was 4.6%. Equivocal results were found in 6.3%. In the positive group, the majority were male (62.5%); 75% were born in Africa (P=0.004) and 81.2% lived in refugee camps in Africa (P=0.002). Eosinophilia was present in 25% of the positive subjects (P=0.05), in none of the equivocal group and in 8.7% of the negative group.

DISCUSSION:

Persistent asymptomatic Strongyloides infection is maintained for years through autoinfection. Traditionally, eosinophilia was used as one of the key tools to diagnose chronic but stable diseases, but it was shown to have a poor predictive value for strongyloidiasis in returning expatriates as well as in those presenting with a disseminated form of the disease. It is important to raise awareness of the severe limitations of eosinophilia as a marker for strongyloidiasis when managing patients who either are immunocompromised, or about to start immunosuppressive therapy.

CONCLUSIONS:

The present study indicated that eosinophilia is a poor predictor of seropositivity and, thus, Strongyloides infection. Residence in Africa (birth/refugee camps) proved to be a significantly better predictor of Strongyloides seropositivity.     

Mutations of PHF6 are associated with mutations of NOTCH1, JAK1 and rearrangement of SET-NUP214 in T-cell acute lymphoblastic leukemia

Background

Mutations in the PHF6 gene were recently described in patients with T-cell acute lymphoblastic leukemia and in those with acute myeloid leukemia. The present study was designed to determine the prevalence of PHF6 gene alterations in T-cell acute lymphoblastic leukemia.

Design and Methods

We analyzed the incidence and prognostic value of PHF6 mutations in 96 Chinese patients with T-cell acute lymphoblastic leukemia. PHF6 deletions were screened by real-time quantitative polymerase chain reaction and array-based comparative genomic hybridization. Patients were also investigated for NOTCH1, FBXW7, WT1, and JAK1 mutations together with CALM-AF10, SET-NUP214, and SIL-TAL1 gene rearrangements.

Results

PHF6 mutations were identified in 11/59 (18.6%) adult and 2/37 (5.4%) pediatric cases of T-cell acute lymphoblastic leukemia, these incidences being significantly lower than those recently reported. Although PHF6 is X-linked and mutations have been reported to occur almost exclusively in male patients, we found no sex difference in the incidences of PHF6 mutations in Chinese patients with T-cell acute lymphoblastic leukemia. PHF6 deletions were detected in 2/79 (2.5%) patients analyzed. NOTCH1 mutations, FBXW7 mutations, WT1 mutations, JAK1 mutations, SIL-TAL1 fusions, SET-NUP214 fusions and CALM-AF10 fusions were present in 44/96 (45.8%), 9/96 (9.4%), 4/96 (4.1%), 3/49 (6.1%), 9/48 (18.8%), 3/48 (6.3%) and 0/48 (0%) of patients, respectively. The molecular genetic markers most frequently associated with PHF6 mutations were NOTCH1 mutations (P=0.003), SET-NUP214 rearrangements (P=0.002), and JAK1 mutations (P=0.005). No differences in disease-free survival and overall survival between T-cell acute lymphoblastic leukemia patients with and without PHF6 mutations were observed in a short-term follow-up.

Conclusions

Overall, these results indicate that, in T-cell acute lymphoblastic leukemia, PHF6 mutations are a recurrent genetic abnormality associated with mutations of NOTCH1, JAK1 and rearrangement of SET-NUP214.     

Testicular and epididymal pathology in Yankasa rams experimentally infected with Trypanosoma congolense

Objective

To investigate the pathological effect of experimental Trypanosoma congolense (T. congolense) infection on the testes and epididymis of Yankasa rams.

Methods

Nine intact un-castrated rams were obtained and divided into 2 groups of 6 infected with 1×10⁶ T. congolense and 3 uninfected controls. Four infected and one uninfected control rams were sacrificed on Day 75 post infection and the remaining four rams (two each of infected and control groups) on Day 86 post infection.

