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Sample records for nonresponders hiv-coinfected patients

  1. Hepatitis C virus–HIV-coinfected patients and liver transplantation

    PubMed Central

    Kardashian, Ani A.; Price, Jennifer C.

    2016-01-01

    Purpose of review To review the experience to date and unique challenges associated with liver transplantation in hepatitis C virus (HCV)/HIV-coinfected patients. Recent findings The prevalence of cirrhosis and hepatocellular carcinoma is rising among HIV-infected individuals. With careful patient selection and in the absence of HCV infection, HIV-infected and HIV-uninfected liver transplant recipients have comparable posttransplant outcomes. However, in the presence of HCV infection, patient and graft survival are significantly poorer in HIV-infected recipients, who have a higher risk of aggressive HCV recurrence, acute rejection, sepsis, and multiorgan failure. Outcomes may be improved with careful recipient and donor selection and with the availability of new highly potent all-oral HCV direct acting antivirals (DAAs). Although all-oral DAAs have not been evaluated in HIV/HCV-coinfected transplant patients, HIV does not adversely impact treatment success in nontransplant populations. Therefore, there is great hope that HCV can be successful eradicated in HIV/HCV-coinfected transplant patients and will result in improved outcomes. Careful attention to drug–drug interactions with HIV antiretroviral agents, DAAs, and posttransplant immunosuppressants is required. Summary Liver transplant outcomes are poorer in HIV/HCV-coinfected recipients compared with those with HCV-monoinfection. The new HCV DAAs offer tremendous potential to improve outcomes in this challenging population. PMID:25944240

  2. HBV/HIV coinfection is associated with poorer outcomes in hospitalized patients with HBV or HIV.

    PubMed

    Rajbhandari, R; Jun, T; Khalili, H; Chung, R T; Ananthakrishnan, A N

    2016-10-01

    We examined the impact of HBV/HIV coinfection on outcomes in hospitalized patients compared to those with HBV or HIV monoinfection. Using the 2011 US Nationwide Inpatient Sample, we identified patients who had been hospitalized with HBV or HIV monoinfection or HBV/HIV coinfection using ICD-9-CM codes. We compared liver-related admissions between the three groups. Multivariable logistic regression was performed to identify independent predictors of in-hospital mortality, length of stay and total charges. A total of 72 584 discharges with HBV monoinfection, 133 880 discharges with HIV monoinfection and 8156 discharges with HBV/HIV coinfection were included. HBV/HIV coinfection was associated with higher mortality compared to HBV monoinfection (OR 1.67, 95% CI 1.30-2.15) but not when compared to HIV monoinfection (OR 1.22, 95% CI 0.96-1.54). However, the presence of HBV along with cirrhosis or complications of portal hypertension was associated with three times greater in-hospital mortality in patients with HIV compared to those without these complications (OR 3.00, 95% CI 1.80-5.02). Length of stay and total hospitalization charges were greater in the HBV-/HIV-coinfected group compared to the HBV monoinfection group (+1.53 days, P < 0.001; $17595, P < 0.001) and the HIV monoinfection group (+0.62 days, P = 0.034; $8840, P = 0.005). In conclusion, HBV/HIV coinfection is a risk factor for in-hospital mortality, particularly in liver-related admissions, compared to HBV monoinfection. Overall healthcare utilization from HBV/HIV coinfection is also higher than for either infection alone and higher than the national average for all hospitalizations, thus emphasizing the healthcare burden from these illnesses.

  3. HIV coinfection shortens the survival of patients with hepatitis C virus-related decompensated cirrhosis.

    PubMed

    Pineda, Juan A; Romero-Gómez, Manuel; Díaz-García, Fernando; Girón-González, José A; Montero, José L; Torre-Cisneros, Julián; Andrade, Raúl J; González-Serrano, Mercedes; Aguilar, José; Aguilar-Guisado, Manuela; Navarro, José M; Salmerón, Javier; Caballero-Granado, Francisco J; García-García, José A

    2005-04-01

    The impact of human immunodeficiency virus (HIV) coinfection on the survival of patients with hepatitis C virus (HCV)-related end-stage liver disease (ESLD) is unknown. Because HIV infection is no longer considered an absolute contraindication for liver transplantation in some countries, it has become a priority to address this topic. The objective of this study was to compare the survival of HIV-infected and HIV-uninfected patients with decompensated cirrhosis due to HCV. In a retrospective cohort study, the survival of 1,037 HCV monoinfected and 180 HCV/HIV-coinfected patients with cirrhosis after the first hepatic decompensation was analyzed. Of the group, 386 (37%) HCV-monoinfected and 100 (56%) HCV/HIV-coinfected subjects died during the follow-up. The median survival time of HIV-infected and HIV-uninfected patients was 16 and 48 months, respectively (P < .001). The relative risk (95% CI) of death for HIV-infected patients was 2.26 (1.51-3.38). Other independent predictors of survival were age older than 63 years (2.25 [1.53-3.31]); Child-Turcotte-Pugh class B versus class A (1.95 [1.41-2.68]) and class C versus class A (2.78 [1.66-4.70]); hepatitis D virus infection (1.56 [1.12-4.77]); model for end-stage liver disease score, (1.05 [1.01-1-11]); more than one simultaneous decompensation (1.23 [1.12-3.33]); and the type of the first hepatic decompensation, with a poorer prognosis associated with encephalopathy compared with portal hypertensive gastrointestinal bleeding (2.03 [1.26-3.10]). In conclusion, HIV coinfection reduces considerably the survival of patients with HCV-related ESLD independently of other markers of poor prognosis. This fact must be taken into account to establish the adequate timing of liver transplantation in HIV-coinfected subjects.

  4. Modulation of HCV Replication After Combination Antiretroviral Therapy in HCV/HIV Coinfected Patients

    PubMed Central

    Sherman, Kenneth E.; Guedj, Jeremie; Shata, Mohamed Tarek; Blackard, Jason T.; Rouster, Susan D.; Castro, Mario; Feinberg, Judith; Sterling, Richard K.; Goodman, Zachary; Aronow, Bruce J.; Perelson, Alan S.

    2015-01-01

    The hepatitis C virus (HCV) is an important contributor to morbidity and mortality in patients coinfected with human immunodeficiency virus (HIV). Coinfection results in increased HCV replication and more rapid rates of liver disease progression. The effect of HIV combination antiretroviral therapy (cART) on HCV replication has not been studied in depth. To address this issue, we enrolled a small cohort of HCV/HIV coinfected patients into a cART initiation trial, and used dynamic modeling combined with evaluation of immune responses and microarray profiles to determine how effective treatment of HIV affects HCV. Treatment with cART resulted in HCV flare and alanine aminotransferase (ALT) increase (2× or more increase from baseline) in a subset of treated patients. Subjects with evidence of hepatic injury (increased ALT) were more likely to have HCV-specific immune responses directed against HCV epitopes. Over time, HCV viral loads declined. Reproducible and biologically important gene expression changes occurred in patients who underwent successful cART, particularly with respect to downregulation of genes with known antiviral roles. Our findings suggest that the effective suppression of HIV by cART initiates a cascade of early and late events in treated patients with HCV. Early events involving downregulation of interferon-stimulated genes may lead to transiently increased viral replication and hepatic injury. At later time points, HCV viral load declines to levels comparable to those seen in the setting of HCV monoinfection. These findings support early antiretroviral therapy in those with HCV/HIV coinfection. PMID:25101888

  5. Sustained Long-term Antiviral Maintenance Therapy in HCV/HIV Coinfected Patients (SLAM-C)

    PubMed Central

    Sherman, Kenneth E; Andersen, Janet W; Butt, Adeel A; Umbleja, Triin; Alston, Beverly; Koziel, Margaret J; Peters, Marion G; Sulkowski, Mark; Goodman, Zachary D; Chung, Raymond T

    2010-01-01

    Background HCV/HIV coinfection treatment is suboptimal with low SVR rates to standard therapies. A multicenter randomized clinical trial designed to assess the efficacy/safety of pegylated-interferon maintenance therapy was performed by the NIH-funded ACTG network. Methods HCV treatment naïve and non-responding interferon-experienced subjects with confirmed HCV and HIV, CD4>200 cells/mm3, and at least Stage 1 fibrosis were enrolled, and treated for 12 weeks with pegylated interferon alfa 2a 180 mcg/week (PEG) + weight-based ribavirin to determine response status. Non-responder subjects (failure to clear HCV RNA or achieve 2-log drop) underwent liver biopsy and were randomized to receive full dose PEG or observation only for 72 weeks. Paired biopsies were evaluated by a central pathologist. Results 330 subjects were enrolled; median age was 48 years; 43% White, 37% Black, non-Hispanic; 83% male; CD4+ 498 cells/mm3; 32% were interferon experienced; 74% had entry HIV RNA<50 cp/ml. EVR was observed in 55.9% and 42.5% achieved cEVR. A planned interim analysis of occurred when 84 subjects were randomized. With data on 40 paired biopsies available, a safety monitoring board stopped the trial due to lack of fibrosis progression (median = 0 Metavir units/year) in the observation arm. Conclusion Lack of fibrotic progression in the control arm was unexpected, and may represent a short-term PEG/ribavirin therapy effect, high levels of HIV viral suppression and use of antiretroviral regimens that may be less toxic than prior generations of therapy. PMID:20921898

  6. Cytokine Response Associated with Hepatitis C Virus Clearance in HIV Coinfected Patients Initiating Peg Interferon-α Based Therapy

    PubMed Central

    Nguyen, Truong Tam; Niloofar, Reihani; Rubbo, Pierre-Alain; Nils, Kuster; Bollore, Karine; Ducos, Jacques; Pageaux, Georges-Philippe; Reynes, Jacques; Van de Perre, Philippe; Tuaillon, Edouard

    2016-01-01

    Background Treatment of hepatitis C virus (HCV) infection based on peginterferon-α (pegIFNα) and ribavirin induces important changes in cytokine release and T cell activation. Objective Immune response to pegIFNα-ribavirin therapy was explored in patients coinfected by HCV and HIV. Methods Concentrations of 25 cytokines and CD8+ T cell activation were monitored in HCV/HIV coinfected patients classified as sustained virological responders (SVR, n=19) and non-responders (NR, n=11). Results High pretreatment concentrations of IP-10 (CXCL-10) and MCP-1 (CCL-2) were associated with a poor anti-HCV response. PegIFNα-ribavirin therapy increased CD8+ T cell activation and induced significant changes in levels of eleven cytokines related to both Th1 and Th2 responses in SVR (IL-1β, IL-1RA, IL-4, IL-5, IL-6, IL-7, IL-12p40/70, IL-13, IP-10, eotaxin, MCP-1) but of only six cytokines in NR (IL-1β, IL-2, IL-5, IL-12p40/70, IL-13, eotaxin). The highest rise in MIP-1β and MCP-1 levels was observed four weeks after anti-HCV treatment initiation in SVR compared to NR (p=0.002 and p=0.03, respectively), whereas a decrease in IL-8 concentration was associated with treatment failure (p= 0.052). Conclusions Higher and broader cytokine responses to pegIFNα-ribavirin therapy were observed in SVR patients compared to NR. Changes in IL-8, MIP-1β, and MCP-1 serum concentrations may be associated with efficacy of pegIFNα- and ribavirin-based therapies in patients coinfected by HCV and HIV. PMID:26740864

  7. Diagnostic accuracy of the genotype MTBDRsl assay for rapid diagnosis of extensively drug-resistant tuberculosis in HIV-coinfected patients.

    PubMed

    Kontsevaya, Irina; Ignatyeva, Olga; Nikolayevskyy, Vladyslav; Balabanova, Yanina; Kovalyov, Alexander; Kritsky, Andrey; Matskevich, Olesya; Drobniewski, Francis

    2013-01-01

    The Russian Federation is a high-tuberculosis (TB)-burden country with high rates of Mycobacterium tuberculosis multidrug resistance (MDR) and extensive drug resistance (XDR), especially in HIV-coinfected patients. Rapid and reliable diagnosis for detection of resistance to second-line drugs is vital for adequate patient management. We evaluated the performance of the GenoType MTBDRsl (Hain Lifescience GmbH, Nehren, Germany) assay on smear-positive sputum specimens obtained from 90 HIV-infected MDR TB patients from Russia. Test interpretability was over 98%. Specificity was over 86% for all drugs, while sensitivity varied, being the highest (71.4%) for capreomycin and lowest (9.4%) for kanamycin, probably due to the presence of mutations in the eis gene. The sensitivity of detection of XDR TB was 13.6%, increasing to 42.9% if kanamycin (not commonly used in Western Europe) was excluded. The assay is a highly specific screening tool for XDR detection in direct specimens from HIV-coinfected TB patients but cannot be used to rule out XDR TB. PMID:23152552

  8. Evolution of hepatitis C virus in HIV coinfected patients under antiretroviral therapy.

    PubMed

    Sede, Mariano; Parra, Micaela; Manrique, Julieta M; Laufer, Natalia; Jones, Leandro R; Quarleri, Jorge

    2016-09-01

    Five patients (P) were followed-up for an average of 7.73years after highly active antiretroviral therapy (HAART) initiation. Patients' immune and virological status were determined by periodical CD4+T-cell counts and HIV and HCV viral load. HCV populations were studied using longitudinal high throughput sequence data obtained in parallel by virological and immunological parameters. Two patients (P7, P28) with sub-optimal responses to HAART presented HCV viral loads significantly higher than those recorded for two patients (P1, P18) that achieved good responses to HAART. Interestingly, HCV populations from P7 and P28 displayed a stable phylogenetic structure, whereas HCV populations from P1 and P18showeda significant increase in their phylogenetic structure, followed by a decrease after achieving acceptable CD4+T-cell counts (>500 cell/μl). The fifth patient (P25) presented high HCV viral loads, preserved CD4+T-cell counts from baseline and all along the follow-up, and displayed a constant viral phylogenetic structure. These results strongly suggest that HAART-induced immune recovery induces a decrease in HCV viral load and an increase in the HCV population phylogenetic structure likely reflecting the virus diversification in response to the afresh immune response. The relatively low HCV viral load observed in the HAART responder patients suggests that once HCV is adapted it reaches a maximum number of haplotypes higher than that achieved during the initial stages of the immune response as inferred from the two recovering patients. Future studies using larger number of patients are needed to corroborate these hypotheses. PMID:27234841

  9. Evolution of hepatitis C virus in HIV coinfected patients under antiretroviral therapy.

    PubMed

    Sede, Mariano; Parra, Micaela; Manrique, Julieta M; Laufer, Natalia; Jones, Leandro R; Quarleri, Jorge

    2016-09-01

    Five patients (P) were followed-up for an average of 7.73years after highly active antiretroviral therapy (HAART) initiation. Patients' immune and virological status were determined by periodical CD4+T-cell counts and HIV and HCV viral load. HCV populations were studied using longitudinal high throughput sequence data obtained in parallel by virological and immunological parameters. Two patients (P7, P28) with sub-optimal responses to HAART presented HCV viral loads significantly higher than those recorded for two patients (P1, P18) that achieved good responses to HAART. Interestingly, HCV populations from P7 and P28 displayed a stable phylogenetic structure, whereas HCV populations from P1 and P18showeda significant increase in their phylogenetic structure, followed by a decrease after achieving acceptable CD4+T-cell counts (>500 cell/μl). The fifth patient (P25) presented high HCV viral loads, preserved CD4+T-cell counts from baseline and all along the follow-up, and displayed a constant viral phylogenetic structure. These results strongly suggest that HAART-induced immune recovery induces a decrease in HCV viral load and an increase in the HCV population phylogenetic structure likely reflecting the virus diversification in response to the afresh immune response. The relatively low HCV viral load observed in the HAART responder patients suggests that once HCV is adapted it reaches a maximum number of haplotypes higher than that achieved during the initial stages of the immune response as inferred from the two recovering patients. Future studies using larger number of patients are needed to corroborate these hypotheses.

  10. Treatment of Genotype 1 HCV Infection in the HIV Coinfected Patient in 2014

    PubMed Central

    Chastain, Cody A.; Naggie, Susanna

    2016-01-01

    Hepatitis C (HCV) coinfection is the leading cause of liver-related morbidity and is a leading cause of mortality in human immunodeficiency virus (HIV)-infected individuals in the antiretroviral therapy era. Direct-acting antiviral (DAA) therapies are transforming how HCV is treated with significant improvements in efficacy and tolerability. In this article, DAA agents expected to be available in 2014 are reviewed, including telaprevir, boceprevir, sofosbuvir, simeprevir, faldaprevir, and daclatasvir. Available data regarding clinical efficacy, adverse effects, and drug interactions in HIV-HCV coinfection are discussed. The management of adverse effects of HCV therapy and treatment considerations in patients with cirrhosis are also reviewed. PMID:24272069

  11. Phylogenetic and similarity analysis of HTLV-1 isolates from HIV-coinfected patients from the south and southeast regions of Brazil.

    PubMed

    Magri, Mariana Cavalheiro; Brigido, Luis Fernando de Macedo; Rodrigues, Rosangela; Morimoto, Helena Kaminami; Ferreira, João Leandro de Paula; Caterino-de-Araujo, Adele

    2012-01-01

    HTLV-1 is endemic in Brazil and HIV/HTLV-1 coinfection has been detected, mostly in the northeast region. Cosmopolitan HTLV-1a is the main subtype that circulates in Brazil. This study characterized 17 HTLV-1 isolates from HIV coinfected patients of southern (n=7) and southeastern (n=10) Brazil. HTLV-1 provirus DNA was amplified by nested PCR (env and LTR) and sequenced. Env sequences (705 bp) from 15 isolates and LTR sequences (731 bp) from 17 isolates showed 99.5% and 98.8% similarity among sequences, respectively. Comparing these sequences with ATK (HTLV-1a) and Mel5 (HTLV-1c) prototypes, similarities of 99% and 97.4%, respectively, for env and LTR with ATK, and 91.6% and 90.3% with Mel5, were detected. Phylogenetic analysis showed that all sequences belonged to the transcontinental subgroup A of the Cosmopolitan subtype, clustering in two Latin American clusters.

  12. Major Challenges in Clinical Management of TB/HIV Coinfected Patients in Eastern Europe Compared with Western Europe and Latin America

    PubMed Central

    Efsen, Anne Marie W.; Schultze, Anna; Post, Frank A.; Panteleev, Alexander; Furrer, Hansjakob; Miller, Robert F.; Losso, Marcelo H.; Toibaro, Javier; Skrahin, Aliaksandr; Miro, Jose M.; Caylà, Joan A.; Girardi, Enrico; Bruyand, Mathias; Obel, Niels; Podlekareva, Daria N.; Lundgren, Jens D.; Mocroft, Amanda; Kirk, Ole

    2015-01-01

    Objectives Rates of TB/HIV coinfection and multi-drug resistant (MDR)-TB are increasing in Eastern Europe (EE). We aimed to study clinical characteristics, factors associated with MDR-TB and predicted activity of empiric anti-TB treatment at time of TB diagnosis among TB/HIV coinfected patients in EE, Western Europe (WE) and Latin America (LA). Design and Methods Between January 1, 2011, and December 31, 2013, 1413 TB/HIV patients (62 clinics in 19 countries in EE, WE, Southern Europe (SE), and LA) were enrolled. Results Significant differences were observed between EE (N = 844), WE (N = 152), SE (N = 164), and LA (N = 253) in the proportion of patients with a definite TB diagnosis (47%, 71%, 72% and 40%, p<0.0001), MDR-TB (40%, 5%, 3% and 15%, p<0.0001), and use of combination antiretroviral therapy (cART) (17%, 40%, 44% and 35%, p<0.0001). Injecting drug use (adjusted OR (aOR) = 2.03 (95% CI 1.00–4.09), prior anti-TB treatment (3.42 (1.88–6.22)), and living in EE (7.19 (3.28–15.78)) were associated with MDR-TB. Among 585 patients with drug susceptibility test (DST) results, the empiric (i.e. without knowledge of the DST results) anti-TB treatment included ≥3 active drugs in 66% of participants in EE compared with 90–96% in other regions (p<0.0001). Conclusions In EE, TB/HIV patients were less likely to receive a definite TB diagnosis, more likely to house MDR-TB and commonly received empiric anti-TB treatment with reduced activity. Improved management of TB/HIV patients in EE requires better access to TB diagnostics including DSTs, empiric anti-TB therapy directed at both susceptible and MDR-TB, and more widespread use of cART. PMID:26716686

  13. Phylogenetic and Similarity Analysis of HTLV-1 Isolates from HIV-Coinfected Patients from the South and Southeast Regions of Brazil

    PubMed Central

    Magri, Mariana Cavalheiro; de Macedo Brigido, Luis Fernando; Rodrigues, Rosangela; Morimoto, Helena Kaminami; de Paula Ferreira, João Leandro

    2012-01-01

    Abstract HTLV-1 is endemic in Brazil and HIV/HTLV-1 coinfection has been detected, mostly in the northeast region. Cosmopolitan HTLV-1a is the main subtype that circulates in Brazil. This study characterized 17 HTLV-1 isolates from HIV coinfected patients of southern (n=7) and southeastern (n=10) Brazil. HTLV-1 provirus DNA was amplified by nested PCR (env and LTR) and sequenced. Env sequences (705 bp) from 15 isolates and LTR sequences (731 bp) from 17 isolates showed 99.5% and 98.8% similarity among sequences, respectively. Comparing these sequences with ATK (HTLV-1a) and Mel5 (HTLV-1c) prototypes, similarities of 99% and 97.4%, respectively, for env and LTR with ATK, and 91.6% and 90.3% with Mel5, were detected. Phylogenetic analysis showed that all sequences belonged to the transcontinental subgroup A of the Cosmopolitan subtype, clustering in two Latin American clusters. PMID:21591992

  14. Influence of IL28B Polymorphisms on Response to a Lower-Than-Standard Dose peg-IFN-α 2a for Genotype 3 Chronic Hepatitis C in HIV-Coinfected Patients

    PubMed Central

    López-Cortés, Luis F.; Ruiz-Valderas, Rosa; Jimenez-Jimenez, Luis; González-Escribano, María F.; Torres-Cornejo, Almudena; Mata, Rosario; Rivero, Antonio; Pineda, Juan A.; Marquez-Solero, Manuel; Viciana, Pompeyo

    2012-01-01

    Background Data on which to base definitive recommendations on the doses and duration of therapy for genotype 3 HCV/HIV-coinfected patients are scarce. We evaluated the efficacy of a lower peginterferon-α 2a dose and a shorter duration of therapy than the current standard of care in genotype 3 HCV/HIV-coinfected patients. Methods and Findings Pilot, open-label, single arm clinical trial which involved 58 Caucasian HCV/HIV-coinfected patients who received weekly 135 µg peginterferon-α 2a plus ribavirin 400 mg twice daily during 20 weeks after attaining undetectable viremia. The relationships between baseline patient-related variables, including IL28B genotype, plasma HCV-RNA, ribavirin dose/kg, peginterferon-α 2a and ribavirin levels with virological responses were analyzed. Only 4 patients showed lack of response and 5 patients dropped out due to adverse events related to the study medication. Overall, sustained virologic response (SVR) rates were 58.3% by intention-to-treat and 71.4% by per protocol analysis, respectively. Among patients with rapid virologic response (RVR), SVR and relapses rates were 92.6% and 7.4%, respectively. No relationships were observed between viral responses and ribavirin dose/kg, peginterferon-α 2a concentrations, ribavirin levels or rs129679860 genotype. Conclusions Weekly 135 µg pegIFN-α 2a could be as effective as the standard 180 µg dose, with a very low incidence of severe adverse events. A 24-week treatment duration appears to be appropriate in patients achieving RVR, but extending treatment up to just 20 weeks beyond negativization of viremia is associated with a high relapse rate in those patients not achieving RVR. There was no influence of IL28B genotype on the virological responses. Trial Registration: ClinicalTrials.gov NCT00553930 PMID:22235243

  15. Visceral Leishmaniasis and HIV Coinfection in the Mediterranean Region

    PubMed Central

    Monge-Maillo, Begoña; Norman, Francesca F.; Cruz, Israel; Alvar, Jorge; López-Vélez, Rogelio

    2014-01-01

    Visceral leishmaniasis is hypoendemic in Mediterranean countries, where it is caused by the flagellate protozoan Leishmania infantum. VL cases in this area account for 5%–6% of the global burden. Cases of Leishmania/HIV coinfection have been reported in the Mediterranean region, mainly in France, Italy, Portugal, and Spain. Since highly active antiretroviral therapy was introduced in 1997, a marked decrease in the number of coinfected cases in this region has been reported. The development of new diagnostic methods to accurately identify level of parasitemia and the risk of relapse is one of the main challenges in improving the treatment of coinfected patients. Clinical trials in the Mediterranean region are needed to determine the most adequate therapeutic options for Leishmania/HIV patients as well as the indications and regimes for secondary prophylaxis. This article reviews the epidemiological, diagnostic, clinical, and therapeutic aspects of Leishmania/HIV coinfection in the Mediterranean region. PMID:25144380

  16. The effect of HIV coinfection, HAART and TB treatment on cytokine/chemokine responses to Mycobacterium tuberculosis (Mtb) antigens in active TB patients and latently Mtb infected individuals.

    PubMed

    Kassa, Desta; de Jager, Wilco; Gebremichael, Gebremedhin; Alemayehu, Yodit; Ran, Leonie; Fransen, Justin; Wolday, Dawit; Messele, Tsehaynesh; Tegbaru, Belete; Ottenhoff, Tom H M; van Baarle, Debbie

    2016-01-01

    Identification of Mtb specific induced cytokine/chemokine host biomarkers could assist in developing novel diagnostic, prognostic and therapeutic tools for TB. Levels of IFN-γ, IL-2, IL-17, IL-10, IP-10 and MIP-1α were measured in supernatants of whole blood stimulated with Mtb specific fusion protein ESAT-6/CFP-10 using xMAP technology. The study groups were HIV positive TB patients (HIV(+)TB(+)), HIV negative TB patients (HIV(-)TB(+)), HIV positive tuberculin skin test positive (TST+) (HIV(+)TST(+)), HIV negative TST+ (HIV(-)TST(+)), and HIV(-)TST(-) individuals. Compared to HIV(-)TST(-), latent TB infection led to increased levels of IP-10, IFN-γ and IL-17, while levels of IL-2 and IP-10 were increased with active TB. Levels of IFN-γ, IL-17, MIP-1α, and IL-10 were increased in HIV(-)TST(+) individuals compared to HIV(-)TB(+) patients. HIV coinfection decreased the level of IFN-γ, IL-17, IP-10 and IL-2. After six months (M6) of anti-TB treatment (ATT) in HIV(-)TB(+) patients, IFN-γ, IL-10, and MIP-1α levels normalized. After M6 and M18 of ATT plus HAART in HIV(+)TB(+) patients, levels of MIP-1α and IL-10 normalized, while this was not the case for IFN-γ, IL-2, IL-17, and IP-10 levels. In HIV(+)TST(+) patients on HAART, levels of IFN-γ, IL-17, IL-10 and MIP-1α normalized, while no change in the levels of IL-2 and IP-10 were observed. In conclusion, the simultaneous measurement of IFN-γ, IL-17 and IP-10 may assist in diagnosing LTBI; IL-2 and IP-10 may assist in diagnosing active TB; while IFN-γ, IL-17, MIP-1α, and IL-10 levels could help to discriminate LTBI and active TB. In addition, IL-10 and MIP-1α levels could help to monitor responses to TB treatment and HAART.

  17. The Need to Reevaluate Nonresponding Ergonomic Patients

    NASA Technical Reports Server (NTRS)

    Scarpa, Philip J.; Field, Steven A.

    1999-01-01

    The Kennedy Space Center (KSC) Environmental Health (EH) contractor performs ergonomic evaluations under its Ergonomic Program. Any KSC employee may request one or the reviewing physician may request one for a patient during a visit to an onsite medical facility. As part of the ergonomic evaluation, recommendations are given to the patient to help reduce any ergonomic problems they experience. The recommendations, if implemented, are successful in the majority of KSC patients; however, a group of patients do not seem to improve. Those who don't improve may be identified by reevaluations, which are performed to implement maximum resolution of ergonomic problems.

  18. Visceral leishmaniasis and HIV coinfection in Latin America.

    PubMed

    Lindoso, José Angelo; Cota, Gláucia Fernandes; da Cruz, Alda Maria; Goto, Hiro; Maia-Elkhoury, Ana Nilce Silveira; Romero, Gustavo Adolfo Sierra; de Sousa-Gomes, Márcia Leite; Santos-Oliveira, Joanna Reis; Rabello, Ana

    2014-09-01

    Visceral leishmaniasis (VL) is an endemic zoonotic disease in Latin America caused by Leishmania (Leishmania) infantum, which is transmitted by sand flies from the genus Lutzomyia. VL occurs in 12 countries of Latin America, with 96% of cases reported in Brazil. Recently, an increase in VL, primarily affecting children and young adults, has been observed in urban areas of Latin America. The area in which this spread of VL is occurring overlaps regions with individuals living with HIV, the number of whom is estimated to be 1.4 million people by the World Health Organization. This overlap is suggested to be a leading cause of the increased number of reported VL-HIV coinfections. The clinical progression of HIV and L. infantum infections are both highly dependent on the specific immune response of an individual. Furthermore, the impact on the immune system caused by either pathogen and by VL-HIV coinfection can contribute to an accelerated progression of the diseases. Clinical presentation of VL in HIV positive patients is similar to patients without HIV, with symptoms characterized by fever, splenomegaly, and hepatomegaly, but diarrhea appears to be more common in coinfected patients. In addition, VL relapses are higher in coinfected patients, affecting 10% to 56.5% of cases and with a lethality ranging from 8.7% to 23.5% in Latin America, depending on the study. With regards to the diagnosis of VL, parasitological tests of bone marrow aspirates have proven to be the most sensitive test in HIV-infected patients. Serologic tests have demonstrated a variable sensitivity according to the method and antigens used, with the standard tests used for diagnosing VL in Latin America displaying lower sensitivity. For this review, few articles were identified that related to VL-HIV coinfections and originated from Latin America, highlighting the need for improving research within the regions most greatly affected. We strongly support the formation of a Latin American network for

  19. Leishmaniasis–HIV coinfection: current challenges

    PubMed Central

    Lindoso, José Angelo Lauletta; Cunha, Mirella Alves; Queiroz, Igor Thiago; Moreira, Carlos Henrique Valente

    2016-01-01

    Leishmaniasis – human immunodeficiency virus (HIV) coinfection can manifest itself as tegumentary or visceral leishmaniasis. Almost 35 countries have reported autochthonous coinfections. Visceral leishmaniasis is more frequently described. However, usual and unusual manifestations of tegumentary leishmaniasis have been reported mainly in the Americas, but the real prevalence of Leishmania infection in HIV-infected patients is not clear. Regarding the clinical manifestations, there are some reports showing unusual manifestations in visceral leishmaniasis and tegumentary leishmaniasis in HIV-infected patients; yet, the usual manifestations are more frequent. Leishmaniasis diagnosis relies on clinical methods, but serological tests are used to diagnose visceral leishmaniasis despite them having a low sensitivity to tegumentary leishmaniasis. The search for the parasite is used to diagnose both visceral leishmaniasis and tegumentary leishmaniasis. Nevertheless, in HIV-infected patients, the sensitivity of serology is very low. Drugs available to treat leishmaniasis are more restricted and cause severe side effects. Furthermore, in HIV-infected patients, these side effects are more prominent and relapses and lethality are more recurrent. In this article, we discuss the current challenges of tegumentary leishmaniasis and visceral leishmaniasis–HIV infection, focusing mainly on the clinical manifestations, diagnosis, and treatment of leishmaniasis. PMID:27785103

  20. Comparison between histopathologic features of leprosy in reaction lesions in HIV coinfected and non-coinfected patients*

    PubMed Central

    Pires, Carla Andréa Avelar; de Miranda, Mario Fernando Ribeiro; Bittencourt, Maraya de Jesus Semblano; de Brito, Arival Cardoso; Xavier, Marília Brasil

    2015-01-01

    BACKGROUND Leprosy and HIV are diseases that have a major impact on public health in Brazil. Patients coinfected with both diseases, appear to be at higher risk to develop leprosy reactions. OBJECTIVE The aim of this study is to describe the histopathological aspects of cutaneous lesions during reactional states in a group of patients with HIV-leprosy coinfection, compared to patients with leprosy, without coinfection. METHODS Two groups were established: group 1 comprised of 40 patients coinfected with HIV-leprosy; group 2, comprised of 107 patients with leprosy only. Patients presenting reactional states of leprosy had their lesions biopsied and comparatively evaluated. RESULTS Reversal reaction was the most frequent feature in both groups, with dermis edema as the most common histopathological finding. Giant cells were seen in all group 1 histopathological examinations. Dermis edema was the most common finding in patients with erythema nodosum leprosum. CONCLUSION Few histopathological differences were found in both groups, with reversal reaction as the most significant one, although this fact should be analyzed considering the predominant BT clinical form in the coinfected group and BB form in the group without HIV. Larger prospective studies in patients with HIV-leprosy coinfection are needed to confirm and broaden these results. PMID:25672296

  1. Spontaneous reactivation of hepatitis B virus replication in an HIV coinfected patient with isolated anti-Hepatitis B core antibodies

    PubMed Central

    2014-01-01

    Co-infections with HBV (hepatitis B virus) occur in HIV (human immunodeficiency virus) patients frequently. It has been reported that an effective treatment of HIV can also lead to a suppression of HBV and to anti-HBs seroconversion in HBV-infected patients. Here, we report a spontaneous reactivation of HBV replication in an HIV-infected patient with anti-HBc as the only marker of chronic HBV infection. The patient was known to be coinfected with HIV and HBV for years and the HBV DNA was measured repeatedly at low levels. A significant increase of HBV DNA up to 1.7x107 IU/ml was found accompanied with clinical symptoms of hepatitis. Multiple mutations occurred in the S gene during the flare-up of HBV as shown by sequencing, including I103T, K122R, M133I, F134V, D144E, V164E and L175S. Anti-HIV/HBV treatment led to a resolution of symptoms and to a decrease in the HIV RNA and HBV DNA viral load. It is possible that the accumulated mutations during HBV replication were selected and responsible for the reactivation. PMID:24444423

  2. Deconvoluting the Composition of Low-Frequency Hepatitis C Viral Quasispecies: Comparison of Genotypes and NS3 Resistance-Associated Variants between HCV/HIV Coinfected Hemophiliacs and HCV Monoinfected Patients in Japan

    PubMed Central

    Ogishi, Masato; Yotsuyanagi, Hiroshi; Tsutsumi, Takeya; Gatanaga, Hiroyuki; Ode, Hirotaka; Sugiura, Wataru; Moriya, Kyoji; Oka, Shinichi; Kimura, Satoshi; Koike, Kazuhiko

    2015-01-01

    Pre-existing low-frequency resistance-associated variants (RAVs) may jeopardize successful sustained virological responses (SVR) to HCV treatment with direct-acting antivirals (DAAs). However, the potential impact of low-frequency (∼0.1%) mutations, concatenated mutations (haplotypes), and their association with genotypes (Gts) on the treatment outcome has not yet been elucidated, most probably owing to the difficulty in detecting pre-existing minor haplotypes with sufficient length and accuracy. Herein, we characterize a methodological framework based on Illumina MiSeq next-generation sequencing (NGS) coupled with bioinformatics of quasispecies reconstruction (QSR) to realize highly accurate variant calling and genotype-haplotype detection. The core-to-NS3 protease coding sequences in 10 HCV monoinfected patients, 5 of whom had a history of blood transfusion, and 11 HCV/HIV coinfected patients with hemophilia, were studied. Simulation experiments showed that, for minor variants constituting more than 1%, our framework achieved a positive predictive value (PPV) of 100% and sensitivities of 91.7–100% for genotyping and 80.6% for RAV screening. Genotyping analysis indicated the prevalence of dominant Gt1a infection in coinfected patients (6/11 vs 0/10, p = 0.01). For clinical samples, minor genotype overlapping infection was prevalent in HCV/HIV coinfected hemophiliacs (10/11) and patients who experienced whole-blood transfusion (4/5) but none in patients without exposure to blood (0/5). As for RAV screening, the Q80K/R and S122K/R variants were particularly prevalent among minor RAVs observed, detected in 12/21 and 6/21 cases, respectively. Q80K was detected only in coinfected patients, whereas Q80R was predominantly detected in monoinfected patients (1/11 vs 7/10, p < 0.01). Multivariate interdependence analysis revealed the previously unrecognized prevalence of Gt1b-Q80K, in HCV/HIV coinfected hemophiliacs [Odds ratio = 13.4 (3.48–51.9), p < 0.01]. Our study

  3. Impact of lopinavir-ritonavir or nevirapine on bedaquiline exposures and potential implications for patients with tuberculosis-HIV coinfection.

