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Find video protocols related to scientific articles indexed in Pubmed.
Methods of rapid diagnosis for the etiology of meningitis in adults.
Biomark Med
PUBLISHED: 11-18-2014
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Infectious meningitis may be due to bacterial, mycobacterial, fungal or viral agents. Diagnosis of meningitis must take into account numerous items of patient history and symptomatology along with regional epidemiology and basic cerebrospinal fluid testing (protein, etc.) to allow the clinician to stratify the likelihood of etiology possibilities and rationally select additional diagnostic tests. Culture is the mainstay for diagnosis in many cases, but technology is evolving to provide more rapid, reliable diagnosis. The cryptococcal antigen lateral flow assay (Immuno-Mycologics) has revolutionized diagnosis of cryptococcosis and automated nucleic acid amplification assays hold promise for improving diagnosis of bacterial and mycobacterial meningitis. This review will focus on a holistic approach to diagnosis of meningitis as well as recent technological advances.
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Epidemiology of Meningitis in an HIV-Infected Ugandan Cohort.
Am. J. Trop. Med. Hyg.
PUBLISHED: 11-12-2014
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There is limited understanding of the epidemiology of meningitis among human immunodeficiency virus (HIV)-infected populations in sub-Saharan Africa. We conducted a prospective cohort study of HIV-infected adults with suspected meningitis in Uganda, to comprehensively evaluate the etiologies of meningitis. Intensive cerebrospiral fluid (CSF) testing was performed to evaluate for bacterial, viral, fungal, and mycobacterial etiologies, including neurosyphilis,16s ribosomal DNA (rDNA) polymerase chain reaction (PCR) for bacteria, Plex-ID broad viral assay, quantitative-PCR for HSV-1/2, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and Toxoplasma gondii; reverse transcription-PCR (RT-PCR) for Enteroviruses and arboviruses, and Xpert MTB/RIF assay. Cryptococcal meningitis accounted for 60% (188 of 314) of all causes of meningitis. Of 117 samples sent for viral PCR, 36% were EBV positive. Among cryptococcal antigen negative patients, the yield of Xpert MTB/RIF assay was 22% (8 of 36). After exclusion of cryptococcosis and bacterial meningitis, 61% (43 of 71) with an abnormal CSF profile had no definitive diagnosis. Exploration of new TB diagnostics and diagnostic algorithms for evaluation of meningitis in resource-limited settings remains critical.
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Central nervous system cryptococcoma in a Ugandan patient with Human Immunodeficiency Virus.
Med Mycol Case Rep
PUBLISHED: 10-01-2014
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Mortality due to AIDS-related Cryptococcal meningitis (CM) is often >50% in low-middle income countries. Dissemination of CM can result in intracranial mass lesions known as cryptococcoma. Patients who develop cryptococcomas often have worse outcomes when compared to patients with cryptococcosis without cryptococcoma. We describe a cryptococcoma in the central nervous system (CNS) in a Ugandan patient with AIDS, and review the diagnosis and management with special focus on difficulties encountered in low or middle-income countries.
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The effect of therapeutic lumbar punctures on acute mortality from cryptococcal meningitis.
Clin. Infect. Dis.
PUBLISHED: 07-23-2014
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Cryptococcal meningitis is the most common cause of adult meningitis in sub-Saharan Africa. Raised intracranial pressure (ICP) is common in cryptococcosis. Prior studies suggest elevated ICP is associated with mortality, and guidelines recommend frequent lumbar punctures (LPs) to control ICP. However, the magnitude of the impact of LPs on cryptococcal-related mortality is unknown.
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Unmasking cryptococcal meningitis immune reconstitution inflammatory syndrome in pregnancy induced by HIV antiretroviral therapy with postpartum paradoxical exacerbation.
Med Mycol Case Rep
PUBLISHED: 07-01-2014
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Cryptococcosis is the most common cause of meningitis in Africa due to the high burden of HIV. Immune reconstitution inflammatory syndrome (IRIS) is a frequent and deadly complication of cryptococcal meningitis. We report a fatal case of cryptococcal-IRIS in a pregnant woman that began after starting antiretroviral therapy (unmasking IRIS) and markedly worsened postpartum after delivery (paradoxical IRIS).
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Timing of antiretroviral therapy after diagnosis of cryptococcal meningitis.
N. Engl. J. Med.
PUBLISHED: 06-26-2014
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Cryptococcal meningitis accounts for 20 to 25% of acquired immunodeficiency syndrome-related deaths in Africa. Antiretroviral therapy (ART) is essential for survival; however, the question of when ART should be initiated after diagnosis of cryptococcal meningitis remains unanswered.
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Effect of docosahexaenoic acid supplementation on inflammatory cytokine levels in infants at high genetic risk for type 1 diabetes.
Pediatr Diabetes
PUBLISHED: 03-05-2014
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Type 1 diabetes (T1D) results from the inflammatory destruction of pancreatic ?-cells. In this study, we investigated the effect of docosahexaenoic acid (DHA) supplementation on stimulated inflammatory cytokine production in white blood cells (WBC) from infants with a high genetic risk for T1D.
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AIDS-related mycoses: the way forward.
Trends Microbiol.
PUBLISHED: 03-04-2014
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The contribution of fungal infections to the morbidity and mortality of HIV-infected individuals is largely unrecognized. A recent meeting highlighted several priorities that need to be urgently addressed, including improved epidemiological surveillance, increased availability of existing diagnostics and drugs, more training in the field of medical mycology, and better funding for research and provision of treatment, particularly in developing countries.
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Use of the Diabetes Prevention Trial-Type 1 Risk Score (DPTRS) for improving the accuracy of the risk classification of type 1 diabetes.
