Search

Purpose: The correct risk categorization and staging of upper tract urothelial cancer (UTUC) is key for disease management. Computerized tomography urography and urinary cytology have limited accuracy for risk stratification of UTUC. Ureteroscopy may increase the risk of bladder cancer recurrence. Recently, Bladder EpiCheckTM (EpiCheck) showed a high accuracy in the detection of bladder cancer. The aim of the study is to investigate the diagnostic accuracy of EpiCheck in the clinical management of UTUC and to compare it with urinary cytology. Materials and Methods: In this single-arm, blinded, prospective, single-center study (February 2019eDecember 2020), all patients who were candidates for ureteroscopy for suspicion of UTUC were included. Bladder and upper urinary tract (UUT) samples were collected before ureteroscopy to test for cytology and Epicheck. EpiCheck accuracy was calculated in bladder and UUT samples and compared to cytology. Results: EpiCheck resulted diagnostic in 83/86 (97%) and 73/75 (97%) of UUT and bladder samples. Histology was positive in 47/83 (57%) and 42/73 (58%) cases, respectively. In UUT samples, EpiCheck yielded a sensitivity/specificity/negative predictive value (NPV)/positive predictive value of 83%/79%/77%/84% vs 59%/88%/61%/87% of cytology. The sensitivity/NPV for high-grade tumors was 96%/97% for EpiCheck vs 71%/86% for cytology. EpiCheck indicated ureteroscopy in 45/80 (56%) patients, missing 17%/4% of all/high-grade UTUC with 9% of unnecessary ureteroscopy. In bladder samples, the sensitivity/NPV for high-grade tumors was 71%/88% for EpiCheck and 59%/87% for cytology. Conclusions: Epicheck may be an important tool to decrease the number of unnecessary ureteroscopy. The clinical implementation of EpiCheck in UTUC warrants further investigation in multicentric prospective randomized trials.

INTRODUCTION AND OBJECTIVE:Transurethral resection of bladder tumor (TURBT) is considered the gold standard in the diagnosis and risk stratification bladder cancer (BC). En-bloc resection of bladde...

Viral hepatitis is the leading cause of liver disease worldwide and can be caused by several agents, including hepatitis A (HAV), B (HBV), and C (HCV) virus. We employed multiplexed protein immune assays to identify biomarker signatures of viral hepatitis in order to define unique and common responses for three different acute viral infections of the liver. We performed multianalyte profiling, measuring the concentrations of 182 serum proteins obtained from acute HAV- (18), HBV- (18), and HCV-infected (28) individuals, recruited as part of a hospital-based surveillance program in Cairo, Egypt. Virus-specific biomarker signatures were identified and validation was performed using a unique patient population. A core signature of 46 plasma proteins was commonly modulated in all three infections, as compared to healthy controls. Principle component analysis (PCA) revealed a host response based upon 34 proteins, which could distinguish HCV patients from HAV- and HBV-infected individuals or healthy controls. When HAV and HBV groups were compared directly, 34 differentially expressed serum proteins allowed the separation of these two patient groups. A validation study was performed on an additional 111 patients, confirming the relevance of our initial findings, and defining the 17 analytes that reproducibly segregated the patient populations. Conclusions: This combined discovery and biomarker validation approach revealed a previously unrecognized virus-specific induction of host proteins. The identification of hepatitis virus specific signatures provides a foundation for functional studies and the identification of potential correlates of viral clearance. (Hepatology 2014;59:1273-1282)