    PubMed

    Svensson, Elin M; Dooley, Kelly E; Karlsson, Mats O

    2014-11-01

    Concomitant treatment of tuberculosis (TB) and HIV is recommended and improves outcomes. Bedaquiline is a novel drug for the treatment of multidrug-resistant (MDR) TB; combined use with antiretroviral drugs, nevirapine, or ritonavir-boosted lopinavir (LPV/r) is anticipated, but no clinical data from coinfected patients are available. Plasma concentrations of bedaquiline and its M2 metabolite after single doses were obtained from interaction studies with nevirapine or LPV/r in healthy volunteers. The antiretrovirals' effects on bedaquiline and M2 pharmacokinetics were assessed by nonlinear mixed-effects modeling. Potential dose adjustments were evaluated with simulations. No significant effects of nevirapine on bedaquiline pharmacokinetics were identified. LPV/r decreased bedaquiline and M2 clearances to 35% (relative standard error [RSE], 9.2%) and 58% (RSE, 8.4%), respectively, of those without comedication. As almost 3-fold (bedaquiline) and 2-fold (M2) increases in exposures during chronic treatment with LPV/r are expected, dose adjustments are suggested for evaluation. Efficacious, safe bedaquiline dosing for MDR-TB patients receiving antiretrovirals is important. Modeling results suggest that bedaquiline can be coadministered with nevirapine without dose adjustments. The predicted elevation of bedaquiline and M2 levels during LPV/r coadministration may be a safety concern, and careful monitoring is recommended. Further data are being collected in coinfected patients to determine whether dose adjustments are needed. (These studies have been registered at ClinicalTrials.gov under registration numbers NCT00828529 [study C110] and NCT00910806 [study C117].).

  4. Impact of Lopinavir-Ritonavir or Nevirapine on Bedaquiline Exposures and Potential Implications for Patients with Tuberculosis-HIV Coinfection

    PubMed Central

    Dooley, Kelly E.; Karlsson, Mats O.

    2014-01-01

    Concomitant treatment of tuberculosis (TB) and HIV is recommended and improves outcomes. Bedaquiline is a novel drug for the treatment of multidrug-resistant (MDR) TB; combined use with antiretroviral drugs, nevirapine, or ritonavir-boosted lopinavir (LPV/r) is anticipated, but no clinical data from coinfected patients are available. Plasma concentrations of bedaquiline and its M2 metabolite after single doses were obtained from interaction studies with nevirapine or LPV/r in healthy volunteers. The antiretrovirals' effects on bedaquiline and M2 pharmacokinetics were assessed by nonlinear mixed-effects modeling. Potential dose adjustments were evaluated with simulations. No significant effects of nevirapine on bedaquiline pharmacokinetics were identified. LPV/r decreased bedaquiline and M2 clearances to 35% (relative standard error [RSE], 9.2%) and 58% (RSE, 8.4%), respectively, of those without comedication. As almost 3-fold (bedaquiline) and 2-fold (M2) increases in exposures during chronic treatment with LPV/r are expected, dose adjustments are suggested for evaluation. Efficacious, safe bedaquiline dosing for MDR-TB patients receiving antiretrovirals is important. Modeling results suggest that bedaquiline can be coadministered with nevirapine without dose adjustments. The predicted elevation of bedaquiline and M2 levels during LPV/r coadministration may be a safety concern, and careful monitoring is recommended. Further data are being collected in coinfected patients to determine whether dose adjustments are needed. (These studies have been registered at ClinicalTrials.gov under registration numbers NCT00828529 [study C110] and NCT00910806 [study C117].) PMID:25114140

  5. Tax Gene Characterization of Human T-Lymphotropic Virus Type 1 Strains from Brazilian HIV-Coinfected Patients

    PubMed Central

    Magri, Mariana Cavalheiro; Brigido, Luis Fernando de Macedo; Rodrigues, Rosangela; Morimoto, Helena Kaminami

    2012-01-01

    Abstract The tax gene of human T-lymphotropic virus type 1 (HTLV-1) diverges among isolates according to geographic regions and has been classified into two genotypes: taxA and taxB. In Brazil, taxA is the most prevalent genotype in symptomatic and asymptomatic carriers. Few studies have been conducted in HIV-infected patients. The present study characterized the tax gene (1059 bp) in 13 Brazilian HIV-1/HTLV-1-coinfected patients from the south and southeast regions. The results confirmed the transcontinental HTLV-1 subgroup A of the Cosmopolitan subtype and showed high nucleotide similarity both among Brazilian sequences and in relation to the ATK prototype (99.5% and 99.2%, respectively). Six nucleotide substitutions were highly conserved among isolates, ranging from 76.9% to 100%: C7401T, T7914C, C7920T, C7982T, G8231A, and A8367C. The presence of the Brazilian molecular signature of genotype taxA was confirmed in all of the isolates, and they clustered into two Latin American clusters, which confirms the double introduction of HTLV-1 in Brazil. PMID:22449200

  6. Tax gene characterization of human T-lymphotropic virus type 1 strains from Brazilian HIV-coinfected patients.

    PubMed

    Magri, Mariana Cavalheiro; Brigido, Luis Fernando de Macedo; Rodrigues, Rosangela; Morimoto, Helena Kaminami; Caterino-de-Araujo, Adele

    2012-12-01

    The tax gene of human T-lymphotropic virus type 1 (HTLV-1) diverges among isolates according to geographic regions and has been classified into two genotypes: taxA and taxB. In Brazil, taxA is the most prevalent genotype in symptomatic and asymptomatic carriers. Few studies have been conducted in HIV-infected patients. The present study characterized the tax gene (1059 bp) in 13 Brazilian HIV-1/HTLV-1-coinfected patients from the south and southeast regions. The results confirmed the transcontinental HTLV-1 subgroup A of the Cosmopolitan subtype and showed high nucleotide similarity both among Brazilian sequences and in relation to the ATK prototype (99.5% and 99.2%, respectively). Six nucleotide substitutions were highly conserved among isolates, ranging from 76.9% to 100%: C7401T, T7914C, C7920T, C7982T, G8231A, and A8367C. The presence of the Brazilian molecular signature of genotype taxA was confirmed in all of the isolates, and they clustered into two Latin American clusters, which confirms the double introduction of HTLV-1 in Brazil.

  7. Frequent injection cocaine use increases the risk of renal impairment among hepatitis C and HIV coinfected patients

    PubMed Central

    Rossi, Carmine; Cox, Joseph; Cooper, Curtis; Martel-Laferrière, Valérie; Walmsley, Sharon; Gill, John; Sapir-Pichhadze, Ruth; Moodie, Erica E.M.; Klein, Marina B.

    2016-01-01

    Objective: To examine the association between injection cocaine use, hepatitis C virus (HCV) infection, and chronic renal impairment (CRI). Design: Prospective observational cohort study of HIV–HCV coinfected patients. Methods: Data from 1129 participants in the Canadian Co-Infection Cohort with baseline and follow-up serum creatinine measurements between 2003 and 2014 were analyzed. Prevalent and incident cohorts were created to examine the association between self-reported past, current, and cumulative cocaine use and chronic HCV with CRI. CRI was defined as an estimated glomerular filtration rate below 70 ml/min per 1.73 m2. Multivariate logistic regression was used to calculate odds ratios, and discrete-time proportional-hazards models were used to calculate hazard ratios for cocaine use, in the two respective cohorts, adjusted for HCV RNA and important demographic, HIV disease stage, and comorbidity confounders. Results: Eighty-seven participants (8%) had prevalent CRI. Past injection cocaine use was associated with a two-fold greater risk of prevalent CRI [odds ratio 2.03, 95% confidence interval (CI) 0.96, 4.32]. During follow-up, 126 of 1061 participants (12%) developed incident CRI (31 per 1000 person-years). Compared to nonusers, heavy (≥ 3 days/week) and frequent injection cocaine users (≥75% of follow-up time) experienced more rapid progression to CRI (hazard ratio 2.65, 95% CI 1.35, 5.21; and hazard ratio 1.82, 95% CI 1.07, 3.07, respectively). There was no association between chronic HCV and CRI in either cohort. Conclusion: After accounting for HCV RNA, frequent and cumulative injection cocaine abuse was associated with CRI progression and should be taken into consideration when evaluating impaired renal function in HIV–HCV coinfection. PMID:26859371

  8. Predictive factors of HTLV1-HIV coinfections in French Guiana.

    PubMed

    Gouhier, Elise; Gaubert-Maréchal, Emilie; Abboud, Philippe; Couppié, Pierre; Nacher, Mathieu

    2013-09-01

    French Guiana, the French territory most affected by human immunodeficiency virus (HIV) (1.3% of pregnant women), is also endemic for human T lymphotropic virus 1 (HTLV1). The objective of this study was to determine if the HTLV1/HIV coinfected patients had particular characteristics. All HIV-infected patients having a computerized medical file containing an HTLV1 serology were included: there were 1,333 HIV monoinfections and 76 HTLV1/VIH coinfections. The prevalence of HTLV1/HIV coinfections was 5.39%. Women (odds ratio [OR] = 1.91[1.13-3.24]), subjects > 40 years of age, and patients of Surinamese origin (OR = 2.65 [1.25-5.61]) were overrepresented among the coinfected. CD4 count at the time of diagnosis and viral loads were higher among coinfected patients. The clinical stage was not significantly different between the two groups. The number of CD4 cells was not higher among the coinfected, unlike most reports from the literature. Prevalence of HTLV1 among HIV-infected patients is high in French Guiana, and physicians seem to omit the prescription of serology for this potentially serious coinfection.

  9. Prevalence of malaria and HIV coinfection and influence of HIV infection on malaria disease severity in population residing in malaria endemic area along the Thai-Myanmar border.

    PubMed

    Rattanapunya, Siwalee; Kuesap, Jiraporn; Chaijaroenkul, Wanna; Rueangweerayut, Ronnatrai; Na-Bangchang, Kesara

    2015-05-01

    The objective of the study is to investigate the prevalence of malaria and HIV coinfection and assess the effect of HIV coinfection on malaria disease severity in malaria patients from the endemic area of Thailand along the Thai-Myanmar border. Blood samples were collected from a total of 867 patients with malaria (all species and severity) who attended Mae Tao clinic for migrant workers, Tak Province during 2005-2007 (439 samples), 2008-2010 (273 samples), and 2011-2013 (155 samples). The average prevalence rate of malaria and HIV coinfected cases in this malaria endemic area of the country during the three periods was 1.85%. HIV coinfection was observed only in samples with mono-infection of Plasmodium falciparum or Plasmodium vivax, with similar proportions (0.81 vs. 1.04%). Patients' admission parasite density, an indicator of disease severity, was significantly higher in cases with HIV coinfection observed during 2008-2010. Anemia was found at a significantly higher frequency in patients coinfected with malaria and HIV observed during 2005-2007 compared with those infected with malaria alone. No association was observed between malaria and HIV coinfection and gender, and infected malaria species during the three observation periods. Patients with malaria and HIV coinfection had a significantly lower hemoglobin level than those with malaria infection alone. In conclusion, the prevalence of malaria and HIV coinfection in population of the malaria endemic area along the Thai-Myanmar border is low. HIV coinfection tended to increase parasite density, an indicator of malaria disease severity.

  10. Diagnosis, Clinical Presentation, and In-Hospital Mortality of Severe Malaria in HIV-Coinfected Children and Adults in Mozambique

    PubMed Central

    Hendriksen, Ilse C. E.; Ferro, Josefo; Montoya, Pablo; Chhaganlal, Kajal D.; Seni, Amir; Gomes, Ermelinda; Silamut, Kamolrat; Lee, Sue J.; Lucas, Marcelino; Chotivanich, Kesinee; Fanello, Caterina I.; Day, Nicholas P. J.; White, Nicholas J.; von Seidlein, Lorenz; Dondorp, Arjen M.

    2012-01-01

    Background. Severe falciparum malaria with human immunodeficiency virus (HIV) coinfection is common in settings with a high prevalence of both diseases, but there is little information on whether HIV affects the clinical presentation and outcome of severe malaria. Methods. HIV status was assessed prospectively in hospitalized parasitemic adults and children with severe malaria in Beira, Mozambique, as part of a clinical trial comparing parenteral artesunate versus quinine (ISRCTN50258054). Clinical signs, comorbidity, complications, and disease outcome were compared according to HIV status. Results. HIV-1 seroprevalence was 11% (74/655) in children under 15 years and 72% (49/68) in adults with severe malaria. Children with HIV coinfection presented with more severe acidosis, anemia, and respiratory distress, and higher peripheral blood parasitemia and plasma Plasmodium falciparum histidine-rich protein-2 (PfHRP2). During hospitalization, deterioration in coma score, convulsions, respiratory distress, and pneumonia were more common in HIV-coinfected children, and mortality was 26% (19/74) versus 9% (53/581) in uninfected children (P < .001). In an age- and antimalarial treatment–adjusted logistic regression model, significant, independent predictors for death were renal impairment, acidosis, parasitemia, and plasma PfHRP2 concentration. Conclusions. Severe malaria in HIV-coinfected patients presents with higher parasite burden, more complications, and comorbidity, and carries a higher case fatality rate. Early identification of HIV coinfection is important for the clinical management of severe malaria. PMID:22752514

  11. Risk factors for TB and HIV coinfection in Scotland, 2001 to 2010.

    PubMed

    McDonald, E; Smith-Palmer, A; Wallace, L A; Blatchford, O

    2015-03-19

    The number of patients with tuberculosis (TB) increased steadily in Scotland between 2005 and 2010. Human immunodeficiency virus (HIV) infection has been a contributory factor to increases in TB in a number of comparable industrialised countries. This study investigated the extent of, and risk factors for, TB and HIV coinfection in Scotland from 2001 to 2010. Patients with TB in the national TB database were linked to those in the national HIV database using probabilistic data linkage. Patient records were anonymised to maintain confidentiality. From 2001 to 2010, 106/4, 097 (2.6%, 95% CI: 2.1 to 3.1) TB patients matched with HIV patients, equating to a 10-year incidence of 2.1 cases per million population. Patients with both TB and HIV were more often born outside the United Kingdom,were of black African ethnicity, had refugee status and had extra-thoracic lymph node involvement or cryptic/disseminated TB disease. Individuals with TB and HIV coinfection were younger and symptomatic for a shorter time before their diagnosis of TB, compared with TB patients without HIV. TB and HIV coinfection was relatively uncommon in Scotland in the study period. Clinicians should recognise the potential for HIV infection among TB patients and the importance of offering an HIV test to all TB patients.

  12. Generalized Linear Model (GLM) framework for the association of host variables and viral strains with liver fibrosis in HCV/HIV coinfected patients.

    PubMed

    Matas, Marina; Picornell, Antònia; Cifuentes, Carmen; Payeras, Antoni; Bassa, Antoni; Homar, Francesc; González-Candelas, Fernando; López-Labrador, F Xavier; Moya, Andrés; Ramon, Maria M; Castro, José A

    2013-01-01

    Chronic hepatitis C virus (HCV) infection is the main cause of advanced and end-stage liver disease world-wide, and an important factor of morbidity and mortality in Human Immunodeficiency virus-1 (HIV-1) co-infected individuals. Whereas the genetic variability of HCV has been studied extensively in monoinfected patients, comprehensive analyses of both patient and virus characteristics are still scarce in HCV/HIV co-infection. In order to find correlates for liver damage, we sought to analyze demographic, epidemiological and clinical features of HCV/HIV co-infected patients along with the genetic makeup of HCV (viral subtypes and lineage studied by nucleotide sequencing and phylogenetic analysis of the NS5B region). We used the Generalized Linear Model (GLM) methodology in order to integrate data from the virus and the infected host to find predictors for liver damage. The degree of liver disease was evaluated indirectly by means of two indexes (APRI and FIB-4) and accounting for the time since infection, to estimate fibrosis progression rates. Our analyses identified a reduced number of variables (both from the virus and the host) implicated in liver damage, which included the stage of HIV infection, levels of gamma-glutamil transferase and cholesterol, and some distinct HCV phylogenetic clades. PMID:23174528

  13. Peginterferon and ribavirin for treatment of recurrent hepatitis C disease in HCV-HIV coinfected liver transplant recipients.

    PubMed

    Terrault, N; Reddy, K R; Poordad, F; Curry, M; Schiano, T; Johl, J; Shaikh, O; Dove, L; Shetty, K; Millis, M; Schiff, E; Regenstein, F; Barnes, D; Barin, B; Peters, M; Roland, M; Stock, P

    2014-05-01

    Achievement of a sustained virologic response (SVR) with antiviral therapy significantly improves graft survival in hepatitis C virus (HCV) monoinfected liver transplant (LT) patients. Risks and benefits of HCV therapy in HCV-human immunodeficiency virus (HIV) coinfected LT recipients are not well established. Among 89 HCV-HIV LT recipients in the HIVTR cohort, 39 (23% Black, 79% genotype 1, 83% fibrosis stage ≤ 1) were treated with peginterferon-a2a or a2b plus ribavirin for a median 363 days (14-1373). On intent-to-treat basis, 22% (95% CI: 10-39) and 14% (95% CI: 5-30) achieved an end-of-treatment response (EOTR) and SVR, respectively. By per-protocol analysis (completed 48 weeks of therapy ± dose reductions), 42% and 26% had EOTR and SVR, respectively. Severe adverse events occurred in 85%, with 26% hospitalized with infections and 13% developing acute rejection. Early discontinuations and dose reductions occurred in 38% and 82%, respectively, despite use of growth factors in 85%. Eighteen of 39 treated patients (46%) subsequently died/had graft loss, with 10 (26%) attributed to recurrent HCV. In conclusion, SVR rates are low and tolerability is poor in HCV-HIV coinfected transplant recipients treated with peginterferon and ribavirin. These results highlight the critical need for better tolerated and more efficacious HCV therapies for HCV-HIV coinfected transplant recipients.

  14. Analysis of sequences of hepatitis C virus NS5A genotype 1 in HIV-coinfected patients with a null response to nitazoxanide or peg-interferon plus ribavirin.

    PubMed

    Sede, M; Laufer, N; Ojeda, D; Gun, A; Cahn, P; Quarleri, J

    2013-09-01

    Even though new drugs have been approved for treatment of hepatitis C virus (HCV) infection, the risk of drug-drug interactions and concern about overlapping toxicities has hindered the development of studies in HIV/HCV-coinfected individuals. Traditional treatment with pegylated interferon plus ribavirin (peg-IFN + RBV) is very expensive and has a low rate of sustained virological response in coinfected patients, especially if they are infected with HCV genotype 1. Nitazoxanide (NTZ) is a drug that is being evaluated for the treatment of chronic HCV infection, both in HCV-monoinfected and HIV/HCV-coinfected patients. Understanding the NTZ resistance mechanism could allow the development of resistance to be minimized and would expand the treatment options, mainly in special populations such as HIV/HCV-coinfected patients. Similarly to IFN, NTZ increases the activity of the cellular protein kinase activated by double-stranded RNA (PKR), a key kinase in the innate antiviral response. In order to elucidate whether sequence heterogeneity in the PKR-binding domain of HCV NS5A genotype 1 could influence the antiviral activity of either NTZ monotherapy or peg-IFN + RBV, baseline and end-of-therapy plasma samples from two groups of eleven non-responder HIV/HCV-coinfected patients that had received NTZ or peg-IFN + RBV were studied. Most of the HCV NS5A sequences examined at the end of therapy did not change from the baseline, even after 30 days course of antiviral therapy. An extensive comparison of HCV NS5A genotype 1 and 4 sequences from the database with reported IFN therapy outcome was performed in order to infer their phylogenetic relationships. The HCV genotype 1 NS5A nucleotide sequences from therapy-non-responder patients were intermingled amongst those from the database, irrespective of their IFN-therapy outcome. When comparing NS5A-PKRBD amino acid sequences, significant differences were observed in genotype 4, but not in genotype 1 (p < 0.0001 and p

  15. Re-treatment of patients with hepatitis C who failed to respond (nonresponders) to previous treatment.

    PubMed

    Sharvadze, L G; Gogichaishvili, Sh Sh; Sakandelidze, Ts G; Zhamutashvili, M T; Chkhartishvili, N I

    2009-01-01

    to previous treatment was effective in relapsers. Re-treatment in non responders, partial responders and breakthrough non responders was less effective (especially in non responders). Re-treatment effectiveness was higher in HCV genotype non 1 patients in comparison with HCV genotype 1. Thus re-treatment will be considered for relapsers. For making decision on re-treatment for other nonresponders, severity of disease (advance disease) should be considered. PMID:19202222

  16. Hepatitis C Virus (HCV) NS3 sequence diversity and antiviral resistance-associated variant frequency in HCV/HIV coinfection.

    PubMed

    Jabara, Cassandra B; Hu, Fengyu; Mollan, Katie R; Williford, Sara E; Menezes, Prema; Yang, Yan; Eron, Joseph J; Fried, Michael W; Hudgens, Michael G; Jones, Corbin D; Swanstrom, Ronald; Lemon, Stanley M

    2014-10-01

    HIV coinfection accelerates disease progression in chronic hepatitis C and reduces sustained antiviral responses (SVR) to interferon-based therapy. New direct-acting antivirals (DAAs) promise higher SVR rates, but the selection of preexisting resistance-associated variants (RAVs) may lead to virologic breakthrough or relapse. Thus, pretreatment frequencies of RAVs are likely determinants of treatment outcome but typically are below levels at which the viral sequence can be accurately resolved. Moreover, it is not known how HIV coinfection influences RAV frequency. We adopted an accurate high-throughput sequencing strategy to compare nucleotide diversity in HCV NS3 protease-coding sequences in 20 monoinfected and 20 coinfected subjects with well-controlled HIV infection. Differences in mean pairwise nucleotide diversity (π), Tajima's D statistic, and Shannon entropy index suggested that the genetic diversity of HCV is reduced in coinfection. Among coinfected subjects, diversity correlated positively with increases in CD4(+) T cells on antiretroviral therapy, suggesting T cell responses are important determinants of diversity. At a median sequencing depth of 0.084%, preexisting RAVs were readily identified. Q80K, which negatively impacts clinical responses to simeprevir, was encoded by more than 99% of viral RNAs in 17 of the 40 subjects. RAVs other than Q80K were identified in 39 of 40 subjects, mostly at frequencies near 0.1%. RAV frequency did not differ significantly between monoinfected and coinfected subjects. We conclude that HCV genetic diversity is reduced in patients with well-controlled HIV infection, likely reflecting impaired T cell immunity. However, RAV frequency is not increased and should not adversely influence the outcome of DAA therapy.

  17. [Patient with testosterone deficit syndrome and erectile dysfunction non-responder to PDE-5 inhibitors].

    PubMed

    Rodríguez-Izquierdo, Marta; Martínez-Salamanca, Juan I; Moncada, Ignacio; Linares Espinós, Estefanía; del Portillo, Luis; Areche, Jennifer; Carballido, Joaquín

    2013-09-01

    Androgens play an essential role in the corporo-venous occlusive mechanism that provokes erection. Accordingly to various studies based on animal models,testosterone deficit syndrome causes an endothelial disorder in the corpora cavernosa with diminished secretion of NO, alteration of penile smooth muscle and tunica albuginea structure, and increase of the number of adipocytes within the erectile tissue, which favors fibrosis and impairs erection. All these alterations are reversible with the exogenous administration of androgens. There are not enough studies to get definitive conclusions about androgen supply improving erectile dysfunction in patients with hypogonadism. Studies have been published in which seems that exogenous testosterone could be useful in the treatment of this type of patients. Nevertheless,in most published randomized double blind studies comparing with placebo, testosterone supply does not provide greater benefit on erectile dysfunction than PDE-5 Inhibitors exclusively. All studies coincide in the need to optimize the treatment with PDE-5 Inhibitors since they do have proven to be effective for the treatment of erectile dysfunction in patients with testosterone deficit syndrome. PMID:24047632

  18. CD4+ T-cell-independent mechanisms suppress reactivation of latent tuberculosis in a macaque model of HIV coinfection.

    PubMed

    Foreman, Taylor W; Mehra, Smriti; LoBato, Denae N; Malek, Adel; Alvarez, Xavier; Golden, Nadia A; Bucşan, Allison N; Didier, Peter J; Doyle-Meyers, Lara A; Russell-Lodrigue, Kasi E; Roy, Chad J; Blanchard, James; Kuroda, Marcelo J; Lackner, Andrew A; Chan, John; Khader, Shabaana A; Jacobs, William R; Kaushal, Deepak

    2016-09-20

    The synergy between Mycobacterium tuberculosis (Mtb) and HIV in coinfected patients has profoundly impacted global mortality because of tuberculosis (TB) and AIDS. HIV significantly increases rates of reactivation of latent TB infection (LTBI) to active disease, with the decline in CD4(+) T cells believed to be the major causality. In this study, nonhuman primates were coinfected with Mtb and simian immunodeficiency virus (SIV), recapitulating human coinfection. A majority of animals exhibited rapid reactivation of Mtb replication, progressing to disseminated TB and increased SIV-associated pathology. Although a severe loss of pulmonary CD4(+) T cells was observed in all coinfected macaques, a subpopulation of the animals was still able to prevent reactivation and maintain LTBI. Investigation of pulmonary immune responses and pathology in this cohort demonstrated that increased CD8(+) memory T-cell proliferation, higher granzyme B production, and expanded B-cell follicles correlated with protection from reactivation. Our findings reveal mechanisms that control SIV- and TB-associated pathology. These CD4-independent protective immune responses warrant further studies in HIV coinfected humans able to control their TB infection. Moreover, these findings will provide insight into natural immunity to Mtb and will guide development of novel vaccine strategies and immunotherapies. PMID:27601645

  19. Hepatitis B Virus-HIV Coinfection: Forgotten but Not Gone

    PubMed Central

    Sterling, Richard K.

    2014-01-01

    Owing to shared routes of transmission and common risk factors, coinfection with hepatitis B virus (HBV) and HIV is common. As AIDS-related opportunistic infections have declined with successful antiretroviral therapy (ART), liver-related mortality has emerged as the second leading cause of death among patients infected with HIV HIV infection negatively impacts the natural history of HBV, increasing the risks for cirrhosis, hepatocellular carcinoma, and liver-related mortality. With the availability of effective antiviral therapy active against both HIV and HBV and simplified treatment algorithms, it has become easier than ever to treat coinfected patients. However, the issues of suboptimal response, incomplete viral suppression, adverse effects of long-term antiviral treatment, and potential hepatotoxicity of ART remain major challenges. PMID:27524946

  20. MRP1 and P-glycoprotein expression assays would be useful in the additional detection of treatment non-responders in CML patients without ABL1 mutation.

    PubMed

    Park, Sang Hyuk; Park, Chan-Jeoung; Kim, Dae-Young; Lee, Bo-Ra; Kim, Young Jin; Cho, Young-Uk; Jang, Seongsoo

    2015-10-01

    We evaluated the ability of the rhodamine-123 efflux assay, multidrug resistance-associated protein-1 (MRP1) expression assay and P-glycoprotein (Pgp) expression assay to discriminate chronic myelogenous leukemia (CML) patients who had failed treatment or were at risk of failure. Each assay was performed in blood samples from CML patients (n=224) treated with tyrosine kinase inhibitors, taken at diagnosis (n=14) and follow-up (n=210). Patient samples were categorized as optimal response (n=120), suboptimal response (n=54), and treatment failure (n=36). Treatment-failed patients had a significantly higher MRP1 expression (5.24% vs. 3.54%, P=0.006) and Pgp expression (5.25% vs. 3.48%, P=0.005) than responders. Both MRP1 (%) and Pgp (%) were highly specific (95.2% and 94.5%) and relatively accurate (83.0% and 82.5%) in the detection of treatment non-responders. Of treatment-failed patients, 41.2% had a positive result in at least one assay and of these patients without ABL1 kinase domain mutation, 51.9% were positive in at least one assay. However, the rhodamine-123 efflux assay failed to discriminate two patient groups. Thus, both MRP1 and Pgp expression assays could be useful for additional identification of treatment non-responders in CML patients without ABL1 mutation.

  1. Mollicutes/HIV Coinfection and the Development of AIDS: Still Far from a Definitive Response

    PubMed Central

    Lange, Leonardo

    2016-01-01

    Background. Mycoplasmas are known to cause various infections in humans, mainly in the respiratory and urogenital tracts. The different species are usually host-specific and cause diseases in well-defined sites. New species have been isolated, including those from HIV-infected persons. Summary. Its in vitro properties, combined with clinical findings, have led to the hypothesis that these microorganisms may act as cofactors of HIV in AIDS development. Even today this point of view is quite polemic among infectious disease specialists and many aspects remain to be clarified, in contrast to what happens, for instance, with HIV/Mycobacterium tuberculosis coinfection. Dozens of papers have been published covering aspects of Mollicutes/HIV coinfection, but they add little to no information about the putative contribution of Mollicutes to the evolution of AIDS. Very few researchers have devoted their efforts to trying to answer this question, which remains open. In this review, we discuss the evidences that may support this statement in the light of current knowledge in the field of mycoplasmology. PMID:27413383

  2. Insulin-like Growth Factor 1 Differentially Affects Lithium Sensitivity of Lymphoblastoid Cell Lines from Lithium Responder and Non-responder Bipolar Disorder Patients.

    PubMed

    Milanesi, Elena; Hadar, Adva; Maffioletti, Elisabetta; Werner, Haim; Shomron, Noam; Gennarelli, Massimo; Schulze, Thomas G; Costa, Marta; Del Zompo, Maria; Squassina, Alessio; Gurwitz, David

    2015-07-01

    Bipolar disorder (BD) is a chronic psychiatric illness with an unknown etiology. Lithium is considered the cornerstone in the management of BD, though about 50-60 % of patients do not respond sufficiently to chronic treatment. Insulin-like growth factor 1 (IGF1) has been identified as a candidate gene for BD susceptibility, and its low expression has been suggested as a putative biomarker for lithium unresponsiveness. In this study, we examined the in vitro effects of insulin-like growth factor 1 (IGF-1) on lithium sensitivity in lymphoblastoid cell lines (LCLs) from lithium responder (R) and non-responder (NR) bipolar patients. Moreover, we evaluated levels of microRNA let-7c, a small RNA predicted to target IGF1. We found that exogenous IGF-1 added to serum-free media increased lithium sensitivity selectively in LCLs from NR BD patients. However, no significant differences were observed when comparing let-7c expression in LCLs from R vs. NR BD patients. Our data support a key role for IGF-1 in lithium resistance/response in the treatment of bipolar disorder.

  3. St. John's Wort in patients non-responders to clopidogrel undergoing percutaneous coronary intervention: a single-center randomized open-label trial (St. John's Trial).

    PubMed

    Trana, Catalina; Toth, Gabor; Wijns, William; Barbato, Emanuele

    2013-06-01

    We assessed if St. John's Wort (SJW) improves platelet response in patients (pts) resistant to clopidogrel after percutaneous coronary intervention (PCI). Stable angina pts non-responders to 600 mg clopidogrel (P2Y12 reaction units (PRU) >240) were randomized (2:1) to SJW (n = 15) or placebo (n = 8). SJW (300 mg × 3/day) was administrated for 2 weeks after PCI. Platelet reactivity was assessed by VerifyNowTM before (BL), 2 (T1), and 4 weeks (T2) after PCI. PRU significantly changed during protocol in SJW (BL (316 ± 60) vs. T1 (170 ± 87) vs. T2 (220 ± 96), p < 0.0001) and placebo group (BL (288 ± 36) vs. T1 (236 ± 31) vs. T2 (236 ± 62), p = 0.046). Yet, PRU changes from BL were higher at T1 in SJW than in placebo group (Δ%, -47 ± 24 vs. -16 ± 15, p = 0.0033), with no differences at T2 between the groups (Δ%, -30 ± 29 vs. -17 ± 24, p = 0.30). Residual platelet reactivity improved with SJW during the first month post-PCI.

  4. The Proton Pump Inhibitor Non-Responder: A Clinical Conundrum

    PubMed Central

    Hussain, Zilla H; Henderson, Emily E; Maradey-Romerao, Carla; George, Nina; Fass, Ronnie; Lacy, Brian E

    2015-01-01

    Gastroesophageal reflux disease (GERD) is a highly prevalent chronic condition where in stomach contents reflux into the esophagus causing symptoms, esophageal injury, and subsequent complications. Proton pump inhibitors (PPI) remain the mainstay of therapy for acid suppression. Despite their efficacy, significant proportions of GERD patients are either partial or non-responders to PPI therapy. Patients should be assessed for mechanisms that can lead to PPI failure and may require further evaluation to investigate for alternative causes. This monograph will outline a diagnostic approach to the PPI non-responder, review mechanisms associated with PPI failure, and discuss therapeutic options for those who fail to respond to PPI therapy. PMID:26270485

  5. [What are the reasons for patient dropout in nursing home residents in an intervention study. An analysis of unit nonresponders in 12 German nursing homes].

    PubMed

    Budnick, Andrea; Jordan, Laura-Maria; Könner, Franziska; Hannemann, Bianca; Wulff, Ines; Kalinowski, Sonja; Kreutz, Reinhold; Dräger, Dagmar

    2015-02-01

    Hintergrund: Nonresponse verursacht zweifelsohne ein Bias in Studienergebnissen. Ausfallursachen in Studien mit Pflegeheimbewohner(inne)n sind bisher unzureichend untersucht. Ziel und Methode: Ziel dieser Studie war es, nach dem Prozessmodell induktiver Kategorienbildung nach Mayring (2010) reliable und valide Kategorien zu entwickeln, welche detailliert Ausfallgründe von Pflegeheimbewohner(inne)n abbilden. Zudem wurden Charakteristika der Unit-Nonresponder und der Responder verglichen. Ergebnisse: Die Kategorisierung der Ausfallgründe erfolgte im Längsschnitt mit insgesamt 522 Pflegeheimbewohner(inne)n. Identifiziert wurden vier Oberkategorien («generelle Ablehnung», «gesundheitliche Aspekte», «Erreichbarkeit», «Überforderung») sowie 17 Subkategorien. Unit-Nonresponder und Responder unterscheiden sich hinsichtlich Alter und Geschlecht nicht; jedoch zeigten sich Unterschiede im Follow-up bei Familienstand, Berufsabschluss und kognitivem Status. Schlussfolgerungen: Das vorgelegte Kategorienschema kann zukünftig zur Erfassung von Ausfallgründen im Setting Pflegeheim verwendet werden. Die detaillierte Erfassung der Ausfallursachen kann zur Optimierung der Responserate beitragen.

  6. [Hepatitis C treatment in special patient groups].

    PubMed

    Berenguer, Marina; Jorquera, Francisco; Ángel Serra, Miguel; Sola, Ricard; Castellano, Gregorio

    2014-07-01

    The treatment plan for chronic hepatitis C in special populations varies according to comorbidity and the current evidence on treatment. In patients with hepatitis C virus and HIV coinfection, the results of dual therapy (pegylated interferon plus ribavirin) are poor. In patients with genotype 1 infection, triple therapy (dual therapy plus boceprevir or telaprevir) has doubled the response rate, but protease inhibitors can interact with some antiretroviral drugs and provoke more adverse effects. These disadvantages are avoided by the new, second-generation, direct-acting antiviral agents. In patients who are candidates for liver transplantation or are already liver transplant recipients, the optimal therapeutic option at present is to combine the new antiviral agents, with or without ribavirin and without interferon. The treatment of patients under hemodialysis due to chronic renal disease continues to be dual therapy (often with reduced doses of pegylated interferon and ribavirin), since there is still insufficient information on triple therapy and the new antiviral agents. In mixed cryoglobulinemia, despite the scarcity of experience, triple therapy seems to be superior to dual therapy and may be used as rescue therapy in non-responders to dual therapy. However, a decision must always be made on whether antiviral treatment should be used concomitantly or after immunosuppressive therapy.