Diabetes Care
PUBLISHED: 02-18-2014
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OBJECTIVE We studied the utility of the Diabetes Prevention Trial-Type 1 Risk Score (DPTRS) for improving the accuracy of type 1 diabetes (T1D) risk classification in TrialNet Natural History Study (TNNHS) participants. RESEARCH DESIGN AND METHODS The cumulative incidence of T1D was compared between normoglycemic individuals with DPTRS values >7.00 and dysglycemic individuals in the TNNHS (n = 991). It was also compared between individuals with DPTRS values <7.00 or >7.00 among those with dysglycemia and those with multiple autoantibodies in the TNNHS. DPTRS values >7.00 were compared with dysglycemia for characterizing risk in Diabetes Prevention Trial-Type 1 (DPT-1) (n = 670) and TNNHS participants. The reliability of DPTRS values >7.00 was compared with dysglycemia in the TNNHS. RESULTS The cumulative incidence of T1D for normoglycemic TNNHS participants with DPTRS values >7.00 was comparable to those with dysglycemia. Among those with dysglycemia, the cumulative incidence was much higher (P < 0.001) for those with DPTRS values >7.00 than for those with values <7.00 (3-year risks: 0.16 for <7.00 and 0.46 for >7.00). Dysglycemic individuals in DPT-1 were at much higher risk for T1D than those with dysglycemia in the TNNHS (P < 0.001); there was no significant difference in risk between the studies among those with DPTRS values >7.00. The proportion in the TNNHS reverting from dysglycemia to normoglycemia at the next visit was higher than the proportion reverting from DPTRS values >7.00 to values <7.00 (36 vs. 23%). CONCLUSIONS DPTRS thresholds can improve T1D risk classification accuracy by identifying high-risk normoglycemic and low-risk dysglycemic individuals. The 7.00 DPTRS threshold characterizes risk more consistently between populations and has greater reliability than dysglycemia.
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The Cryptococcus neoformans transcriptome at the site of human meningitis.
MBio
PUBLISHED: 02-06-2014
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Cryptococcus neoformans is the leading cause of fungal meningitis worldwide. Previous studies have characterized the cryptococcal transcriptome under various stress conditions, but a comprehensive profile of the C. neoformans transcriptome in the human host has not been attempted. Here, we extracted RNA from yeast cells taken directly from the cerebrospinal fluid (CSF) of two AIDS patients with cryptococcal meningitis prior to antifungal therapy. The patients were infected with strains of C. neoformans var. grubii of molecular type VNI and VNII. Using RNA-seq, we compared the transcriptional profiles of these strains under three environmental conditions (in vivo CSF, ex vivo CSF, and yeast extract-peptone-dextrose [YPD]). Although we identified a number of differentially expressed genes, single nucleotide variants, and novel genes that were unique to each strain, the overall expression patterns of the two strains were similar under the same environmental conditions. Specifically, yeast cells obtained directly from each patient's CSF were more metabolically active than cells that were incubated ex vivo in CSF. Compared with growth in YPD, some genes were identified as significantly upregulated in both in vivo and ex vivo CSF, and they were associated with genes previously recognized for contributing to pathogenicity. For example, genes with known stress response functions, such as RIM101, ENA1, and CFO1, were regulated similarly in the two clinical strains. Conversely, many genes that were differentially regulated between the two strains appeared to be transporters. These findings establish a platform for further studies of how this yeast survives and produces disease.
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Predictors of neurocognitive outcomes on antiretroviral therapy after cryptococcal meningitis: a prospective cohort study.
Metab Brain Dis
PUBLISHED: 01-09-2014
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Cryptococcal meningitis is the most common cause of adult meningitis in Africa, yet neurocognitive outcomes are unknown. We investigated the incidence and predictors of neurologic impairment among cryptococcal survivors. HIV-infected, antiretroviral-naive Ugandans with cryptococcal meningitis underwent standardized neuropsychological testing at 1, 3, 6, and 12 months. A quantitative neurocognitive performance z-score (QNPZ) was calculated based on population z-scores from HIV-negative Ugandans (n?=?100). Comparison was made with an HIV-infected, non-meningitis cohort (n?=?110). Among 78 cryptococcal meningitis survivors with median CD4 count of 13 cells/?L (interquartile range: 6-44), decreased global cognitive function occurred through 12 months compared with the HIV-infected, non-cryptococcosis cohort (QNPZ-6 at 12 months, P?=?0.036). Tests of performance in eight cognitive domains was impaired 1 month after cryptococcal diagnosis; however, cryptococcal meningitis survivors improved their global neurocognitive function over 12 months with residual impairment (mean z-scores?
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Performance of cryptococcal antigen lateral flow assay using saliva in Ugandans with CD4 <100.
PLoS ONE
PUBLISHED: 01-01-2014
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Cryptococcal meningitis can best be diagnosed by cerebrospinal fluid India ink microscopy, cryptococcal antigen detection, or culture. These require invasive lumbar punctures. The utility of cryptococcal antigen detection in saliva is unknown. We evaluated the diagnostic performance of the point-of-care cryptococcal antigen lateral flow assay (CrAg LFA) in saliva.
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Unmasking Cryptococcal Meningitis Immune Reconstitution Inflammatory Syndrome due to Granulocyte Colony-Stimulating Factor Use in a Patient with a Poorly Differentiated Germ Cell Neoplasm.
Case Rep Oncol
PUBLISHED: 01-01-2014
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Cryptococcal meningitis immune reconstitution inflammatory syndrome (IRIS) is frequently seen in patients with HIV and less frequently in patients on immune suppressive medications for other conditions. Here, we describe the first reported case of unmasking cryptococcal IRIS due to granulocyte colony-stimulating factor used in an HIV-negative patient with chemotherapy-induced neutropenia.
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Multisite validation of cryptococcal antigen lateral flow assay and quantification by laser thermal contrast.
Emerging Infect. Dis.
PUBLISHED: 01-01-2014
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Cryptococcal meningitis is common in sub-Saharan Africa. Given the need for data for a rapid, point-of-care cryptococcal antigen (CRAG) lateral flow immunochromatographic assay (LFA), we assessed diagnostic performance of cerebrospinal fluid (CSF) culture, CRAG latex agglutination, India ink microscopy, and CRAG LFA for 832 HIV-infected persons with suspected meningitis during 2006-2009 (n = 299) in Uganda and during 2010-2012 (n = 533) in Uganda and South Africa. CRAG LFA had the best performance (sensitivity 99.3%, specificity 99.1%). Culture sensitivity was dependent on CSF volume (82.4% for 10 ?L, 94.2% for 100 ?L). CRAG latex agglutination test sensitivity (97.0%-97.8%) and specificity (85.9%-100%) varied between manufacturers. India ink microscopy was 86% sensitive. Laser thermal contrast had 92% accuracy (R = 0.91, p<0.001) in quantifying CRAG titers from 1 LFA strip to within <1.5 dilutions of actual CRAG titers. CRAG LFA is a major advance for meningitis diagnostics in resource-limited settings.
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Diagnosis and Management of Cryptococcal Relapse.