Results

All infected rams became parasitaemic within 7-11 days post infection with clinical trypanosomosis characterized by peri-orbital oedema and a transient period of scrotal oedema, this was followed by progressive decrease in scrotal size. At postmortem, the organs from infected rams were pale and emaciated but no observable lesion was seen in the uninfected control group. At histology, the testes showed areas of necrosis on the interstitial tissue characterized by destruction of cellular structures within the tissues and seminiferous tubules. There was moderate to severe testicular degeneration manifested by loss of tissue architecture and infiltration with macrophages, neutrophils, lymphocytes and plasma cells. Fibrous connective tissues were also seen in the testes of the infected rams indicative of replacement of normal cells by fibrous connective tissue. The epididymis of the infected rams had collection of some spermatocytes and desquamated epithelial cells in the epithelial ducts although others were devoid of spermatocytes in their ducts leading to loss of epididymal sperm reserves. However, these were not seen in the uninfected control rams.

Conclusions

T. congolense causes testicular and epididymal damage which may render the rams infertile or sterile.     

Differences in clinical presentation of non-small cell lung cancer in never-smokers versus smokers

Objectives

This study was conducted to evaluate whether or not tumor spread and the diagnostic process in non-small cell lung cancer (NSCLC) is different based on smoking history.

Methods

Associations between smoking status and clinical presentation were evaluated controlling for the effect of histology. Lung cancer with delayed diagnosis (LCDD) and incidental detection (LCID) were determined based on medical records.

Results

Of 914 patients, frequency of distant metastases was more common in never-smokers than in smokers (59% and 36%, respectively; P<0.001). Although never-smokers were more likely to have LCDD than smokers (18% and 11%, respectively; P=0.038), LCDD were not significantly associated with frequency of distant metastases [49% (LCDD) vs. 42% (non-LCDD); P=0.189] as well as tumor [29% (T3-4) vs. 24% (T1-2); P=0.134] and node [43% (N2-3) vs. 44% (N0-1); P=0.838] stage. Interestingly, never-smokers are more likely to have LCID than smokers (31% and 19%, respectively; P=0.010). In survival analysis, LCID (P=0.001; HR, 0.63) remained a prognostic factor, while LCDD did not.

Conclusions

This study suggests distinct metastatic pattern and diagnostic processes of never-smokers. The link between survival and incidental detection was also indicated.KEYWORDS : Non-small cell lung cancer (NSCLC), advanced stage, incidental detection, smoking history     

Leishmania infantum DNA detection in Phlebotomus tobbi in a new northern focus of visceral leishmaniasis in Iran

Objective

To identify the vector(s), the parasite and the species composition of sand flies in the district during May-October 2012.

Methods

For reaching our objectives we used polymerase chain reaction of kDNA, ITS1-rDNA, followed by restriction fragment length polymorphism.

Results

Two species of Phlebotomus sergenti and Phlebotomus tobbi were the most prevalent among 8 species identified comprising 51.1% and 32.9% respectively. Among the 160 specimens of female sand flies tested by polymerase chain reaction of kDNA, ITS1-rDNA, followed by restriction fragment length polymorphisms, only 1 out of 80 Phlebotomus tobbi (1.25%) were positive to Leishmania infantum parasites.

Conclusions

Our finding showed that Phlebotomus tobbi may play as a vector to circulate the parasite of Leishmania infantum among reservoir(s) and human.     

Association Between LYPLAL1 rs12137855 Polymorphism With Ultrasound-Defined Non-Alcoholic Fatty Liver Disease in a Chinese Han Population

Background:

Recent genome-wide association studies (GWAS) identified that gene Lysophospholipase-like 1 (LYPLAL1) rs12137855 associated with non-alcoholic fatty liver disease (NAFLD). No research has been performed regarding the association between LYPLAL1 and NAFLD in China.

Objectives:

The aim of the present study was to investigate the association between the gene LYPLAL1 rs12137855 and NAFLD, and the effect on serum lipid profiles in a Chinese Han population.