  7. [Hepatitis C treatment in special patient groups].

    PubMed

    Berenguer, Marina; Jorquera, Francisco; Ángel Serra, Miguel; Sola, Ricard; Castellano, Gregorio

    2014-07-01

    The treatment plan for chronic hepatitis C in special populations varies according to comorbidity and the current evidence on treatment. In patients with hepatitis C virus and HIV coinfection, the results of dual therapy (pegylated interferon plus ribavirin) are poor. In patients with genotype 1 infection, triple therapy (dual therapy plus boceprevir or telaprevir) has doubled the response rate, but protease inhibitors can interact with some antiretroviral drugs and provoke more adverse effects. These disadvantages are avoided by the new, second-generation, direct-acting antiviral agents. In patients who are candidates for liver transplantation or are already liver transplant recipients, the optimal therapeutic option at present is to combine the new antiviral agents, with or without ribavirin and without interferon. The treatment of patients under hemodialysis due to chronic renal disease continues to be dual therapy (often with reduced doses of pegylated interferon and ribavirin), since there is still insufficient information on triple therapy and the new antiviral agents. In mixed cryoglobulinemia, despite the scarcity of experience, triple therapy seems to be superior to dual therapy and may be used as rescue therapy in non-responders to dual therapy. However, a decision must always be made on whether antiviral treatment should be used concomitantly or after immunosuppressive therapy. PMID:25907435

  8. Genetic variability in the 5' UTR and NS5A regions of hepatitis C virus RNA isolated from non-responding and responding patients with chronic HCV genotype 1 infection.

    PubMed

    Araújo, Flávio M G; Sonoda, Ivan V; Rodrigues, Nilton B; Teixeira, Rosangela; Redondo, Rodrigo A F; Oliveira, Guilherme C

    2008-09-01

    Sequence variation among different hepatitis C virus (HCV) isolates has adaptive significance and reflects the modes and intensities of selection mechanisms operating on the virus. In this work, we sought to investigate using classical population genetics parameters, the genetic variability of HCV genotype 1 using the 5' UTR and NS5A regions from treatment non-responding and responding groups of patients. Both regions showed low genetic variability and the 5' UTR showed neutral deviation. No differences were observed in the nonsynonymous/synonymous nucleotide substitution ratio among groups for NS5A. The analysis of molecular variance test of the 5' UTR region showed an 11.94% variation among groups. Phylogenetic analysis showed no correlation between sequence variations and therapeutic responses.

  9. Low Efficacy of Pegylated Interferon plus Ribavirin plus Nitazoxanide for HCV Genotype 4 and HIV Coinfection

    PubMed Central

    Macías, Juan; López-Cortés, Luis F.; Téllez, Francisco; Recio, Eva; Ojeda-Burgos, Guillermo; Ríos, MªJosé; Rivero-Juárez, Antonio; Delgado, Marcial; Jeremías, Rivas-; Pineda, Juan A.

    2015-01-01

    Background Nitazoxanide (NTZ) plus pegylated interferon and ribavirin (Peg-IFN/RBV) improved the sustained virological response (SVR) achieved with Peg-IFN/RBV in hepatitis C virus genotype 4 (HCV-4)-monoinfected patients. There are no data currently on the efficacy of Peg-IFN/RBV plus NTZ for human immunodeficiency virus (HIV)/HCV-4 coinfection. Therefore, the objectives of this clinical trial were to assess the efficacy and to evaluate the safety of Peg-IFN/RBV plus NTZ in HIV/HCV-4-coinfected patients. Patients and Methods This was an open-label, single arm, multicenter phase II pilot clinical trial (NCT01529073) enrolling HIV-infected individuals with HCV-4 chronic infection, naïve to HCV therapy. Patients were treated with NTZ 500 mg bid for 4 weeks, followed by NTZ 500 mg bid plus Peg-IFN alpha-2b 1.5 μg/kg/week plus weight-adjusted RBV during 48 weeks. Analyses were done by intention-to-treat (ITT, missing = failure). A historical cohort of HIV/HCV-4-infected patients treated with Peg-IFN alpha-2b and RBV at the same area was used as control. Results Two (9.5%) of 21 patients included in the trial compared with 5 (21.7%) of 23 patients included in the historical cohort achieved SVR (SVR risk difference, -12.2%; 95% confidence interval, -33.2% to 8.8%; p = 0.416). Virological failure was due to lack of response in 13 (62%) individuals recruited in the trial. Two (9.5%) patients included in the trial and two (9.5%) individuals from the historical cohort discontinued permanently due to adverse events. Conclusions No increase in SVR was observed among HIV/HCV-4-coinfected patients receiving Peg-IFN/RBV plus NTZ compared with a historical cohort treated with Peg-IFN/RBV. Interruptions due to adverse events of Peg-IFN/RBV plus NTZ were similar to those of dual therapy. Trial Registration ClinicalTrials.gov NCT01529073 PMID:26640956

  10. Fatal Pediatric Cerebral Malaria Is Associated with Intravascular Monocytes and Platelets That Are Increased with HIV Coinfection.

    PubMed

    Hochman, Sarah E; Madaline, Theresa F; Wassmer, Samuel C; Mbale, Emmie; Choi, Namjong; Seydel, Karl B; Whitten, Richard O; Varughese, Julie; Grau, Georges E R; Kamiza, Steve; Molyneux, Malcolm E; Taylor, Terrie E; Lee, Sunhee; Milner, Danny A; Kim, Kami

    2015-09-22

    Cerebral malaria (CM) is a major contributor to malaria deaths, but its pathophysiology is not well understood. While sequestration of parasitized erythrocytes is thought to be critical, the roles of inflammation and coagulation are controversial. In a large series of Malawian children hospitalized with CM, HIV coinfection was more prevalent than in pediatric population estimates (15% versus 2%, P < 0.0001, chi-square test), with higher mortality than that seen in HIV-uninfected children (23% versus 17%, P = 0.0178, chi-square test). HIV-infected (HIV(+)) children with autopsy-confirmed CM were older than HIV-uninfected children (median age, 99 months versus 32 months, P = 0.0007, Mann-Whitney U test) and appeared to lack severe immunosuppression. Because HIV infection is associated with dysregulated inflammation and platelet activation, we performed immunohistochemistry analysis for monocytes, platelets, and neutrophils in brain tissue from HIV(+) and HIV-uninfected children with fatal CM. Children with autopsy-confirmed CM had significantly (>9 times) more accumulations of intravascular monocytes and platelets, but not neutrophils, than did children with nonmalarial causes of coma. The monocyte and platelet accumulations were significantly (>2-fold) greater in HIV(+) children than in HIV-uninfected children with autopsy-confirmed CM. Our findings indicate that HIV is a risk factor for CM and for death from CM, independent of traditional measures of HIV disease severity. Brain histopathology supports the hypotheses that inflammation and coagulation contribute to the pathogenesis of pediatric CM and that immune dysregulation in HIV(+) children exacerbates the pathological features associated with CM. IMPORTANCE : There are nearly 1 million malaria deaths yearly, primarily in sub-Saharan African children. Cerebral malaria (CM), marked by coma and sequestered malaria parasites in brain blood vessels, causes half of these deaths, although the mechanisms causing

  11. Abatacept (cytotoxic T lymphocyte antigen 4-immunoglobulin) improves B cell function and regulatory T cell inhibitory capacity in rheumatoid arthritis patients non-responding to anti-tumour necrosis factor-α agents

    PubMed Central

    Picchianti Diamanti, A; Rosado, M M; Scarsella, M; Germano, V; Giorda, E; Cascioli, S; Laganà, B; D'Amelio, R; Carsetti, R

    2014-01-01

    The use of biological agents combined with methotrexate (MTX) in rheumatoid arthritis (RA) patients has strongly improved disease outcome. In this study, the effects of abatacept on the size and function of circulating B and T cells in RA patients not responding to anti-tumour necrosis factor (TNF)-α have been analysed, with the aim of identifying immunological parameters helpful to choosing suitable tailored therapies. We analysed the frequency of peripheral B and T cell subsets, B cell function and T regulatory cell (Treg) inhibitory function in 20 moderate/severe RA patients, according to the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria, primary non-responders to one TNF-α blocking agent, who received abatacept + MTX. Patients were studied before and 6 months after therapy. We found that abatacept therapy significantly reduced disease activity score on 44 joints (DAS)/erythrocyte sedimentation rate (ESR) values without causing severe side effects. The size of the circulating B and T cell compartments in RA patients was not significantly different from healthy donors, but B cell proliferation and plasma cell differentiation was impaired before therapy and restored by abatacept. While Treg cell frequency was normal, its inhibitory function was absent before therapy and was partially recovered 6 months after abatacept. B and Treg cell function is impaired in RA patients not responding to the first anti-TNF-α agent. Abatacept therapy was able to rescue immune function and led to an effective and safe clinical outcome, suggesting that RA patients, in whom anti-TNF-α failed, are immunologically prone to benefit from an agent targeting a different pathway. PMID:24773026

  12. Clinical-biochemical correlates of migraine attacks in rizatriptan responders and non-responders.

    PubMed

    Sarchielli, P; Pini, L A; Zanchin, G; Alberti, A; Maggioni, F; Rossi, C; Floridi, A; Calabresi, P

    2006-03-01

    The present study was aimed at verifying the clinical characteristics of a typical attack in 20 migraine patients, 10 responders and 10 non-responders to rizatriptan, and at investigating any differences in the levels of neuropeptides of the trigeminovascular or parasympathetic systems [calcitonin gene-related peptide (CGRP), neurokinin A (NKA) and vasoactive intestinal peptide (VIP) measured by radioimmunoassay methods in external jugular blood] between responders and non-responders. In all responders to rizatriptan, pain was unilateral, severe, and pulsating, and in five of them at least one sign suggestive of parasympathetic system activation was recorded. Five patients who were non-responders to rizatriptan referred bilateral and non-pulsating pain, even though severe in most of them. CGRP and NKA levels measured before rizatriptan administration were significantly higher in responders than in non-responders (P < 0.0001 and P < 0.002, respectively). In the five patients with autonomic signs among rizatriptan responders, detectable VIP levels were found at baseline. One hour after rizatriptan administration, a decrease in CGRP and NKA levels was evident in the external jugular venous blood of rizatriptan responders, and this corresponded to a significant pain relief and alleviation of accompanying symptoms. VIP levels were also significantly reduced at the same time in the five patients with autonomic signs. After rizatriptan administration, CGRP and NKA levels in non-responder patients showed less significant variations at all time points after rizatriptan administration compared with rizatriptan responders. The present study, although carried out on a limited number of patients, supports recent clinical evidence of increased trigeminal activation associated with a better triptan response in migraine patients accompanied by parasympathetic activation in a subgroup of patients with autonomic signs. In contrast, the poor response seems to be correlated with a

  13. Incidence of and factors associated with hepatocellular carcinoma among hepatitis C virus and human immunodeficiency virus coinfected patients with decompensated cirrhosis.

    PubMed

    García-García, José A; Romero-Gómez, Manuel; Girón-González, José A; Rivera-Irigoin, Robin; Torre-Cisneros, Julián; Montero, José L; González-Serrano, Mercedes; Andrade, Raúl J; Aguilar-Guisado, Manuela; Grilo, Israel; Martín-Vivaldi, Javier; Salmerón, Javier; Caballero-Granado, Francisco J; Macías, Juan; Vergara-López, Salvador; Pineda, Juan A

    2006-12-01

    We compared the incidence of and factors associated with hepatocellular carcinoma (HCC) among hepatitis C virus (HCV)-monoinfected subjects and human immunodeficiency virus (HIV)/HCV-coinfected individuals, both with decompensated cirrhosis. In a retrospective study, a cohort of 180 individuals with HIV coinfection and 1037 HCV-monoinfected patients with decompensated HCV-related cirrhosis from eight centres in Spain were analyzed. HCC was found in 234 (23%) HCV-monoinfected subjects and in four (2%) HIV-coinfected subjects (p<0.001). At the time of the first hepatic decompensation, 188 (17%) and 4 (2%) (p<0.001) patients in the former and in the latter group, respectively, showed HCC. Fifty-four (11%) patients without HCC at baseline developed such a disease during follow-up. There were no incident cases among the HIV-coinfected population. The density of incidence (95% IC) of HCC in HIV/HCV-coinfected and HCV-monoinfected patients was 0 (0-1.70) and 3.31 (2.70-4.64) cases per 100 person-years (p<0.001), respectively. Lack of HIV infection [adjusted odds risk (AOR) (95% IC)=16.7 (3.9-71.1)] and high alanine aminotransferase levels [AOR (95% IC)=2.5 (1.1-5)] were the only two independent predictors of the emergence of HCC. In the group of patients in whom the date of HCV infection could be estimated, the time elapsed until HCC diagnosis was shorter among HIV-coinfected subjects. The incidence of HCC in patients with HCV-related cirrhosis after the first hepatic decompensation is lower in HIV-coinfected patients. This is probably due to the fact that HIV infection shortens the survival of HCV-coinfected patients with end-stage liver disease to such an extent that HCC not had a chance to emerge.

  14. Boceprevir or Telaprevir Based Triple Therapy against Chronic Hepatitis C in HIV Coinfection: Real-Life Safety and Efficacy

    PubMed Central

    Neukam, Karin; Munteanu, Daniela I.; Rivero-Juárez, Antonio; Lutz, Thomas; Fehr, Jan; Mandorfer, Mattias; Bhagani, Sanjay; López-Cortés, Luis F.; Haberl, Annette; Stoeckle, Marcel; Márquez, Manuel; Scholten, Stefan; de los Santos-Gil, Ignacio; Mauss, Stefan; Rivero, Antonio; Collado, Antonio; Delgado, Marcial; Rockstroh, Juergen K.; Pineda, Juan A.

    2015-01-01

    Background and Aims Clinical trials of therapy against chronic hepatitis C virus (HCV) infection including boceprevir (BOC) or telaprevir (TVR) plus pegylated interferon and ribavirin (PR) have reported considerably higher response rates than those achieved with PR alone. This study sought to evaluate the efficacy and safety of triple therapy including BOC or TVR in combination with PR in HIV/HCV-coinfected patients under real-life conditions. Methods In a multicentre study conducted in 24 sites throughout five European countries, all HIV/HCV-coinfected patients who initiated a combination of BOC or TVR plus PR and who had at least 60 weeks of follow-up, were analyzed. Sustained virologic response 12 weeks after the scheduled end of therapy date (SVR12) and the rate of discontinuations due to adverse events (AE) were evaluated. Results Of the 159 subjects included, 127 (79.9%) were male, 45 (34.4%) were treatment-naïve for PR and 60 (45.4%) showed cirrhosis. SVR12 was observed in 31/46 (67.4%) patients treated with BOC and 69/113 (61.1%) patients treated with TVR. Overall discontinuations due to AE rates were 8.7% for BOC and 8% for TVR. Grade 3 or 4 hematological abnormalities were frequently observed; anemia 7%, thrombocytopenia 17.2% and neutropenia 16.4%. Conclusion The efficacy and safety of triple therapy including BOC or TVR plus PR under real-life conditions of use in the HIV/HCV-coinfected population was similar to what is observed in clinical trials. Hematological side effects are frequent but manageable. PMID:25923540

  15. Psychodynamic Treatment for Separation Anxiety in a Treatment Nonresponder.

    PubMed

    Busch, Fredric N; Milrod, Barbara L

    2015-10-01

    Separation anxiety, long an area of interest for psychoanalysts, has been included in DSM-5 among general "anxiety disorders" that span across age groups. The syndrome of separation anxiety has been shown to correlate with nonresponse to treatments for anxiety and mood disorders (Milrod et al. 2014). It is therefore of public health importance to develop targeted treatments for this syndrome. Some psychoanalysts have suggested that brief psychoanalytic interventions may be of particular value in addressing separation anxiety. Our clinical work with patients with anxiety disorders with high levels of separation anxiety indicates that they have such intense anger and ambivalence in fraught intimate relationships that they feel stuck and helpless, almost eliminating more positive feelings. This ambivalence and associated unconscious conflicts inevitably emerge in the therapeutic relationship and can threaten to disrupt treatment efforts. We propose a set of focused psychodynamic psychotherapeutic interventions to address separation anxiety, developed as part of Panic-Focused Psychodynamic Psychotherapy-eXtended Range (PFPP-XR; Busch et al. 2012). We present a case from our research study of treatment nonresponders with anxiety disorders and separation anxiety. The patient was successfully treated with PFPP-XR in a 21-session treatment.

  16. Brain Changes in Responders vs. Non-Responders in Chronic Migraine: Markers of Disease Reversal

    PubMed Central

    Hubbard, Catherine S.; Becerra, Lino; Smith, Jonathan H.; DeLange, Justin M.; Smith, Ryan M.; Black, David F.; Welker, Kirk M.; Burstein, Rami; Cutrer, Fred M.; Borsook, David

    2016-01-01

    The aim of this study was to identify structural and functional brain changes that accompanied the transition from chronic (CM; ≥15 headache days/month) to episodic (EM; <15 headache days/month) migraine following prophylactic treatment with onabotulinumtoxinA (BoNT-A). Specifically, we examined whether CM patients responsive to prophylaxis (responders; n = 11), as evidenced by a reversal in disease status (defined by at least a 50% reduction in migraine frequency and <15 headache days/month), compared to CM patients whose migraine frequency remained unchanged (non-responders; n = 12), showed differences in cortical thickness using surface-based morphometry. We also investigated whether areas showing group differences in cortical thickness displayed altered resting-state functional connectivity (RS-FC) using seed-to-voxel analyses. Migraine characteristics measured across groups included disease duration, pain intensity and headache frequency. Patient reports of headache frequency over the 4 weeks prior to (pre-treatment) and following (post-treatment) prophylaxis were compared (post minus pre) and this measure served as the clinical endpoint that determined group assignment. All patients were scanned within 2 weeks of the post-treatment visit. Results revealed that responders showed significant cortical thickening in the right primary somatosensory cortex (SI) and anterior insula (aINS), and left superior temporal gyrus (STG) and pars opercularis (ParsOp) compared to non-responders. In addition, disease duration was negatively correlated with cortical thickness in fronto-parietal and temporo-occipital regions in responders but not non-responders, with the exception of the primary motor cortex (MI) that showed the opposite pattern; disease duration was positively associated with MI cortical thickness in responders versus non-responders. Our seed-based RS-FC analyses revealed anti-correlations between the SI seed and lateral occipital (LOC) and dorsomedial

  17. A comparison of placebo responders and nonresponders in subgroups of depressive disorder.

    PubMed Central

    Bialik, R J; Ravindran, A V; Bakish, D; Lapierre, Y D

    1995-01-01

    The objective of this study was to determine if the placebo treatment response varied in subgroups of depressed patients (single episode, recurrent, and double depression). Data from placebo-treated patients from seven placebo-controlled clinical trials were pooled and analyzed retrospectively. The placebo response rate was highest for females with a single episode of depression (66.7%) and lowest for females with recurrent depressive episodes (13.3%). Among patients experiencing their first episode, placebo responders had lower Hamilton Rating Scale for Depression (HAMD) total scores at baseline and lower ratings of pschomotor retardation than nonresponders. For patients having a recurrence of an episode, placebo responders had lower baseline ratings of somatic anxiety. The major finding was that patients suffering from their first depressive episode differed from patients with recurrent depressive episodes in the rate of placebo response, effect of gender, and the clinical symptoms that were associated with a positive placebo response. PMID:7647079

  18. Early identification of non-responding locally advanced breast tumors receiving neoadjuvant chemotherapy

    NASA Astrophysics Data System (ADS)

    Van de Giessen, Martijn; Schaafsma, Boudewijn E.; Charehbili, Ayoub; Smit, Vincent T. H. B. M.; Kroep, Judith R.; Lelieveldt, Boudewijn P. F.; Liefers, Gerrit-Jan; Chan, Alan; Löwik, Clemens W. G. M.; Dijkstra, Jouke; van de Velde, Cornelis J. H.; Wasser, Martin N. J. M.; Vahrmeijer, Alexander L.

    2015-02-01

    Diffuse optical spectroscopy (DOS) may be advantageous for monitoring tumor response during chemotherapy treatment, particularly in the early treatment stages. In this paper we perform a second analysis on the data of a clinical trial with 25 breast cancer patients that received neoadjuvant chemotherapy. Patients were monitored using delayed contrast enhanced MRI and additionally with diffuse optical spectroscopy at baseline, after 1 cycle of chemotherapy, halfway therapy and before surgery. In this analysis hemoglobin content between tumor tissue and healthy tissue of the same breast is compared on all four monitoring time points. Furthermore, the predictive power of the tumor-healthy tissue difference of HbO2 for non-responder prediction is assessed. The difference in HbO2 content between tumor and healthy tissue was statistically significantly higher in responding tumors than in non-responding tumors at baseline (10.88 vs -0.57 μM, P=0.014) and after one cycle of chemotherapy (6.45 vs -1.31 μM, P=0.048). Before surgery this difference had diminished. In the data of this study, classification on the HbO2 difference between tumor and healthy tissue was able to predict tumor (non-)response at baseline and after 1 cycle with an area-under-curve of 0.95 and 0.88, respectively. While this result suggests that tumor response can be predicted before chemotherapy onset, one should be very careful with interpreting these results. A larger patient population is needed to confirm this finding.

  19. A comparison of small monetary incentives to convert survey non-respondents: a randomized control trial

    PubMed Central

    2011-01-01

    Background Maximizing response rates is critically important in order to provide the most generalizable and unbiased research results. High response rates reduce the chance of respondents being systematically different from non-respondents, and thus, reduce the risk of results not truly reflecting the study population. Monetary incentives are often used to improve response rates, but little is known about whether larger incentives improve response rates in those who previously have been unenthusiastic about participating in research. In this study we compared the response rates and cost-effectiveness of a $5 versus $2 monetary incentive accompanying a short survey mailed to patients who did not respond or refused to participate in research study with a face-to-face survey. Methods 1,328 non-responders were randomly assigned to receive $5 or $2 and a short, 10-question survey by mail. Reminder postcards were sent to everyone; those not returning the survey were sent a second survey without incentive. Overall response rates, response rates by incentive condition, and odds of responding to the larger incentive were calculated. Total costs (materials, postage, and labor) and incremental cost-effectiveness ratios were also calculated and compared by incentive condition. Results After the first mailing, the response rate within the $5 group was significantly higher (57.8% vs. 47.7%, p < .001); after the second mailing, the difference narrowed by 80%, resulting in a non-significant difference in cumulative rates between the $5 and $2 groups (67.3% vs. 65.4%, respectively, p = .47). Regardless of incentive or number of contacts, respondents were significantly more likely to be male, white, married, and 50-75 years old. Total costs were higher with the larger versus smaller incentive ($13.77 versus $9.95 per completed survey). Conclusions A $5 incentive provides a significantly higher response rate than a $2 incentive if only one survey mailing is used but not if two survey

  20. On the nature of non-responding in discrimination learning with and without errors1

    PubMed Central

    Terrace, H. S.

    1974-01-01

    In human subjects, discrimination learning with errors results in active responding incompatible with the reinforced response. The direction of such incompatible behavior is opposite to that of the reinforced response. Responding occurs only during the stimulus correlated with extinction. The frequency of active non-responding is maximal shortly after the start of discrimination training (the time at which the frequency of errors decreases most rapidly) and approaches zero as discrimination training continues. The magnitude of behavioral contrast is not related systematically to the number of errors. Instead it is related directly to the frequency of active non-responding. Active non-responding appears to be motivated by the aversiveness of self-produced frustration, in the sense that active non-responding allows the subject to avoid the aversiveness of non-reinforced responding. ImagesFig. 1.Fig. 2. PMID:16811774

  1. The Influence of Clinical and Biological Factors on Transfusion-Associated Non-ABO Antigen Alloimmunization: Responders, Hyper-Responders, and Non-Responders.

    PubMed

    Gehrie, Eric A; Tormey, Christopher A

    2014-11-01

    In the context of transfusion medicine, alloimmunization most often refers to the development of antibodies to non-ABO red blood cell (RBC) antigens following pregnancy, transfusion, or transplantation. The development of RBC alloantibodies can have important clinical consequences, particularly in patients who require chronic transfusions. It has been suggested that alloimmunization is more common in some clinical circumstances and patient populations than in others. As such, individuals that develop alloantibodies are frequently referred to as 'responders' in the medical literature. In contrast, individuals that do not develop alloantibodies despite repeated exposures to non-self blood group antigens have been referred to as 'non-responders'. The purpose of this article is to review the phenomenon of RBC alloimmunization in the context of responders and non-responders to: i) establish a basic framework for alloimmunization as reported across several diverse patient populations; ii) more fully explore literature reports which support the concept of responders/non-responders regarding blood group antigen alloimmunization; iii) summarize the mechanisms that have been shown to predispose an individual to alloimmunization to determine how these factors may differentiate 'responders' from 'non-responders'; and iv) briefly discuss some practical approaches to prevent alloimmunization in patients who may be prone to alloantibody development.

  2. Non-Responders to Intravenous Immunoglobulin and Coronary Artery Dilatation in Kawasaki Disease: Predictive Parameters in Korean Children

    PubMed Central

    Kim, Bo Young; Kim, Dongwan; Kim, Yong Hyun; Ryoo, Eell; Sun, Yong Han; Jeon, In-sang; Jung, Mi-Jin; Cho, Hye Kyung; Tchah, Hann; Choi, Deok Young

    2016-01-01

    Background and Objectives In Kawasaki disease (KD), high dose intravenous immunoglobulin (IVIG) significantly lowers the coronary complications. However, some patients either do not respond to initial therapy or develop coronary complications. We aimed to identify the predictive factors for unresponsiveness to initial IVIG therapy and coronary artery dilatation (CAD; defined by Z-score≥2.5) in the acute phase and convalescent phase. Subjects and Methods A retrospective review was conducted of 703 patients with KD, admitted to Gachon University Gil Medical Center between January 2005 and June 2013. The patients were divided into two groups—IVIG responders vs. non-responders—based on the IVIG treatments, and presence of fever after treatment. Further, these groups were divided into two subgroups based on their CAD. Results Among the 703 patients with KD, the rate of non-responders to initial IVIG was 16.8%. Serum total bilirubin, platelet count, and neutrophil proportion were independent predictive parameters of unresponsiveness (p<0.05). CAD was found in 234 patients (33.3%) in the acute phase, and in 32 patients (4.6%) in the convalescent phase. Male gender, fever duration, serum C-reactive protein, and white blood cell count were related to CAD (p<0.05). CAD was detected more frequently in non-responders than in the responders (47.5% vs. 31.5%, p=0.001). Kobayashi, Egami, and Sano scoring systems applied to our study population reflected low sensitivities (28.0-33.9%). Conclusion Several independent parameters were related to unresponsiveness to the initial IVIG or CAD. These parameters might be helpful in establishing more focused and careful monitoring of high-risk KD patients in Korea. PMID:27482264

  3. Magnitude of visceral leishmaniasis and poor treatment outcome among HIV patients: meta-analysis and systematic review

    PubMed Central

    Alemayehu, Mekuriaw; Wubshet, Mamo; Mesfin, Nebiyu

    2016-01-01

    Background Visceral leishmaniasis (VL) coinfection with HIV/AIDS most often results in unfavorable responses to treatment, frequent relapses, and premature deaths. Scarce data are available, regarding the magnitude and poor treatment outcomes of VL-HIV coinfection. Objective The main objective of this systematic review was to describe the pooled prevalence of VL and poor treatment outcome among HIV patients. Review methods Electronic databases mainly PubMed were searched. Databases, such as Google and Google scholar, were searched for gray literature. Articles were selected based on their inclusion criterion, whether they included HIV-positive individuals with VL diagnosis. STATA 11 software was used to conduct a meta-analysis of pooled prevalence of VL-HIV coinfection. Results Fifteen of the 150 articles fulfilled the inclusion criteria. A majority of the study participants were males between 25 years and 41 years of age. The pooled prevalence of VL-HIV coinfection is 5.2% with 95% confidence interval of (2.45–10.99). Two studies demonstrated the impact of antiretroviral treatment on reduction in relapse rate compared with patients who did not start antiretroviral treatment. One study showed that the higher the baseline CD4+ cell count (>100 cells/mL) the lower the relapse rate. Former VL episodes were identified as risk factors for relapse in two articles. In one of the articles, an earlier bout of VL remains significant in the model adjusted to other variables. Conclusion The pooled prevalence of VL in HIV-infected patients is low and an earlier bout of VL and CD4+ count <100 cells/mL at the time of primary VL diagnosis are factors that predict poor treatment outcome. PMID:27042142

  4. A Comparison of Community College Responders and Nonresponders to the VEDS Student Follow-Up Survey.

    ERIC Educational Resources Information Center

    Carifio, James; And Others

    1991-01-01

    A survey of respondents and nonrespondents to the Vocational Education Data System's follow-up survey of Massachusetts community college graduates was designed to measure response bias. The survey investigated employment patterns, wages, and degree of job relatedness. Results suggest original data was biased, if at all, toward underestimation, not…

  5. Understanding Faculty Survey Nonrespondents: Their Characteristics, Organizational Citizenship Behaviors, Workplace Attitudes, and Reasons for Nonparticipation

    ERIC Educational Resources Information Center

    Mathews, Kiernan Robert

    2013-01-01

    College and university administrators frequently survey their faculty to inform decisions affecting the academic workplace. Higher education researchers, too, rely heavily on survey methodologies in their scholarly work. Survey response rates, however, have been declining steadily for decades, and when nonrespondents and respondents systematically…

  6. Human cysticercosis: antigens, antibodies and non-responders.

    PubMed Central

    Flisser, A; Woodhouse, E; Larralde, C

    1980-01-01

    Immunoelectrophoresis of sera from patients with brain cysticercosis against a crude antigenic extract from Cysticercus cellulosae indicates that nearly 50% of the patients do not make sufficient antibodies to ostensively precipitate. The other 50% of the patients who do make precipitating antibodies show a very heterogeneous response in the number of antigens they recognize as well as in the type of antigen--as classified by their electrophoretic mobilities. The most favoured, called antigen B, is recognized by 84% of positive sera and corresponds to one or a limited number of antigens isoelectric at pH 8.6. Indirect immunofluorescence with monospecific anti-human immunoglobulins, performed upon the immunoelectrophoretic preparations, reveal that all cysticercus antigens induced the synthesis of antibodies in the immunoglobulin classes in the order G greater than M greater than E greater than A greater than D. Finally, antigen H (an anodic component) seems to favour IgE relative to its ability to induce IgG. Thus, although in natural infection a good proportion of cysticercotic patients do not seem to mount an energetic antibody response against the parasite, giving rise to some speculations about immunosuppression, the fact that 50% do synthesize antibodies allows for some optimistic expectations from vaccination of humans--in view of the good results of vaccination in experimental animals mediated by IgG antibodies. A likely prospect for a human vaccine would be antigen B because it is the most frequently detected by humans, although its immunizing and toxic properties remain to be properly studied. Images FIG. 1 FIG. 3 FIG. 6 PMID:7389197

  7. Human cysticercosis: antigens, antibodies and non-responders.

    PubMed

    Flisser, A; Woodhouse, E; Larralde, C

    1980-01-01

    Immunoelectrophoresis of sera from patients with brain cysticercosis against a crude antigenic extract from Cysticercus cellulosae indicates that nearly 50% of the patients do not make sufficient antibodies to ostensively precipitate. The other 50% of the patients who do make precipitating antibodies show a very heterogeneous response in the number of antigens they recognize as well as in the type of antigen--as classified by their electrophoretic mobilities. The most favoured, called antigen B, is recognized by 84% of positive sera and corresponds to one or a limited number of antigens isoelectric at pH 8.6. Indirect immunofluorescence with monospecific anti-human immunoglobulins, performed upon the immunoelectrophoretic preparations, reveal that all cysticercus antigens induced the synthesis of antibodies in the immunoglobulin classes in the order G greater than M greater than E greater than A greater than D. Finally, antigen H (an anodic component) seems to favour IgE relative to its ability to induce IgG. Thus, although in natural infection a good proportion of cysticercotic patients do not seem to mount an energetic antibody response against the parasite, giving rise to some speculations about immunosuppression, the fact that 50% do synthesize antibodies allows for some optimistic expectations from vaccination of humans--in view of the good results of vaccination in experimental animals mediated by IgG antibodies. A likely prospect for a human vaccine would be antigen B because it is the most frequently detected by humans, although its immunizing and toxic properties remain to be properly studied.

  8. [Prevention of hepatitis B--HLA DR/DQ in HBs Ag nonresponder].

    PubMed

    Ouchi, E; Hoshino, A; Miura, T; Nagahara, N; Kudo, Y; Tamura, M

    1989-11-01

    To evaluate the immunological background in HBs Ag nonresponders against hepatitis B vaccine, the lymphocyte surface marker and HLA-DR/DQ antigen were determined on hospital personnel, 70 males and 256 females, injected hepatitis B vaccine for three times. The vaccine made from the plasma of HBs Ag carriers was injected at the first and second vaccination and recombinant hepatitis B vaccine was injected at the third vaccination. A month after the third vaccination, blood was withdrawn for HBs antigen test by RIA. Border line cases (cut off index 1.0-1.9) are included in nonresponder (cut off index less than 0.9). Both nonresponders and low responders (cut off index 2-49) are more often seen in males than females and high responder (cut off index 50 or more) are seen more often in young females than males. Lymphocyte surface markers were studied by flow cytometry using the following monoclonal antibodies; OKT 3, 4, 8, DR, NK, Ia 1 and B7. No differences between lymphocyte surface markers of nonresponders and responders were noted. HLA-DR/DQ antigens were studied by the cytotoxicity test using Locus DR/DQ, Terasaki Second DR W-60 Tray and using following antibodies; DR 1, DR 2, DRW 15, DR 4, DR 5, DR 7, DR 9, DRW 10, DRW 8, DRW 12, DRW 13, DRW 6, DRW 52, DRW 53, DQW 1, DQW 6, DQW 2, DQW 3, DQW 7 and DQW 4. No significant differences between HLA-DR/DQ of nonresponders and responders were noted. PMID:2601078

  9. Responders and non-responders to bifemelane hydrochloride in Alzheimer-type and multi-infarct dementia.

    PubMed

    Shigeta, M; Nishikawa, Y; Shimizu, M; Usui, M; Hyoki, K; Kawamuro, Y

    1993-01-01

    Although metabolically active compounds sometime attenuate cognitive deficits of dementia patients, this mechanism has not been discussed or investigated. We hypothesized that these compounds improve cognitive disorders not by directly acting on this cognitive function, but by increasing the arousal level. Based on this hypothesis, we investigated the change of arousal levels and the improvement of intellectual functions in 10 patients with Alzheimer-type dementia (ATD) and 10 patients with multi-infarct dementia (MID) before and 3 months after pharmacotherapy using bifemelane hydrochloride. For each patient, a psychological test battery was carried out and the arousal level was evaluated using the frequency of rapid eye movements in the electro-oculogram (EOG) and the frequency analysis of electroencephalogram (EEG) before and after the treatment. Evaluation of the cognitive improvement was made and eight out of the 20 patients were regarded as responders to the treatment. The frequency of small rapid eye movements (SREM) in the EOG increased significantly only in responders and the rate of change in SREM appearance in responders was significantly different from that in non-responders. This finding suggests that a part of the intellectual improvement in ATD and MID results from the increased level of arousal.

  10. Repeated vaccinations do not improve specific immune defenses against Hepatitis B in non-responder health care workers.

    PubMed

    Zaffina, Salvatore; Marcellini, Valentina; Santoro, Anna Paola; Scarsella, Marco; Camisa, Vincenzo; Vinci, Maria Rosaria; Musolino, Anna Maria; Nicolosi, Luciana; Rosado, M Manuela; Carsetti, Rita

    2014-12-01

    Hepatitis B is a major infectious occupational hazard for health care workers and can be prevented with a safe and effective vaccine. The serum titer of anti-HBsAg antibodies is the most commonly used correlate of protection and post-vaccination anti-HBsAg concentrations of ≥ 10 mIU/ml are considered protective. Subjects with post-vaccination anti-HBsAg titers of <10 mIU/ml 1-6 months post-vaccination, who tested negative for HBsAg and anti-HBc, are defined as non-responders. The question of whether non-responders should be repeatedly vaccinated is still open. The aim of the study was to (i) evaluate the distribution of lymphocyte subpopulations and the percentage of HBsAg-specific memory B cells in responders and non-responders (ii) assess whether non-responders can be induced to produce antibodies after administration of a booster dose of vaccine (iii) determine whether booster vaccination increases the number of specific memory B cells in non-responders. Combining flow-cytometry, ELISPOT and serology we tested the integrity and function of the immune system in 24 health care workers, confirmed to be non-responders after at least three vaccine injections. We compared the results with those obtained in 21 responders working in the same institution. We found that the great majority of the non-responders had a functional immune system and a preserved ability to respond to other conventional antigens. Our most important findings are that the frequency of HBsAg-specific memory B cells is comparable in non-responders and controls and that booster immunization does not lead either to antibody production or memory B cell increase in non-responders.