J AIDS Clin Res
PUBLISHED: 12-28-2013
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Despite improvements in the antifungal regimens and the roll out of antiretroviral therapy (ART) in sub-Saharan Africa, mortality due to cryptococcal meningitis remains high. Relapse of an initially successfully treated infection contributes to this mortality and is often a clinical dilemma in differentiating between paradoxical immune reconstitution inflammatory syndrome (IRIS) and culture-positive relapse or treatment failure. Herein, we present a clinical case scenario and review the case definitions, differential diagnosis, and management of relapse with an emphasis on the current diagnostic and management strategies. We also highlight the challenges of resistance testing and management of refractory relapse cases. The risk of relapse is influenced by: 1) the choice of induction therapy, with higher mortality risk with fluconazole monotherapy which can select for resistance; 2) non-adherence to or lack of secondary prophylaxis; 3) failure of linkage-to-care or retention-in-care of HIV ART programs.
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Central nervous system immune reconstitution inflammatory syndrome.
Curr Infect Dis Rep
PUBLISHED: 11-01-2013
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Central nervous system immune reconstitution inflammatory syndrome (CNS-IRIS) develops in 9 %-47 % of persons with HIV infection and a CNS opportunistic infection who start antiretroviral therapy and is associated with a mortality rate of 13 %-75 %. These rates vary according to the causative pathogen. Common CNS-IRIS events occur in relation to Cryptococcus, tuberculosis (TB), and JC virus, but several other mycobacteria, fungi, and viruses have been associated with IRIS. IRIS symptoms often mimic the original infection, and diagnosis necessitates consideration of treatment failure, microbial resistance, and an additional neurological infection. These diagnostic challenges often delay IRIS diagnosis and treatment. Corticosteroids have been used to treat CNS-IRIS, with variable responses; the best supportive evidence exists for the treatment of TB-IRIS. Pathogenic mechanisms vary: Cryptococcal IRIS is characterized by a paucity of cerebrospinal inflammation prior to antiretroviral therapy, whereas higher levels of inflammatory markers at baseline predispose to TB meningitis IRIS. This review focuses on advances in the understanding of CNS-IRIS over the past 2 years.
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Utility of the Xpert MTB/RIF assay for diagnosis of tuberculous meningitis.
PLoS Med.
PUBLISHED: 10-01-2013
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David Boulware discusses the challenges of diagnosing tuberculous meningitis and the implications of the study by Patel and colleagues using the Xpert MTB/RIF assay for diagnosis. Please see later in the article for the Editors Summary.
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Point-of-Care Diagnosis and Prognostication of Cryptococcal Meningitis With the Cryptococcal Antigen Lateral Flow Assay on Cerebrospinal Fluid.
Clin. Infect. Dis.
PUBLISHED: 09-24-2013
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The cryptococcal antigen (CRAG) lateral flow assay (LFA) had 100% sensitivity and specificity on cerebrospinal fluid samples. Pretreatment LFA titers correlated with quantitative cultures (R(2) = 0.7) and predicted 2- and 10-week mortality. The CRAG LFA is an accurate diagnostic assay for CSF and should be considered for point-of-care diagnosis of cryptococcal meningitis.
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Cryptococcus neoformans Ex Vivo Capsule Size Is Associated With Intracranial Pressure and Host Immune Response in HIV-associated Cryptococcal Meningitis.
J. Infect. Dis.
PUBLISHED: 08-14-2013
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Background.?The Cryptococcus neoformans polysaccharide capsule is a well-characterized virulence factor with immunomodulatory properties. The organism and/or shed capsule is postulated to raise intracranial pressure (ICP) in cryptococcal meningitis (CM) by mechanical obstruction of cerebrospinal fluid (CSF) outflow. Little is known regarding capsule phenotype in human cryptococcosis. We investigated the relationship of ex vivo CSF capsular phenotype with ICP and CSF immune response, as well as in vitro phenotype. Methods.?In total, 134 human immunodeficiency virus (HIV)-infected Ugandan adults with CM had serial lumbar punctures with measurement of CSF opening pressures, quantitative cultures, ex vivo capsule size and shedding, viscosity, and CSF cytokines; 108 had complete data. Induced capsular size and shedding were measured in vitro for 48 C. neoformans isolates. Results.?Cryptococcal strains producing larger ex vivo capsules in the baseline (pretreatment) CSF correlated with higher ICP (P = .02), slower rate of fungal clearance (P = .02), and paucity of CSF inflammation, including decreased CSF white blood cell (WBC) count (P < .001), interleukin (IL)-4 (P = .02), IL-6 (P = .01), IL-7 (P = .04), IL-8 (P = .03), and interferon ? (P = .03). CSF capsule shedding did not correlate with ICP. On multivariable analysis, capsule size remained independently associated with ICP. Ex vivo capsular size and shedding did not correlate with that of the same isolates grown in vitro. Conclusions.?Cryptococcal capsule size ex vivo is an important contributor to virulence in human cryptococcal meningitis.
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The prediction of type 1 diabetes by multiple autoantibody levels and their incorporation into an autoantibody risk score in relatives of type 1 diabetic patients.
Diabetes Care
PUBLISHED: 07-01-2013
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We assessed whether a risk score that incorporates levels of multiple islet autoantibodies could enhance the prediction of type 1 diabetes (T1D).
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Strategies to reduce mortality and morbidity due to AIDS-related cryptococcal meningitis in Latin America.
Braz J Infect Dis
PUBLISHED: 05-10-2013
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Latin America is the region with the third most AIDS-related cryptococcal meningitis infections globally. Highly active antiretroviral therapy (HAART) has reduced the number of infections; however, the number of deaths and the case-fatality rate continues to be unacceptable. In this review, we focus on the burden of AIDS-related cryptococcosis in Latin America and discuss potential strategies to reduce early mortality from Cryptococcus. In this review, we highlight the importance of: (1) earlier HIV diagnosis and HAART initiation with retention-in-care to avoid AIDS; (2) pre-HAART cryptococcal antigen (CRAG) screening with preemptive fluconazole treatment; (3) better diagnostics (e.g. CRAG testing); and (4) optimal treatment with aggressive management of intracranial pressure and induction therapy with antifungal combination. Implementation of these strategies can reduce cryptococcal-related deaths, improve care, and reduce healthcare costs.
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Effect of abatacept on immunogenicity of vaccines in individuals with type 1 diabetes.