There is increasing awareness of an ongoing epidemic of acute hepatitis C virus (HCV) infection in HIV-infected MSM. The epidemiology has been reviewed in this journal recently [1]; however, there is a lack of guidance on the management of acute HCV infection in HIV-infected individuals. To address this issue, the European AIDS Treatment Network (NEAT) invited members of the European AIDS Clinical Society (EACS) hepatitis group, the European Association for the Study of the Liver (EASL), the European Study Group on Viral Hepatitis of the European Society of Clinical Microbiology and Infectious Diseases, the European AIDS Treatment group and other experts to draw up a consensus statement at a conference held in Paris, France, in May 2010. Four working groups prepared draft guidelines for consideration at the conference on case definition and diagnosis; transmission risk and epidemiology; pathogenesis and natural history; and acute HCV infection management in the HIV-infected population. A literature search using the PubMed database of the National Library of Medicine and abstract databases of the Conference on Retroviruses and Opportunistic Infections, the Interscience Conference on Antimicrobial Agents and Chemotherapy, the Liver Meetings of the American Association for the Study of Liver Disease and EASL was utilized by all groups. Statements and recommendations were graded by the strength of recommendation and level of evidence (Table 1) [2]. A consensus was reached if 80% or more of the participants were in favour.

UNLABELLED: Self-blood pressure (BP) measurement (SBPM) and ambulatory BP measurement (ABPM) are suitable for the isolated clinical hypertension (ICH) or 'white-coat' hypertension diagnosis. However, patients with ICH have a different cardiovascular risk according to the measurement technique used for the diagnosis. OBJECTIVE: To describe baseline cardiovascular risk of patients with hypertension and with ICH according to SBPM and daytime ABPM. METHODS: Six hundred and sixty-four newly diagnosed and never treated patients with hypertension and with an average age of 59.3 years (standard deviation=12.0) were included (52% men) in this study. Clinical data, analytical data with urinary albumin excretion rate, estimated glomerular filtration rate, retinography, SBPM, and ABPM were performed. Cardiovascular risk was estimated from the European Society of Hypertension and Systemic Coronary Risk Evaluation tables. RESULTS: ICH prevalence varies according to the ambulatory measurement technique used: SBPM=24.2%, daytime ABPM=8.1, and 5.2% if criteria are required from both techniques. In the 403 patients with hypertension and who had SBPM and ABPM, the percentage of patients with high or very high baseline cardiovascular risk, falls progressively from 31.2% of patients with sustained hypertension to 20.0% of patients with ICH measured using SBPM, to 15.1% of patients with ICH measured using ABPM-day and to 9.5% of patients who present ICH using both techniques (P

Objectives: To identify predictors of Pneumocystis jiroveci pneumonia (PCP) or pulmonary tuberculosis (TB) in acid-fast bacillus smear-negative HIV-infected patients and to develop clinical prediction rules. Design: A cohort study conducted in consecutive hospitalized Asian patients. Methods: Multivariate analyses were performed on the Cambodian sample to determine clinical, radiological, and biological predictors of PCP or TB at hospital admission. The Vietnamese sample was kept for independent validation. Results: In Cambodia, the gold standard technique for TB and PCP were fulfilled in 172 (27 cases) and 160 (84 cases) patients, respectively. For TB, independent predictors included the following: headache [odds ratio (OR) 3.0; 95% confidence interval (CI) 1.04 to 8.6], localized radiological opacity (OR 5.8; 95% Cl 1.9-17.9), and mediastinal adenopathy (OR 10.1; 95% CI 3.5 to 29.0); and for PCP: resting oxygen saturation

Background and Objectives: The influence of the polymorphisms of the CX3CR1 chemokine receptor gene on the natural history of HIV-1 infection is controversial. This study aimed to determine whether functionally active CX3CR1 genetic variants are associated with long-term nonprogressive infection of > 15 years in HIV-1-infected Spanish patients. Patients and Methods: Two single-nucleotide polymorphisms, V249I (G > A) and T280M (C > T), of the CX3CR1 gene were assessed in 271 Spaniards. These included 60 HIV-1-infected patients who were long-term nonprogressors (LTNPs) of > 15 years, 109 HIV-1-infected patients who were usual progressors (UPs), and 102 control subjects. The CCR5Δ32 was also assessed. Genotyping was performed using polymerase chain reaction and automatic sequencing analysis methods on white cell DNA. Genotype and allele frequencies were compared by the χ 2 test and the Fisher exact test. Results: The frequencies of the 249I variant allele were 42% for LTNPs, 24.5% for UPs, and 35% for healthy controls; the differences between LTNPs and UPs were significant (odds ratio 0.46; 95% CI: 0.27 to 0.75; P = 0.0017). For 280M the distribution was 16% for LTNPs, 14% for UPs, and 17% for healthy controls (P = NS). The haplotype 249I280T was significantly more common in LTNPs than in UPs (P = 0.0007). These results persisted after excluding from the analysis the individuals carrying the CCR5Δ32. Conclusions: CX3CR1 249I variant allele is more frequent in Spanish HIV-1-infected LTNPs of > 15 years. This effect is independent of the presence of the CCR5Δ32 allele.