  11. Long-term treatment with the combination of amantadine and ribavirin in hepatitis C nonresponders. A case series.

    PubMed

    Riley, Thomas R; Taheri, Mohammad R

    2007-12-01

    In this report, we describe five cases of chronic hepatitis C that have been treated with the combination of amantadine and ribavirin for an average of 44 months, emphasizing one case where the patient showed improvement in liver biopsy after treatment, worsening on removal, then a repeated improvement with re-initiation. The five patients in this report belong to a pool of sixty patients from a 6 month pilot study using amantadine and ribavirin where treatment was subsequently continued. The mean ALT was 82.8+/-32 U/L pre-treatment and 33.8+/-17.3 U/L post-treatment (p=0.02). The mean Knodell score was 7+/-1 pre-treatment and 3.6+/-1.5 post-treatment (p=0.13). The mean viral load was 584,155+/-248,027 lU/ml pre-treatment and 225,878+/-190,143 IU/ml post-treatment (p=0.05). In this case series we provide provocative data on the long-term use of ribavirin and amantadine in the HCV non-responder. PMID:17401686

  12. Comparative Proteomic Analysis of Advanced Ovarian Cancer Tissue to Identify Potential Biomarkers of Responders and Nonresponders to First-Line Chemotherapy of Carboplatin and Paclitaxel

    PubMed Central

    Sehrawat, Urmila; Pokhriyal, Ruchika; Gupta, Ashish Kumar; Hariprasad, Roopa; Khan, Mohd Imran; Gupta, Divya; Naru, Jasmine; Singh, Sundararajan Baskar; Mohanty, Ashok Kumar; Vanamail, Perumal; Kumar, Lalit; Kumar, Sunesh; Hariprasad, Gururao

    2016-01-01

    Conventional treatment for advanced ovarian cancer is an initial debulking surgery followed by chemotherapy combination of carboplatin and paclitaxel. Despite initial high response, three-fourths of these women experience disease recurrence with a dismal prognosis. Patients with advanced-stage ovarian cancer who underwent cytoreductive surgery were enrolled and tissue samples were collected. Post surgery, these patients were started on chemotherapy and followed up till the end of the cycle. Fluorescence-based differential in-gel expression coupled with mass spectrometric analysis was used for discovery phase of experiments, and real-time polymerase chain reaction, Western blotting, and pathway analysis were performed for expression and functional validation of differentially expressed proteins. While aldehyde reductase, hnRNP, cyclophilin A, heat shock protein-27, and actin are upregulated in responders, prohibitin, enoyl-coA hydratase, peroxiredoxin, and fibrin-β are upregulated in the nonresponders. The expressions of some of these proteins correlated with increased apoptotic activity in responders and decreased apoptotic activity in nonresponders. Therefore, the proteins qualify as potential biomarkers to predict chemotherapy response. PMID:26997873

  13. New use of an old drug: chloroquine reduces viral and ALT levels in HCV non-responders (a randomized, triple-blind, placebo-controlled pilot trial).

    PubMed

    Peymani, Payam; Yeganeh, Behzad; Sabour, Siamak; Geramizadeh, Bita; Fattahi, Mohammad Reza; Keyvani, Hossein; Azarpira, Negar; Coombs, Kevin M; Ghavami, Saied; Lankarani, Kamran B

    2016-06-01

    Hepatitis C virus (HCV) infection induces autophagy, but the virus assimilates the autophagic response into its own life cycle. Chloroquine (CQ) is an autophagy inhibitor that is clinically used to treat malaria. The aims of this pilot clinical trial were to evaluate the therapeutic potential and short-term safety of CQ in patients with chronic HCV genotype 1, who were unresponsive to a combination of pegylated interferon alpha and ribavirin. Ten non-responders to previous antiviral treatment(s) were randomized to receive either CQ (150 mg daily for 8 weeks) or placebo, and were followed for 4 weeks after CQ therapy. HCV RNA load and plasma alanine transaminase (ALT) levels were measured at baseline, week 4 (initial response), week 8 (end-of-treatment response), and at the end of 12 weeks. A significant decrease in HCV RNA after the treatments (week 8) was observed in all patients in the CQ group (P = 0.04). However, HCV RNA levels increased within 4 weeks after discontinuation of CQ treatment although they were still lower than baseline. In addition, the ALT normalized during treatment in the CQ group. However, this response was also lost after treatment cessation. This study provides preliminary evidence that CQ is possibly a safe treatment option for HCV non-responders.

  14. Characterising the immune profile of the kidney biopsy at lupus nephritis flare differentiates early treatment responders from non-responders

    PubMed Central

    Parikh, Samir V; Malvar, Ana; Song, Huijuan; Alberton, Valeria; Lococo, Bruno; Vance, Jay; Zhang, Jianying; Yu, Lianbo; Rovin, Brad H

    2015-01-01

    Introduction The kidney biopsy is used to diagnose and guide initial therapy in patients with lupus nephritis (LN). Kidney histology does not correlate well with clinical measurements of kidney injury or predict how patients will respond to standard-of-care immunosuppression. We postulated that the gene expression profile of kidney tissue at the time of biopsy may differentiate patients who will from those who will not respond to treatment. Methods The expression of 511 immune-response genes was measured in kidney biopsies from 19 patients with proliferative LN and 4 normal controls. RNA was extracted from formalin-fixed, paraffin-embedded kidney biopsies done at flare. After induction therapy, 5 patients achieved a complete clinical response (CR), 10 had a partial response (PR) and 4 patients were non-responders (NRs). Transcript expression was compared with normal controls and between renal response groups. Results A principal component analysis showed that intrarenal transcript expression from normal kidney, CR biopsies and NR biopsies segregated from each other. The top genes responsible for CR clustering included several interferon pathway genes (STAT1, IRF1, IRF7, MX1, STAT2, JAK2), while complement genes (C1R, C1QB, C6, C9, C5, MASP2) were mainly responsible for NR clustering. Overall, 35 genes were uniquely expressed in NR compared with CR. Pathway analysis revealed that interferon signalling and complement activation pathways were upregulated in both groups, while BAFF, APRIL, nuclear factor-κB and interleukin-6 signalling were increased in CR but suppressed in NR. Conclusions These data suggest that molecular profiling of the kidney biopsy at LN flare may be useful in predicting treatment response to induction therapy. PMID:26629350

  15. Efficacy of sofosbuvir-based therapies in HIV/HCV infected patients and persons who inject drugs.

    PubMed

    Puoti, Massimo; Panzeri, Claudia; Rossotti, Roberto; Baiguera, Chiara

    2014-12-15

    In the era of Directly Acting anti HCV Antivirals treatment of hepatitis C is successful in the majority of persons treated. However, treatment of persons with HIV or who inject drugs remains challenging because of special issues: drug-drug interactions with antiretroviral, psychiatric and drug substitution therapies, treatment adherence, impact of treatment on HIV disease course or on risk of bacterial infections. Sofosbuvir induced sustained virologic response in 91% of 23 HIV/HCV coinfected persons treated in combination with ribavirin and pegylated interferon, in 83% of 497 treated in combination with ribavirin and in all 50 patients infected with HCV GT1 treated in combination with ledipasvir and ribavirin. The rates of efficacy in HCV-HIV coinfected were almost the same as those observed in HCV monoinfected suggesting that the efficacy of sofosbuvir is not reduced by HIV coinfection. There are no data on the efficacy of sofosbuvir in injection drugs users. The pangenotypic activity, the high barrier to resistance, the modest potential for drug-drug interactions makes sofosbuvir a reference drug for the treatment of these two special populations.

  16. Modulation of TIM-3 expression on NK and T cell subsets in HIV immunological non-responders.

    PubMed

    de Kivit, Sander; Lempsink, Ludwijn J R; Plants, Jill; Martinson, Jeffrey; Keshavarzian, Ali; Landay, Alan L

    2015-01-01

    Highly active antiretroviral therapy (HAART) for the treatment of HIV infection sustains viral suppression and increases CD4(+) T cells in HIV patients. However, in 10-25% of subjects, known as immunological non-responders (INRs), HAART does not increase CD4 count. We investigated a potential role for galectin-9 and TIM-3 in INRs as galectin-9 and TIM-3 have been described to modulate NK and T cell function. PBMCs were isolated from healthy controls, HIV immunological responders (IRs, >350CD4(+) cells/mm(3)) and HIV INRs (<350CD4(+) cells/mm(3)) and TIM-3 and galectin-9 expressions on NK cell subsets and CD4(+) T cells were assessed. HIV INRs and HIV IRs showed increased galectin-9 expression on CD16(-)CD56(bright) and CD16(+)CD56(+) NK cells and CD4(+) T cells. Only HIV INRs showed a reduced frequency of TIM-3-expressing CD16(+)CD56(+), CD16(+)CD56(-) and CD4(+) cells, which correlated with low peripheral CD4 counts. These data suggest that TIM-3 expression may be characteristic for HIV INRs. PMID:25450337

  17. Haplotype Analysis of GSK-3β Gene Polymorphisms in Bipolar Disorder Lithium Responders and Nonresponders

    PubMed Central

    Iwahashi, Kazuhiko; Nishizawa, Daisuke; Narita, Shin; Numajiri, Maki; Murayama, Ohoshi; Yoshihara, Eiji; Onozawa, Yuuya; Nagahori, Kenta; Fukamauchi, Fumihiko; Ikeda, Kazutaka; Ishigooka, Jun

    2014-01-01

    Abstract The GSK-3β gene, GSK3B, codes for an enzyme that is a target for the action of mood stabilizers, lithium and possibly valproic acid. In this study, the relationship between haplotypes consisting of single nucleotide polymorphisms (SNPs) of GSK3B −50T/C and −1727A/T and the effect of lithium was studied among Japanese bipolar disorder lithium nonresponders and responders. The distributions of the GSK3B haplotypes (−50T/C and −1727A/T) showed a trend for significant difference between the lithium nonresponders and responders (global P=0.07074). Haplotype 1 (T-A) was associated with a higher lithium response (haplotype-specific P=0.03477), whereas haplotype 2 (C-A) was associated with a lower lithium response (haplotype-specific P=0.03443). The pairwise D′ and r2 values between the 2 SNPs in this study were 1.0 and 0.097, respectively. The 2 SNPs showed weak linkage disequilibrium with each other. PMID:24992082

  18. Characterization of clinical and immunological features in patients coinfected with dengue virus and HIV.

    PubMed

    Torrentes-Carvalho, Amanda; Hottz, Eugênio Damaceno; Marinho, Cintia Ferreira; da Silva, Jéssica Badolato-Corrêa; Pinto, Luzia Maria de Oliveira; Fialho, Luciana Gomes; Bozza, Fernando Augusto; Cunha, Rivaldo Venâncio; Damasco, Paulo Vieira; Kubelka, Claire Fernandes; de Azeredo, Elzinandes Leal

    2016-03-01

    The pathogenesis of dengue in subjects coinfected with HIV remains largely unknown. We investigate clinical and immunological parameters in coinfected DENV/HIV patients. According to the new dengue classification, most coinfected DENV/HIV patients presented mild clinical manifestations of dengue infection. Herein, we show that DENV/HIV coinfected patients had higher CD8 T cells percentages reflected as a lower CD4/CD8 ratio. Furthermore, CCR5 expression on CD4 T cells and CD107a expression on both T subsets were significantly higher in coinfected patients when compared with monoinfected DENV and HIV individuals respectively. Increased inflammatory response was observed in treated HAART coinfected patients despite undetectable HIV load. These data indicate that DENV infection may influence the clinical profile and immune response in individuals concomitantly infected with HIV.

  19. Severe Pulmonary Arterial Hypertension in Patients Treated for Hepatitis C With Sofosbuvir.

    PubMed

    Renard, Sébastien; Borentain, Patrick; Salaun, Erwan; Benhaourech, Sanaa; Maille, Baptiste; Darque, Albert; Bregigeon, Sylvie; Colson, Philippe; Laugier, Delphine; Gaubert, Martine Reynaud; Habib, Gilbert

    2016-03-01

    Development of direct-acting antiviral agents against hepatitis C virus (HCV) has changed the management of chronic HCV infection. We report three cases of newly diagnosed or exacerbated pulmonary arterial hypertension (PAH) in patients treated with sofosbuvir. All patients had PAH-associated comorbidities (HIV coinfection in two, portal hypertension in one) and one was already being treated for PAH. At admission, all patients presented with syncope, World Health Organization functional class IV, right-sided heart failure, and extremely severe hemodynamic parameters. After specific PAH therapy, the clinical and hemodynamic properties for all patients were improved. Severity and acuteness of PAH, as well as chronology, could suggest a causal link between HCV treatment and PAH onset. We hypothesize that suppression of HCV replication promotes a decrease in vasodilatory inflammatory mediators leading to worsening of underlying PAH. The current report suggests that sofosbuvir-based therapy may be associated with severe PAH.

  20. Mycobacterium tuberculosis infection in a HIV-positive patient.

    PubMed

    Montales, Maria Theresa; Beebe, Alexandria; Chaudhury, Arun; Patil, Naveen

    2015-01-01

    Mycobacterium tuberculosis (MTB) and human immunodeficiency virus (HIV) coinfection remains a global public health challenge. We report a 40 year old African American male who is a known HIV-positive patient, non-compliant with his antiretrovirals and developed pulmonary tuberculosis. His chief complaints were chronic cough, fever, night sweats and undocumented weight loss. He had a prior positive T-SPOT-TB test; however, chest radiograph and sputum smear examination revealed normal results. PCR-based GeneXPERT MTB/RIF assay was ordered and confirmed MTB infection. The sputum cultures grew MTB and sensitivities showed susceptibility to all primary anti-tuberculosis medications. A delay in diagnosis and initiation of MTB therapy, in the setting of HIV or AIDS, may result in rapid disease progression and worse clinical outcome. PMID:26744689

  1. Adult separation anxiety in treatment nonresponders with anxiety disorders: delineation of the syndrome and exploration of attachment-based psychotherapy and biomarkers.

    PubMed

    Milrod, Barbara; Altemus, Margaret; Gross, Charles; Busch, Fredric; Silver, Gabrielle; Christos, Paul; Stieber, Joshua; Schneier, Franklin

    2016-04-01

    Clinically significant separation anxiety [SA] has been identified as being common among patients who do not respond to psychiatric interventions, regardless of intervention type (pharmacological or psychotherapeutic), across anxiety and mood disorders. An attachment formation and maintenance domain has been proposed as contributing to anxiety disorders. We therefore directly determined prevalence of SA in a population of adult treatment non-responders suffering from primary anxiety. In these separation anxious nonresponders, we pilot-tested an SA-focused, attachment-based psychotherapy for anxiety, Panic-Focused Psychodynamic Psychotherapy-eXtended Range [PFPP-XR], and assessed whether hypothesized biomarkers of attachment were engaged. We studied separation anxiety [SA] in 46 adults (ages 23-70 [mean 43.9 (14.9)]) with clinically significant anxiety symptoms (Hamilton Anxiety Rating Scale [HARS]≥15), and reporting a history of past non-response to psychotherapy and/or medication treatments. Thirty-seven (80%) had clinically significant symptoms of separation anxiety (Structured Clinical Interview for Separation Anxiety Symptoms [SCI-SAS] score≥8). Five of these subjects completed an open clinical trial of Panic Focused Psychodynamic Psychotherapy eXtended Range [PFPP-XR], a 21-24 session, 12-week manualized attachment-focused anxiolytic psychodynamic psychotherapy for anxiety. Patients improved on "adult threshold" SCI-SAS (current separation anxiety) (p=.016), HARS (p=0.002), and global severity, assessed by the Clinical Global Impression Scale (p=.0006), at treatment termination. Salivary oxytocin levels decreased 67% after treatment (p=.12). There was no significant change in high or low frequency HRV after treatment, but change in high frequency HRV inversely correlated with treatment change in oxytocin (p<.02), and change in low frequency HRV was positively associated with change in oxytocin (p<.02). SA is surprisingly prevalent among non-responders to

  2. Dyarrheal Syndrome in a Patient Co-Infected with Leishmania infantum and Schistosoma mansoni

    PubMed Central

    Cota, Gláucia Fernandes; Gomes, Luciana Inácia; Pinto, Bruna Fernandes; Santos-Oliveira, Joanna R.; Da-Cruz, Alda Maria; Pedrosa, Moisés Salgado; Tafuri, Wagner Luiz; Rabello, Ana

    2012-01-01

    This case report describes an atypical clinical presentation of visceral leishmaniasis affecting the digestive tract and causing malabsorption syndrome in a patient without recognized immunosuppressive condition. After appropriate treatment for the classical visceral form of the disease, diarrhea persisted as the main symptom and massive infection by Leishmania was detected by histopathology analysis of the duodenal mucosa. Schistosoma mansoni coinfection was also confirmed and treated without impact on diarrhea. New course of amphotericin B finally led to complete improvement of diarrhea. Atypical visceral leishmaniasis involving the gastrointestinal tract is well recognized in HIV coinfection but very rare in immunocompetent patients. The factors determining the control or evolution of the Leishmania infection have not been completely identified. This case stresses the importance of atypical symptoms and the unusual location of visceral leishmaniasis, not only in immunodepressed patients, and raises the possible influence of chronic infection by S. mansoni reducing the immune response to Leishmania. PMID:23213338

  3. Successful treatment of activated occult hepatitis B in a non-responder chronic hepatitis C patient

    PubMed Central

    2011-01-01

    We reported a 23 years old male with chronic hepatitis C virus infection, discontinued from pegylated interferon/ribavirin combination therapy due to a lack of early virological response. He has developed activation of occult hepatitis B virus that was successfully treated by a one year of lamivudine therapy. PMID:22078891

  4. Factors Related to Outcome in a School-Based Intensive Mental Health Program: An Examination of Nonresponders

    ERIC Educational Resources Information Center

    Jacobs, Anne K.; Roberts, Michael C.; Vernberg, Eric M.; Nyre, Joseph E.; Randall, Camille J.; Puddy, Richard W.

    2008-01-01

    We examined factors related to treatment responders (n = 35) and nonresponders (n = 16) in a group of 51 children admitted to the Intensive Mental Health Program (IMHP). Children's response to treatment was coded based on their functioning at intake and discharge using total CAFAS scores. Demographic variables, length of treatment, number of…

  5. The influence of multilevel upper airway surgery on CPAP tolerance in non-responders to obstructive sleep apnea surgery.

    PubMed

    Azbay, Sule; Bostanci, Asli; Aysun, Yasin; Turhan, Murat

    2016-09-01

    The aim of this study was to evaluate the influence of multilevel upper airway surgery on subsequent continuous positive airway pressure (CPAP) use and tolerance in patients with moderate to severe obstructive sleep apnea (OSA). The study cohort enrolled 67 consecutive patients, who underwent septoplasty plus modified uvulopharyngopalatoplasty (mUPPP) with or without modified tongue base suspension (mTBS) due to CPAP intolerance, and who had residual OSA requiring CPAP therapy [non-responders to surgery, apnea-hypopnea index (AHI) >15 events/h] that had been confirmed by control polysomnography at the sixth month postoperatively. A questionnaire including questions on postoperative CPAP use, problems faced during CPAP use after the surgery, change in OSA symptoms, and satisfaction with the surgery was designed, and filled through interviews. Seventeen (25.4 %) patients had septoplasty plus mUPPP and 50 (74.6 %) had septoplasty plus mUPPP combined with mTBS. Postoperatively, mean AHI (45.00 ± 19.76 vs. 36.60 ± 18.34), Epworth sleepiness scale (ESS) score (18.00 ± 4.45 vs. 13.00 ± 4.72), oxygen desaturation index (ODI) (48.98 ± 16.73 vs. 37.81 ± 17.03), and optimal CPAP level (11.80 ± 1.40 vs. 8.96 ± 1.20) were decreased (p < 0.001 for all parameters). Fifty-nine percent of patients reported that they fairly satisfied with the surgery and 49.2 % reported that their symptoms were completely resolved. While none of the cases could tolerate CPAP before surgery, almost half (47.8 %) of the cases used CPAP without problems postoperatively. Postoperative CPAP users had significantly higher postoperative AHI (p = 0.001), supine AHI (p = 0.009), ESS (p = 0.019), and ODI (p = 0.014), and significantly lower postoperative minimum O2 saturation (p = 0.001) compared with non-users. Multilevel upper airway surgery with less invasive techniques may improve CPAP tolerance in well-selected patients.

  6. Constraints of nonresponding flows based on cross layers in the networks

    NASA Astrophysics Data System (ADS)

    Zhou, Zhi-Chao; Xiao, Yang; Wang, Dong

    2016-02-01

    In the active queue management (AQM) scheme, core routers cannot manage and constrain user datagram protocol (UDP) data flows by the sliding window control mechanism in the transport layer due to the nonresponsive nature of such traffic flows. However, the UDP traffics occupy a large part of the network service nowadays which brings a great challenge to the stability of the more and more complex networks. To solve the uncontrollable problem, this paper proposes a cross layers random early detection (CLRED) scheme, which can control the nonresponding UDP-like flows rate effectively when congestion occurs in the access point (AP). The CLRED makes use of the MAC frame acknowledgement (ACK) transmitting congestion information to the sources nodes and utilizes the back-off windows of the MAC layer throttling data rate. Consequently, the UDP-like flows data rate can be restrained timely by the sources nodes in order to alleviate congestion in the complex networks. The proposed CLRED can constrain the nonresponsive flows availably and make the communication expedite, so that the network can sustain stable. The simulation results of network simulator-2 (NS2) verify the proposed CLRED scheme.

  7. Recent advances in vaccination of non-responders to standard dose hepatitis B virus vaccine

    PubMed Central

    Walayat, Saqib; Ahmed, Zohair; Martin, Daniel; Puli, Srinivas; Cashman, Michael; Dhillon, Sonu

    2015-01-01

    Hepatitis B virus (HBV) infection is a global health problem. It is estimated there are more than 2 billion individuals exposed to the virus and 250 million are chronically infected. Hepatitis B is the cause of more than 600000 annual deaths due to cirrhosis and hepatocellular carcinoma. An effective vaccine exists and preventative initiatives center around universal vaccination especially in those at highest risk. Effective vaccination algorithms have led to a significant decline in the development of new infections and its devastating consequences. The vaccine is administered intramuscularly in three doses, with 95% showing long lasting serologic immunity. An additional fourth dose or a repeated higher dose three course regimen is given to those that fail to show immunity. Despite these additional regimens, some remain vulnerable to hepatitis B and are deemed non-responders. Individuals with chronic disease states such as kidney disease, liver disease, diabetes mellitus, as well as those with a genetic predisposition, and those on immunomodulation therapy, have the highest likelihood of non-response. Various strategies have been developed to elicit an immune response in these individuals. These include increased vaccination dose, intradermal administration, alternative adjuvants, alternative routes of administration, co-administration with other vaccines, and other novel therapies. These alternative strategies can show improved response and lasting immunity. In summary, HBV vaccination is a major advance of modern medicine and all individuals at risk should be sought and vaccinated with subsequent adequate titers demonstrated. PMID:26523203

  8. Hansen's disease and HIV coinfection with facial nerve palsy

    PubMed Central

    Yadav, Nidhi; Kar, Sumit; Madke, Bhushan; Gangane, Nitin

    2015-01-01

    There are very few published reports of HIV leprosy co infection in India in spite of having a large burden of both leprosy and HIV. Herein we are reporting a case of co-infection of Hansen's disease and HIV with facial nerve palsy. PMID:25883486

  9. Total Delay Is Associated with Unfavorable Treatment Outcome among Pulmonary Tuberculosis Patients in West Gojjam Zone, Northwest Ethiopia: A Prospective Cohort Study

    PubMed Central

    Gebreegziabher, Senedu Bekele; Bjune, Gunnar Aksel; Yimer, Solomon Abebe

    2016-01-01

    Background delay in diagnosis and treatment of tuberculosis (TB) may worsen the disease, increase mortality and enhance transmission in the community. This study aimed at assessing the association between total delay and unfavorable treatment outcome among newly diagnosed pulmonary TB (PTB) patients. Methods A prospective cohort study was conducted in West Gojjam Zone, Amhara Region of Ethiopia from October 2013 to May 2015. Newly diagnosed PTB patients who were ≥15 years of age were consecutively enrolled in the study from 30 randomly selected public health facilities. Total delay (the time period from onset of TB symptoms to first start of anti-TB treatment) was measured. Median total delay was calculated. Mixed effect logistics regression was used to analyze factors associated with unfavorable treatment outcome. Results Seven hundred six patients were enrolled in the study. The median total delay was 60 days. Patients with total delay of > 60 days were more likely to have unfavorable TB treatment outcome than patients with total delay of ≤ 60 days (adjusted odds ratio [AOR], 2.33; 95% confidence interval [CI], 1.04–5.26). Human immunodeficiency virus (HIV) positive TB patients were 8.46 times more likely to experience unfavorable treatment outcome than HIV negative TB patients (AOR, 8.46; 95% CI, 3.14–22.79). Conclusions Long total delay and TB/HIV coinfection were associated with unfavorable treatment outcome. Targeted interventions that can reduce delay in diagnosis and treatment of TB, and early comprehensive management of TB/HIV coinfection are needed to reduce increased risk of unfavorable treatment outcome. PMID:27442529

  10. Real-time quantitative PCR in the diagnosis of tuberculosis in formalin-fixed paraffin-embedded pleural tissue in patients from a high HIV endemic area.

    PubMed

    Baba, Kamaldeen; Pathak, Sharad; Sviland, Lisbeth; Langeland, Nina; Hoosen, Anwar A; Asjo, Birgitta; Dyrhol-Riise, Anne M; Mustafa, Tehmina

    2008-06-01

    The aim of the study was to improve the diagnosis of pleural tuberculosis (TB) based on formalin-fixed biopsies from patients living in high TB and human immunodeficiency virus (HIV) endemic areas. A real-time polymerase chain reaction (real-time PCR) assay targeting a segment of the gene for mycobacterial 65-kd heat shock protein was developed and evaluated on pleural biopsies from 25 patients clinically diagnosed as having TB, on the basis of the good response to treatment, and from 11 controls. A nested polymerase chain reaction (N-PCR) assay for the repetitive genetic sequence insert IS6110, common to Mycobacterium tuberculosis complex organisms, was performed for comparison. When compared with N-PCR, the real-time PCR assay gave a sensitivity and specificity of 83% and 72%, respectively. When compared with clinical diagnosis, the sensitivity and specificity of real-time PCR (68% and 73%, respectively) was comparable with the sensitivity and specificity of the N-PCR assay (64% and 82%, respectively). There were no major differences in the diagnostic validity for the confirmed TB/HIV coinfected patients compared with the results from the whole TB group. In conclusion, the overall accuracy of the real-time PCR assay was comparable with that of the N-PCR and both were equally useful as diagnostic tools in the setting of a HIV coinfection. The real-time PCR has the additional advantage of a short turn-around time, low risk of sample contamination, and offers the possibility to quantify bacterial load, making it a powerful tool for the rapid diagnosis of TB pleuritis.

  11. Real-time quantitative PCR in the diagnosis of tuberculosis in formalin-fixed paraffin-embedded pleural tissue in patients from a high HIV endemic area.

    PubMed

    Baba, Kamaldeen; Pathak, Sharad; Sviland, Lisbeth; Langeland, Nina; Hoosen, Anwar A; Asjo, Birgitta; Dyrhol-Riise, Anne M; Mustafa, Tehmina

    2008-06-01

    The aim of the study was to improve the diagnosis of pleural tuberculosis (TB) based on formalin-fixed biopsies from patients living in high TB and human immunodeficiency virus (HIV) endemic areas. A real-time polymerase chain reaction (real-time PCR) assay targeting a segment of the gene for mycobacterial 65-kd heat shock protein was developed and evaluated on pleural biopsies from 25 patients clinically diagnosed as having TB, on the basis of the good response to treatment, and from 11 controls. A nested polymerase chain reaction (N-PCR) assay for the repetitive genetic sequence insert IS6110, common to Mycobacterium tuberculosis complex organisms, was performed for comparison. When compared with N-PCR, the real-time PCR assay gave a sensitivity and specificity of 83% and 72%, respectively. When compared with clinical diagnosis, the sensitivity and specificity of real-time PCR (68% and 73%, respectively) was comparable with the sensitivity and specificity of the N-PCR assay (64% and 82%, respectively). There were no major differences in the diagnostic validity for the confirmed TB/HIV coinfected patients compared with the results from the whole TB group. In conclusion, the overall accuracy of the real-time PCR assay was comparable with that of the N-PCR and both were equally useful as diagnostic tools in the setting of a HIV coinfection. The real-time PCR has the additional advantage of a short turn-around time, low risk of sample contamination, and offers the possibility to quantify bacterial load, making it a powerful tool for the rapid diagnosis of TB pleuritis. PMID:18382372

  12. Parents' difficulties as co-therapists in CBT among non-responding youths with anxiety disorders: Parent and therapist experiences.

    PubMed

    Lundkvist-Houndoumadi, Irene; Thastum, Mikael; Nielsen, Klaus

    2016-07-01

    No increased effect has been associated with parent involvement in cognitive behavioral therapy (CBT) for youths with anxiety disorders. The purpose of this study was to explore parent and therapist experiences of CBT among non-responding youths with anxiety disorders, with a primary focus on parent involvement in therapy. Interpretative phenomenological analysis was applied to 24 sets of semi-structured interviews with families and therapists of anxiety-disordered youths who had not profited from CBT with parental inclusion. From the superordinate theme parents' difficulties acting as co-therapists, which emerged from the analyses, two master themes represented the perspectives of parents (difficulty working together with the youth and feeling unqualified, with limited resources), and two represented the perspectives of therapists (family dynamics stood in the way of progress and difficulty transferring control to parents). Parent and therapist experiences complemented each other, offering two different perspectives on parent difficulties as co-therapists. However, the two groups' views on their respective roles in therapy were in conflict. Parents wished to remain being "just the parents" and for the experts to take over, while therapists wished to act as facilitators transferring the control to parents. Clinical implications are drawn for parental involvement and enhancement of treatment outcomes for likely non-responders.

  13. P2X7 Receptor Inhibition Improves CD34 T-Cell Differentiation in HIV-Infected Immunological Nonresponders on c-ART

    PubMed Central

    Menkova-Garnier, Inna; Hocini, Hakim; Foucat, Emile; Tisserand, Pascaline; Bourdery, Laure; Delaugerre, Constance; Benne, Clarisse; Lévy, Yves; Lelièvre, Jean-Daniel

    2016-01-01

    Peripheral CD4+ T-cell levels are not fully restored in a significant proportion of HIV+ individuals displaying long-term viral suppression on c-ART. These immunological nonresponders (INRs) have a higher risk of developing AIDS and non-AIDS events and a lower life expectancy than the general population, but the underlying mechanisms are not fully understood. We used an in vitro system to analyze the T- and B-cell potential of CD34+ hematopoietic progenitor cells. Comparisons of INRs with matched HIV+ patients with high CD4+ T-cell counts (immune responders (IRs)) revealed an impairment of the generation of T-cell progenitors, but not of B-cell progenitors, in INRs. This impairment resulted in the presence of smaller numbers of recent thymic emigrants (RTE) in the blood and lower peripheral CD4+ T-cell counts. We investigated the molecular pathways involved in lymphopoiesis, focusing particularly on T-cell fate specification (Notch pathway), survival (IL7R-IL7 axis) and death (Fas, P2X7, CD39/CD73). P2X7 expression was abnormally strong and there was no CD73 mRNA in the CD34+ cells of INRs, highlighting a role for the ATP pathway. This was confirmed by the demonstration that in vitro inhibition of the P2X7-mediated pathway restored the T-cell potential of CD34+ cells from INRs. Moreover, transcriptomic analysis revealed major differences in cell survival and death pathways between CD34+ cells from INRs and those from IRs. These findings pave the way for the use of complementary immunotherapies, such as P2X7 antagonists, to restore T-cell lymphopoiesis in INRs. PMID:27082982

  14. P2X7 Receptor Inhibition Improves CD34 T-Cell Differentiation in HIV-Infected Immunological Nonresponders on c-ART.

    PubMed

    Menkova-Garnier, Inna; Hocini, Hakim; Foucat, Emile; Tisserand, Pascaline; Bourdery, Laure; Delaugerre, Constance; Benne, Clarisse; Lévy, Yves; Lelièvre, Jean-Daniel

    2016-04-01

    Peripheral CD4+ T-cell levels are not fully restored in a significant proportion of HIV+ individuals displaying long-term viral suppression on c-ART. These immunological nonresponders (INRs) have a higher risk of developing AIDS and non-AIDS events and a lower life expectancy than the general population, but the underlying mechanisms are not fully understood. We used an in vitro system to analyze the T- and B-cell potential of CD34+ hematopoietic progenitor cells. Comparisons of INRs with matched HIV+ patients with high CD4+ T-cell counts (immune responders (IRs)) revealed an impairment of the generation of T-cell progenitors, but not of B-cell progenitors, in INRs. This impairment resulted in the presence of smaller numbers of recent thymic emigrants (RTE) in the blood and lower peripheral CD4+ T-cell counts. We investigated the molecular pathways involved in lymphopoiesis, focusing particularly on T-cell fate specification (Notch pathway), survival (IL7R-IL7 axis) and death (Fas, P2X7, CD39/CD73). P2X7 expression was abnormally strong and there was no CD73 mRNA in the CD34+ cells of INRs, highlighting a role for the ATP pathway. This was confirmed by the demonstration that in vitro inhibition of the P2X7-mediated pathway restored the T-cell potential of CD34+ cells from INRs. Moreover, transcriptomic analysis revealed major differences in cell survival and death pathways between CD34+ cells from INRs and those from IRs. These findings pave the way for the use of complementary immunotherapies, such as P2X7 antagonists, to restore T-cell lymphopoiesis in INRs. PMID:27082982

  15. D-Cycloserine for Treatment Nonresponders with Obsessive-Compulsive Disorder: A Case Report

    ERIC Educational Resources Information Center

    Norberg, Melissa M.; Gilliam, Christina M.; Villavicencio, Anna; Pearlson, Godfrey D.; Tolin, David F.

    2012-01-01

    Despite being the most effective treatment available, as many as one third of patients who receive exposure and response prevention (ERP) for obsessive-compulsive disorder (OCD) do not initially respond to treatment. Recent research suggests that the n-methyl d-aspartate (NMDA) receptor partial agonist D-Cycloserine (DCS) may speed up the course…

  16. An Open Trial of Intensive Family Based Cognitive-Behavioral Therapy in Youth with Obsessive-Compulsive Disorder Who Are Medication Partial Responders or Nonresponders

    ERIC Educational Resources Information Center

    Storch, Eric A.; Lehmkuhl, Heather D.; Ricketts, Emily; Geffken, Gary R.; Marien, Wendi; Murphy, Tanya K.

    2010-01-01

    This study reports an open-trial of family-based cognitive-behavioral therapy (CBT) in children and adolescents with obsessive-compulsive disorder (OCD). Thirty primarily Caucasian youth with OCD (range = 7-19 years; 15 girls) who were partial responders or nonresponders to two or more medication trials that were delivered either serially or…

  17. Visual Motor Integration as a Screener for Responders and Non-Responders in Preschool and Early School Years: Implications for Inclusive Assessment in Oman

    ERIC Educational Resources Information Center

    Emam, Mahmoud Mohamed; Kazem, Ali Mahdi

    2016-01-01

    Visual motor integration (VMI) is the ability of the eyes and hands to work together in smooth, efficient patterns. In Oman, there are few effective methods to assess VMI skills in children in inclusive settings. The current study investigated the performance of preschool and early school years responders and non-responders on a VMI test. The full…

  18. Nonresponders to Daily Paroxetine and Another SSRI in Men With Lifelong Premature Ejaculation: A Pharmacokinetic Dose-Escalation Study for a Rare Phenomenon

    PubMed Central

    Janssen, Paddy KC; Touw, Daan; Schweitzer, Dave H.