Vaccine
PUBLISHED: 04-25-2013
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Abatacept delayed progression of type 1 diabetes (T1D) when administered soon after diagnosis. Its use in T1D is expanding to prevention trials and, therefore, it is important to fully characterize its immunosuppressive effect. We compared antibody responses to trivalent inactivated influenza vaccine (TIIV) administered during 2 consecutive seasons and to tetanus toxoid (TT) vaccine administered after 24 months of treatment in115 early onset T1D subjects randomly assigned to 24 months of abatacept (N=71) or placebo (N=34). Anti-influenza titers before TIIV were similar between the 2 treatment groups and both groups had significant increases after vaccination. Although the magnitude of antibody responses against some influenza serotypes was significantly lower (p<0.05) in abatacept compared with placebo recipients, no differences were observed in the proportion of subjects with protective titers against influenza after vaccination. The magnitude of antibody responses against TT also tended to be lower (p=0.06) in abatacept compared with placebo recipients, without affecting the proportion of subjects who achieved protective titers. We conclude that abatacept moderately decreases the magnitude of antibody responses to recall vaccination. Further studies are needed to assess its effect on primary immunization.
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Cost-effective diagnostic checklists for meningitis in resource-limited settings.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 03-08-2013
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Checklists can standardize patient care, reduce errors, and improve health outcomes. For meningitis in resource-limited settings, with high patient loads and limited financial resources, central nervous system diagnostic algorithms may be useful to guide diagnosis and treatment. However, the cost effectiveness of such algorithms is unknown.
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Estimating the burden of pneumococcal pneumonia among adults: a systematic review and meta-analysis of diagnostic techniques.
PLoS ONE
PUBLISHED: 02-26-2013
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Pneumococcal pneumonia causes significant morbidity and mortality among adults. Given limitations of diagnostic tests for non-bacteremic pneumococcal pneumonia, most studies report the incidence of bacteremic or invasive pneumococcal disease (IPD), and thus, grossly underestimate the pneumococcal pneumonia burden. We aimed to develop a conceptual and quantitative strategy to estimate the non-bacteremic disease burden among adults with community-acquired pneumonia (CAP) using systematic study methods and the availability of a urine antigen assay.
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Reactivation of latent viruses in individuals receiving rituximab for new onset type 1 diabetes.
J. Clin. Virol.
PUBLISHED: 01-26-2013
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Rituximab has been successfully used as an experimental therapy in different autoimmune diseases. Recently, a double-blind placebo-controlled phase-2 study in early onset type 1 diabetes showed that rituximab delayed progression of the disease. However, like with any immunosuppressive therapy, there is a concern of opportunistic viral reactivations with the use of rituximab, including herpes and polyomaviruses.
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Biomarkers of inflammation and coagulation are associated with mortality and hepatitis flares in persons coinfected with HIV and hepatitis viruses.
J. Infect. Dis.
PUBLISHED: 01-18-2013
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Hepatitis C virus (HCV) and/or hepatitis B virus (HBV) coinfection with human immunodeficiency virus (HIV) has a greater risk of mortality than either HCV or HBV infection alone and is frequently associated with hepatitis flares after antiretroviral therapy (ART) initiation.
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Comparison of Cryptococcal Antigenemia between Antiretroviral Naïve and Antiretroviral Experienced HIV Positive Patients at Two Hospitals in Ethiopia.
PLoS ONE
PUBLISHED: 01-01-2013
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Cryptococcal meningitis is a major cause of HIV/AIDS-related deaths in Africa. Cryptococcosis is a neglected killer. However, meningitis can be prevented by early cryptococcal antigen (CrAg) screening and preemptive antifungal treatment during a prolonged period of detectable, subclinical infection. We determined the prevalence of cryptococcal antigenemia in comparison to CD4 count and clinical symptoms.
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Cryptococcus-Related Immune Reconstitution Inflammatory Syndrome(IRIS): Pathogenesis and Its Clinical Implications.
Curr Fungal Infect Rep
PUBLISHED: 12-15-2011
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This review provides an overview of Cryptococcus neoformans immunology and focuses on the pathogenesis of Cryptococcus-related paradoxical immune reconstitution inflammatory syndrome (IRIS). Cryptococcal IRIS has three phases: (1) before antiretroviral therapy (ART), with a paucity of cerebrospinal fluid (CSF) inflammation and defects in antigen clearance; (2) during initial ART immune recovery, with pro-inflammatory signaling by antigen-presenting cells without an effector response; and (3) at IRIS, a cytokine storm with a predominant type-1 helper T-cell (Th(1)) interferon-gamma (IFN-?) response. Understanding IRIS pathogenesis allows for risk stratification and customization of HIV/AIDS care. In brief, persons at high IRIS risk may benefit from enhancing microbiologic clearance by use of adjunctive agents in combination with amphotericin, prolonging initial induction therapy, and/or increasing the initial consolidation antifungal therapy dose to at least 800 mg of fluconazole daily until the 2-week CSF culture is known to be sterile. Prophylactic anti-inflammatory therapies or undue delay of ART initiation in an attempt to prevent IRIS is unwarranted and may be dangerous.
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Impact of global health residency training on medical knowledge of immigrant health.
Am. J. Trop. Med. Hyg.
PUBLISHED: 09-08-2011
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Lack of global health knowledge places immigrants at risk of iatrogenic morbidity. Although global health education programs have grown in popularity, measurable impact is lacking. We previously surveyed 363 physicians in training across 15 programs in four countries in 2004 regarding basic parasite knowledge and recognition of Strongyloides risk through a theoretical case scenario. In 2005, the University of Minnesota implemented a formal global health training program (GHP). In 2009, the identical survey was repeated. Strongyloidiasis recognition increased from 11.1% (19/171) in 2004 to 39.4% (50/127) in 2009 (P < 0.001). Trainees participating in formal didactic and interactive curriculum had superior recognition (77% versus 29%; P < 0.001). In a multivariate model of GHP training activities, participation in an American Society of Tropical Medicine and Hygiene-accredited global health certificate course increased recognition (odds ratio = 9.5, 95% confidence interval = 2.5-36, P = 0.001), whereas participation in international electives alone did not (P = 0.9). A formal GHP curriculum was associated with improved knowledge regarding common parasitic infections and the risk of iatrogenic morbidity and mortality due to strongyloidiasis.
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Validation of the Diabetes Prevention Trial-Type 1 Risk Score in the TrialNet Natural History Study.
Diabetes Care
PUBLISHED: 06-16-2011
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We assessed the accuracy of the Diabetes Prevention Trial-Type 1 Risk Score (DPTRS), developed from the Diabetes Prevention Trial-Type 1 (DPT-1), in the TrialNet Natural History Study (TNNHS).
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Higher levels of CRP, D-dimer, IL-6, and hyaluronic acid before initiation of antiretroviral therapy (ART) are associated with increased risk of AIDS or death.