Background: Immune reconstitution inflammatory syndrome (IRIS) in association with cryptococcosis has been anecdotically reported following administration of highly active antiretroviral therapy (HAART). Objective: To analyse the incidence and risk factors for IRIS-associated cryptococcosis among HIV-infected patients. Design: Retrospective multicentre study between 1996 and 2000 through the French Cryptococcosis Database. Methods: Subsequent occurrence of IRIS examined in 120 HIV-infected adult patients treated with HAARTand experiencing a first episode of culture-confirmed cryptococcosis. Results: Ten patients developed IRIS during the study period, giving an incidence of 10/239, or 4.2/100 person-years [95% confidence interval (Cl), 2.2-7.8]. IRIS consisted of acute symptoms consistent with inflammation occurring within a median of 8 months (range, 2 -3 7) after the diagnosis of cryptococcosis in the context of negative cultures and immunological and/or virological response to HAART. Radiology and histopathology detected features compatible with inflammation. Symptom severity required transfer into intensive care units for three patients and use of anti-inflammatory drugs for four. Three patients with evolutive IRIS died. Compared with patients without IRIS for whom complete clinical and microbiological information were available at baseline, previously unknown HIV infection [odds ratio (OR), 4.8; 95% Cl, 1.0-21.7], CD4 cell count < 7 x 106 cells/I (OR, 4.0; 95% CI, 0.9-17.2), fungaemia (OR, 6.1; 95% Cl, 1.1-35.2) and HAART initiation within 2 months of cryptococcosis diagnosis (OR, 5.50; 95% CI, 1.0-29.6) were independently associated with the risk of subsequent IRIS. Conclusions: IRIS-related cryptococcosis was observed more frequently in severely immunocompromised patients with disseminated infection and HAART initiation soon after the diagnosis.

Objective: To analyse the epidemiological evolution of cryptococcosis in France after the introduction of highly active antiretroviral therapy (HAART). Design: Retrospective study of cryptococcosis cases recorded at the National Reference Center for Mycoses in France since 1985. Methods: Using the national surveillance data, we reviewed 1644 cases of HIV-associated cryptococcosis diagnosed in France (population, 59 million) between 1985 and 2001 and compared them to 335 cases recorded in HIV-negative patients. Results: The total number of cryptococcosis cases evolved in parallel to that recorded for HIV-infected patients. Changes occurring after HAART introduction were analysed. A negative binomial regression model established a 46% decrease of the incidence of cryptococcosis during the post-HAART era (1997-2001, n = 292) compared to the pre-HAART era (1985-1996, n = 1352). According to multivariate analysis, African origin, older age, heterosexual HIV contamination, no previous AIDS-defining illness, and no previous HIV infection diagnosis were variables independently associated with an increased risk of cryptococcosis during the post-HAART era. During the same period, the characteristics of the HIV-negative population did not change. Conclusions: Our analysis of the national surveillance identified demographic factors associated with an increased risk of cryptococcosis in the post-HAART era suggesting that failure to consult and considering oneself not at risk were determinant in the current epidemiology of HIV-related cryptococcosis in France.