    2014-01-01

    Purpose Nonresponse to any selective serotonin reuptake inhibitor (SSRI) treatment is rare. In this study, we aimed to investigate ejaculation delay nonresponse to paroxetine treatment in men with lifelong premature ejaculation (PE) who were also known to be nonresponders to other SSRIs. Materials and Methods Five males with lifelong PE who were known nonresponders to paroxetine and other serotonergic antidepressants and eight males with lifelong PE who were specifically recruited were included. Blood sampling occurred 1 month and 1 day before the start of treatment and at the end of three consecutive series of 4 weeks of daily treatment with 10-, 20-, and 30-mg paroxetine, respectively. Blood samples for measurement of leptin and paroxetine were taken at 8:30 AM, 9:30 AM, 10:30 AM, and 11:30 AM, respectively. At 9:00 AM, one tablet of 10-, 20-, or 30-mg paroxetine was taken during the first, second, and third month, respectively. Intravaginal ejaculatory latency time (IELT) was measured with a stopwatch. The main outcome measures were the fold increase in the geometric mean IELT, serum leptin and paroxetine concentrations, body mass index (BMI), 5-HT1A receptor C-1019G polymorphism, and CYP2D6 mutations. Results Between the 7 paroxetine responders and 6 nonresponders, the fold increase in the geometric mean IELT was significantly different after daily 10-mg (p=0.003), 20-mg (p=0.002), and 30-mg paroxetine (p=0.026) and ranged from 2.0 to 8.8 and from 1.1 to 1.7, respectively. BMI at baseline and at the end of the study was not significantly different between responders and nonresponders. Serum leptin levels at baseline were similar in responders and nonresponders and did not change during treatment. The serum paroxetine concentration increased with increasing dosage and was not significantly different between responders and nonresponders. There was no association between the fold increase in the geometric mean IELT and serum paroxetine levels during the three

  19. Hepatitis C virus infection in HIV-infected patients.

    PubMed

    Sulkowski, Mark S

    2004-09-01

    Because of shared routes of transmission, hepatitis C and HIV coinfection is common in the United States, affecting 15% to 30% of HIV-infected individuals. In the era of highly effective antiretroviral therapy, hepatitis C virus (HCV)-related liver disease has emerged as a significant cause of morbidity and mortality. Accordingly, the Infectious Diseases Society of America and the American Association for the Study of Liver Disease guidelines for the management of HCV recommend that patients with HIV/HCV undergo medical evaluation for HCV-related liver disease and consideration for HCV treatment and, if indicated, orthotopic liver transplantation. However, the treatment of patients with HIV/HCV is complicated by the relatively high prevalence of medical and psychiatric comorbidities and the challenges of anti-HCV therapy in the setting of HIV disease and antiretroviral therapy. Nonetheless, recently completed randomized controlled trials provide evidence of the safety, tolerability, and efficacy of HCV treatment with pegylated interferon-alpha plus ribavirin in HIV-infected individuals. This review focuses on the epidemiology, natural history, and management of HCV in the HIV-infected patient.

  20. The failure of nonresponder mice to develop IgG memory assessed by in vitro culture with an antigen-LPS conjugate.

    PubMed

    Furman, A; Sercarz, E E

    1981-06-01

    A hen egg-white lysozyme-lipopolysaccharide complex (HEL-LPS) can stimulate an in vitro IgG response, but only from HEL-primed B lymphocytes; unprimed cells only produce an IgM response. These conditions were used to determine whether IgG memory B cells are cryptically induced in B10 nonresponder (H-2b) mice after an HEL injection protocol. The usual i.p. immunization that triggers IgG memory production in congenic responder strain mice fails to yield IgG in vitro from HEL-primed B10 spleen cells after stimulation with HEL-LPS. However, injection protocols immunogenic for B10 mice do engender IgG-memory cells. These results imply that the T helper cell population necessary for triggering B cells to the IgG memory stage cannot develop in the nonresponder mouse, presumably due to HEL-specific T suppressor cells.

  1. Safety and efficacy of daclatasvir in the management of patients with chronic hepatitis C

    PubMed Central

    Manolakopoulos, Spilios; Zacharakis, George; Zissis, Miltiadis; Giannakopoulos, Vassilis

    2016-01-01

    Daclatasvir (Daklinza™), a new oral direct-acting antiviral, is an inhibitor of hepatitis C virus NS5A protein and has recently been approved in the United States, Europe and Japan in chronic hepatitis C. It shows potent pangenotypic activity and moderately high genetic barrier to resistance improving the sustained virological response (SVR) rates. In COMMAND phase 2 trials, daclatasvir demonstrated high SVR rates in HCV genotype 1-4 chronically infected patients treated with peginterferon-a (pegIFNα) plus ribavirin (RBV). Furthermore, it produced even higher response rates in all-oral combination with sofosbuvir, an interferon-free regimen, with or without ribavirin, in patients with advanced liver disease, HCV/HIV coinfection, liver transplantation in ALLY studies and other real-world studies. This narrative review provides information on the pharmacological properties, role, efficacy and safety of daclatasvir-containing regimens in chronic hepatitis C patients. Daclatasvir administered once-daily in combination with sofosbuvir is an effective 12-week treatment in adult patients with chronic hepatitis C and is generally safe and well tolerated. PMID:27366028

  2. Brief Report: A High Rate of β7+ Gut-Homing Lymphocytes in HIV-Infected Immunological Nonresponders is Associated With Poor CD4 T-Cell Recovery During Suppressive HAART

    PubMed Central

    Girard, Alexandre; Vergnon-Miszczycha, Delphine; Depincé-Berger, Anne-Emmanuelle; Roblin, Xavier; Lutch, Frederic; Lambert, Claude; Rochereau, Nicolas; Bourlet, Thomas; Genin, Christian

    2016-01-01

    Objective: Correlation between GALT homing markers on lymphocytes and the low blood CD4 T-cell reconstitution in immunological nonresponders (INRs) has been studied. Design: Thirty-one INRs, 19 immunological responders (IRs), and 12 noninfected controls were enrolled in this study. INRs were defined by an undetectable plasma viral load RNA less than 40 copies per milliliter and CD4+ T-cell count <500 cells per cubic milliliter in at least 3 years. Methods: A complete peripheral and mucosal lymphocyte immunophenotyping was performed on these patients with a focus on the CCR9, CCR6, and α4β7 gut-homing markers. Results: A highly significant upregulation of α4β7 on INRs peripheral lymphocytes compared with that of IRs has been observed. This upregulation impacts different lymphocyte subsets namely CD4+, CD8+, and B lymphocytes. The frequency of β7+ Th17 and Treg cells are increased compared with IRs and healthy controls. The frequency of β7+ CD8+ T cells in the blood is negatively correlated with integrated proviral DNA in rectal lymphoid cells in contrast to β7+ CD4+ T cells associated with HIV integration. Conclusions: Alteration of lymphocyte homing abilities would have deleterious effects on GALT reconstitution and could participate to HIV reservoir constitution. These results emphasize the great interest to consider α4β7-targeted therapy in INR patients to block homing of lymphocytes and/or to directly impair gp120-α4β7 interactions. PMID:27306505

  3. Hepatitis B revaccination in healthy non-responder Chinese children: five-year follow-up of immune response and immunologic memory.

    PubMed

    Zhuang, Gui-Hua; Yan, Hong; Wang, Xue-Liang; Hwang, Lu-Yu; Wu, Qian; Wang, Li-Rong; Gao, Hai-Yan

    2006-03-15

    To assess persistence of anti-HBs and immunologic memory of non-responders after revaccination, 40 healthy non-responder children were given a three-dose recombinant hepatitis B vaccine revaccination randomly by intramuscular (10 microg per dose) or intradermal (2 microg per dose) route and followed up to five years. All 17 intramuscular and 22 of 23 intradermal children developed a seroprotective antibody response (anti-HBs>or=10 mIU/mL) after revaccination. Children of intramuscular group had significantly higher seroprotection rates and anti-HBs geometric mean titers than the intradermal group. At year 5, 50% of children in intramuscular group, but only 18.2% of intradermal group still maintained seroprotection (P=0.075). By the end of follow-up, a booster dose (5 microg) was given to those who had lost seroprotection. All the eight intramuscular children developed an anamnestic response with increase of anti-HBs level by 215 times, but two of the 18 intradermal children failed to produce seroprotective level. Three-routine-dose intramuscular revaccination was significantly more effective than low-dose intradermal revaccination with the same number of injections. No child seroconverted to HBsAg, and 11 had transient infections indicated by seroconversion to anti-HBc. These results demonstrated that non-responders could benefit from three doses intramuscular revaccination not only in high proportion of anti-HBs conversion but also in long-term persistence of seroprotection, and more importantly in preservation of the immunologic memory years after loss of protective anti-HBs.

  4. Early initiation of antiretroviral therapy: the current best way to reduce liver-related deaths in HIV/hepatitis C virus-coinfected patients.

    PubMed

    Shafran, Stephen D

    2007-04-15

    Approximately 25% to 35% of HIV-infected persons in developed countries are coinfected with hepatitis C virus (HCV). HCV liver disease is accelerated by HIV coinfection, especially at low CD4 cell counts. Highly active antiretroviral therapy (HAART) dramatically reduces HIV-related mortality, and liver disease has emerged as a major cause of death in HIV/HCV-coinfected persons. Anti-HCV therapy with pegylated interferon plus ribavirin can cure HCV infection in up to 40% of coinfected patients; however, only approximately 10% of coinfected patients are considered candidates. Hence, HCV therapy cures approximately 4% of coinfected patients. Eleven cohort studies have shown that HAART is associated with a reduced rate of progression of HCV liver disease, and 4 of these studies have demonstrated a reduction in liver-related mortality. Although offering HCV therapy to the few eligible HIV/HCV-coinfected patients is important, early initiation of HAART in coinfected patients has a greater public health impact in reducing liver-related mortality than in curing HCV infection in approximately 4% of these patients.

  5. Cellular immune responses in multiple sclerosis patients treated with interferon-beta

    PubMed Central

    Bustamante, M. F.; Rio, J.; Castro, Z.; Sánchez, A.; Montalban, X.; Comabella, M.

    2013-01-01

    Summary We investigated cellular immune responses at baseline in peripheral blood mononuclear cells (PBMC) of patients with multiple sclerosis (MS) treated with interferon (IFN)-β and classified into responders and non-responders according to clinical response criteria. Levels for IFN-γ, interleukin (IL)-17A, IL-17F, IL-10 and IL-4 were determined in activated PBMC of 10 responders, 10 non-responders and 10 healthy controls by cytometric bead arrays. Cytokine levels in cell culture supernatants were similar between responders and non-responders, and comparable to those obtained in healthy controls. These findings do not support differential cellular immune responses in PBMC at baseline between IFN-β responders and non-responders. PMID:23379429

  6. Performance of Interferon-Gamma and IP-10 Release Assays for Diagnosing Latent Tuberculosis Infections in Patients with Concurrent Malaria in Tanzania.

    PubMed

    Drabe, Camilla H; Vestergaard, Lasse S; Helleberg, Marie; Nyagonde, Nyagonde; Rose, Michala V; Francis, Filbert; Theilgaard, Ola P; Asbjørn, Jens; Amos, Ben; Bygbjerg, Ib Christian; Ruhwald, Morten; Ravn, Pernille

    2016-04-01

    Interferon-gamma (IFN-γ) release assays (IGRAs) are used to detect cellular immune recognition of Mycobacterium tuberculosis The chemokine IFN-γ-inducible protein 10 (IP-10) is an alternative diagnostic biomarker to IFN-γ. Several conditions interfere with IGRA test performance. We aimed to assess the possible influence of Plasmodium falciparum infection on the IGRA test QuantiFERON-TB GOLD® In-Tube (QFT) test and an in-house IP-10 release assay. In total, 241 Tanzanian adults were included; 184 patients with uncomplicated malaria (88 human immunodeficiency virus [HIV] coinfected) and 57 HIV-infected patients without malaria infection. Malaria was treated with artemether-lumefantrine (Coartem®). QFT testing was performed before initiation of malaria treatment and at days 7 and 42. In total, 172 patients completed follow-up. IFN-γ and IP-10 was measured in QFT supernatants. We found that during malaria infection IFN-γ and IP-10 levels in the unstimulated samples were elevated, mitogen responsiveness was impaired, and CD4 cell counts were decreased. These alterations reverted after malaria treatment. Concurrent malaria infection did not affect QFT test results, whereas there were more indeterminate IP-10 results during acute malaria infection. We suggest that IGRA and IP-10 release assay results of malaria patients should be interpreted with caution and that testing preferably should be postponed until after malaria treatment.

  7. Improved cell mediated immune responses after successful re-vaccination of non-responders to the hepatitis B virus surface antigen (HBsAg) vaccine using the combined hepatitis A and B vaccine.

    PubMed

    Nyström, Jessica; Cardell, Kristina; Björnsdottir, Thora Björg; Fryden, Aril; Hultgren, Catharina; Sällberg, Matti

    2008-11-01

    We successfully re-vaccinated hepatitis B virus (HBV) vaccine non-responders using a double dose of the combined hepatitis A virus (HAV) and HBV vaccine. The hope was to improve priming of hepatitis B surface antigen (HBsAg)-specific cell mediated immune response (CMI) by an increased antigen dose and a theoretical adjuvant-effect from the local presence of a HAV-specific CMI. A few non-responders had a detectable HBsAg-specific CMI before re-vaccination. An in vitro detectable HBsAg-specific CMI was primed equally effective in non-responders (58%) as in first time vaccine recipients (68%). After the third dose a weak, albeit significant, association was observed between the magnitude of HBsAg-specific proliferation and anti-HBs levels. This regimen improves the priming of HBsAg-specific CMIs and antibodies.

  8. Human T Cell Lymphotropic Virus Type 2a Strains Among HIV Type 1-Coinfected Patients from Brazil Have Originated Mostly from Brazilian Amerindians

    PubMed Central

    Magri, Mariana Cavalheiro; Brigido, Luis Fernando de Macedo; Morimoto, Helena Kaminami

    2013-01-01

    Abstract The human T cell lymphotropic virus type 2 (HTLV-2) is found mainly in Amerindians and in intravenous drug users (IDUs) from urban areas of the United States, Europe, and Latin America. Worldwide, HTLV-2a and HTLV-2b subtypes are the most prevalent. Phylogenetic analysis of HTLV-2 isolates from Brazil showed the HTLV-2a subtype, variant -2c, which spread from Indians to the general population and IDUs. The present study searched for the types of HTLV-2 that predominate among HIV-1-coinfected patients from southern and southeastern Brazil. Molecular characterization of the LTR, env, and tax regions of 38 isolates confirmed the HTLV-2c variant in 37 patients, and one HTLV-2b in a patient from Paraguay. Phylogenetic analysis of sequences showed different clades of HTLV-2 associated with risk factors and geographic region. These clades could represent different routes of virus transmission and/or little diverse evolutionary rates of virus. Taking into account the results obtained in the present study and the lack of the prototypic North American HTLV-2a strain and HTLV-2b subtypes commonly detected among HIV-coinfected individuals worldwide, we could speculate on the introduction of Brazilian HTLV-2 strains in such populations before the introduction of HIV. PMID:23484539

  9. Human T cell lymphotropic virus type 2a strains among HIV type 1-coinfected patients from Brazil have originated mostly from Brazilian Amerindians.

    PubMed

    Magri, Mariana Cavalheiro; Brigido, Luis Fernando de Macedo; Morimoto, Helena Kaminami; Caterino-de-Araujo, Adele

    2013-07-01

    The human T cell lymphotropic virus type 2 (HTLV-2) is found mainly in Amerindians and in intravenous drug users (IDUs) from urban areas of the United States, Europe, and Latin America. Worldwide, HTLV-2a and HTLV-2b subtypes are the most prevalent. Phylogenetic analysis of HTLV-2 isolates from Brazil showed the HTLV-2a subtype, variant -2c, which spread from Indians to the general population and IDUs. The present study searched for the types of HTLV-2 that predominate among HIV-1-coinfected patients from southern and southeastern Brazil. Molecular characterization of the LTR, env, and tax regions of 38 isolates confirmed the HTLV-2c variant in 37 patients, and one HTLV-2b in a patient from Paraguay. Phylogenetic analysis of sequences showed different clades of HTLV-2 associated with risk factors and geographic region. These clades could represent different routes of virus transmission and/or little diverse evolutionary rates of virus. Taking into account the results obtained in the present study and the lack of the prototypic North American HTLV-2a strain and HTLV-2b subtypes commonly detected among HIV-coinfected individuals worldwide, we could speculate on the introduction of Brazilian HTLV-2 strains in such populations before the introduction of HIV.

  10. Hepatocellular carcinoma surveillance rates in commercially insured patients with noncirrhotic chronic hepatitis B.

    PubMed

    Goldberg, D S; Valderrama, A; Kamalakar, R; Sansgiry, S S; Babajanyan, S; Lewis, J D

    2015-09-01

    American association for the study of liver diseases (AASLD) and European Association for the Study of the Liver (EASL) guidelines recommend biannual hepatocellular carcinoma (HCC) screening for noncirrhotic patients with chronic hepatitis B infection (HBV), yet there are no data estimating surveillance rates or factors associated with surveillance. We performed a retrospective cohort study of US patients using the Truven Health Analytics databases from 2006 to 2010 and identified patients with noncirrhotic chronic HBV. Surveillance patterns were characterized using categorical and continuous outcomes, with the continuous measure of the proportion of time 'up to date' with surveillance (PUTDS), with the 6-month interval following each ultrasound categorized as 'up to date'. During a median follow-up of 26.0 (IQR: 16.2-40.0) months among 4576 noncirrhotic patients with chronic HBV (median age: 44 years, IQR: 36-52), only 306 (6.7%) had complete surveillance (one ultrasound every 6-month interval), 2727 (59.6%) incomplete (≥1 ultrasound) and 1543 (33.7%) none. The mean PUTDS was 0.34 ± 0.29, and the median was 0.32 (IQR: 0.03-0.52). In multinomial logistic regression models, patients diagnosed by a nongastroenterologist were significantly less likely to have complete surveillance (P < 0.001), as were those coinfected with HBV/HIV (P < 0.001). In linear regression models, nongastroenterologist provider, health insurance subtype, HBV/HIV coinfection, rural status and metabolic syndrome were independently associated with decreased surveillance. Patients with HIV had an absolute decrease in the PUTDS of 0.24, while patients in less populated rural areas had an absolute decrease of 0.10. HCC surveillance rates in noncirrhotic patients with chronic HBV in the United States are poor and lower than reported rates of HCC surveillance in cirrhotic patients.

  11. Rifapentine for latent tuberculosis infection treatment in the general population and human immunodeficiency virus-positive patients: summary of evidence.

    PubMed

    Vidal, Júlia Souza; Silva, Marcus Tolentino; Sanchez, Mauro Niskier

    2015-01-01

    Latent tuberculosis infection (LTBI) and human immunodeficiency virus (HIV)-coinfection are challenges in the control of tuberculosis transmission. We aimed to assess and summarize evidence available in the literature regarding the treatment of LTBI in both the general and HIV-positive population, in order to support decision making by the Brazilian Tuberculosis Control Program for LTBI chemoprophylaxis. We searched MEDLINE, Cochrane Library, Centre for Reviews and Dissemination, Embase, LILACS, SciELO, Trip database, National Guideline Clearinghouse, and the Brazilian Theses Repository to identify systematic reviews, randomized clinical trials, clinical guidelines, evidence-based synopses, reports of health technology assessment agencies, and theses that investigated rifapentine and isoniazid combination compared to isoniazid monotherapy. We assessed the quality of evidence from randomized clinical trials using the Jadad Scale and recommendations from other evidence sources using the Grading of Recommendations, Assessment, Development, and Evaluations approach. The available evidence suggests that there are no differences between rifapentine + isoniazid short-course treatment and the standard 6-month isoniazid therapy in reducing active tuberculosis incidence or death. Adherence was better with directly observed rifapentine therapy compared to self-administered isoniazid. The quality of evidence obtained was moderate, and on the basis of this evidence, rifapentine is recommended by one guideline. Available evidence assessment considering the perspective of higher adherence rates, lower costs, and local peculiarity context might support rifapentine use for LTBI in the general or HIV-positive populations. Since novel trials are ongoing, further studies should include patients on antiretroviral therapy. PMID:26516958

  12. Combination Treatment for Visceral Leishmaniasis Patients Coinfected with Human Immunodeficiency Virus in India

    PubMed Central

    Mahajan, Raman; Das, Pradeep; Isaakidis, Petros; Sunyoto, Temmy; Sagili, Karuna D; Lima, Marıa Angeles; Mitra, Gaurab; Kumar, Deepak; Pandey, Krishna; Van geertruyden, Jean-Pierre; Boelaert, Marleen; Burza, Sakib

    2015-01-01

    Background. There are considerable numbers of patients coinfected with human immunodeficiency virus (HIV) and visceral leishmaniasis (VL) in the VL-endemic areas of Bihar, India. These patients are at higher risk of relapse and death, but there are still no evidence-based guidelines on how to treat them. In this study, we report on treatment outcomes of coinfected patients up to 18 months following treatment with a combination regimen. Methods. This retrospective analysis included all patients with confirmed HIV-VL coinfection receiving combination treatment for VL at a Médecins Sans Frontières treatment center between July 2012 and September 2014. Patients were treated with 30 mg/kg body weight intravenous liposomal amphotericin B (AmBisome) divided as 6 equal dose infusions combined with 14 days of 100 mg/day oral miltefosine (Impavido). All patients were encouraged to start or continue on antiretroviral therapy (ART). Results. 102 patients (76% males, 57% with known HIV infection, 54% with a prior episode of VL) were followed-up for a median of 11 months (interquartile range: 4–18). Cumulative incidence of all-cause mortality and VL relapse at 6, 12, and 18 months was 11.7%, 14.5%, 16.6% and 2.5%, 6.0%,13.9%, respectively. Cumulative incidence of poor outcome at 6, 12, and 18 months was 13.9%, 18.4%, and 27.2%, respectively. Not initiating ART and concurrent tuberculosis were independent risk factors for mortality, whereas no factors were associated with relapse. Conclusions. In this Bihar-based study, combination therapy appeared to be well tolerated, safe, and effective and may be considered as an option for treatment of VL in HIV coinfected patients. PMID:26129756

  13. Social constraints to TB/HIV healthcare: accounts from coinfected patients in South Africa.

    PubMed

    Daftary, Amrita; Padayatchi, Nesri

    2012-01-01

    There is a growing imperative to improve the coordination and collaboration of tuberculosis (TB) and HIV healthcare services in response to escalating rates of TB/HIV coinfection. Patient-specific challenges associated with the delivery of TB/HIV care have been minimally explored in this regard. As part of a larger study conducted in South Africa, this article highlights coinfected patients' experiences with TB and HIV healthcare in light of their broader social environments. Qualitative, in-depth interviews were conducted with 40 adult, coinfected patients (24 women and 16 men) and eight key-informant healthcare workers at three urban/peri-urban, ambulatory, public health clinics in the high-burden province of KwaZulu-Natal. Transcribed interviews were analyzed under a modified grounded theory approach to capture subjective meanings of healthcare experience subsequent to patients' codiagnosis with TB and HIV. Emerging analytic themes highlighted critical sociomedical constraints to TB/HIV care in relation to patients' income and employment, eligibility for social assistance and antiretroviral treatment, fears around illness disclosure, social and material support, and treatment adherence. Patients' healthcare experiences were bound by their poor access to essential resources, multiple life responsibilities, disparate gender roles, limits within the healthcare system, and the stigmatizing social symbolism of their illness. Overlapping social inequalities perpetuated coinfected patients' experiences with stigma and collectively mediated their health decisions around disclosure, adherence, and retention in medical care. The study urges a contextualized understanding of the social challenges associated with TB/HIV healthcare and helps inform more patient-sensitive and socially responsive interventions against the co-epidemic.

  14. HIV Coinfection With Hepatitis C Virus: Evolving Epidemiology and Treatment Paradigms

    PubMed Central

    Taylor, Lynn E.; Swan, Tracy; Mayer, Kenneth H.

    2012-01-01

    Chronic hepatitis C virus (HCV) infection has become a major threat to the survival of human immunodeficiency virus (HIV)–infected persons in areas where antiretroviral therapy is available. In coinfection, viral eradication has been difficult to attain, and HCV therapy is underused. Novel therapies may be particularly beneficial for this population, yet studies lag behind those for HCV monoinfection. Increasingly, incident HCV among HIV-infected men who have sex with men is associated with sexual risk behavior further research should be performed to refine understanding of the causal mechanism of this association. The phenomenon of aggressive hepatic fibrogenesis when HIV infection precedes HCV acquisition requires longer-term observation to ensure optimal timing of HCV therapy. Medical management in coinfection will be improved by enhancing HCV detection, with annual serologic testing, screening with HCV RNA to detect acute infection, and HIV testing of HCV-infected individuals; by addressing HCV earlier in coinfected persons; and by universal consideration for HCV therapy. HCV drug trials in individuals coinfected with HIV should be expedited. HIV/HCV coinfection remains a growing and evolving epidemic; new developments in therapeutics and improved care models offer promise. PMID:22715212

  15. Population Pharmacokinetics of Rifampin in Pregnant Women with Tuberculosis and HIV Coinfection in Soweto, South Africa

    PubMed Central

    Denti, Paolo; Martinson, Neil; Cohn, Silvia; Mashabela, Fildah; Hoffmann, Jennifer; Msandiwa, Reginah; Castel, Sandra; Wiesner, Lubbe; Chaisson, Richard E.; McIlleron, Helen

    2015-01-01

    Effective treatment of tuberculosis during pregnancy is essential for preventing maternal and fetal mortality, but little is known about the effects of pregnancy on the disposition of antituberculosis drugs. We explored the effects of pregnancy on the pharmacokinetics of rifampin, the key sterilizing drug in tuberculosis treatment, in Tshepiso, a prospective cohort study involving pregnant HIV-infected women with or without tuberculosis in Soweto, South Africa. Participants receiving standard first-line tuberculosis treatment underwent sparse sampling for rifampin at 37 weeks' gestation or delivery and then postpartum. Cord blood was collected when possible. A population pharmacokinetic model was developed to investigate the effects of pregnancy on rifampin pharmacokinetics. Among the 48 participants, median age and weight were 28 years and 67 kg, respectively. A one-compartment model with first-order elimination, transit compartment absorption, and allometric scaling described the data well. Pregnancy reduced rifampin clearance by 14%. The median (interquartile range) model-estimated rifampin area under the concentration-time curve over 24 h (AUC0–24) during pregnancy or intrapartum was 40.8 h · mg/liter (27.1 to 54.2 h · mg/liter) compared to 37.4 h · mg/liter (26.8 to 50.3 h · mg/liter) postpartum. The maximum concentrations were similar during pregnancy and postpartum. Rifampin was detectable in 36% (8/22) of cord blood samples, and 88% (42/48) of the women had successful treatment outcomes. There was one case of perinatal tuberculosis. In conclusion, rifampin clearance is modestly reduced during the last trimester of pregnancy. Exposures are only slightly increased, so dose adjustment during pregnancy is not needed. Rifampin was detected in cord blood samples when delivery occurred soon after dosing. The consequences of exposure to this potent inducer of metabolizing enzymes among HIV-exposed infants are unclear. PMID:26643345

  16. Relationship Between HIV Coinfection, Interleukin 10 Production, and Mycobacterium tuberculosis in Human Lymph Node Granulomas

    PubMed Central

    Diedrich, Collin R.; O'Hern, Jennifer; Gutierrez, Maximiliano G.; Allie, Nafiesa; Papier, Patricia; Meintjes, Graeme; Coussens, Anna K.; Wainwright, Helen; Wilkinson, Robert J.

    2016-01-01

    Background. Human immunodeficiency virus type 1 (HIV)–infected persons are more susceptible to tuberculosis than HIV–uninfected persons. Low peripheral CD4+ T-cell count is not the sole cause of higher susceptibility, because HIV–infected persons with a high peripheral CD4+ T-cell count and those prescribed successful antiretroviral therapy (ART) remain more prone to active tuberculosis than HIV–uninfected persons. We hypothesized that the increase in susceptibility is caused by the ability of HIV to manipulate Mycobacterium tuberculosis–associated granulomas. Methods. We examined 71 excised cervical lymph nodes (LNs) from persons with HIV and M. tuberculosis coinfection, those with HIV monoinfection, and those with M. tuberculosis monoinfection with a spectrum of peripheral CD4+ T-cell counts and ART statuses. We quantified differences in M. tuberculosis levels, HIV p24 levels, cellular response, and cytokine presence within granulomas. Results. HIV increased M. tuberculosis numbers and reduced CD4+ T-cell counts within granulomas. Peripheral CD4+ T-cell depletion correlated with granulomas that contained fewer CD4+ and CD8+ T cells, less interferon γ, more neutrophils, more interleukin 10 (IL-10), and increased M. tuberculosis numbers. M. tuberculosis numbers correlated positively with IL-10 and interferon α levels and fewer CD4+ and CD8+ T cells. ART reduced IL-10 production. Conclusions. Peripheral CD4+ T-cell depletion correlated with increased M. tuberculosis presence, increased IL-10 production, and other phenotypic changes within granulomas, demonstrating the HIV infection progressively changes these granulomas. PMID:27462092

  17. Complex Regional Pain Syndrome in Children: a Multidisciplinary Approach and Invasive Techniques for the Management of Nonresponders.

    PubMed

    Rodriguez-Lopez, Manuel J; Fernandez-Baena, Mariano; Barroso, Alex; Yáñez-Santos, Jose A

    2015-11-01

    Complex regional pain syndrome (CRPS) is multifactorial condition with complex pathogenesis characterized by spontaneous or stimulus-induced pain that is disproportionate to the inciting event. It is also commonly accompanied by a myriad of autonomic and motor disturbances in highly variable combinations. This condition has been underreported in children until recently. Consequently, the management of CRPS in the pediatric population presents an even greater challenge than in adults, partly because there is a lack of clinical data concerning the efficacy of the diverse treatment methods available, and partly because successful treatment of CRPS involves a multidisciplinary approach. In this retrospective case series, a multidisciplinary management plan is presented in 10 children for whom the standard noninvasive treatment was unsuccessful. Within this management plan, novel drugs were included such as the capsaicin 8% patch, in addition to invasive techniques in patients who did not respond to noninvasive therapies.

  18. Comparing recidivism rates of treatment responders/nonresponders in a sample of 413 child molesters who had completed community-based sex offender treatment in the United kingdom.

    PubMed

    Beech, Anthony R; Mandeville-Norden, Rebecca; Goodwill, Alasdair

    2012-02-01

    Analysis of psychometric data from a sample of 413 child molesters who had completed a U.K. probation-based sex offender treatment program was carried out to assess (a) the effectiveness of therapy in the short term and (b) the longer term implications of treatment in relation to sexual recidivism. It was found that 12% (51 offenders) of the sample had recidivated within 2 to 4 years. Of these recidivists, 86% (44 offenders) had been reconvicted for a sexually related offense. One hundred thirty-five offenders (33%) demonstrated a treated profile (i.e., demonstrated no offense-specific problems and few, or no, socioaffective problems at the posttreatment stage). This group was compared with a sample of offenders deemed as not responding to treatment, matched by their levels of pretreatment risk/need. It was found that a significantly smaller proportion (n = 12, 9%) of treatment responders had recidivated, compared to the treatment nonresponders (n = 20, 15%), indicating a 40% reduction in recidivism in those who had responded to treatment (effect size = .18). Matching length of treatment to the offenders' level of pretreatment risk/need (i.e., higher risk/treatment-need offenders typically undertook longer treatment) reduced the rate of recidivism among this group to the level of recidivism observed among the lower risk/need offenders.

  19. Co-infection assessment in HBV, HCV, and HIV patients in Western Saudi Arabia.

    PubMed

    Al-Mughales, Jamil A

    2016-09-01

    To estimate the prevalence of diagnosed and undiagnosed coinfections among HIV, HBV, and HCV infected patients. Retrospective analysis of laboratory records for HIV, HBV, and HCV patients presenting at the HIV outpatient clinic. Serological data including hepatitis B surface antigen (HBsAg), hepatitis B e-antigen (HBeAg), hepatitis B e-antibody (anti-HBe), antibodies to HIV and HCV, anti-toxoplasmosis IgG and IgM antibodies, and anti-syphilis antibodies (VDRL) were collected. We obtained data for 628 (218 HCV, 268 HBV, and 142 HIV) patients. Male-to-female ratios were 1:1 for HCV, 3:4 for HBV, and 5:3 for HIV. Age means (SD) were 54.24 (16.40), 44.53 (18.83), and 40.39 (15.92) years for HCV, HBV, and HIV, respectively. In HIV group, the prevalence of HBV and HCV coinfections was 8.5% and 2.8%, respectively. In HBV group, the prevalence of HCV and HIV coinfections was 1.1% and 1.5%, respectively. In HCV group, HIV or HBV coinfections occurred at the same frequency (1.4%). An absence of screening for coinfections was detected in 7.0-48.5% patients as per the group and the infectious agent; which represents an estimated proportion of 20 out of 1,000 patients with an undiagnosed coinfection. Despite a relatively low prevalence of coinfections, a significant proportion of cases remain undiagnosed because of a lack of systematic screening. J. Med. Virol. 88:1545-1551, 2016. © 2016 Wiley Periodicals, Inc. PMID:26895691

  20. Hematological and Biochemistry Profile and Risk Factors Associated with Pulmonary Tuberculosis Patients in Guyana.

    PubMed

    Kurup, Rajini; Flemming, Keon; Daniram, Sudish; Marks-James, Shenika; Roberts Martin, Roberta

    2016-01-01

    Objective. To evaluate the hematological and biochemistry profile of patients with or without HIV-TB at the Georgetown Chest Clinic, Guyana. Methods. An observational, laboratory based study was designed to assess the relationship of PTB and HIV with patients routine biochemical and hematological values. The study was conducted during the period January 2013 to December 2014; a total sample size of 316 patients was enrolled following exclusion and inclusion criteria. Results. Mean age of study population was 40.1 ± 13.8 (95% CI 38.6-41.7) and most were between 40 and 49 age group (27.8%, 95% CI 23.2-33.0). More males were in the study 74.4% (95% CI 69.3-78.8) than females 81% (95% CI 21.1-30.7). 30% (95% CI 25.3-35.3) had a sputum smear grade of 3+ and 62.5% (95% CI 47.0-75.7) showed a CD4 count <200. The study demonstrated significantly low hemoglobin (Hb) 91.7% (95% CI 78.2-97.1), low WBC 27.8% (95% CI 15.8-44.0), high indirect bilirubin 7.4% (95% CI 2.1-23.3), ALT 41.8% (95% CI 28.4-56.7), and AST 72.2% (95% CI 57.3-83.3) among TB-HIV patients. Homelessness RR (relative risk) 2.2 (95% CI 0.48-12.3), smoking RR 1.09 (95% CI 1.01-1.19), and gender (male) RR 1.2 (95% CI 0.61-2.26) were main associated risk factors. Conclusions. There is slight variation among PTB and PTB-HIV coinfected patients in some hematological and biochemistry parameters. PMID:27190646

  1. Co-infection assessment in HBV, HCV, and HIV patients in Western Saudi Arabia.

    PubMed

    Al-Mughales, Jamil A

    2016-09-01

    To estimate the prevalence of diagnosed and undiagnosed coinfections among HIV, HBV, and HCV infected patients. Retrospective analysis of laboratory records for HIV, HBV, and HCV patients presenting at the HIV outpatient clinic. Serological data including hepatitis B surface antigen (HBsAg), hepatitis B e-antigen (HBeAg), hepatitis B e-antibody (anti-HBe), antibodies to HIV and HCV, anti-toxoplasmosis IgG and IgM antibodies, and anti-syphilis antibodies (VDRL) were collected. We obtained data for 628 (218 HCV, 268 HBV, and 142 HIV) patients. Male-to-female ratios were 1:1 for HCV, 3:4 for HBV, and 5:3 for HIV. Age means (SD) were 54.24 (16.40), 44.53 (18.83), and 40.39 (15.92) years for HCV, HBV, and HIV, respectively. In HIV group, the prevalence of HBV and HCV coinfections was 8.5% and 2.8%, respectively. In HBV group, the prevalence of HCV and HIV coinfections was 1.1% and 1.5%, respectively. In HCV group, HIV or HBV coinfections occurred at the same frequency (1.4%). An absence of screening for coinfections was detected in 7.0-48.5% patients as per the group and the infectious agent; which represents an estimated proportion of 20 out of 1,000 patients with an undiagnosed coinfection. Despite a relatively low prevalence of coinfections, a significant proportion of cases remain undiagnosed because of a lack of systematic screening. J. Med. Virol. 88:1545-1551, 2016. © 2016 Wiley Periodicals, Inc.