J. Infect. Dis.
PUBLISHED: 05-20-2011
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Substantial morbidity occurs during the first year of antiretroviral therapy (ART) in persons with advanced human immunodeficiency virus (HIV) disease despite HIV suppression. Biomarkers may identify high-risk groups.
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Comparison of two insulin assays for first-phase insulin release in type 1 diabetes prediction and prevention studies.
Clin. Chim. Acta
PUBLISHED: 05-13-2011
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Detection of below-threshold first-phase insulin release or FPIR (1+3 minute insulin concentrations during an intravenous glucose tolerance test [IVGTT]) is important in type 1 diabetes prediction and prevention studies including the TrialNet Oral Insulin Prevention Trial. We assessed whether an insulin immunoenzymometric assay (IEMA) could replace the less practical but current standard of a radioimmunoassay (RIA) for FPIR.
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Comparative genome sequencing of an isogenic pair of USA800 clinical methicillin-resistant Staphylococcus aureus isolates obtained before and after daptomycin treatment failure.
Antimicrob. Agents Chemother.
PUBLISHED: 02-22-2011
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We describe here a clinical daptomycin treatment failure in a patient with recurrent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in whom daptomycin was administered after a failed empirical treatment course with vancomycin and piperacillin-tazobactam. We had the opportunity to compare the genome sequences of an isogenic pair of daptomycin-susceptible and -resistant MRSA isolates obtained before and after initiation of daptomycin therapy, respectively. The genotype of both isolates was USA800, ST5, SCCmec type IV, agr type II. There was no increase in cell wall thickness in the daptomycin-resistant strain despite having decreased susceptibility to both vancomycin and daptomycin. By comparing the genome sequences by pyrosequencing, we identified a polymorphism (S337L) in the tenth transmembrane segment of the multiple peptide resistance factor, MprF, encoding lysyl phosphatidylglycerol transferase. This enzyme has been shown previously to promote repulsion of daptomycin at the cell surface by addition of positively charged lysine to phosphatidylglycerol. Also, the hlb open reading frame (ORF) encoding the ?-toxin was interrupted by a prophage in the daptomycin-susceptible strain; this phage was missing in the daptomycin-resistant isolate and the hlb ORF was restored. Loss of the phage in the resistant isolate also resulted in loss of the virulence factor genes clpP, scn, and sak. This is the first study to use pyrosequencing to compare the genomes of a daptomycin-susceptible/resistant MRSA isolate pair obtained during failed daptomycin therapy in humans.
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Activation of the serine/theronine protein kinase Akt in enteropancreatic neuroendocrine tumors.
Anticancer Res.
PUBLISHED: 12-29-2010
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Akt is a regulator of cell proliferation, tumorigenesis and apoptosis. This study evaluated the incidence of Akt activation in a subset of neuroendocrine tumors (NETs) and its correlation to clinical pathological parameters.
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Cryptococcal immune reconstitution inflammatory syndrome in HIV-1-infected individuals: proposed clinical case definitions.
Lancet Infect Dis
PUBLISHED: 10-30-2010
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Cryptococcal immune reconstitution inflammatory syndrome (IRIS) may present as a clinical worsening or new presentation of cryptococcal disease after initiation of antiretroviral therapy (ART), and is thought to be caused by recovery of cryptococcus-specific immune responses. We have reviewed reports of cryptococcal IRIS and have developed a consensus case definition specifically for paradoxical crytopcoccal IRIS in patients with HIV-1 and known cryptococcal disease before ART, and a separate definition for incident cryptococcosis developed during ART (termed ART-associated cryptococcosis), for which a proportion of cases are likely to be unmasking cryptococcal IRIS. These structured case definitions are intended to aid design of future clinical, epidemiological, and immunopathological studies of cryptococcal IRIS, to standardise diagnostic criteria, and to facilitate comparisons between studies. As for definitions of tuberculosis-associated IRIS, definitions for cryptococcal IRIS should be regarded as preliminary until further insights into the immunopathology of IRIS permit their refinement.
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Reduction of immune activation with chloroquine therapy during chronic HIV infection.
J. Virol.
PUBLISHED: 09-15-2010
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Increased levels of activated T cells are a hallmark of the chronic stage of human immunodeficiency virus (HIV) infection and are highly correlated with HIV disease progression. We evaluated chloroquine (CQ) as a potential therapy to reduce immune activation during HIV infection. We found that the frequency of CD38(+) HLA-DR(+) CD8 T cells, as well as Ki-67 expression in CD8 and CD4 T cells, was significantly reduced during CQ treatment. Our data indicate that treatment with CQ reduces systemic T-cell immune activation and, thus, that its use may be beneficial for certain groups of HIV-infected individuals.
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Antiretroviral therapy down-regulates innate antiviral response genes in patients with AIDS in sub-saharan Africa.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 09-15-2010
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HIV pathogenesis is characterized by destructive imbalances between virus-mediated immune damage, antiviral immune responses, and immune activation. We characterized the effects of successful antiretroviral therapy (ART) to identify the breadth and patterns of HIV-associated gene expression.
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Paucity of initial cerebrospinal fluid inflammation in cryptococcal meningitis is associated with subsequent immune reconstitution inflammatory syndrome.
J. Infect. Dis.
PUBLISHED: 08-04-2010
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Cryptococcal meningitis (CM)-related immune reconstitution inflammatory syndrome (IRIS) complicates antiretroviral therapy (ART) in 20%-40% of ART-naive persons with AIDS and prior CM. Pathogenesis is unknown.
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Cancer in nonagenarians: profile, treatments and outcomes.
Crit. Rev. Oncol. Hematol.
PUBLISHED: 07-27-2010
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An increasing number of nonagenarians are treated for cancer. However, very few data are available to guide treatment choices in this often frail population. The charts of all patients registered at Moffitt Cancer Center between 1993 and 2006 who were aged 90 or older at the time of treatment/evaluation were reviewed, and those treated for an active cancer (n=177) were included in the analysis. For 23.5% of patients, the index cancer was a second malignancy. Initial treatments were: surgery 41%, chemotherapy 9%, radiation therapy 15%, concomitant chemo-radiation therapy 2%, hormonal therapy 12%, targeted therapy 8%, photodynamic therapy 1%, observation/supportive care 3%, hospice 9%. The median survival was 1.69 years [95% CI=1.34, 2.17, range 0.1-6.21]. For early stage cancer it was 2.02 years [95% CI=1.56, 2.87], and for advanced stage cancer, 1.06 years [95% CI=0.58, 1.63] (p=0.02 by log-rank). Treatment related mortality was low (1.1%). In conclusion, our nonagenarians underwent a broad range of treatments with low treatment related mortality. Advanced cancer still limits the survival of nonagenarians. Second cancers are frequent in older cancer survivors.