Objective: To identify mechanisms of resistance to HIV-1 infection in exposed uninfected individuals. Design: We examined in-vitro cell susceptibility to HIV-1 infection in highly exposed Vietnamese intravascular drug users (IDU) who despite a history of more than 10 years of drug use and a high prevalence of other blood-borne viral infections remain apparently HIV uninfected. Methods: Forty-five exposed uninfected IDU and 50 blood donors were included in the study. Peripheral blood mononuclear cells (PBMC) or CD4 cell susceptibilities to HIV infection were evaluated using three HIV-1 isolates with different tropisms. Polymerase chain reaction analysis of HIV-1-DNA replication intermediates was used to characterize the restriction of HIV-1 replication in CD4 cells. Homologous CD8 cells were mixed with infected CD4 cells to evaluate their role in virus suppression. Results: We observed a relative resistance to PBMC infection with HIV-1 in 21 out of 45 exposed uninfected IDU but only in five out of 50 unexposed controls (P < 0.001). PBMC resistance was related either to an inhibition of HIV-1 replication in CD4 cells or to CD8 cell-mediated viral suppression. HIV-1 replication in CD4 cells was restricted at the early stages of the viral cycle. Conclusion: Reduced PBMC susceptibility to HIV-1 infection was associated with resistance to infection in exposed uninfected IDU. Distinct mechanisms are involved in in-vitro resistance and may contribute to the apparent protection from HIV-1 transmission in this systemically exposed population. (authors)

OBJECTIVE: To assess changes in sexual behaviours among male factory workers in Ethiopia. DESIGN: Open cohort studies in two factories near Addis Ababa. DATA AND METHODS: At intake and biannual follow-up visits, data were collected on sexual behaviours including casual sex, sex with commercial sex workers (CSW), condom use, and history of sexually transmitted diseases (STDs) as indicated by genital discharge and genital ulcer. Health education, HIV testing, and counselling were offered to all participants. RESULTS: Between February 1997 and December 1999, 1124 males were enrolled in the two cohort studies. At intake, the prevalence of casual sex in the past year, sex with CSWs, condom use with the last casual partner, history of genital discharge in the past 5 years, and history of genital ulcer in the past 5 years were 9.7, 43.4, 38.8 (Akaki site only), 10.6 and 2.1%, respectively. At the Wonji site, the intake prevalence of casual sex, sex with CSW, and history of genital discharge decreased significantly by calendar year between 1997 and 1999. At both sites combined, between the first and the fourth follow-up visits, there was a decline in the proportion of males reporting recent casual sex (from 17.5 to 3.5%, < 0.001), sex with CSWs (from 11.2 to 0.75%, < 0.001), and genital discharge (from 2.1 to 0.6%, = 0.004). CONCLUSION: There was a decline over time in risky sexual behaviours reported by cohort participants. Part of this decline occurred independently of cohort interventions.

Between 1997 and 2001, 1624 Ethiopian factory workers were enrolled in prospective HIV-1 cohorts in Ethiopia, at Akaki and Wonji towns. HIV-1 seroprevalence at intake was 11.8% (Akaki) and 7.1% (Wonji). HIV-1 incidence was .75 per 100 person-years (Akaki) and .35 per 100 person-years (Wonji). During follow up, CD4 T-cell counts remained significantly lower and CD8 T-cell counts significantly higher in Ethiopian seroconverters compared with Dutch seroconverters. Viral loads were lower in Ethiopian seroconverters versus Dutch seroconverters in the first months after seroconversion, subsequently increasing to similar levels. All 20 Ethiopian seroconverters were infected with HIV-1 subtype C (15 with sub-cluster C' and 5 with sub-cluster C). Viral loads were higher in sub-cluster C'-infected Ethiopian seroconverters. One subject demonstrated a window period of at least 204 days, combined with a high preseroconversion viral load and no decline of CD4 T cells over a follow-up period of at least 3 years.