Patients and Methods:

LYPLAL1 rs12137855 gene was genotyped in 184 patients with NAFLD and 114 healthy controls using sequencing and polymerase chain reaction analysis (PCR). We tested serum lipid profiles using biochemical methods.

Results:

No significant differences in genotype and allele frequencies of LYPLAL1 rs12137855 was found between the NAFLD group and the controls group (P > 0.05). Subjects with the variant LYPLAL1 rs12137855 CC genotype had a higher mean weight, body mass index (BMI) and low density lipoprotein (LDL).

Conclusions:

Our results showed for the first time that LYPLAL1 gene is not associated with a risk of NAFLD development in the Chinese Han population. The variant carriers of overall subjects significantly increased weight, BMI and LDL.     

Tumor-infiltrating macrophages correlate with adverse prognosis and Epstein-Barr virus status in classical Hodgkin's lymphoma

Background

Classical Hodgkin’s lymphoma is characterized by a minority of neoplastic cells surrounded by a heterogeneous background population of non-neoplastic cells including lymphoma-associated macrophages. High levels of expression of both the monocyte/macrophage lineage-associated antigens CD68 and CD163 have been suggested to have pro-tumor effects. The aim of our study was to correlate expression of CD68 and CD163 with the clinico-pathological features and prognosis of a cohort of patients with previously untreated Hodgkin’s lymphoma.

Design and Methods

A tissue microarray was constructed from paraffin-embedded tumor tissues from 288 cases of classical Hodgkin’s lymphoma. CD68 and CD163 expression was assessed immunohistochemically and the degree of macrophage infiltration within the tumor was scored using point grid counting. Clinical data were obtained from clinical records.

Results

The patients’ median age was 37 years (range, 6–86 years). The male to female ratio was 1.2. In classical Hodgkin’s lymphoma (n = 288) high CD68 and CD163 expression correlated, at the univariate level, with poorer overall survival (P=0.002 and P=0.03, respectively) and event-free survival (P=0.03 and P=0.04, respectively). At the multivariate level, high CD68 expression remained significantly predictive of overall survival (P=0.004). In addition, we demonstrated that both high CD68 and CD163 expression were associated with the presence of Epstein-Barr virus in the neoplastic cells (P=0.001 and P=0.0002, respectively).

Conclusions

In classical Hodgkin’s lymphoma, high expression of the macrophage/monocyte-related antigens CD68 and CD163 correlates with adverse outcome and with the presence of Epstein-Barr virus in the tumor cell population.     

Prevalence and incidence of antimicrobial-resistant organisms among hospitalized inflammatory bowel disease patients

BACKGROUND:

Patients with inflammatory bowel disease (IBD) experience frequent hospitalizations and use of immunosuppressive medications, which may predispose them to colonization with antimicrobial-resistant organisms (ARO).

OBJECTIVE:

To determine the prevalence of ARO colonization on admission to hospital and the incidence of infection during hospitalization among hospitalized IBD patients.

METHODS:

A chart review comparing the prevalence of colonization and incidence of infection with methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL) in hospitalized IBD patients with those of non-IBD controls was performed.

RESULTS:

On admission, there were no significant differences between IBD inpatients and controls in the prevalence of colonization of methicillin-resistant S aureus (1.0% versus 1.2%; P=0.74), vancomycin-resistant enterococci (0.2% versus 0%; P=1.0) or ESBL (4.1% versus 5.5%; P=0.33). Pooling data from historical clinic-based cohorts, IBD patients were more likely than controls to have ESBL colonization (19% versus 6.6%; P<0.05). Antibiotic use on admission was associated with ESBL colonization among IBD inpatients (OR 4.2 [95% CI 1.4 to 12.6]). The incidence of ARO infections during hospitalization was not significantly different between IBD patients and controls. Among IBD patients who acquired ARO infections during hospitalizations, the mean time interval from admission to infection was shorter for those who were already colonized with ARO on admission.

CONCLUSIONS:

This particular population of hospitalized IBD patients was not shown to have a higher prevalence or incidence of ARO colonization or infection compared with non-IBD inpatients.