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The clinical pattern, prevalence, and factors associated with immune reconstitution inflammatory syndrome in Ugandan children.
AIDS
PUBLISHED: 07-10-2010
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To determine clinical pattern, prevalence, and factors associated with pediatric immune reconstitution inflammatory syndrome (IRIS) in Uganda.
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Cost-effectiveness of serum cryptococcal antigen screening to prevent deaths among HIV-infected persons with a CD4+ cell count < or = 100 cells/microL who start HIV therapy in resource-limited settings.
Clin. Infect. Dis.
PUBLISHED: 07-06-2010
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Cryptococcal meningitis (CM) remains a common AIDS-defining illness in Africa and Asia. Subclinical cryptococcal antigenemia is frequently unmasked with antiretroviral therapy (ART). We sought to define the cost-effectiveness of serum cryptococcal antigen (CRAG) screening to identify persons with subclinical cryptococcosis and the efficacy of preemptive fluconazole therapy.
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Clinical features and serum biomarkers in HIV immune reconstitution inflammatory syndrome after cryptococcal meningitis: a prospective cohort study.
PLoS Med.
PUBLISHED: 05-25-2010
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Although antiretroviral therapy (ART) improves survival in persons with cryptococcal meningitis (CM) and AIDS, ART frequently elicits HIV immune reconstitution inflammatory syndrome (IRIS), an exaggerated and frequently deadly inflammatory reaction that complicates recovery from immunodeficiency. The pathogenesis of IRIS is poorly understood and prediction of IRIS is not possible.
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Targeting the Fanconi anemia/BRCA pathway circumvents drug resistance in multiple myeloma.
Cancer Res.
PUBLISHED: 11-24-2009
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The Fanconi anemia/BRCA (FA/BRCA) DNA damage repair pathway plays a pivotal role in the cellular response to replicative stress induced by DNA alkylating agents and greatly influences drug response in cancer treatment. We recently reported that FA/BRCA genes are overexpressed and causative for drug resistance in human melphalan-resistant multiple myeloma cell lines. However, the transcriptional regulation of the FA/BRCA pathway is not understood. In this report, we describe for the first time a novel function of the NF-kappaB subunits, RelB/p50, as transcriptional activators of the FA/BRCA pathway. Specifically, our findings point to constitutive phosphorylation of IkappaB kinase alpha and subsequent alterations in FANCD2 expression and function as underlying events leading to melphalan resistance in repeatedly exposed multiple myeloma cells. Inhibiting NF-kappaB by small interfering RNA, blocking the IkappaB kinase complex with BMS-345541, or using the proteasome inhibitor bortezomib drastically reduced FA/BRCA gene expression and FANCD2 protein expression in myeloma cells, resulting in diminished DNA damage repair and enhanced melphalan sensitivity. Importantly, we also found that bortezomib decreases FA/BRCA gene expression in multiple myeloma patients. These results show for the first time that NF-kappaB transcriptionally regulates the FA/BRCA pathway and provide evidence for targeting Fanconi anemia-mediated DNA repair to enhance chemotherapeutic response and circumvent drug resistance in myeloma patients.
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Randomized phase III trial of gemcitabine-based chemotherapy with in situ RRM1 and ERCC1 protein levels for response prediction in non-small-cell lung cancer.
J. Clin. Oncol.
PUBLISHED: 11-02-2009
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We evaluated the efficacy of gemcitabine versus gemcitabine and carboplatin in patients with advanced non-small-cell lung cancer (NSCLC) and a performance status (PS) of 2 and assessed if tumoral RRM1 and ERCC1 protein levels are predictive of response to therapy.
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Diagnostic performance of rapid diagnostic tests versus blood smears for malaria in US clinical practice.
Clin. Infect. Dis.
PUBLISHED: 08-19-2009
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Approximately 4 million US travelers to developing countries are ill enough to seek health care, with 1500 malaria cases reported in the United States annually. The diagnosis of malaria is frequently delayed because of the time required to prepare malaria blood films and lack of technical expertise. An easy, reliable rapid diagnostic test (RDT) with high sensitivity and negative predictive value (NPV), particularly for Plasmodium falciparum, would be clinically useful. The objective of this study was to determine the diagnostic performance of a RDT approved by the US Food and Drug Administration compared with traditional thick and thin blood smears for malaria diagnosis.
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Serum insulin-like growth factor (IGF)-1 and IGF binding protein-3 in relation to breast cancer among Hispanic and white, non-Hispanic women in the US Southwest.
Breast Cancer Res. Treat.
PUBLISHED: 08-11-2009
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Insulin-like growth factor 1 (IGF-1) and IGF binding protein 3 (IGFBP-3) have been positively associated with breast cancer, especially among premenopausal women. Hispanic women have lower levels of IGF-1 and IGFBP-3 than non-Hispanic white (NHW) women, although no studies have adequately assessed the relationship among IGF-1, IGFBP-3, and breast cancer in Hispanic women. We investigated the association among IGF-1, IGFBP-3, and breast cancer within a subset of participants (n = 184 cases, 522 controls) of a population-based case-control study of women living in the U.S. Southwest. Serum levels of IGF-1 and IGFBP-3 were measured in fasting blood samples, and associations among IGF-1, IGFBP-3, and breast cancer were calculated using logistic regression, adjusting for age, study center, ethnicity, education, recent hormone exposure, body mass index, parity, total energy expenditure, total calories, and cholesterol. Both IGF-1 and IGFBP-3 were statistically significantly associated with breast cancer overall (highest vs. lowest quartile (Q4 vs. Q1) for IGF-1: odds ratio (OR) = 1.92, 95% confidence interval (CI) = 1.07-3.43); for IGFBP-3: OR = 3.04, 95% CI = 1.63-5.67). Positive associations were observed for both premenopausal breast cancer and postmenopausal breast cancer. IGF-1 was associated with breast cancer in NHW women (Q4 vs. Q1: OR = 2.82, 95% CI = 1.36-5.83), but not in Hispanic women (Q4 vs. Q1: OR = 0.81, 95% CI = 0.29-2.27). IGFBP-3 was associated with breast cancer in both ethnic groups (Q4 vs. Q1 for NHW: OR = 3.32, 95% CI = 1.45-7.60; Q4 vs. Q1 for Hispanics: OR = 2.15, 95% CI = 0.76-6.04). In conclusion, the association between IGF-1 and breast cancer differed by ethnicity, while no ethnic differences were observed in IGFBP-3-associated breast cancer.