BACKGROUND: Although several surveys investigating the epidemiology of herpes simplex virus type 2 (HSV-2) infection using type-specific immunologic assays have been carried out in Africa, none has examined the risk factors for HSV-2 infection in a representative sample from an urban adult population. GOALS: To estimate the prevalence of HSV-2 infection in the adult population of Addis Ababa, Ethiopia, and to identify risk factors for HSV-2 infection. STUDY DESIGN: Two cross-sectional surveys, one community-based (June to September 1996, n = 506) and one factory-based (February to November 1997, n = 657), were conducted. Samples were tested for HSV-2 immunoglobulin G antibodies using type-specific enzyme-linked immunoassays (ELISA). RESULTS: In the community-based survey, HSV-2 prevalence increased with age until 25 years, then leveled off at 50% in both genders. The same independent predictors of HSV-2 infection were identified in both genders: older age, higher lifetime number of sexual partners, positive HIV serology, and positive Treponema pallidum hemagglutination serology. CONCLUSIONS: This study confirmed the high prevalence of HSV-2 infection among adults in an African urban population and its association with HIV infection. Prevention of HSV-2 and other sexually transmitted infections through partner reduction and condom use should be encouraged.

The female condom may provide women with the first female- controlled barrier method that is effective against sexually transmitted diseases including HIV infection. This study evaluated the acceptability of the female condom among sex workers in Thailand. Data on use and acceptability of the female condom were collected using a structured questionnaire during an 8-week follow-up. Analyses included 148 women who were still in follow- up at week 8. Sex workers used on average 2.8 female condoms per week. The overall satisfaction rate with the female condom was 68% although among users 31% had difficulties in device insertion 37% had pain from the inner ring and 22% reported itching sensations. The main reason for using the female condom in the future was its perceived safety and the main reason for not using it would be the clients refusal. Two-thirds of the sex workers were satisfied with the female condom. Difficulties at insertion discomfort during use and clients attitude were potential obstacles to the use of the female condom in the future. (authors)

OBJECTIVE: To study the prevalence and risk factors for HIV infection among sex workers of Addis Ababa, Ethiopia. Design and methods: Cross-sectional survey on socio-demographic characteristics, behaviours, and HIV serological status of sex workers attending two health centres of Addis Ababa. RESULTS: HIV prevalence among sex workers was 274 of 372 (73.7%). Several factors were significantly associated with an increased risk of being HIV-infected [among others, working in 'shared rooms', high number of clients, use of injectable hormones, and positive Treponema pallidum particle agglutination (TPPA) serology], and others with a decreased risk (being born in Addis Ababa, high level of education, peer education on sex work, condom use, use of oral pill, and use of condoms for contraception). Of interest, sex workers who were using condoms for contraception were, compared with others, more likely to use condoms consistently (65 versus 24%, respectively; P < 0.001), and less likely to be HIV-infected (55 versus 86%, respectively; P < 0.001). In multivariate analysis [log-binomial model, giving estimates of the prevalence ratio (PR)], being born in Addis Ababa (PR = 0.74; 95% confidence interval (CI), 0.61-0.91), using condoms for contraception (PR = 0.73; 95% CI, 0.64-0.85), and a positive TPPA serology (PR = 1.21; 95% CI, 1.09-1.36), remained significantly associated with HIV infection. CONCLUSIONS: HIV prevalence was remarkably high among sex workers of Addis Ababa. Condom use was higher, and HIV prevalence lower, in sex workers using condoms not only for prevention of HIV and sexually transmitted diseases, but also for contraceptive purpose. This finding is of particular interest for its implications for prevention strategies among sex workers in the developing world

In this study the authors investigated the diversity of the current HIV-1 strains circulating in Addis Ababa Ethiopia; in addition they evaluated the applicability of peptide enzyme-linked immunosorbent assay (ELISA) and heteroduplex mobility assay (HMA) for HIV-1 subtyping. Previous studies have indicated that HIV-1 subtype C is the major subtype present in HIV-positive samples collected from various risk groups between 1988 and 1995 in Addis Ababa. To assess the possible influx of new HIV-1 subtypes 150 commercial sex workers (CSW) reporting in 1997 to two Health Centers in Addis Ababa were enrolled in an unlinked anonymous cross-sectional study. Subtyping was performed according to the World Health Organization algorithm of peptide ELISA followed by HMA and DNA sequencing. As a result the HIV-1 prevalence among these CSWs was found to be 45% (67 of 150). Of the 67 samples 66 contained HIV-1 of subtype C and only 1 was of subtype D. This confirms the persistent overall presence of HIV-1 subtype C in Addis Ababa and a low influx of other subtypes into this location. (author’s)