  2. Combination chemotherapy followed by surgery or radiotherapy in patients with locally advanced cervical cancer.

    PubMed

    Kirsten, F; Atkinson, K H; Coppleson, J V; Elliott, P M; Green, D; Houghton, R; Murray, J C; Russell, P; Solomon, H J; Friedlander, M

    1987-06-01

    Forty-seven patients with locally advanced cervical cancer at high risk of relapse received three cycles of chemotherapy with PVB (cisplatin, vinblastine and bleomycin) before definitive local treatment with either radical surgery or radiotherapy. Thirty-one of the 47 patients (66%) responded to initial chemotherapy, and 11 of them have relapsed compared with 13 of the 16 non-responders. Median time to recurrence was 31 weeks for PVB non-responders but has not yet been reached for PVB responders. After a median follow-up of 128 weeks, 14 of the 31 responders (45%) are alive and disease free compared with 3 of the 16 non-responders (19%). There was a positive correlation between response to chemotherapy and subsequent response to radiotherapy. PVB was in general well tolerated although one death is probably attributable to chemotherapy. A randomized study comparing radiotherapy alone with initial PVB chemotherapy followed by radiotherapy is in progress. PMID:2441736

  3. Diagnostic accuracy of APRI, FIB-4 and Forns for the detection of liver cirrhosis in HIV/HCV-coinfected patients.

    PubMed

    Merli, Marco; Castagna, Antonella; Salpietro, Stefania; Gianotti, Nicola; Messina, Emanuela; Poli, Andrea; Morsica, Giulia; Bagaglio, Sabrina; Cernuschi, Massimo; Bigoloni, Alba; Uberti-Foppa, Caterina; Lazzarin, Adriano; Hasson, Hamid

    2016-04-01

    Non-invasive assessment of liver fibrosis represents an appealing method to monitor liver disease in HCV-infected patients. Currently, transient elastography (TE) is the most accurate non-invasive tool to measure liver stiffness (LS), with the diagnostic accuracy increasing together with the stage of fibrosis (Friedrich Rust et al., 2008; Degos et al., 2010). Stiffness measurement is widely used in the assessment of fibrosis in patients with chronic hepatitis C given its good reproducibility (Fraquelli et al., 2007) and its association with the risk of liver-related complications and death in HIV/HCV-coinfected patients (Fernandez-Montero et al., 2013) and also in patients with compensated HCV-related liver cirrhosis (with or without concomitant HIV-coinfection) (Pérez-Latorre et al., 2014). In the last decade, direct and indirect biomarkers for predicting liver fibrosis have also been developed. Direct fibrosis biomarkers (e.g. FibroTest, FibroMeter) are calculated using serum molecules produced in the presence of liver fibrosis and released in the circulatory system while indirect biomarkers (e.g. APRI, FIB-4, Forns) result from the combination of routine blood tests. Even though indirect biomarkers had a lower diagnostic performance than direct biomarkers and especially TE (Sánchez-Conde et al., 2010; Degos et al., 2010; Castéra et al., 2014), the absence of additional costs and the ready availability make indirect biomarkers a quick and easy non-invasive method to periodically assess liver fibrosis. Since the early detection of liver cirrhosis has a significant impact on both clinical management and treatment decision regarding chronic hepatitis C, we evaluated the threshold and the diagnostic accuracy of APRI, FIB-4 and Forns for the diagnosis of liver cirrhosis in HIV/HCV-coinfected patients. PMID:27196548

  4. Diagnostic accuracy of APRI, FIB-4 and Forns for the detection of liver cirrhosis in HIV/HCV-coinfected patients.

    PubMed

    Merli, Marco; Castagna, Antonella; Salpietro, Stefania; Gianotti, Nicola; Messina, Emanuela; Poli, Andrea; Morsica, Giulia; Bagaglio, Sabrina; Cernuschi, Massimo; Bigoloni, Alba; Uberti-Foppa, Caterina; Lazzarin, Adriano; Hasson, Hamid

    2016-04-01

    Non-invasive assessment of liver fibrosis represents an appealing method to monitor liver disease in HCV-infected patients. Currently, transient elastography (TE) is the most accurate non-invasive tool to measure liver stiffness (LS), with the diagnostic accuracy increasing together with the stage of fibrosis (Friedrich Rust et al., 2008; Degos et al., 2010). Stiffness measurement is widely used in the assessment of fibrosis in patients with chronic hepatitis C given its good reproducibility (Fraquelli et al., 2007) and its association with the risk of liver-related complications and death in HIV/HCV-coinfected patients (Fernandez-Montero et al., 2013) and also in patients with compensated HCV-related liver cirrhosis (with or without concomitant HIV-coinfection) (Pérez-Latorre et al., 2014). In the last decade, direct and indirect biomarkers for predicting liver fibrosis have also been developed. Direct fibrosis biomarkers (e.g. FibroTest, FibroMeter) are calculated using serum molecules produced in the presence of liver fibrosis and released in the circulatory system while indirect biomarkers (e.g. APRI, FIB-4, Forns) result from the combination of routine blood tests. Even though indirect biomarkers had a lower diagnostic performance than direct biomarkers and especially TE (Sánchez-Conde et al., 2010; Degos et al., 2010; Castéra et al., 2014), the absence of additional costs and the ready availability make indirect biomarkers a quick and easy non-invasive method to periodically assess liver fibrosis. Since the early detection of liver cirrhosis has a significant impact on both clinical management and treatment decision regarding chronic hepatitis C, we evaluated the threshold and the diagnostic accuracy of APRI, FIB-4 and Forns for the diagnosis of liver cirrhosis in HIV/HCV-coinfected patients.

  5. Nanomedicines in the treatment of patients with hepatitis C co-infected with HIV--focus on pegylated interferon-alpha.

    PubMed

    Zoller, Heinz; Vogel, Wolfgang

    2006-01-01

    In immuno-competent individuals, the natural course of chronic hepatitis C virus (HCV) infection is highly variable and 5%-30% of patients develop cirrhosis over 20 years. Co-infection with HCV and human immunodeficiency virus (HIV) is an important prognostic factor and associated with more frequent and accelerated progression to cirrhosis. Until recently HIV/AIDS-related complications were life limiting in patients co-infected with HCV; the introduction of highly active antiretroviral treatment (HAART) and the better prognosis of HIV infection has made HCV-related complications an emerging health problem in HCV/HIV coinfected individuals. Treatment of chronic HCV infection has also evolved since the introduction of interferon-alpha. Recently, introduction of pegylated interferon-alpha (peginterferon-alpha) has resulted in an increase in sustained virus clearance rates of up to 80% in selected genotypes and patient populations. The safety and efficacy of modern anti HCV treatment regimens - based on peginterferon-alpha in combination with ribavirin - was evaluated in 4 controlled trials. Sustained clearance of hepatitis C virus can be achieved in up to 35% of patients with HIV/HCV co-infection, and novel HCV treatment regimens based on peginterferon-alpha have no negative effect on the control of HIV disease. In conclusion, if HIV infection is well controlled and CD4+ cell counts >100/mm3, treatment of chronic hepatitis C with peginterferon in combination with ribavirin is safe and should be given for 48 weeks regardless of the HCV genotype. Introduction of peginterferon-alpha has significantly improved adherence to treatment and treatment efficacy; in particular sustained virologic response in patients with HCV genotype 1 or 4 infection improved, but sustained viral clearance in only 7%-38% of patients infected with genotype I and 4 cannot be the final step in development of effective treatments in patients with HCV/HIV co-infection.

  6. Efficacy of and risk of bleeding during pegylated interferon plus ribavirin treatment in HIV/HCV-coinfected patients with pretreatment thrombocytopenia.

    PubMed

    Mira, J A; Neukam, K; López-Cortés, L F; Rivero-Juárez, A; Téllez, F; Girón-González, J A; de los Santos-Gil, I; Ojeda-Burgos, G; Merino, D; Ríos-Villegas, M J; Collado, A; Torres-Cornejo, A; Macías, J; Rivero, A; Pérez-Pérez, M; Pineda, J A

    2015-09-01

    The aim of this study was to assess the efficacy of and the risk of major bleeding during pegylated interferon (peg-IFN)/ribavirin (RBV) treatment among human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients according to the pretreatment platelet count. Two hundred and seventy-four HCV/HIV-coinfected, previously naïve individuals with compensated cirrhosis enrolled in one Spanish prospective cohort who received peg-IFN/RBV were included in this study. The frequency of severe bleeding and sustained virological response (SVR) rate were compared between patients with a pretreatment platelet count ≤70,000/mm(3) and >70,000/mm(3), respectively. Sixty-one (22 %) patients had a baseline platelet count ≤70,000/mm(3). The median (Q1-Q3) pretreatment platelet count was 58,000 (49,000-65,000) cells/mm(3) in the platelet ≤70,000 group and 129,000 (102,500-166,000) cells/mm(3) in the platelet >70,000 group (p < 0.0001). Seventeen (28 %) subjects of the platelet ≤70,000 group and 71 (33 %) patients of the platelet >70,000 group achieved SVR (p = 0.4). Only 2 (3.2 %) patients in the platelet ≤70,000 group developed a severe hemorrhagic event, specifically esophageal variceal bleeding. The efficacy of therapy with peg-IFN/RBV in HIV/HCV-coinfected patients with low pretreatment platelet counts is comparable to that found in the overall subset of subjects with compensated cirrhosis. The frequency of severe hemorrhagic events related with this therapy is low in this population. PMID:26115631

  7. Efficacy of and risk of bleeding during pegylated interferon plus ribavirin treatment in HIV/HCV-coinfected patients with pretreatment thrombocytopenia.

    PubMed

    Mira, J A; Neukam, K; López-Cortés, L F; Rivero-Juárez, A; Téllez, F; Girón-González, J A; de los Santos-Gil, I; Ojeda-Burgos, G; Merino, D; Ríos-Villegas, M J; Collado, A; Torres-Cornejo, A; Macías, J; Rivero, A; Pérez-Pérez, M; Pineda, J A

    2015-09-01

    The aim of this study was to assess the efficacy of and the risk of major bleeding during pegylated interferon (peg-IFN)/ribavirin (RBV) treatment among human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients according to the pretreatment platelet count. Two hundred and seventy-four HCV/HIV-coinfected, previously naïve individuals with compensated cirrhosis enrolled in one Spanish prospective cohort who received peg-IFN/RBV were included in this study. The frequency of severe bleeding and sustained virological response (SVR) rate were compared between patients with a pretreatment platelet count ≤70,000/mm(3) and >70,000/mm(3), respectively. Sixty-one (22 %) patients had a baseline platelet count ≤70,000/mm(3). The median (Q1-Q3) pretreatment platelet count was 58,000 (49,000-65,000) cells/mm(3) in the platelet ≤70,000 group and 129,000 (102,500-166,000) cells/mm(3) in the platelet >70,000 group (p < 0.0001). Seventeen (28 %) subjects of the platelet ≤70,000 group and 71 (33 %) patients of the platelet >70,000 group achieved SVR (p = 0.4). Only 2 (3.2 %) patients in the platelet ≤70,000 group developed a severe hemorrhagic event, specifically esophageal variceal bleeding. The efficacy of therapy with peg-IFN/RBV in HIV/HCV-coinfected patients with low pretreatment platelet counts is comparable to that found in the overall subset of subjects with compensated cirrhosis. The frequency of severe hemorrhagic events related with this therapy is low in this population.

  8. Hepatitis C virus long-term persistence in peripheral blood mononuclear cells in patients with haemophilia. Detection of occult genotype 1.

    PubMed

    Parodi, C; García, G; Monzani, M C; Culasso, A; Aloisi, N; Corti, M; Campos, R; de E de Bracco, M M; Baré, P

    2015-07-01

    Peripheral blood mononuclear cells (PBMC) from chronic hepatitis C virus-infected persons can harbour viral variants that are not detected in plasma samples. We explored the presence and persistence of HCV genotypes in plasma and PBMC cultures from 25 HCV-monoinfected and 25 HIV/HCV-coinfected patients with haemophilia. Cell cultures were performed at different time points between 1993 and 2010-2011, and the HCV genome was examined in culture supernatants. Sequential plasma samples were studied during the same time period. Analysing sequential plasma samples, 21% of patients had mixed-genotype infections, while 50% had mixed infections determined from PBMC culture supernatants. HIV coinfection was significantly associated with the presence of mixed infections (OR = 4.57, P = 0.02; 95% CI = 1.38-15.1). In our previous study, genotype 1 was found in 72% of 288 patients of this cohort. Similar results were obtained with the sequential plasma samples included in this study, 69% had genotype 1. However, when taking into account plasma samples and the results from PBMC supernatants, genotype 1 was identified in 94% of the population. The PBMC-associated variants persisted for 10 years in some subjects, emphasizing their role as long-term reservoirs. The presence of genotype 1 in PBMC may be associated with therapeutic failure and should not be disregarded when treating haemophilic patients who have been infected by contaminated factor concentrates. The clinical implications of persistent lymphotropic HCV variants deserve further examination among multiple exposed groups of HCV-infected patients.

  9. Time trends of seroepidemiology of hepatitis C virus and hepatitis B virus coinfection in human immunodeficiency virus-infected patients in a Super Specialty Hospital in New Delhi, India: 2012–2014

    PubMed Central

    Sharma, Abha; Halim, Jasmin; Jaggi, Tavleen; Mishra, Bibhabati; Thakur, Archana; Dogra, Vinita; Loomba, Poonam Sood

    2016-01-01

    Background: Hepatitis viruses and human immunodeficiency virus (HIV) coinfection is a major cause of liver diseases worldwide. High prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) in Asia makes it important to understand HBV and HCV coinfection with HIV in this part of the globe. This study was done with the aim of assessing the time trends of seroepidemiology of HBV and HCV coinfection in HIV patients over the last 3 years. Materials and Methods: Year wise retrospective analysis of data between January 2012 and December 2014 was done. Results: The prevalence of HIV infection among 0–20 years and >60 years age group decreased over the last 3 years (2012–2014), 8.4%, 6.4%, and 3.1% and 3.6%, 3.8%, and 1.5%, respectively. While increasing prevalence was seen among 21–40 years age group, 57.8%, 60.2%, and 67.1%, respectively in 2012, 2013, and 2014. There was no significant relationship between age/gender and HBV/HCV seropositivity among HIV-positive patients. The risk of acquiring HBV infection was more in HIV-positive patients who were >60 years of age (odds ratio = 3.3182; 95% confidence interval: 0.3669–30.005). The prevalence of HCV seropositivity is less in HIV-positive patients as only one case was anti-HCV antibody positive in last 3 years who was a male patient in the age group 21–40 years. A declining trend was observed for HIV positive cases over 2012–2014 while no significant trend change is seen in HBV/HCV seropositivity among HIV patients from 2012 to 2104. Conclusion: It is recommended to screen HIV patients routinely for concurrent HBV/HCV infection as hepatotropic viruses with HIV increase the risk of liver mortalities. PMID:27190410

  10. Treatment outcome expectancies and hypnotic susceptibility as moderators of pain reduction in patients with chronic tension-type headache.

    PubMed

    Spinhoven, P; ter Kuile, M M

    2000-07-01

    The aim of this study was to determine whether hypnotic susceptibility (a) predicts pain reduction posttreatment and at follow-up independent of generic expectations of treatment outcome and mode of treatment and (b) predicts persistence of pain reduction during the follow-up period. In 169 patients with chronic tension-type headaches randomly allocated to either self-hypnosis or autogenic training, pain reduction posttreatment and at follow-up was significantly associated with hypnotic susceptibility independent of generic expectations of treatment outcome and treatment condition. Moreover, it was found that early responders obtained significantly higher hypnotic susceptibility scores than nonresponders, although there were no significant differences in hypnotic susceptibility between late responders in comparison to early and nonresponders. However, almost one fourth of those who were nonresponders posttreatment did respond at follow-up.

  11. Rifaximin has a Marginal Impact on Microbial Translocation, T-cell Activation and Inflammation in HIV-Positive Immune Non-responders to Antiretroviral Therapy – ACTG A5286

    PubMed Central

    Tenorio, Allan R.; Chan, Ellen S.; Bosch, Ronald J.; Macatangay, Bernard J. C.; Read, Sarah W.; Yesmin, Suria; Taiwo, Babafemi; Margolis, David M.; Jacobson, Jeffrey M.; Landay, Alan L.; Wilson, Cara C.; Mellors, John W.; Keshavarzian, Ali; Rodriguez, Benigno; Aziz, Mariam; Presti, Rachel; Deeks, Steven; Ebiasah, Ruth; Myers, Laurie; Borowski, LuAnn; Plants, Jill; Palm, David A.; Weibel, Derek; Putnam, Beverly; Lindsey, Elizabeth; Player, Amy; Albrecht, Mary; Kershaw, Andrea; Sax, Paul; Keenan, Cheryl; Walton, Patricia; Baum, Jane; Stroberg, Todd; Hughes, Valery; Coster, Laura; Kumar, Princy N.; Yin, Michael T.; Noel-Connor, Jolene; Tebas, Pablo; Thomas, Aleshia; Davis, Charles E.; Redfield, Robert R.; Sbrolla, Amy; Flynn, Teri; Davis, Traci; Whitely, Kim; Singh, Baljinder; Swaminathan, Shobha; McGregor, Donna; Palella, Frank; Aberg, Judith; Cavanagh, Karen; Santana Bagur, Jorge L.; Flores, Olga Méndez; Fritsche, Janice; Sha, Beverly; Slamowitz, Debbie; Valle, Sandra; Tashima, Karen; Patterson, Helen; Harber, Heather; Para, Michael; Eaton, Molly; Maddox, Dale; Currier, Judith; Cajahuaringa, Vanessa; Luetkemeyer, Annie; Dwyer, Jay; Fichtenbaum, Carl J.; Saemann, Michelle; Ray, Graham; Campbell, Thomas; Fischl, Margaret A.; Bolivar, Hector; Oakes, Jonathan; Chicurel-Bayard, Miriam; Tripoli, Christine; Weinman, D. Renee; Adams, Mary; Hurley, Christine; Dunaway, Shelia; Storey, Sheryl; Klebert, Michael; Royal, Michael

    2015-01-01

    Background. Rifaximin, a nonabsorbable antibiotic that decreases lipopolysaccharide (LPS) in cirrhotics, may decrease the elevated levels of microbial translocation, T-cell activation and inflammation in human immunodeficiency virus (HIV)-positive immune nonresponders to antiretroviral therapy (ART). Methods. HIV-positive adults receiving ART for ≥96 weeks with undetectable viremia for ≥48 weeks and CD4+ T-cell counts <350 cells/mm3 were randomized 2:1 to rifaximin versus no study treatment for 4 weeks. T-cell activation, LPS, and soluble CD14 were measured at baseline and at weeks 2, 4, and 8. Wilcoxon rank sum tests compared changes between arms. Results. Compared with no study treatment (n = 22), rifaximin (n = 43) use was associated with a significant difference between study arms in the change from baseline to week 4 for CD8+T-cell activation (median change, 0.0% with rifaximin vs +0.6% with no treatment; P = .03). This difference was driven by an increase in the no-study-treatment arm because there was no significant change within the rifaximin arm. Similarly, although there were significant differences between study arms in change from baseline to week 2 for LPS and soluble CD14, there were no significant changes within the rifaximin arm. Conclusions. In immune nonresponders to ART, rifaximin minimally affected microbial translocation and CD8+T-cell activation. Trial registration number. NCT01466595. PMID:25214516

  12. Quantification of Hepatitis C Virus (HCV) in Liver Specimens and Sera from Patients with Human Immunodeficiency Virus Coinfection by Using the Versant HCV RNA 3.0 (Branched DNA-Based) DNA Assay

    PubMed Central

    Tedeschi, Rosamaria; Pivetta, Eliana; Zanussi, Stefania; Bidoli, Ettore; Ros, Mirna; di Gennaro, Giampiero; Nasti, Guglielmo; De Paoli, Paolo

    2003-01-01

    The new generation assay Versant HCV RNA 3.0v (Bayer Diagnostics) was evaluated to quantify hepatitis C virus (HCV) RNA levels in liver biopsy specimens from patients with HCV and human immunodeficiency virus (HIV) coinfection. A total of 25 liver biopsies and sera collected at the time of liver biopsy were used. The efficiency of HCV RNA recovery from spiked samples was between 38.6 and 50.7%, and reproducible measurements of viral load were observed (the intra- and interrun coefficients of variation were 0.5 to 13% and 3.5 to 24.7%, respectively), with good specificity and sensitivity. Linearity was evaluated in the range of 96,154 to 769 IU/μg by using a serially diluted high-titer sample. Coinfected patients had high HCV RNA viral loads in serum and liver (498,471 IU/ml and 231,495 IU/μg, respectively), and both levels were correlated (r = 0.63; P < 0.01). The amount of hepatic HCV RNA was significantly higher among patients with genotype 1 than among patients with genotype 3 (P < 0.01). The virological end-of-treatment response in the serum was associated with a lower pretreatment intrahepatic HCV viral load (P = 0.03). The new version of b-DNA is a sensitive, specific, and reproducible method for quantitating HCV RNA in the liver. Given its positive analytical performance, the assay will be used to evaluate the HCV RNA levels in the serum and liver during follow-up of patients treated with an anti-HCV therapeutic regimen. PMID:12843041

  13. Patients with Poor Response to Antipsychotics Have a More Severe Pattern of Frontal Atrophy: A Voxel-Based Morphometry Study of Treatment Resistance in Schizophrenia

    PubMed Central

    Palladino, Olga; Schiavone, Vittorio; Carotenuto, Barbara; Brunetti, Arturo; Casiello, Margherita; Muscettola, Giovanni; Salvatore, Marco; de Bartolomeis, Andrea

    2014-01-01

    Approximately 30% of schizophrenia patients do not respond adequately to the therapy. Previous MRI studies have suggested that drug treatment resistance is associated with brain morphological abnormalities, although region-of-interest analysis of MR studies from nonresponder and responder patients failed to demonstrate a statistically significant difference between these two schizophrenia subgroups. We have used a voxel-based analysis of segmented MR studies to assess structural cerebral differences in 20 nonresponder and 15 responder patients and 16 age-matched normal volunteers. Differences between the three groups emerged bilaterally mainly at the level of the superior and middle frontal gyri, primarily due to reduced grey matter volumes in nonresponders, as compared to both normal volunteers and responder patients. Post hoc direct comparison between the two schizophrenia subgroups demonstrated significantly reduced grey matter volumes in middle frontal gyrus bilaterally, in the dorsolateral aspects of left superior frontal gyrus extending into postcentral gyrus and in the right medial temporal cortex. Our results extend and integrate previous findings suggesting a more severe atrophy in nonresponder schizophrenia patients, compared to responder patients, mainly at the level of the superior and middle frontal gyri. Longitudinal studies in drug-naïve patients are needed to assess the role of these associations. PMID:25157354

  14. Slow CD4+ T-Cell Recovery in Human Immunodeficiency Virus/Hepatitis B Virus-Coinfected Patients Initiating Truvada-Based Combination Antiretroviral Therapy in Botswana

    PubMed Central

    Anderson, Motswedi; Gaseitsiwe, Simani; Moyo, Sikhulile; Thami, Kerapetse P.; Mohammed, Terence; Setlhare, Ditiro; Sebunya, Theresa K.; Powell, Eleanor A.; Makhema, Joseph; Blackard, Jason T.; Marlink, Richard; Essex, Max; Musonda, Rosemary M.

    2016-01-01

    Background. Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection has emerged as an important cause of morbidity and mortality. We determined the response to Truvada-based first-line combination antiretroviral therapy (cART) in HIV/HBV-coinfected verus HIV-monoinfected patients in Botswana. Methods. Hepatitis B virus surface antigen (HBsAg), HBV e antigen (HBeAg), and HBV deoxyribonucleic acid (DNA) load were determined from baseline and follow-up visits in a longitudinal cART cohort of Truvada-based regimen. We assessed predictors of HBV serostatus and viral suppression (undetectable HBV DNA) using logistic regression techniques. Results. Of 300 participants, 28 were HBsAg positive, giving an HIV/HBV prevalence of 9.3% (95% confidence interval [CI], 6.3–13.2), and 5 of these, 17.9% (95% CI, 6.1–36.9), were HBeAg positive. There was a reduced CD4+ T-cell gain in HIV/HBV-coinfected compared with HIV-monoinfected patients. Hepatitis B virus surface antigen and HBeAg loss was 38% and 60%, respectively, at 24 months post-cART initiation. The HBV DNA suppression rates increased with time on cART from 54% to 75% in 6 and 24 months, respectively. Conclusions. Human immunodeficiency virus/HBV coinfection negatively affected immunologic recovery compared with HIV-1C monoinfection. Hepatitis B virus screening before cART initiation could help improve HBV/HIV treatment outcomes and help determine treatment options when there is a need to switch regimens. PMID:27800524

  15. Defective antigen presentation by monocytes in ESRD patients not responding to hepatitis B vaccination: impaired HBsAg internalization and expression of ICAM-1 and HLA-DR/Ia molecules

    PubMed Central

    Barth, C.; Pollok, M.; Michałkiewicz, J.; Madaliński, K.; Maciejewski, J.; Baldamis, C. A.

    1995-01-01

    This study was undertaken to evaluate the monocyte function of uraemic non-responders to hepatitis B vaccination. Therefore, some parameters concerning antigen processing by monocytes (Mo) as antigen presenting cells (APC) were analysed. It was found that in uraemic non-responders, (1) the internalization of HBsAg by monocytes was significantly decreasjed—HBsAg complexed with specific IgG or as immune complex isolated from patients is better internalized compared with free HBsAg; (2) during antigen presentation the expression of adhesion (ICAM-1) and accessory (HLA-DR/Ia) molecules was significantly decreased in uraemic patients, especially in non-responders; and (3) impaired internalization of HBsAg as well as a decrease in ICAM-1 and HLA-DR/Ia expression, correlated well with the blunted proliferation of CD4+ T cells stimulated by autologous monocytes induced by HBsAg. PMID:18475616

  16. Use of a 12 months' self-referral reminder to facilitate uptake of bowel scope (flexible sigmoidoscopy) screening in previous non-responders: a London-based feasibility study

    PubMed Central

    Kerrison, Robert S; McGregor, Lesley M; Marshall, Sarah; Isitt, John; Counsell, Nicholas; Wardle, Jane; von Wagner, Christian

    2016-01-01

    Background: In March 2013, NHS England extended its national Bowel Cancer Screening Programme to include ‘one-off' Flexible Sigmoidoscopy screening (NHS Bowel Scope Screening, BSS) for men and women aged 55. With less than one in two people currently taking up the screening test offer, there is a strong public health mandate to develop system-friendly interventions to increase uptake while the programme is rolling out. This study aimed to assess the feasibility of sending a reminder to previous BSS non-responders, 12 months after the initial invitation, with consideration for its potential impact on uptake. Method: This study was conducted in the ethnically diverse London Boroughs of Brent and Harrow, where uptake is below the national average. Between September and November 2014, 160 previous non-responders were randomly selected to receive a reminder of the opportunity to self-refer 12 months after their initial invitation. The reminder included instructions on how to book an appointment, and provided options for the time and day of the appointment and the gender of the endoscopist performing the test. To address barriers to screening, the reminder was sent with a brief locally tailored information leaflet designed specifically for this study. Participants not responding within 4 weeks were sent a follow-up reminder, after which there was no further intervention. Self-referral rates were measured 8 weeks after the delivery of the follow-up reminder and accepted as final. Results: Of the 155 participants who received the 12 months' reminder (returned to sender, n=5), 30 (19.4%) self-referred for an appointment, of which 24 (15.5%) attended and were successfully screened. Attendance rates differed by gender, with significantly more women attending an appointment than men (20.7% vs 8.8%, respectively; OR=2.73, 95% CI=1.02–7.35, P=0.05), but not by area (Brent vs Harrow) or area-level deprivation. Of the 30 people who self-referred for an appointment, 27 (90

  17. Retinopathy in chronic hepatitis C patients during interferon treatment with ribavirin

    PubMed Central

    Jain, K; Lam, W; Waheeb, S; Thai, Q; Heathcote, J

    2001-01-01

    AIM—To assess the ocular effect of interferon alfa 2b prescribed with ribavirin in patients undergoing therapy for chronic hepatitis C.
METHODS—19 patients with chronic hepatitis C who satisfied the follow up criteria were assessed for ocular complications using slit lamp biomicroscopy and indirect ophthalmoscopy before, during, and after the treatment at regular intervals.
RESULTS—8/19 patients, while on treatment, developed an asymptomatic retinopathy. Among these 3/8 were relapsers and 5/9 were non-responders to interferon monotherapy. All retinal changes faded, often while the patients continued the therapy. There was no significant association in occurrence of retinopathy with haematological and/or biochemical changes.
CONCLUSION—Retinopathy was more common in interferon monotherapy non-responders than relapsers when treated with interferon alfa 2b with the addition of ribavirin. The changes were transient, disappearing while the patients were still being treated.

 PMID:11567959

  18. Test-retest stability of the oral niacin test and electrodermal activity in patients with schizophrenia.

    PubMed

    Nilsson, B M; Hultman, C M; Ekselius, L

    2009-01-01

    In schizophrenia, well-replicated findings support an attenuated niacin skin-flush response. We have previously reported a delayed skin-flush after niacin ingestion and also an association between niacin non-responding and electrodermal non-responding in schizophrenia. The stability of the niacin and electrodermal tests was now studied in a test-retest design. An additional aim was to assess the association previously found. Twenty-three patients with schizophrenia underwent two sessions 3 months apart during which an oral niacin test was conducted and electrodermal activity was measured. Despite similar values for niacin outcome variables at the group level, there was high intraindividual variation. Test-retest stability for the oral niacin test was thus low, although a trend toward correlation for the dichotomous response criterion was found. Most electrodermal measures correlated between baseline and retest. A significant association between the tests was again found; niacin non-responding implied electrodermal non-responding, providing further support for a common underlying aberration in schizophrenia. PMID:19864122

  19. Predictors of biochemical aspirin and clopidogrel resistance in patients with ischemic stroke.

    PubMed

    Fong, Joanna; Cheng-Ching, Esteban; Hussain, Muhammad Shazam; Katzan, Irene; Gupta, Rishi

    2011-01-01

    Variable platelet response to aspirin and clopidogrel is a well-established phenomenon in patients with coronary artery disease. We sought to determine the predictors of an impaired biochemical response to aspirin and clopidogrel in patients with ischemic stroke. Patients with established cerebrovascular disease who underwent an aspirin/clopidogrel response panel (ie, light transmittance aggregometry) between June 2003 and March 2007 were identified through an electronic database. The medical records of these patients were retrospectively reviewed, and demographic characteristics, medical history, and laboratory results were recorded. Univariate and multivariate logistic regression analyses were performed to assess for factors associated with antiplatelet resistance. Of the 465 patients included in this study, 120 (28%) were biochemical aspirin nonresponders and 83 (28%) were biochemical clopidogrel nonresponders. Of the 270 patients on dual antiplatelet therapy, 25 (9.3%) were dual biochemical nonresponders. In binary logistic regression modeling, patients with congestive heart failure (odds ratio [OR] = 4.54; 95% confidence interval [CI] = 1.33-15.5; P = .02) and those with higher hemoglobin A1c values (OR = 1.41; 95% CI = 1.12-1.79; P = .004) had a significantly greater likelihood of having a biochemical nonresponse to aspirin therapy. African-American patients (OR = 2.19; 95% CI = 1.23-3.91; P < .007) were significantly more likely to be nonresponders to clopidogrel. This preliminary study shows that aspirin and clopidogrel biochemical nonresponse frequently occurs in ischemic stroke patients. In addition, some associated variables may affect the biochemical response to antiplatelet therapy. Further study is needed to explore whether this nonresponse has an impact on clinical outcomes. PMID:20621513

  20. Baseline Gene Expression Signatures in Monocytes from Multiple Sclerosis Patients Treated with Interferon-beta

    PubMed Central

    Bustamante, Marta F.; Nurtdinov, Ramil N.; Río, Jordi; Montalban, Xavier; Comabella, Manuel

    2013-01-01

    Background A relatively large proportion of relapsing-remitting multiple sclerosis (RRMS) patients do not respond to interferon-beta (IFNb) treatment. In previous studies with peripheral blood mononuclear cells (PBMC), we identified a subgroup of IFNb non-responders that was characterized by a baseline over-expression of type I IFN inducible genes. Additional mechanistic experiments carried out in IFNb non-responders suggested a selective alteration of the type I IFN signaling pathway in the population of blood monocytes. Here, we aimed (i) to investigate whether the type I IFN signaling pathway is up-regulated in isolated monocytes from IFNb non-responders at baseline; and (ii) to search for additional biological pathways in this cell population that may be implicated in the response to IFNb treatment. Methods Twenty RRMS patients classified according to their clinical response to IFNb treatment and 10 healthy controls were included in the study. Monocytes were purified from PBMC obtained before treatment by cell sorting and the gene expression profiling was determined with oligonucleotide microarrays. Results and discussion Purified monocytes from IFNb non-responders were characterized by an over-expression of type I IFN responsive genes, which confirms the type I IFN signature in monocytes suggested from previous studies. Other relevant signaling pathways that were up-regulated in IFNb non-responders were related with the mitochondrial function and processes such as protein synthesis and antigen presentation, and together with the type I IFN signaling pathway, may also be playing roles in the response to IFNb. PMID:23637780

  1. Retreatment of patients who do not respond to initial therapy for chronic hepatitis C.

    PubMed

    Shiffman, Mitchell L

    2004-05-01

    Despite improvements in the treatment of chronic hepatitis C virus (HCV) infection, nearly half of all patients do not respond to initial therapy. Retreatment of these patients with pegylated interferon and ribavirin has been successful in only a limited percentage of cases. Factors associated with sustained virologic response (SVR) following retreatment include prior treatment with interferon monotherapy, HCV genotype 2 or 3, a low serum HCV RNA level, and the absence of cirrhosis. Fewer than 6% of nonresponders who were previously treated with interferon and ribavirin and who have cirrhosis, genotype 1, and a high viral load achieve SVR following retreatment with pegylated interferon and ribavirin. No therapy has been shown to yield SVR in patients who do not respond to pegylated interferon and ribavirin. Long-term maintenance therapy with pegylated interferon is currently being evaluated in nonresponders with advanced fibrosis and cirrhosis. Its use should be considered investigational at this time. PMID:15468612

  2. Reboxetine for ADHD in children non-responders or with poor tolerance to methylphenidate: a prospective long-term open-label study.

    PubMed

    Quintero, Javier; López-Muñoz, Francisco; Alamo, Cecilio; Loro, Mercedes; García-Campos, Natalia

    2010-11-01

    Up to 30% of patients with attention-deficit hyperactivity disorder (ADHD) treated with psychostimulants discontinue the treatment because of intolerance or lack of therapeutic response. Therapeutic alternatives are needed for such patients. In the present case series, we study the effectiveness of reboxetine over a period of 6 months in a sample of 14 children diagnosed with ADHD according to DSM-IV-TR criteria, who had responded only partially or had presented poor tolerance to conventional treatment with methylphenidate. Clinical efficacy was evaluated through the application of the 18-item Attention-Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) and the Clinical Global Impressions-Global Improvement Scale (CGI-I). Percentages of responders (ADHD-RS ≥ 25%) and improvers (CGI-I absolute value < 4) were 90.9 and 72.7%, respectively. No serious side-effects were observed during treatment, the most frequent effects being headaches and insomnia. The initial findings of our study show that reboxetine may constitute an effective tool for long-term treatment of children with ADHD who present poor response or poor tolerance to initial treatment with methylphenidate.