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Outcomes of postoperative concurrent chemoradiotherapy for locally advanced major salivary gland carcinoma.
Arch. Otolaryngol. Head Neck Surg.
PUBLISHED: 07-22-2009
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To investigate the potential value of postoperative concurrent chemoradiation among patients with high-risk salivary gland carcinomas.
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WITHDRAWN: Cancer in nonagenarians: Profile, treatments and outcomes.
Crit. Rev. Oncol. Hematol.
PUBLISHED: 07-20-2009
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This article has been withdrawn with the permission of the authors, it has been published in volume1, issue 1 of the Journal of Geriatric Oncology (www.geriatriconcology.net). The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
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Assessment of elementary school students sun protection behaviors.
Pediatr Dermatol
PUBLISHED: 07-20-2009
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Studies suggest that excessive sun exposure in childhood contributes to the development of skin cancer later in life.
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Systems biology modeling of the radiation sensitivity network: a biomarker discovery platform.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 05-28-2009
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The discovery of effective biomarkers is a fundamental goal of molecular medicine. Developing a systems-biology understanding of radiosensitivity can enhance our ability of identifying radiation-specific biomarkers.
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Patterns of care and survival in cancer patients with cognitive impairment.
Crit. Rev. Oncol. Hematol.
PUBLISHED: 05-10-2009
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To address the emerging concern of oncologists who can expect to see an increasing number of older cancer patients with dementia, this retrospective case-control study compared a sample of older cancer patients with cognitive impairment (N=86) to a non-cognitively impaired control group (N=172) as to patterns of care and survival by age, site and stage. Treatment patterns presented much less differences between both groups than in other series. After adjusting for age, sex, performance status, ADLs/IADLs and comorbidity, results showed significantly greater survival (values p<.001) in the non-impaired control group (Mdn=72.6 months) compared to the cognitively impaired cases (Mdn=23.0 months). Similar results were found when we compared these groups according to tumor stage and cancer site (breast versus other). Across tumor types and stages, cognitively impaired patients have approximately one-third the median survival of the control group. This survival can still be a significant number of years.
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A gene expression model of intrinsic tumor radiosensitivity: prediction of response and prognosis after chemoradiation.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 04-25-2009
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Development of a radiosensitivity predictive assay is a central goal of radiation oncology. We reasoned a gene expression model could be developed to predict intrinsic radiosensitivity and treatment response in patients.
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Physician preferences for elements of effective consultations.
J Gen Intern Med
PUBLISHED: 03-17-2009
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Effective communication is vital for optimal medical consultation, but there is little current information about physician preferences for effective consultation.
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Prognostic factors for survival after salvage reirradiation of head and neck cancer.
J. Clin. Oncol.
PUBLISHED: 03-16-2009
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Patients who develop recurrent or new primary head and neck cancer in a previously irradiated site have poor prognosis. Reirradiation is a treatment option, although it is associated with substantial toxicities. We investigated potential prognostic factors, including comorbidity and pre-existing organ dysfunction, for survival after reirradiation.
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Substantially reduced expression of PIAS1 is associated with colon cancer development.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 01-20-2009
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Protein inhibitors of activated STATs (PIAS) regulate the interferon-gamma (IFN-gamma) signaling pathway, which has numerous effects on tumor development and tumor cell biology. PIASs also regulate STAT family members not directly involved in IFN-gamma signaling. This project was designed to assess PIAS1 expression in colon cancer.
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Sampling strategies for tissue microarrays to evaluate biomarkers in ovarian cancer.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 01-07-2009
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Tissue microarrays (TMA) enable rapid analysis of biomarkers in large-scale studies involving archival tumor specimens, however, their utility in heterogeneous tumors such as ovarian cancer is limited.
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Long term 5-year survival of persons with cryptococcal meningitis or asymptomatic subclinical antigenemia in Uganda.
PLoS ONE
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Data presented previously as an abstract at the 2011 CUGH Global Health Conference in Montreal, Canada on 15 Nov 2011. The long-term survival of HIV-infected persons with symptomatic cryptococcal meningitis and asymptomatic, subclinical cryptococcal antigenemia (CRAG+) is unknown. We prospectively enrolled 25 asymptomatic, antiretroviral therapy (ART)-naïve CRAG+ Ugandans with CD4<100 cells/mcL who received pre-emptive fluconazole treatment (CRAG+ cohort) and 189 ART-naïve Ugandans with symptomatic cryptococcal meningitis treated with amphotericin (CM cohort). The 10-week survival was 84% (95%CI: 70-98%) in the CRAG+ cohort and 57% (95%CI: 50%-64%) in the CM cohort. The CRAG+ cohort had improved five-year survival of 76% (95%CI: 59%-93%) compared to 42% (95%CI: 35%-50%) in the CM cohort (P = 0.001). The two cohorts had similar immunosuppression pre-ART with median CD4 counts of 15 vs. 21 CD4/mcL in the CRAG+ and CM cohorts, respectively (P = 0.45). Despite substantial early mortality, subsequent 5-year survival of persons surviving 6-months was excellent (>88%), demonstrating that long term survival is possible in resource-limited settings. Pre-ART CRAG screening with preemptive fluconazole treatment and improved CM treatment(s) are needed to reduce AIDS-attributable mortality due to cryptococcosis which remains 20-25% in sub-Saharan Africa.
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Cryptococcal meningitis treatment strategies in resource-limited settings: a cost-effectiveness analysis.
PLoS Med.
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Cryptococcal meningitis (CM) is the most common form of meningitis in Africa. World Health Organization guidelines recommend 14-d amphotericin-based induction therapy; however, this is impractical for many resource-limited settings due to cost and intensive monitoring needs. A cost-effectiveness analysis was performed to guide stakeholders with respect to optimal CM treatment within resource limitations.
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Epstein-Barr and other herpesvirus infections in patients with early onset type 1 diabetes treated with daclizumab and mycophenolate mofetil.
Clin. Infect. Dis.
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We assessed the morbidity of herpesviruses in patients with type 1 diabetes mellitus (T1D) enrolled in immunosuppressive treatment studies.
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Cryptococcal genotype influences immunologic response and human clinical outcome after meningitis.