Measurements of Bcl-2 and CD25 expression suggested that IL-7R function is modified in CD4 lymphocytes of untreated viraemic patients. The extent of IL-7R function restoration post-HAART was analysed. A positive linear relationship was demonstrated between IL-7Ralpha expression and the magnitude of IL-7-induced responses in healthy individuals, whereas this relationship is lost in HIV-infected patients, suggesting that viraemic patients suffer a receptor signaling transduction defect in IL-7R function. IL-7 responsiveness is only partly restored by HAART.

Highly active antiretroviral therapy (HAART) in HIV patients generally increases the CD4 cell count, but the level of CD4 cell restoration remains very heterogeneous. IL-7 is the main cytokine controlling the size of the T-cell pool. We assessed the hypothesis that pre-HAART IL-7 plasma levels may affect CD4 cell restoration after treatment. A positive correlation was found in a cohort of 18 patients between pre-HAART IL-7 plasma levels and CD4 cell increases after 20 +/- 7.8 months of HAART.

Pressure overload of the left ventricle induces synthesis of creatine kinase isoenzymes. To determine whether this response is associated with an altered pattern of creatine kinase gene expression, we induced arterial hypertension in rats by suprarenal aortic banding. After 4 days, left ventricular myocardium from hypertensive (n = 7) and normotensive, sham-operated (n = 5) rats was analyzed for isoenzyme activities by chromatography; M and B creatine kinase subunit protein by Western blot; and M, B, and mitochondrial creatine kinase mRNA by Northern blot. Although total creatine kinase activity increased in hypertensive (1,096 +/- 214 IU/g left ventricle) compared with normotensive rats (648 +/- 81 IU/g left ventricle, p less than 0.01), the relative proportions of the cytoplasmic and mitochondrial isoenzymes did not change. The mass of M and B subunits increased 1.9- and 2.7-fold, respectively, in hypertensive compared with control rats. Similarly, the mRNA for M and B subunits as well as mitochondrial creatine kinase increased 2.6-, 1.6-, and 1.8-fold, respectively, in hypertensive rats compared with control rats. Thus, increased energy requirements in acute pressure overload are met by generalized induction of creatine kinase mRNA and subunit protein and not by an isoenzyme switch.

Polymorphisms in the IL28B gene region are important in predicting outcome following therapy for chronic hepatitis C virus (HCV) infection. We evaluated the role of IL28B in spontaneous and treatment-induced clearance following recent HCV infection. The Australian Trial in Acute Hepatitis C was a study of the natural history and treatment of recent HCV, as defined by positive anti-HCV antibody, preceded by either acute clinical HCV infection within the prior 12 months or seroconversion within the prior 24 months. Factors associated with spontaneous and treatment-induced HCV clearance, including variations in IL28B, were assessed. Among 163 participants, 132 were untreated (n=52) or had persistent infection (infection duration ≥26 weeks) at treatment initiation (n=80). Spontaneous clearance was observed in 23% (30 of 132). In Cox proportional hazards analysis (without IL28B), HCV seroconversion illness with jaundice was the only factor predicting spontaneous clearance (AHR 2.86, 95% CI, 1.24, 6.59, P=0.014). Among participants with IL28B genotyping (n=102/163 overall and 79/132 for spontaneous clearance population), rs8099917 TT homozygosity (vs GT/GG) was the only factor independently predicting time to spontaneous clearance (AHR 3.78, 95% CI, 1.04, 13.76, P=0.044). Participants with seroconversion illness with jaundice were more frequently rs8099917 TT homozygotes than other (GG/GT) genotypes (32% versus 5%, P=0.047). Among participants adherent to treatment and had IL28B genotyping (n=54), SVR was similar among TT homozygotes (18/29, 62%) and those with GG/GT genotype (16/25, 64%, P=0.884).