  3. Potential determinants of efficacy of mirror therapy in stroke patients – A pilot study

    PubMed Central

    Brunetti, Maddalena; Morkisch, Nadine; Fritzsch, Claire; Mehnert, Jan; Steinbrink, Jens; Niedeggen, Michael; Dohle, Christian

    2015-01-01

    Abstract Background: Mirror therapy (MT) was found to improve motor function after stroke. However, there is high variability between patients regarding motor recovery. Objectives: The following pilot study was designed to identify potential factors determining this variability between patients with severe upper limb paresis, receiving MT. Methods: Eleven sub-acute stroke patients with severe upper limb paresis participated, receiving in-patient rehabilitation. After a set of pre-assessments (including measurement of brain activity at the primary motor cortex and precuneus during the mirror illusion, using near-infrared spectroscopy as described previously), four weeks of MT were applied, followed by a set of post-assessments. Discriminant group analysis for MT responders and non-responders was performed. Results: Six out of eleven patients were defined as responders and five as non-responders on the basis of their functional motor improvement. The initial motor function and the activity shift in both precunei (mirror index) were found to discriminate significantly between responders and non-responders. Conclusions: In line with earlier results, initial motor function was confirmed as crucial determinant of motor recovery. Additionally, activity response to the mirror illusion in both precunei was found to be a candidate for determination of the efficacy of MT. PMID:26409402

  4. Decreased expression of let-7c is associated with non-response of muscle-invasive bladder cancer patients to neoadjuvant chemotherapy.

    PubMed

    Vinall, Ruth L; Tepper, Clifford G; Ripoll, Alexandra A Z; Gandour-Edwards, Regina F; Durbin-Johnson, Blythe P; Yap, Stanley A; Ghosh, Paramita M; deVere White, Ralph W

    2016-03-01

    The identification and development of biomarkers which predict response of muscle invasive bladder cancer (MIBC) patients to neoadjuvant chemotherapy would likely increase usage of this treatment option and thereby improve patient survival rates. MiRNA array and qRT-PCR validation was used to identify miRNA which are associated with response to neoadjuvant chemotherapy. RNA was extracted from a total of 41 archival, fully annotated, MIBC patient diagnostic biopsies (20 chemo-responders and 21 non-responders (response is defined as > 5 year survival rate and being pT0 post-chemotherapy)). Microarray and qPCR identified let-7c as being differentially expressed in chemo-responder versus non-responder patients. Patients with higher let-7c expression levels had significantly higher odds of responding to chemotherapy (p = 0.023, OR 2.493, 95% CI 1.121, 5.546), and assessment of let-7c levels allowed for prediction of patient response (AUC 0.72, positive predictive value 59%). Decreased let-7c was associated with MIBC incidence (p < 0.001), and significantly correlated with other related miRNA including those that were not differentially expressed between responders and non-responders. The combined data indicate let-7c plays a role in mediating chemoresistance to neoadjuvant chemotherapy in MIBC patients, and is a modest, yet clinically meaningful, predictor of patient response. PMID:27382433

  5. Impact of HIV infection on sustained virological response to treatment against hepatitis C virus with pegylated interferon plus ribavirin.

    PubMed

    Monje-Agudo, P; Castro-Iglesias, A; Rivero-Juárez, A; Martínez-Marcos, F; Ortega-González, E; Real, L M; Pernas, B; Merchante, N; Cid, P; Macías, J; Merino, M D; Rivero, A; Mena, A; Neukam, K; Pineda, J A

    2015-10-01

    It is commonly accepted that human immunodeficiency (HIV) coinfection negatively impacts on the rates of sustained virological response (SVR) to therapy with pegylated interferon plus ribavirin (PR). However, this hypothesis is derived from comparing different studies. The aim of this study was to determine the impact of HIV coinfection on SVR to PR in one single population. In a multicentric, prospective study conducted between 2000 and 2013, all previously naïve hepatitis C virus (HCV)-infected patients who started PR in five Spanish hospitals were analyzed. SVR was evaluated 24 weeks after the scheduled end of therapy. Of the 1046 patients included in this study, 413 (39%) were coinfected with HIV. Three hundred and forty-one (54%) HCV-monoinfected versus 174 (42%) HIV/HCV-coinfected patients achieved SVR (p < 0.001). The corresponding figures for undetectable HCV RNA at treatment week 4 were 86/181 (47%) versus 59/197 (30%), p < 0.001. SVR was observed in 149 (69%) HCV genotype 2/3-monoinfected subjects versus 91 (68%) HIV/HCV genotype 2/3-coinfected subjects (p = 0.785). In the HCV genotype 1/4-infected population, 188 (46%) monoinfected patients versus 82 (30%) with HIV coinfection (p < 0.001) achieved SVR. In this subgroup, absence of HIV coinfection was independently associated with higher SVR [adjusted odds ratio (95% confidence interval): 2.127 (1.135-3.988); p = 0.019] in a multivariate analysis adjusted for age, sex, baseline HCV RNA load, IL28B genotype, fibrosis stage, and type of pegylated interferon. HIV coinfection impacts on the rates of SVR to PR only in HCV genotype 1/4-infected patients, while it has no effect on SVR in the HCV genotype 2/3-infected subpopulation.

  6. Comparative analysis of drug resistance mutations in the human immunodeficiency virus reverse transcriptase gene in patients who are non-responsive, responsive and naive to antiretroviral therapy.

    PubMed

    Misbah, Mohammad; Roy, Gaurav; Shahid, Mudassar; Nag, Nalin; Kumar, Suresh; Husain, Mohammad

    2016-05-01

    Drug resistance mutations in the Pol gene of human immunodeficiency virus 1 (HIV-1) are one of the critical factors associated with antiretroviral therapy (ART) failure in HIV-1 patients. The issue of resistance to reverse transcriptase inhibitors (RTIs) in HIV infection has not been adequately addressed in the Indian subcontinent. We compared HIV-1 reverse transcriptase (RT) gene sequences to identify mutations present in HIV-1 patients who were ART non-responders, ART responders and drug naive. Genotypic drug resistance testing was performed by sequencing a 655-bp region of the RT gene from 102 HIV-1 patients, consisting of 30 ART-non-responding, 35 ART-responding and 37 drug-naive patients. The Stanford HIV Resistance Database (HIVDBv 6.2), IAS-USA mutation list, ANRS_09/2012 algorithm, and Rega v8.02 algorithm were used to interpret the pattern of drug resistance. The majority of the sequences (96 %) belonged to subtype C, and a few of them (3.9 %) to subtype A1. The frequency of drug resistance mutations observed in ART-non-responding, ART-responding and drug-naive patients was 40.1 %, 10.7 % and 20.58 %, respectively. It was observed that in non-responders, multiple mutations were present in the same patient, while in responders, a single mutation was found. Some of the drug-naive patients had more than one mutation. Thymidine analogue mutations (TAMs), however, were found in non-responders and naive patients but not in responders. Although drug resistance mutations were widely distributed among ART non-responders, the presence of resistance mutations in the viruses of drug-naive patients poses a big concern in the absence of a genotyping resistance test. PMID:26801790

  7. High Proportion of HIV-HCV Coinfected Patients with Advanced Liver Fibrosis Requiring Hepatitis C Treatment in Haiphong, Northern Vietnam (ANRS 12262)

    PubMed Central

    Lacombe, Karine; Duong Thi, Huong; Pham Thi Hanh, Phuc; Truong Thi Xuan, Lien; Chu Thi, Nga; Luong Que, Anh; Vu Hai, Vinh; Nagot, Nicolas; Tuaillon, Edouard; Dominguez, Stéphanie; Lemoine, Maud

    2016-01-01

    Rationale and Aims Screening and treatment for chronic hepatitis C are very limited in Vietnam and clinical data on HCV-related liver disease in HIV-coinfected people are almost inexistent. This study aimed to assess the severity of liver fibrosis and its risk factors in HIV-HCV coinfected patients in Haiphong, Northern Vietnam. Methods A cross-sectional study was conducted at a HIV outpatient clinic. Consecutive HIV treated adults with positive HCV serology completed a standardised epidemiological questionnaire and had a comprehensive liver assessment including hepatic elastography (Fibroscan®, Echosens). Results From February to March 2014, 104 HIV-HCV coinfected patients receiving antiretroviral therapy (ART) were prospectively enrolled (99 males, median age: 35.8 (32.7–39.6) years, median CD4 count: 504 (361–624) /mm3. Of them, 93 (89.4%) had detectable HCV RNA (median 6.19 (4.95–6.83 Log10 IU/mL). Patients were mainly infected with genotypes 1a/1b (69%) and genotypes 6a/6e (26%). Forty-three patients (41.3%) had fibrosis ≥F2 including 24 patients (23.1%) with extensive fibrosis (F3) and/or cirrhosis (F4). In univariate analysis, excessive alcohol consumption, estimated time duration from HCV infection, nevirapine and lopinavir-based ARV regimen and CD4 nadir were associated factors of extensive fibrosis/cirrhosis. Alcohol abuse was the only independent factor of extensive fibrosis in multivariate analysis. Using Fibroscan® as a gold standard, the high thresholds of AST-to-platelet ratio index (APRI) and fibrosis-4 score (FIB-4) had very good performances for the diagnosis of extensive fibrosis/cirrhosis (Se: 90 and 100%, Sp:84 and 81%, AUROCs = 0.93, 95%CI: 0.86–0.99 and 0.96 (0.92–0.99), respectively). Conclusion In this study, nearly 25% of HIV-HCV coinfected patients successfully treated with ART have extensive fibrosis or cirrhosis, and therefore require urgently HCV treatment. PMID:27148964

  8. Occult hepatitis B virus infection and S gene escape mutants in HIV-infected patients after hepatitis B virus vaccination.

    PubMed

    Aghakhani, Arezoo; Mohraz, Minoo; Aghasadeghi, Mohammad Reza; Banifazl, Mohammad; Vahabpour, Rouhollah; Karami, Afsaneh; Foroughi, Maryam; Ramezani, Amitis

    2016-10-01

    Hepatitis B virus (HBV) vaccination is recommended for HIV patients. Despite the relative success of HBV vaccination, breakthrough infections can occur infrequently in patients, and it can be due to occult HBV infection, vaccine unresponsiveness and/or emergence of escape mutants. This study assessed the presence of occult HBV infection and S gene escape mutants in HIV-positive patients after HBV vaccination. Ninety-two HIV-positive patients were enrolled in this study, including 52 responders to HBV vaccine and 40 non-responders. All of the cases received HBV vaccine according to routine HBV vaccination protocols. The presence of HBV-DNA was determined by real-time polymerase chain reaction (PCR). In HBV-DNA positive samples, the most conserved regions of S gene sequences were amplified by nested PCR and PCR products were sequenced. Occult HBV infection was detected in two cases. Glycine to arginine mutation at residue 145 (G145R) within the 'a' region of the S gene was detected in one of the occult HBV infection cases who was in the non-responder group. This study showed that the prevalence of occult HBV infection and vaccine escape mutants was low in our HBV-vaccinated HIV-positive patients in both responder and non-responder groups, so there was no alarming evidence indicating breakthrough HBV infection in our vaccinated HIV-positive cases.

  9. Gene Mutation Analysis in EGFR Wild Type NSCLC Responsive to Erlotinib: Are There Features to Guide Patient Selection?

    PubMed Central

    Ulivi, Paola; Delmonte, Angelo; Chiadini, Elisa; Calistri, Daniele; Papi, Maximilian; Mariotti, Marita; Verlicchi, Alberto; Ragazzini, Angela; Capelli, Laura; Gamboni, Alessandro; Puccetti, Maurizio; Dubini, Alessandra; Burgio, Marco Angelo; Casanova, Claudia; Crinò, Lucio; Amadori, Dino; Dazzi, Claudio

    2014-01-01

    Tyrosine kinase inhibitors (TKIs) are very efficacious in non-small-cell lung cancer (NSCLC) patients harboring activating Epidermal Growth Factor Receptor (EGFR) mutations. However, about 10% of EGFR wild type (wt) patients respond to TKI, with unknown molecular mechanisms of sensitivity. We considered a case series of 34 EGFR wt NSCLC patients responsive to erlotinib after at least one line of therapy. Responsive patients were matched with an equal number of non-responsive EGFR wt patients. A panel of 26 genes, for a total of 214 somatic mutations, was analyzed by MassARRAY® System (Sequenom, San Diego, CA, USA). A 15% KRAS mutation was observed in both groups, with a prevalence of G12C in non-responders (80% vs. 40% in responders). NOTCH1, p53 and EGFR-resistance-related mutations were found more frequently in non-responders, whereas EGFR-sensitizing mutations and alterations in genes involved in proliferation pathways were more frequent in responders. In conclusion, our findings indicate that p53, NOTCH1 and exon 20 EGFR mutations seem to be related to TKI resistance. KRAS mutations do not appear to influence the TKI response, although G12C mutation is more frequent in non-responders. Finally, the use of highly sensitive methodologies could lead to the identification of under-represented EGFR mutations potentially associated with TKI sensitivity. PMID:25561229

  10. Extended survival and reduced risk of AML progression in erythroid-responsive lenalidomide-treated patients with lower-risk del(5q) MDS

    PubMed Central

    List, A F; Bennett, J M; Sekeres, M A; Skikne, B; Fu, T; Shammo, J M; Nimer, S D; Knight, R D; Giagounidis, A

    2014-01-01

    Lenalidomide is the approved treatment for patients with red blood cell (RBC) transfusion-dependent lower-risk myelodysplastic syndromes (MDS) and chromosome 5q deletion (del(5q)). We report the long-term outcomes (median follow-up 3.2 years) in patients treated with lenalidomide in the MDS-003 trial. RBC transfusion independence (TI) ⩾8 weeks was achieved in 97 of 148 treated patients (65.5%), with a median response duration of 2.2 years. Partial or complete cytogenetic response was achieved by 63 of 88 evaluable patients (71.6%). Median overall survival (OS) was longer in patients achieving RBC-TI ⩾8 weeks (4.3 vs 2.0 years in non-responders; P<0.0001) or cytogenetic response (4.9 vs 3.1 years in non-responders; P=0.010). Time to acute myeloid leukemia (AML) progression was longer in patients achieving RBC-TI ⩾8 weeks or any cytogenetic response versus non-responders (P=0.001 and P=0.0002, respectively). In a landmark multivariate analysis, RBC-TI ⩾8 weeks was associated with prolonged OS (P<0.001) and a trend toward reduced relative risk of AML progression (P=0.080). Among these lower-risk MDS patients with del(5q), lenalidomide was associated with prolonged RBC-TI and cytogenetic responses, which were linked to improved OS and reduced risk of AML progression. PMID:24150217

  11. Utility of phenylalanine hydroxylase genotype for tetrahydrobiopterin responsiveness classification in patients with phenylketonuria

    PubMed Central

    Quirk, Meghan E.; Dobrowolski, Steven F.; Nelson, Benjamin E.; Coffee, Bradford; Singh, Rani H.

    2014-01-01

    Background A need exists to expand the characterization of tetrahydrobiopterin (BH4) responsiveness in patients with phenylketonuria (PKU), beyond simply evaluating change in blood phenylalanine concentrations. The clinical interpretation of BH4 responsiveness should be evaluated within the context of phenylalanine hydroxylase (PAH) genotype. Aim This investigation seeks to use a modified version of a previously developed PAH genotype severity tool, the assigned value (AV) sum, to assess the molecular basis of responsiveness in a clinical cohort and to explore the tool’s ability to differentiate BH4 responsive groups. Methods BH4 response was previously clinically classified in 58 patients with PKU, with three response groups emerging: definitive responders, provisional responders, and non-responders. Provisional responders represented a clinically ambiguous group, with an initial decrease in plasma phenylalanine concentrations, but limited ability to improve dietary phenylalanine tolerance. In this retrospective analysis, mutations in the PAH gene were identified in each patient. PAH genotype was characterized through the AV sum approach, in which each mutation is given an AV of 1, 2, 4, or 8; the sum of both mutations’ AV corresponds to genotype severity, with a lower number representing a more severe phenotype. An AV sum cutoff of 2 (indicative of the most severe genotypes) was used to dichotomize patients and predict BH4 responsiveness. Provisional responders were classified with the definitive responders then the non-responders to see with which group they best aligned. Results In 17/19 definitive responders, at least one mutation was mild or moderate in severity (AV sum>2). In contrast, 7/9 provisional responders carried two severe or null mutations (AV sum=2), suggesting little molecular basis for responsiveness. Non-responders represent a heterogeneous group with 15/25 patients carrying two severe mutations (AV sum=2), 5/25 patients carrying one

  12. Potentially functional SNPs (pfSNPs) as novel genomic predictors of 5-FU response in metastatic colorectal cancer patients.

    PubMed

    Wang, Jingbo; Wang, Xu; Zhao, Mingjue; Choo, Su Pin; Ong, Sin Jen; Ong, Simon Y K; Chong, Samuel S; Teo, Yik Ying; Lee, Caroline G L

    2014-01-01

    5-Fluorouracil (5-FU) and its pro-drug Capecitabine have been widely used in treating colorectal cancer. However, not all patients will respond to the drug, hence there is a need to develop reliable early predictive biomarkers for 5-FU response. Here, we report a novel potentially functional Single Nucleotide Polymorphism (pfSNP) approach to identify SNPs that may serve as predictive biomarkers of response to 5-FU in Chinese metastatic colorectal cancer (CRC) patients. 1547 pfSNPs and one variable number tandem repeat (VNTR) in 139 genes in 5-FU drug (both PK and PD pathway) and colorectal cancer disease pathways were examined in 2 groups of CRC patients. Shrinkage of liver metastasis measured by RECIST criteria was used as the clinical end point. Four non-responder-specific pfSNPs were found to account for 37.5% of all non-responders (P<0.0003). Five additional pfSNPs were identified from a multivariate model (AUC under ROC = 0.875) that was applied for all other pfSNPs, excluding the non-responder-specific pfSNPs. These pfSNPs, which can differentiate the other non-responders from responders, mainly reside in tumor suppressor genes or genes implicated in colorectal cancer risk. Hence, a total of 9 novel SNPs with potential functional significance may be able to distinguish non-responders from responders to 5-FU. These pfSNPs may be useful biomarkers for predicting response to 5-FU.

  13. A case of successful hepatitis C virus eradication by 24 weeks of telaprevir-based triple therapy for a hemophilia patient with hepatitis C virus/human immunodeficiency virus co-infection who previously failed pegylated interferon-α and ribavirin therapy.

    PubMed

    Murata, Masayuki; Furusyo, Norihiro; Ogawa, Eiichi; Mitsumoto, Fujiko; Hiramine, Satoshi; Ikezaki, Hiroaki; Takayama, Koji; Shimizu, Motohiro; Toyoda, Kazuhiro; Kainuma, Mosaburo; Hayashi, Jun

    2014-05-01

    In Japan, the human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection of some patients with hemophilia was caused by the transfusion of imported blood products, such as unheated coagulation factor. With the development of antiretroviral therapy (ART) for HIV, chronic HCV infection has become a major cause of liver disease and mortality for hemophiliac patients coinfected with HCV/HIV. Data is limited regarding the efficacy and safety of antiviral therapy with the HCV protease inhibitor telaprevir (TVR) in combination with pegylated interferon-α (PegIFN-α) and ribavirin (RBV) for hemophilia patients coinfected with HCV/HIV. We report a case of a Japanese patient with hemophilia and HCV/HIV coinfection who had partial response to prior to PegIFN-α and RBV therapy. This is the first published report of 24-week TVR-based triple therapy for a hemophilia patient coinfected with HCV/HIV. The patient had HCV genotype 1a infection with a high viral load. His single-nucleotide polymorphism of the interleukin 28B (rs8099917) gene was the TT major allele. He presented with undetectable HIV RNA and a high CD4(+) T cell counts by taking ART including tenofovir, emtricitabine and raltegravir. He was again treated for HCV with TVR plus PegIFN-α2b and RBV for the first 12 weeks, followed by the continuation of PegIFN-α2b and RBV for 12 additional weeks while continuing ART. He had rapid virological response and achieved sustained virological response with the 24-week treatment. No serious adverse events such as skin rash, severe anemia or exacerbated bleeding tendency were observed, only a mild headache. No dose adjustment was necessary when tenofovir and raltegravir were used in combined with TVR, and no HIV breakthrough was observed. TVR-based triple therapy with ART could can an effective treatment for hemophilia patients coinfected with HCV (genotype 1)/HIV regardless of prior response. TVR can be used in combination with tenofovir, emtricitabine and

  14. Evaluation of positive and negative predictors of seizure outcomes among patients with immune-mediated epilepsy: a meta-analysis

    PubMed Central

    Dubey, Divyanshu; Farzal, Zehra; Hays, Ryan; Brown, L Steven; Vernino, Steven

    2016-01-01

    Background: The objective of this study was to analyze published literature on autoimmune epilepsy and assess predictors of seizure outcome. Methods: From PubMed and EMBASE databases, two reviewers independently identified publications reporting clinical presentations, management and outcomes of patients with autoimmune epilepsy. A meta-analysis of 46 selected studies was performed. Demographic/clinical variables (sex, age, clinical presentation, epilepsy focus, magnetic resonance imaging [MRI] characteristics, time to diagnosis and initiation of immunomodulatory therapy, and type of immunomodulatory therapy) were compared between two outcome groups (responders and nonresponders). Clinical response was defined as >50% reduction in seizure frequency. Unstandardized effect sizes were collected for the studies for responder and nonresponder groups. Sample size was used as the weight in the meta-analysis. The random effects model was used to account for heterogeneity in the studies. Results: The 46 reports included 186 and 96 patients in responder and nonresponder groups respectively. Mean age of the responders and nonresponders was 43 and 31 years (p < 0.01). Responders were more likely to have cell-surface antibodies (68% versus 39%, p < 0.05), particularly voltage-gated potassium channel complex antibodies (p < 0.01). Mean duration from symptom onset to diagnosis, and symptom onset to initiation of immunomodulation was significantly lower among the responders (75 versus 431 days, p < 0.05, and 80 versus 554, p < 0.01, respectively). There was no outcome difference based on gender, MRI characteristics, seizure type, type of acute immunomodulatory therapy, or use of chronic immunomodulation. Conclusions: Among published cases to date, older age, presence of cell-surface antibodies, early diagnosis and immunomodulatory treatment are associated with better seizure outcomes among patients with autoimmune epilepsy. PMID:27582892

  15. Long-term follow-up of 'cured' prolactinoma patients after successful adenomectomy.

    PubMed

    Ciccarelli, E; Ghigo, E; Miola, C; Gandini, G; Muller, E E; Camanni, F

    1990-05-01

    The long-term follow-up (greater than or equal to 4 years) of clinical, hormonal and radiological aspects in 22 'cured' prolactinoma patients after adenomectomy was studied. Dynamic secretion of PRL and TSH was also evaluated, in order to identify the persistence of any underlying abnormality of hypothalamic pituitary control and to predict relapses. A relapse into hyperprolactinaemia was shown in 36% of patients 5-90 months (mean 46) after surgery. This was accompanied by reappearance of clinical symptoms but not by the radiological demonstration of the adenoma in any patients. A significant PRL rise after domperidone, a dopaminergic antagonist drug, was shown in cured patients after surgery (mean +/- SEM peak, 2977 +/- 645 mU/l) but this was markedly lower than that observed in control subjects (5732 +/- 440 mU/l). In fact, normal PRL increments were shown in only 6/16 (37%) patients. TSH hyper-responsiveness to domperidone normalized in only 46% of patients. Similar PRL responses to those obtained with domperidone were shown when a TRH test was given. A relapse into hyperprolactinaemia was observed in six of ten (60%) non-responders to domperidone and in four of seven (57%) non-responders to TRH, whereas six normal responders to domperidone and TRH had not relapsed at that time. Plasma PRL levels during pregnancy showed increments lower than those observed in normal pregnant women only in domperidone and TRH non-responder patients. These results indicate that a relapse into hyperprolactinaemia and a blunted PRL rise during pregnancy were present only in patients with persistently reduced PRL response to dynamic tests.

  16. Is early response by 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography a predictor of long-term outcome in patients with metastatic colorectal cancer?

    PubMed Central

    Fanelli, Marcello Ferretti; Dettino, Aldo Lourenço Abadde; Nicolau, Ulisses Ribaldo; Cavicchioli, Marcelo; Lima, Eduardo Nóbrega Pereira; de Mello, Celso Abdon Lopes

    2016-01-01

    Background Identify in advance responder patients to chemotherapy in metastatic colorectal cancer (CRC) would allow prompt interruption of ineffective therapies in non-responder patients. Hence, predictive markers are sought in numerous trials to detect responder patients, including tumor shrinkage measured by imaging methods. Usually, Response Evaluation Criteria in Solid Tumors (RECIST) is used to evaluate tumor response in metastatic CRC, but these criteria are questionable with use of biological agents associated to chemotherapy. Our aim was correlate early metabolic response by 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography (18FDG-PET-CT) with long-term outcome in metastatic CRC in first-line therapy. Methods We prospectively evaluated 36 patients with metastatic CRC in first-line treatment with 5-fluorouracil, leucovorin (folinic acid), oxaliplatin (FOLFOX) or 5-fluorouracil, leucovorin (folinic acid), irinotecan (FOLFIRI) associated with cetuximab or bevacizumab. 18FDG-PET-CT was performed at baseline and after two cycles of chemotherapy. The early metabolic response [standardized uptake value (SUV)] was measured to identify responder and non-responder patients and correlated with overall survival (OS) and progression-free survival (PFS). Results Median age was 58.5 years (range, 41–74 years). PFS was 15.5 months for responder and 13.3 months for non-responder (P=0.42), OS was 55.7 months for responder and not reached for non-responder. There was no correlation between delta-SUV and clinical and pathological variables analyzed. In the subgroup of patients who did not undergo resection of metastasis (45%), PFS was higher for responders (15.3×6.8 months, P=0.02). Conclusions According to our findings, early response by 18FDG-PET-CT was not a predictor of long-term outcome for patients with metastatic CRC treated in the first-line chemotherapy with a monoclonal antibody. PMID:27284468

  17. Presence of anti-HBc is associated to high rates of HBV resolved infection and low threshold for Occult HBV Infection in HIV patients with negative HBsAg in Chile.

    PubMed

    Vargas, Jose Ignacio; Jensen, Daniela; Sarmiento, Valeska; Peirano, Felipe; Acuña, Pedro; Fuster, Felipe; Soto, Sabrina; Ahumada, Rodrigo; Huilcaman, Marco; Bruna, Mario; Jensen, Werner; Fuster, Francisco

    2016-04-01

    HBV-HIV coinfection is prevalent. Frequently, anti-HBc is the only serological marker of HBV, which can be indicative of HBV resolved infection, when found together with anti-HBs reactivity; or present as "isolated anti-HBc," related to HBV occult infection with presence of detectable DNA HBV, more prevalent in HIV-positive individuals. Regional data about this condition are scarce. Anti-HBc rapid test has been used as screening, but its performance has not been described in HIV-positive patients. The aim of this study was determine prevalence of anti-HBc in HIV-positive patients, serological pattern of HBV resolved infection and isolated anti-HBc, evaluating presence of HBV occult infection. Assess anti-HBc rapid test compared to ECLIA. Methods included measurement of anti-HBc and anti-HBs in HIV-positive patients with negative HBsAg. Serum HBV DNA quantification and HBV booster vaccination to "isolated anti-HBc" individuals. Detection of anti-HBc by rapid test and ECLIA. In 192 patients, prevalence of anti-HBc was 42.7% (82/192); associated to male gender, drug use, men-sex-men, positive-VDRL, and longer time HIV diagnosis. 34.4% (66/192) had presence of anti-HBs, mean titers of 637 ui/ml. Isolated anti-HBc in 8.3% (16/192), associated to detectable HIV viral load and no-use of HAART; in them, HBV DNA was undetectable, and 60% responded to HBV vaccination booster. Anti-HBc rapid test showed low sensibility (32.9%) compared to ECLIA. These results show that prevalence of anti-HBc in HIV-positive individuals is high, in most cases accompanied with anti-HBs as HBV resolved infection. Low prevalence of "isolated anti-HBc," with undetectable HBV DNA, and most had anamnestic response to HBV vaccination; suggest low possibility of occult HBV infection. Anti-HBc rapid test cannot be recommended as screening method for anti-HBc. PMID:26381185

  18. Presence of anti-HBc is associated to high rates of HBV resolved infection and low threshold for Occult HBV Infection in HIV patients with negative HBsAg in Chile.

    PubMed

    Vargas, Jose Ignacio; Jensen, Daniela; Sarmiento, Valeska; Peirano, Felipe; Acuña, Pedro; Fuster, Felipe; Soto, Sabrina; Ahumada, Rodrigo; Huilcaman, Marco; Bruna, Mario; Jensen, Werner; Fuster, Francisco

    2016-04-01

    HBV-HIV coinfection is prevalent. Frequently, anti-HBc is the only serological marker of HBV, which can be indicative of HBV resolved infection, when found together with anti-HBs reactivity; or present as "isolated anti-HBc," related to HBV occult infection with presence of detectable DNA HBV, more prevalent in HIV-positive individuals. Regional data about this condition are scarce. Anti-HBc rapid test has been used as screening, but its performance has not been described in HIV-positive patients. The aim of this study was determine prevalence of anti-HBc in HIV-positive patients, serological pattern of HBV resolved infection and isolated anti-HBc, evaluating presence of HBV occult infection. Assess anti-HBc rapid test compared to ECLIA. Methods included measurement of anti-HBc and anti-HBs in HIV-positive patients with negative HBsAg. Serum HBV DNA quantification and HBV booster vaccination to "isolated anti-HBc" individuals. Detection of anti-HBc by rapid test and ECLIA. In 192 patients, prevalence of anti-HBc was 42.7% (82/192); associated to male gender, drug use, men-sex-men, positive-VDRL, and longer time HIV diagnosis. 34.4% (66/192) had presence of anti-HBs, mean titers of 637 ui/ml. Isolated anti-HBc in 8.3% (16/192), associated to detectable HIV viral load and no-use of HAART; in them, HBV DNA was undetectable, and 60% responded to HBV vaccination booster. Anti-HBc rapid test showed low sensibility (32.9%) compared to ECLIA. These results show that prevalence of anti-HBc in HIV-positive individuals is high, in most cases accompanied with anti-HBs as HBV resolved infection. Low prevalence of "isolated anti-HBc," with undetectable HBV DNA, and most had anamnestic response to HBV vaccination; suggest low possibility of occult HBV infection. Anti-HBc rapid test cannot be recommended as screening method for anti-HBc.

  19. Triple combination of thymalfasin, peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior interferon and ribavirin treatment: 24-week interim results of a pilot study.

    PubMed

    Poo, Jorge Luis; Sánchez-Avila, F; Kershenobich, D; García-Samper, X; Gongora, J; Uribe, M

    2004-12-01

    Despite steady progress in antiviral treatment for patients with chronic hepatitis C virus (HCV), many patients still have detectable serum HCV RNA levels by the end of interferon-based treatment and are known as virological non-responders. Re-treatment of these patients not responding to previous therapy remains challenging. Studies of the dynamics of the HCV population show a marked decline in new cases since 1996; however, the relative proportion of non-responders is expected to increase over time and, similarly, the number of patients eligible for first-line treatment is expected to decrease. The current standard of care for treatment involves the use of pegylated interferons in combination with ribavirin. However, many difficult-to-treat groups still have low response rates. Newer combinations are being investigated to optimize chances of attaining a sustained response in these groups: one such triple therapy regimen is peginterferon alfa-2a, ribavirin and thymalfasin, which was given to 23 previously non-responder patients. Viral response was 60.8% at week 12 and 47.8% at week 24. These preliminary results encourage further evaluation of this promising combination. PMID:15546256

  20. Triple combination of thymalfasin, peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior interferon and ribavirin treatment: 24-week interim results of a pilot study.

    PubMed

    Poo, Jorge Luis; Sánchez-Avila, F; Kershenobich, D; García-Samper, X; Gongora, J; Uribe, M

    2004-12-01

    Despite steady progress in antiviral treatment for patients with chronic hepatitis C virus(HCV), many patients still have detectable serum HCV RNA levels by the end of interferon-based treatment and are known as virological non-responders. Re-treatment of these patients not responding to previous therapy remains challenging. Studies of the dynamics of the HCV population show a marked decline in new cases since 1996; however, the relative proportion of non-responders is expected to increase over time and, similarly, the number of patients eligible for first-line treatment is expected to decrease. The current standard of care for treatment involves the use of pegylated interferons in combination with ribavirin. However, many difficult-to-treat groups still have low response rates. Newer combinations are being investigated to optimize chances of attaining a sustained response in these groups: one such triple therapy regimen is peginterferon alfa-2a, ribavirin and thymalfasin, which was given to 23 previously non-responder patients. Viral response was 60.8% at week 12 and 47.8% at week 24. These preliminary results encourage further evaluation of this promising combination. PMID:15641210

  1. Six month abstinence rule for liver transplantation in severe alcoholic liver disease patients

    PubMed Central

    Obed, Aiman; Stern, Steffen; Jarrad, Anwar; Lorf, Thomas

    2015-01-01

    Alcoholic liver disease (ALD) is the second most common diagnosis among patients undergoing liver transplantation (LT). The recovery results of patients transplanted for ALD are often at least as good as those of patients transplanted for other diagnoses and better than those suffering from hepatitis C virus, cryptogenic cirrhosis, or hepatocellular carcinoma. In the case of medically non-responding patients with severe acute alcoholic hepatitis or acute-on chronic liver failure, the refusal of LT is often based on the lack of the required alcohol abstinence period of six months. The obligatory abidance of a period of abstinence as a transplant eligibility requirement for medically non-responding patients seems unfair and inhumane, since the majority of these patients will not survive the six-month abstinence period. Data from various studies have challenged the 6-mo rule, while excellent survival results of LT have been observed in selected patients with severe alcoholic hepatitis not responding to medical therapy. Patients with severe advanced ALD should have legal access to LT. The mere lack of pre-LT abstinence should not be an obstacle for being listed. PMID:25892898

  2. Intravenous iron supplementation for the treatment of the anemia of moderate to severe chronic renal failure patients not receiving dialysis.

    PubMed

    Silverberg, D S; Iaina, A; Peer, G; Kaplan, E; Levi, B A; Frank, N; Steinbruch, S; Blum, M

    1996-02-01

    Iron deficiency may develop in hemodialysis patients, especially when erythropoietin is given. The role of iron deficiency in the anemia of predialysis chronic renal failure (CRF), however, is much less clear. We have intravenously (IV) administered iron as ferric saccharate in a total dose of 200 mg elemental iron monthly for 5 months to 33 CRF patients who remained anemic despite oral iron supplementation and who had no laboratory signs of iron overload. None was receiving erythropoietin therapy. In 22 of the patients there was an increase in the hematocrit values by the end of the study. These patients were considered responders to intravenous iron (IV Fe) therapy. In 11 patients the iron administration was not associated with improvement of the anemia (nonresponders). Before onset of the IV Fe therapy there were no differences between the responders and nonresponders with regard to degree of anemia, serum ferritin, iron saturation, renal function, or blood pressure. One additional patient was excluded from the study because of a mild reaction during an IV test dose before the study. No worsening of kidney function and no other side effects were noted. In four patients (three responders and one nonresponder) the control of blood pressure necessitated antihypertensive drug therapy adjustment. In conclusion, IV Fe supplementation in two thirds of anemic CRF patients not receiving dialysis resulted in a significant improvement of the anemia, thus avoiding the necessity of erythropoietin or blood administration. This could be achieved by increasing the plasma ferritin levels to 200 to 400 microns/L and/or increasing the iron saturation to 25% to 35%. Intravenous ferric saccharate appears to be a safe and effective method of administering iron for the correction of anemia in CRF patients not receiving dialysis.