MBio
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In sub-Saharan Africa, cryptococcal meningitis (CM) continues to be a predominant cause of AIDS-related mortality. Understanding virulence and improving clinical treatments remain important. To characterize the role of the fungal strain genotype in clinical disease, we analyzed 140 Cryptococcus isolates from 111 Ugandans with AIDS and CM. Isolates consisted of 107 nonredundant Cryptococcus neoformans var. grubii strains and 8 C. neoformans var. grubii/neoformans hybrid strains. Multilocus sequence typing (MLST) was used to characterize genotypes, yielding 15 sequence types and 4 clonal clusters. The largest clonal cluster consisted of 74 isolates. The results of Burst and phylogenetic analysis suggested that the C. neoformans var. grubii strains could be separated into three nonredundant evolutionary groups (Burst group 1 to group 3). Patient mortality was differentially associated with the different evolutionary groups (P = 0.04), with the highest mortality observed among Burst group 1, Burst group 2, and hybrid strains. Compared to Burst group 3 strains, Burst group 1 strains were associated with higher mortality (P = 0.02), exhibited increased capsule shedding (P = 0.02), and elicited a more pronounced Th(2) response during ex vivo cytokine release assays with strain-specific capsule stimulation (P = 0.02). The results of these analyses suggest that cryptococcal strain variation can be an important determinant of human immune responses and mortality.
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Performance of HbA1c as an early diagnostic indicator of type 1 diabetes in children and youth.
Diabetes Care
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The aim of this study was to evaluate HbA(1c) as an alternative criterion for impaired glucose tolerance (IGT) or type 1 diabetes (T1D) in high-risk subjects <21 years of age.
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Fall in C-peptide during first 2 years from diagnosis: evidence of at least two distinct phases from composite Type 1 Diabetes TrialNet data.
Diabetes
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Interpretation of clinical trials to alter the decline in ?-cell function after diagnosis of type 1 diabetes depends on a robust understanding of the natural history of disease. Combining data from the Type 1 Diabetes TrialNet studies, we describe the natural history of ?-cell function from shortly after diagnosis through 2 years post study randomization, assess the degree of variability between patients, and investigate factors that may be related to C-peptide preservation or loss. We found that 93% of individuals have detectable C-peptide 2 years from diagnosis. In 11% of subjects, there was no significant fall from baseline by 2 years. There was a biphasic decline in C-peptide; the C-peptide slope was -0.0245 pmol/mL/month (95% CI -0.0271 to -0.0215) through the first 12 months and -0.0079 (-0.0113 to -0.0050) from 12 to 24 months (P < 0.001). This pattern of fall in C-peptide over time has implications for understanding trial results in which effects of therapy are most pronounced early and raises the possibility that there are time-dependent differences in pathophysiology. The robust data on the C-peptide obtained under clinical trial conditions should be used in planning and interpretation of clinical trials.
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Role of quantitative CSF microscopy to predict culture status and outcome in HIV-associated cryptococcal meningitis in a Brazilian cohort.
Diagn. Microbiol. Infect. Dis.
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This retrospective study aimed to evaluate the clinical, laboratory, and quantitative cerebrospinal fluid (CSF) cryptococcal cell counts for associations with in-hospital outcomes of HIV-infected patients with cryptococcal meningitis. Ninety-eight HIV-infected adult patients with CSF culture-proven cryptococcal meningitis were admitted between January 2006 and June 2008 at a referral center in Sao Paulo, Brazil. Cryptococcal meningitis was the first AIDS-defining illness in 69%, of whom 97% (95/98) had known prior HIV infection. The median CD4+ T-cell count was 39 cells/?L (interquartile range 17-87 cells/?L). Prior antiretroviral therapy was reported in 50%. Failure to sterilize the CSF by 7-14 days was associated with baseline fungal burden of ? 10 yeasts/?L by quantitative CSF microscopy (odds ratio [OR] = 15.3, 95% confidence interval [CI] 4.1-56.7; P < 0.001) and positive blood cultures (OR = 11.5, 95% CI 1.2-109; P = 0.034). At 7-14 days, ? 10 yeasts/?L CSF was associated with positive CSF cultures in 98% versus 36% with <10 yeasts/?L CSF (P < 0.001). In-hospital mortality was 30% and was associated with symptoms duration for >14 days, altered mental status (P < 0.001), CSF white blood cell counts <5 cells/?L (P = 0.027), intracranial hypertension (P = 0.011), viral loads >50,000 copies/mL (P = 0.036), ? 10 yeasts/?L CSF at 7-14 days (P = 0.038), and intracranial pressure >50 cmH(2)0 at 7-14 days (P = 0.007). In conclusion, most patients were aware of their HIV status. Fungal burden of ? 10 yeasts/?L by quantitative CSF microscopy predicted current CSF culture status and may be useful to customize the induction therapy. High uncontrolled intracranial pressure was associated with mortality.
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The application of the diabetes prevention trial-type 1 risk score for identifying a preclinical state of type 1 diabetes.
Diabetes Care
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We assessed the utility of the Diabetes Prevention Trial-Type 1 Risk Score (DPTRS) for identifying individuals who are highly likely to progress to type 1 diabetes (T1D) within 2 years.
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Zinc transporter-8 autoantibodies improve prediction of type 1 diabetes in relatives positive for the standard biochemical autoantibodies.
Diabetes Care
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We assessed diabetes risk associated with zinc transporter-8 antibodies (ZnT8A), islet cell antibodies (ICA), and HLA type and age in relatives of people with type 1 diabetes with the standard biochemical autoantibodies (BAA) to insulin (IAA), GAD65 (GAD65A), and/or insulinoma-associated protein 2 antigen (IA-2A).
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Integrating cryptococcal antigen screening and pre-emptive treatment into routine HIV care.
J. Acquir. Immune Defic. Syndr.
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Cryptococcal meningitis is a leading cause of death in AIDS patients in sub-Saharan Africa. Cryptococcal antigen (CRAG) can be detected weeks before onset of symptoms, and those who are asymptomatic but CRAG positive have a high risk of subsequent cryptococcal meningitis and mortality. A new CRAG point of care immunochromatographic test is available that is remarkably easy to administer without laboratory infrastructure or expertise and has excellent sensitivity and specificity. We review the benefits of targeted CRAG screening, developments in CRAG diagnostics, and evidence regarding treatment options that can be implemented into routine HIV care in areas of high cryptococcal burden. Based on published CRAG+ prevalence rates of 2%-12%, the cost to save one life is between $20 to $140 in sub-Saharan Africa. We provide recommendations for implementation, pre-emptive treatment, and identify the gaps in our current knowledge.
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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.