  3. Pharmacogenomic study in patients with multiple sclerosis

    PubMed Central

    Bustamante, Marta F.; Morcillo-Suárez, Carlos; Malhotra, Sunny; Rio, Jordi; Leyva, Laura; Fernández, Oscar; Zettl, Uwe K.; Killestein, Joep; Brassat, David; García-Merino, Juan Antonio; Sánchez, Antonio J.; Urcelay, Elena; Alvarez-Lafuente, Roberto; Villar, Lusia M.; Alvarez-Cermeño, Jose Carlos; Farré, Xavier; Lechner-Scott, Jeannette; Vandenbroeck, Koen; Rodríguez-Antigüedad, Alfredo; Drulovic, Jelena S.; Martinelli Boneschi, Filippo; Chan, Andrew; Oksenberg, Jorge; Navarro, Arcadi; Montalban, Xavier

    2015-01-01

    Objectives: We aimed to investigate the association between polymorphisms located in type I interferon (IFN)-induced genes, genes belonging to the toll-like receptor (TLR) pathway, and genes encoding neurotransmitter receptors and the response to IFN-β treatment in patients with multiple sclerosis (MS). Methods: In a first or screening phase of the study, 384 polymorphisms were genotyped in 830 patients with MS classified into IFN-β responders (n = 416) and nonresponders (n = 414) according to clinical criteria. In a second or validation phase, the most significant polymorphisms associated with IFN-β response were genotyped in an independent validation cohort of 555 patients with MS (281 IFN-β responders and 274 nonresponders). Results: Seven single nucleotide polymorphisms (SNPs) were selected from the screening phase for further validation: rs832032 (GABRR3; p = 0.0006), rs6597 (STUB1; p = 0.019), rs3747517 (IFIH1; p = 0.010), rs2277302 (PELI3; p = 0.017), rs10958713 (IKBKB; p = 0.003), rs2834202 (IFNAR1; p = 0.030), and rs4422395 (CXCL1; p = 0.017). None of these SNPs were significantly associated with IFN-β response when genotyped in an independent cohort of patients. Combined analysis of these SNPs in all patients with MS (N = 1,385) revealed 2 polymorphisms associated with IFN-β response: rs2277302 (PELI3; p = 0.008) and rs832032 (GABRR3; p = 0.006). Conclusions: These findings do not support an association between polymorphisms located in genes related to the type I IFN or TLR pathways or genes encoding neurotransmitter receptors and the clinical response to IFN-β. Nevertheless, additional genetic and functional studies of PELI3 and GABRR3 are warranted. PMID:26445728

  4. Empathy in electrodermal responsive and nonresponsive patients with schizophrenia.

    PubMed

    Ikezawa, Satoru; Corbera, Silvia; Liu, Jiacheng; Wexler, Bruce E

    2012-12-01

    Skin conductance response (SCR) to emotion-evoking stimuli has in previous studies suggested the existence of two subgroups of schizophrenia patients. One is characterized by absent SCR and the other by heightened or non-habituating SCR. These subgroups have also been shown to differ in symptoms, prognosis and social integration. The present project compared social cognition in the two subgroups. SCR from 28 patients with schizophrenia and 24 matched healthy controls was measured while they watched emotion-evoking and neutral video tapes. Assessments of symptoms, neurocognition, social cognition, and social function were also performed. Event related potentials (ERP) were recorded in response to pictures of people experiencing pain or not. Subjects were divided into "SCR non-responder" and "SCR responder" groups based on SCR frequency. Schizophrenia SCR responders had significantly higher self-reported personal distress in response to others in distress and lower P300 ERP responses to others in pain than schizophrenia SCR non-responders and healthy controls. SCR responsiveness is a potential marker of subgroups of patients with schizophrenia that differ in pathophysiology, function and prognosis. PMID:23058162

  5. The role of Axis II comorbidity in the management of patients with treatment-resistant depression.

    PubMed

    Thase, M E

    1996-06-01

    A significant proportion of antidepressant nonresponders have personality disorders. The relationship between antidepressant resistance and personality pathology is far from straightforward, however, and reflects a disproportionate "burden" of negative prognostic correlates, psychosocial risk factors, and problems that compromise effective therapeutic relationships. An important clinical ground rule is to avoid the reductionistic logical tautology that explains antidepressant failure as a consequence of personality disorder and, by implication, that the patient may deserve to suffer. In evaluating antidepressant-resistant patients, identification of pathologic personality traits or disorders may help provide important clues for future trials of both pharmacotherapy and psychotherapy, particularly in combination.

  6. Mutations of KRAS/NRAS/BRAF predict cetuximab resistance in metastatic colorectal cancer patients

    PubMed Central

    Hsu, Hung-Chih; Thiam, Tan Kien; Lu, Yen-Jung; Yeh, Chien Yuh; Tsai, Wen-Sy; You, Jeng Fu; Hung, Hsin Yuan; Tsai, Chi-Neu; Hsu, An; Chen, Hua-Chien; Chen, Shu-Jen; Yang, Tsai-Sheng

    2016-01-01

    Approximately 45% of metastatic colorectal cancer (mCRC) patients with wild-type KRAS exon 2 are resistant to cetuximab treatment. We set out to identify additional genetic markers that might predict the response to cetuximab treatment. Fifty-three wild-type KRAS exon 2 mCRC patients were treated with cetuximab/irinotecan-based chemotherapy as a first- or third-line therapy. The mutational statuses of 10 EGFR pathway genes were analyzed in primary tumors using next-generation sequencing. BRAF, PIK3CA, KRAS (exons 3 and 4), NRAS, PTEN, and AKT1 mutations were detected in 6, 6, 5, 4, 1, and 1 patient, respectively. Four of the BRAF mutations were non-V600 variants. Four tumors harbored multiple co-existing (complex) mutations. All patients with BRAF mutations or complex mutation patterns were cetuximab non-responders. All patients but one harboring KRAS, NRAS, or BRAF mutations were non-responders. Mutations in any one of these three genes were associated with a poor response rate (7.1%) and reduced survival (PFS = 8.0 months) compared to wild-type patients (74.4% and 11.6 months). Our data suggest that KRAS, NRAS, and BRAF mutations predict response to cetuximab treatment in mCRC patients. PMID:26989027

  7. IL2/IL21 region polymorphism influences response to rituximab in systemic lupus erythematosus patients.

    PubMed

    Márquez, Ana; Dávila-Fajardo, Cristina Lucía; Robledo, Gema; Rubio, José Luis Callejas; de Ramón Garrido, Enrique; García-Hernández, Francisco J; González-León, Rocío; Ríos-Fernández, Raquel; Barrera, José Cabeza; González-Escribano, Ma Francisca; García, Ma Teresa Camps; Palma, Ma Jesús Castillo; del Mar Ayala, Ma; Ortego-Centeno, Norberto; Martín, Javier

    2013-08-01

    To determine whether the IL2/IL21 region, a general autoimmunity locus, contributes to the observed variation in response to rituximab in patients with systemic lupus erythematosus as well as to analyze its influence in a cohort including other autoimmune diseases. rs6822844 G/T polymorphism at the IL2-IL21 region was analyzed by TaqMan assay in 84 systemic lupus erythematosus (SLE) and 60 different systemic autoimmune diseases Spanish patients receiving rituximab. Six months after the first infusion patients were classified, according to the EULAR criteria, as good responders, partial responders and non-responders. A statistically significant difference was observed in GG genotype frequency between responder (total and partial response) (83.56%) and non-responder (45.45%) SLE patients (p=0.010, odds ratio (OR)=6.10 [1.28-29.06]). No association with the response was evident in the group of patients with autoimmune diseases other than lupus. Furthermore, when both groups of patients were pooled in a meta-analysis, a reduced statistical significance of the association was observed (p=0.024, OR=3.53 [1.06-11.64]). Our results show for a first time that IL2-IL21 region seems to play a role in the response to rituximab in SLE patients but not in other autoimmune diseases.

  8. The causality field (extrinsic and intrinsic factors) in industrial subacute low back pain patients.

    PubMed

    Ohlund, C; Lindström, I; Eek, C; Areskoug, B; Nachemson, A

    1996-04-01

    In a prospective, randomized study, primarily designed to test the efficacy of activation on consecutive blue-collar workers sick-listed for 6 weeks due to subacute low back pain, 25% of the workers were excluded for medical reasons. In the intervention study (n = 103), only a minority of cases (6%) had 'true' subacute complaints, i.e. no prior history of low back pain. Subjective reports on general well-being, health status and work-related ergonomic factors were significantly lower or worse in patients than in reference samples. The randomized intervention study could establish a significant effect of graded activation on work return, but the effect seemed to be restricted to patients moderately disabled, i.e. one-third of the subacute low back pain patients included. A predictive four-factor model on work return increased the possibility of identifing nonresponders (chronic low back pain) more than threefold with a specificity (91%) and sensitivity (74%) comparable to that of clinical disc herniation. The history of a prolonged disablement process, cognitive factors, pain behavior and mentally straining ergonomic factors seemed to be of importance. Psychological reactions, or 'barriers to recovery', were slightly different in treatment and control groups but the type of intervention did not significantly alter the predictive model, suggesting that subsets of the study sample may benefit from other optional functional approaches. Descriptive characteristics of the study sample emphasized that subacute low back pain patients cannot be conceptualized as a homogeneous group. Four sub-groups could be identified: (a) specific medical disorders; (b) spontaneous recovery group; (c) moderately disabled back pain patients; and (d) nonresponders. The results support proposals that treatment should be tailored according to individual needs and that better case management should have priority for those belonging to the nonresponder group.

  9. Inhibition of intracellular hepatitis C virus replication by nelfinavir and synergistic effect with interferon-alpha.

    PubMed

    Toma, S; Yamashiro, T; Arakaki, S; Shiroma, J; Maeshiro, T; Hibiya, K; Sakamoto, N; Kinjo, F; Tateyama, M; Fujita, J

    2009-07-01

    Liver diseases associated with hepatitis C virus (HCV) infection have become the major cause of mortality in patients with human immunodeficiency virus (HIV) infection since the introduction of highly active anti-retroviral therapy. HCV-related liver disease is more severe in HIV-infected patients than in non-HIV-infected patients, but the standard therapies used to treat chronic hepatitis C in HCV/HIV coinfected patients are the same as those for patients infected with HCV alone. HIV protease inhibitors might have potential to down-regulate HCV load of HCV/HIV coinfected patients. In this study, we evaluated the effects of nelfinavir on intracellular HCV replication using the HCV replicon system. We constructed an HCV replicon expressing a neomycin-selectable chimeric firefly luciferase reporter protein. Cytotoxicity and apoptosis induced by nelfinavir were assessed and synergism between nelfinavir and interferon (IFN) was calculated using CalcuSyn analysis. Nelfinavir dose-dependently repressed HCV replication at low concentrations (IC(50), 9.88 micromol/L). Nelfinavir failed to induce cytotoxicity or apoptosis at concentrations that inhibited HCV replication. Clinical concentrations of nelfinavir (5 micromol/L) combined with IFN showed synergistic inhibition of HCV replication in our replicon model. Our results suggest that the direct effects of nelfinavir on the HCV subgenome and its synergism with IFN could improve clinical responses to IFN therapy in HCV/HIV coinfected patients.

  10. Young Cervical Cancer Patients May Be More Responsive than Older Patients to Neoadjuvant Chemotherapy Followed by Radical Surgery

    PubMed Central

    Huang, Kecheng; Jia, Yao; Tang, Fangxu; Sun, Haiying; Zhang, Yuan; Zhang, Qinghua; Ma, Ding; Li, Shuang

    2016-01-01

    Objective To evaluate the effects of age and the clinical response to neoadjuvant chemotherapy (NACT) in patients with cervical cancer who received neoadjuvant chemotherapy followed by radical surgery. Methods A total of 1,014 patients with advanced cervical cancer who received NACT followed by radical surgery were retrospectively selected. Patients were divided into young (aged ≤35 years, n = 177) and older (aged >35 years, n = 837) groups. We compared the short-term responses and survival rates between the groups. The five-year disease-free survival (DFS) and overall survival (OS) rates were stratified by age, NACT response, and FIGO stage. Results The overall response rate was 86.8% in the young group and 80.9% in the older group. The young patients had an earlier FIGO stage (P<0.001), a higher rate of adenocarcinoma (P = 0.022), and more lymph node metastasis (P = 0.033) than the older patients. The presence of adenocarcinoma as the histological type (P = 0.024) and positive lymph node metastasis (P<0.001) were identified as independent risk factors for survival. When stratified by age and clinical response, young patients with no response to NACT had a worse clinicopathological condition compared with the other subgroups. Compared with non-responders, responders to NACT had a higher five-year DFS rate (80.1% versus 71.8%; P = 0.019) and OS rate (82.6% versus 71.8%; P = 0.003) among the young patients but not among the older patients. Conclusions Responders to NACT aged 35 years or younger benefitted the most from NACT, while the young non-responders benefitted the least. Age might represent an important factor to consider when performing NACT in patients with cervical cancer. PMID:26901776

  11. Myocardial gene expression profiles and cardiodepressant autoantibodies predict response of patients with dilated cardiomyopathy to immunoadsorption therapy

    PubMed Central

    Ameling, Sabine; Herda, Lars R.; Hammer, Elke; Steil, Leif; Teumer, Alexander; Trimpert, Christiane; Dörr, Marcus; Kroemer, Heyo K.; Klingel, Karin; Kandolf, Reinhard; Völker, Uwe; Felix, Stephan B.

    2013-01-01

    Aims Immunoadsorption with subsequent immunoglobulin G substitution (IA/IgG) represents a novel therapeutic approach in the treatment of dilated cardiomyopathy (DCM) which leads to the improvement of left ventricular ejection fraction (LVEF). However, response to this therapeutic intervention shows wide inter-individual variability. In this pilot study, we tested the value of clinical, biochemical, and molecular parameters for the prediction of the response of patients with DCM to IA/IgG. Methods and results Forty DCM patients underwent endomyocardial biopsies (EMBs) before IA/IgG. In eight patients with normal LVEF (controls), EMBs were obtained for clinical reasons. Clinical parameters, negative inotropic activity (NIA) of antibodies on isolated rat cardiomyocytes, and gene expression profiles of EMBs were analysed. Dilated cardiomyopathy patients displaying improvement of LVEF (≥20 relative and ≥5% absolute) 6 months after IA/IgG were considered responders. Compared with non-responders (n = 16), responders (n = 24) displayed shorter disease duration (P = 0.006), smaller LV internal diameter in diastole (P = 0.019), and stronger NIA of antibodies. Antibodies obtained from controls were devoid of NIA. Myocardial gene expression patterns were different in responders and non-responders for genes of oxidative phosphorylation, mitochondrial dysfunction, hypertrophy, and ubiquitin–proteasome pathway. The integration of scores of NIA and expression levels of four genes allowed robust discrimination of responders from non-responders at baseline (BL) [sensitivity of 100% (95% CI 85.8–100%); specificity up to 100% (95% CI 79.4–100%); cut-off value: −0.28] and was superior to scores derived from antibodies, gene expression, or clinical parameters only. Conclusion Combined assessment of NIA of antibodies and gene expression patterns of DCM patients at BL predicts response to IA/IgG therapy and may enable appropriate selection of patients who benefit from this

  12. Factors Associated With Upper Extremity Functional Recovery Following Low-Frequency Repetitive Transcranial Magnetic Stimulation in Stroke Patients

    PubMed Central

    2016-01-01

    Objective To investigate the factors related to upper extremity functional improvement following inhibitory repetitive transcranial magnetic stimulation (rTMS) in stroke patients. Methods Forty-one stroke patients received low-frequency rTMS over the contralesional hemisphere according to a standard protocol, in addition to conventional physical and occupational therapy. The rTMS-treated patients were divided into two groups according to their responsiveness to rTMS measured by the self-care score of the Korean version of Modified Barthel Index (K-MBI): responded group (n=19) and non-responded group (n=22). Forty-one age-matched stroke patients who had not received rTMS served as controls. Neurological, cognitive and functional assessments were performed before rTMS and 4 weeks after rTMS treatment. Results Among the rTMS-treated patients, the responded group was significantly younger than the non-responded group (51.6±10.5 years and 65.5±13.7 years, respectively; p=0.001). Four weeks after rTMS, the National Institutes of Health Stroke Scale, the Brunnstrom recovery stage and upper extremity muscle power scores were significantly more improved in the responded group than in the control group. Besides the self-care score, the mobility score of the K-MBI was also more improved in the responded group than in the non-responded group or controls. Conclusion Age is the most obvious factor determining upper extremity functional responsiveness to low-frequency rTMS in stroke patients. PMID:27446773

  13. Clinical profile and treatment outcome of older (>75 years) patients with systemic AL amyloidosis

    PubMed Central

    Sachchithanantham, Sajitha; Offer, Mark; Venner, Christopher; Mahmood, Shameem A.; Foard, Darren; Rannigan, Lisa; Lane, Thirusha; Gillmore, Julian D.; Lachmann, Helen J.; Hawkins, Philip N.; Wechalekar, Ashutosh D.

    2015-01-01

    Systemic AL amyloidosis, a disease with improving outcomes using novel therapies, is increasingly recognized in the elderly but treatment and outcomes have not been systematically studied in this group of patients in whom comorbidities and frailty may compound morbidity and mortality. We report the outcomes of 295 patients with systemic AL amyloidosis ≥75 years seen at the UK National Amyloidosis Centre from 2005–2012. The median age was 78.5 years. The median overall survival was 20 months. Two hundred and thirty-eight patients received chemotherapy and 57 elected for supportive care only (overall survival – 24 and 8.4 months, respectively). On intention-to-treat analysis, 44% achieved a hematologic response including a very good partial response or better in 23%. The median overall survival was 6.2 years in patients achieving very good partial response or better at the 6-month landmark analysis and 1.5 years in non-responders. Factors independently indicating a poor prognosis were: cardiac involvement, performance status ≥2; systolic blood pressure <100 mmHg and, on landmark analysis, achieving less than a very good partial response. Treatment of systemic AL amyloidosis in the elderly is challenging. Deep clonal responses are associated with excellent survival and organ responses. Achieving a response to the first-line regimen appears particularly important as outcomes of non-responders are similar to those of untreated patients. Prospective trials with lower toxicity, outpatient treatment regimens are needed. PMID:26294730

  14. Effect of tolvaptan in patients with chronic kidney disease due to diabetic nephropathy with heart failure.

    PubMed

    Sato, Eiichi; Nakamura, Tsukasa; Amaha, Mayuko; Nomura, Mayumi; Matsumura, Daisuke; Yamagishi, Hidetsugu; Ono, Yuko; Ueda, Yoshihiko

    2014-01-01

    The efficacy of tolvaptan for treating heart failure has already been shown. Adequate data relating to the effect of tolvaptan on the correlation of water balance in renal disease are not available. A retrospective study was conducted on the efficacy and adverse reactions of tolvaptan for treating nephrotic syndrome.The subjects were 26 patients with chronic kidney failure due to diabetic nephropathy with heart failure who were administered tolvaptan and seen between December 2011 and October 2013. The endpoints were urinary output, physical findings, and blood analyses. The expression of aquaporin-2 in the collecting duct, which is related to the action of tolvaptan, was investigated by immunohistochemistry using the kidney tissue obtained for the diagnosis.Responses were seen in 19 of the patients. In the histopathological investigation there was severe glomerulosclerosis in patients with diabetic nephropathy, but the responders were noticeable in that they only had mild tubulointerstitial damage. Non-responders exhibited profound tubulointerstitial damage. The expression of aquaporin-2 was determined in 8 patients, of which 7 were responders who tested positive for aquaporin-2. The remaining case was a non-responder who showed no expression of aquaporin-2.Tolvaptan is considered effective for some cases of nephrotic syndrome. There are no clear parameters for predicting an effect, but the present study showed that aquaporin-2 was expressed in the epithelial cells of the collecting ducts of tolvaptan responders.

  15. Tuberculosis Treatment Outcome and Drug Resistance in Lambaréné, Gabon: A Prospective Cohort Study.

    PubMed

    Bélard, Sabine; Remppis, Jonathan; Bootsma, Sanne; Janssen, Saskia; Kombila, Davy U; Beyeme, Justin O; Rossatanga, Elie G; Kokou, Cosme; Osbak, Kara K; Obiang Mba, Régis M; Kaba, Harry M; Traoré, Afsatou N; Ehrhardt, Jonas; Bache, Emmanuel B; Flamen, Arnaud; Rüsch-Gerdes, Sabine; Frank, Matthias; Adegnika, Ayôla A; Lell, Bertrand; Niemann, Stefan; Kremsner, Peter G; Loembé, Marguerite M; Alabi, Abraham S; Grobusch, Martin P

    2016-08-01

    Despite overall global progress in tuberculosis (TB) control, TB remains one of the deadliest communicable diseases. This study prospectively assessed TB epidemiology in Lambaréné, Gabon, a Central African country ranking 10th in terms of TB incidence rate in the 2014 World Health Organization TB report. In Lambaréné, between 2012 and 2014, 201 adult and pediatric TB patients were enrolled and followed up; 66% had bacteriologically confirmed TB and 95% had pulmonary TB. The human immunodeficiency virus (HIV) coinfection rate was 42% in adults and 16% in children. Mycobacterium tuberculosis and Mycobacterium africanum were identified in 82% and 16% of 108 culture-confirmed TB cases, respectively. Isoniazid (INH) and streptomycin yielded the highest resistance rates (13% and 12%, respectively). The multidrug resistant TB (MDR-TB) rate was 4/91 (4%) and 4/13 (31%) in new and retreatment TB cases, respectively. Treatment success was achieved in 53% of patients. In TB/HIV coinfected patients, mortality rate was 25%. In this setting, TB epidemiology is characterized by a high rate of TB/HIV coinfection and low treatment success rates. MDR-TB is a major public health concern; the need to step-up in-country diagnostic capacity for culture and drug susceptibility testing as well as access to second-line TB drugs urgently requires action. PMID:27352879

  16. Amygdala subregions tied to SSRI and placebo response in patients with social anxiety disorder.

    PubMed

    Faria, Vanda; Appel, Lieuwe; Åhs, Fredrik; Linnman, Clas; Pissiota, Anna; Frans, Örjan; Bani, Massimo; Bettica, Paolo; Pich, Emilio M; Jacobsson, Eva; Wahlstedt, Kurt; Fredrikson, Mats; Furmark, Tomas

    2012-09-01

    The amygdala is a key structure in the pathophysiology of anxiety disorders, and a putative target for anxiolytic treatments. Selective serotonin reuptake inhibitors (SSRIs) and placebo seem to induce anxiolytic effects by attenuating amygdala responsiveness. However, conflicting amygdala findings have also been reported. Moreover, the neural profile of responders and nonresponders is insufficiently characterized and it remains unknown whether SSRIs and placebo engage common or distinct amygdala subregions or different modulatory cortical areas. We examined similarities and differences in the neural response to SSRIs and placebo in patients with social anxiety disorder (SAD). Positron emission tomography (PET) with oxygen-15-labeled water was used to assess regional cerebral blood flow (rCBF) in 72 patients with SAD during an anxiogenic public speaking task, before and after 6-8 weeks of treatment under double-blind conditions. Response rate was determined by the Clinical Global Impression-Improvement scale. Conjunction analysis revealed a common rCBF-attenuation from pre- to post-treatment in responders to SSRIs and placebo in the left basomedial/basolateral and right ventrolateral amygdala. This rCBF pattern correlated with behavioral measures of reduced anxiety and differentiated responders from nonresponders. However, nonanxiolytic treatment effects were also observed in the amygdala. All subgroups, including nonresponders, showed deactivation of the left lateral part of the amygdala. No rCBF differences were found between SSRI responders and placebo responders. This study provides new insights into the brain dynamics underlying anxiety relief by demonstrating common amygdala targets for pharmacologically and psychologically induced anxiety reduction, and by showing that the amygdala is functionally heterogeneous in anxiolysis. PMID:22617357

  17. The Impact of Type 2 Diabetes on the Efficacy of ADP Receptor Blockers in Patients with Acute ST Elevation Myocardial Infarction: A Pilot Prospective Study

    PubMed Central

    Fedor, Marián; Kovář, František; Galajda, Peter; Bolek, Tomáš; Stančiaková, Lucia; Fedorová, Jana; Staško, Ján; Kubisz, Peter; Mokáň, Marián

    2016-01-01

    Background. The aim of this study was to validate the impact of type 2 diabetes (T2D) on the platelet reactivity in patients with acute ST elevation myocardial infarction (STEMI) treated with adenosine diphosphate (ADP) receptor blockers. Methods. A pilot prospective study was performed. Totally 67 patients were enrolled. 21 patients had T2D. Among all study population, 33 patients received clopidogrel and 34 patients received prasugrel. The efficacy of ADP receptor blocker therapy had been tested in two time intervals using light transmission aggregometry with specific inducer and vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) flow cytometry assay. Results. There were no significant differences in platelet aggregability among T2D and nondiabetic (ND) group. The platelet reactivity index of VASP-P did not differ significantly between T2D and ND group (59.4 ± 30.9% versus 60.0 ± 25.2% and 33.9 ± 25.3% versus 38.6 ± 29.3% in second testing). The number of ADP receptor blocker nonresponders did not differ significantly between T2D and ND patients. The time interval from ADP receptor blocker loading dosing to the blood sampling was similar in T2D and ND patients in both examinations. Conclusion. This prospective study did not confirm the higher platelet reactivity and higher prevalence of ADP receptor blocker nonresponders in T2D acute STEMI patients. PMID:27493970

  18. Quantitative analysis of interferon alpha receptor subunit 1 and suppressor of cytokine signaling 1 gene transcription in blood cells of patients with chronic hepatitis C

    PubMed Central

    2010-01-01

    Background Interferon (IFN)-α receptor 1 (ifnar1) and suppressor of cytokine signaling 1 (socs1) transcription levels were quantified in peripheral blood mononuclear cells (PBMC) of 59 patients infected with hepatitis C virus (HCV) and 17 non-infected individuals. Samples were obtained from patients infected with HCV that were either untreated or treated with IFN-α2 plus ribavirin for 1 year and divided into responders and non-responders based on viral load reduction 6 months after treatment. Ifnar1 and socs1 transcription was quantified by real-time RT-PCR, and the fold difference (2-ΔΔCT) with respect to hprt housekeeping gene was calculated. Results Ifnar1 transcription increased significantly in HCV-infected patients either untreated (3.26 ± 0.31), responders (3.1 ± 0.23) and non-responders (2.18 ± 0.23) with respect to non-infected individuals (1 ± 0.34; P = 0.005). Ifnar1 transcription increased significantly (P = 0.003) in patients infected with HCV genotypes 1a (4.74 ± 0.25) and 1b (2.81 ± 0.25) but not in 1a1b (1.58 ± 0.21). No association was found of Ifnar1 transcription with disease progress, initial viral load or other clinical factors. With respect to socs1 transcription, values were similar for non-infected individuals (1 ± 0.28) and untreated patients (0.99 ± 0.41) but increased in responders (2.81 ± 0.17) and non-responder patients (1.67 ± 0.41). Difference between responder and non-responder patients was not statistically significant. Socs1 transcription increased in patients infected with HCV genotypes 1a and 1b (2.87 ± 0.45 and 2.22 ± 0.17, respectively) but not in 1a1b (1.28 ± 0.40). Socs1 transcript was absent in three patients infected with HCV genotype 1b. A weak correlation between ifnar1 and socs1 transcription was found, when Spearman's correlation coefficient was calculated. Conclusion Our results suggest that HCV infection may up-regulate ifnar1 transcription. HCV genotypes differ in their capacity to affect ifnar1 and

  19. A phase Ib study of the effects of black raspberries on rectal polyps in patients with familial adenomatous polyposis.

    PubMed

    Wang, Li-Shu; Burke, Carol A; Hasson, Henrietta; Kuo, Chieh-Ti; Molmenti, Christine L Sardo; Seguin, Claire; Liu, Pengyuan; Huang, Tim H-M; Frankel, Wendy L; Stoner, Gary D

    2014-07-01

    Familial adenomatous polyposis (FAP) is characterized by the early onset of colonic polyposis and a high risk for colorectal cancer. FAP is treated by colectomy followed by lifelong removal of rectal polyps. This study determined whether black raspberries (BRBs) might regress rectal polyps in patients with FAP. Fourteen patients with FAP were treated with BRBs daily for 9 months. Seven patients received BRB powder orally plus two BRB suppositories inserted into the rectum at bedtime. The other 7 received an oral placebo plus the suppositories. Rectal polyp counts and polyp sizes were obtained at time zero and after 9 months of BRB treatment. Polyps and adjacent normal tissue were collected at both time points. The burden (P = 0.036) but not number (P = 0.069) of rectal polyps was significantly decreased. No benefit was noted with the addition of oral BRBs. Three patients were nonresponders. BRBs significantly decreased cellular proliferation, DNA methylation methyl transferase 1 protein expression, and p16 promoter methylation, but not promoter methylation of the Wnt pathway antagonists, SFRP2 and WIF1, in rectal polyps (adenomas) from responders but not from nonresponders. The MBD-seq assay revealed more demethylated transcription start sites (TSS), including those for miRNAs, in BRB-treated adenomas from the responders. In conclusion, BRB suppositories seem sufficient for regressing rectal polyps in patients with FAP.

  20. Genetic polymorphisms, their allele combinations and IFN-β treatment response in Irish multiple sclerosis patients

    PubMed Central

    O’Doherty, Catherine; Favorov, Alexander; Heggarty, Shirley; Graham, Colin; Favorova, Olga; Ochs, Michael; Hawkins, Stanley; Hutchinson, Michael; O’Rourke, Killian; Vandenbroeck, Koen

    2009-01-01

    Introduction IFN-β is widely used as first-line immunomodulatory treatment for multiple sclerosis. Response to treatment is variable (30–50% of patients are nonresponders) and requires a long treatment duration for accurate assessment to be possible. Information about genetic variations that predict responsiveness would allow appropriate treatment selection early after diagnosis, improve patient care, with time saving consequences and more efficient use of resources. Materials & methods We analyzed 61 SNPs in 34 candidate genes as possible determinants of IFN-β response in Irish multiple sclerosis patients. Particular emphasis was placed on the exploration of combinations of allelic variants associated with response to therapy by means of a Markov chain Monte Carlo-based approach (APSampler). Results The most significant allelic combinations, which differed in frequency between responders and nonresponders, included JAK2–IL10RB–GBP1–PIAS1 (permutation p-value was pperm = 0.0008), followed by JAK2–IL10–CASP3 (pperm = 0.001). Discussion The genetic mechanism of response to IFN-β is complex and as yet poorly understood. Data mining algorithms may help in uncovering hidden allele combinations involved in drug response versus nonresponse. PMID:19604093

  1. Potentially functional SNPs (pfSNPs) as novel genomic predictors of 5-FU response in metastatic colorectal cancer patients.

    PubMed

    Wang, Jingbo; Wang, Xu; Zhao, Mingjue; Choo, Su Pin; Ong, Sin Jen; Ong, Simon Y K; Chong, Samuel S; Teo, Yik Ying; Lee, Caroline G L

    2014-01-01

    5-Fluorouracil (5-FU) and its pro-drug Capecitabine have been widely used in treating colorectal cancer. However, not all patients will respond to the drug, hence there is a need to develop reliable early predictive biomarkers for 5-FU response. Here, we report a novel potentially functional Single Nucleotide Polymorphism (pfSNP) approach to identify SNPs that may serve as predictive biomarkers of response to 5-FU in Chinese metastatic colorectal cancer (CRC) patients. 1547 pfSNPs and one variable number tandem repeat (VNTR) in 139 genes in 5-FU drug (both PK and PD pathway) and colorectal cancer disease pathways were examined in 2 groups of CRC patients. Shrinkage of liver metastasis measured by RECIST criteria was used as the clinical end point. Four non-responder-specific pfSNPs were found to account for 37.5% of all non-responders (P<0.0003). Five additional pfSNPs were identified from a multivariate model (AUC under ROC = 0.875) that was applied for all other pfSNPs, excluding the non-responder-specific pfSNPs. These pfSNPs, which can differentiate the other non-responders from responders, mainly reside in tumor suppressor genes or genes implicated in colorectal cancer risk. Hence, a total of 9 novel SNPs with potential functional significance may be able to distinguish non-responders from responders to 5-FU. These pfSNPs may be useful biomarkers for predicting response to 5-FU. PMID:25372392

  2. [Evaluation of blood morphology in patients with refractory multiple myeloma treated with thalidomide].

    PubMed

    Grzaśko, N; Dmoszyńska, A; Krawczyk, S; Hus, M; Soroka-Wojtaszko, M; Ciepłuch, H; Hellmann, A

    2001-07-01

    Thalidomide, a derivative of alpha-N-phthalimidoglutarimide acid, was withdrawn from the market in the 1960s because of severe birth defects. Recent reports have suggested antiangiogenic and antitumor activity of this drug. We have treated 52 patients with refractory multiple myeloma at age from 32 to 79 years (mean 63) with thalidomide at a dose of 200-400 mg daily. Out of the group of 52 patients, 27 patients (52%) responded to the therapy, in 25 patients (48%) a response was not achieved (decline in monoclonal protein was smaller than 25%). There was a systematic improvement in haemoglobin concentration, erythrocyte count and thrombocyte count during thalidomide therapy. Leukocyte count showed an inclination to decrease, however observed changes were not statistically significant. The improvement in morphotic parameters of blood was observed both in responder and nonresponder patients.

  3. Therapeutic benefit of decitabine, a hypomethylating agent, in patients with high-risk primary myelofibrosis and myeloproliferative neoplasm in accelerated or blastic/acute myeloid leukemia phase.

    PubMed

    Badar, Talha; Kantarjian, Hagop M; Ravandi, Farhad; Jabbour, Elias; Borthakur, Gautam; Cortes, Jorge E; Pemmaraju, Naveen; Pierce, Sherry R; Newberry, Kate J; Daver, Naval; Verstovsek, Srdan

    2015-09-01

    Myeloproliferative neoplasm (MPN) transformed to acute myeloid leukemia (MPN-AML), MPN in accelerated phase (MPN-AP), and high-risk primary myelofibrosis (PMF) are associated with a poor response to therapy and very short survival. Several reports have suggested clinical activity of hypomethylating agents in these patients. We conducted a retrospective study of 21 patients with MPN-AML, 13 with MPN-AP and 11 with DIPSS-plus high-risk PMF treated with decitabine at our institution over the last 7 years and evaluated their clinical outcomes. Six patients (29%) with MPN-AML responded to decitabine (3 CR, 2 CRi, and 1 PR); median response duration was 7 months. The median overall survival (OS) was significantly higher in those who responded (10.5 vs 4 months). Among patients with MPN-AP, 8 patients (62%) benefited; the median response duration was 6.5 months. The median OS was 11.8 months in responders vs 4.7 months in non-responders. Among patients with DIPSS-plus high-risk PMF, 9 (82%) benefited; the median response duration was 9 months. The median OS was 32 months in responders vs 16.3 months in non-responders. Decitabine is a viable therapeutic option for patients with MPN-AML, MP-AP and high-risk PMF. Prospective clinical studies combining decitabine with other clinically active agents are needed to improve overall outcome.

  4. Therapeutic benefit of decitabine, a hypomethylating agent, in patients with high-risk primary myelofibrosis and myeloproliferative neoplasm in accelerated or blastic/acute myeloid leukemia phase

    PubMed Central

    Badar, Talha; Kantarjian, Hagop M.; Ravandi, Farhad; Jabbour, Elias; Borthakur, Gautam; Cortes, Jorge E.; Pemmaraju, Naveen; Pierce, Sherry R.; Newberry, Kate J.; Daver, Naval; Verstovsek, Srdan

    2015-01-01

    Myeloproliferative neoplasm (MPN) transformed to acute myeloid leukemia (MPN-AML), MPN in accelerated phase (MPN-AP), and high-risk primary myelofibrosis (PMF) are associated with a poor response to therapy and very short survival. Several reports have suggested clinical activity of hypomethylating agents in these patients. We conducted a retrospective study of 21 patients with MPN-AML, 13 with MPN-AP and 11 with DIPSS-plus high-risk PMF treated with decitabine at our institution over the last 7 years and evaluated their clinical outcomes. Six patients (29%) with MPN-AML responded to decitabine (3 CR, 2 CRi, and 1 PR); median response duration was 7 months. The median overall survival (OS) was significantly higher in those who responded (10.5 vs 4 months). Among patients with MPN-AP, 8 patients (62%) benefited; median response duration was 6.5 months. The median OS was 11.8 months in responders vs 4.7 months in non-responders. Among patients with DIPSS-plus high-risk PMF, 9 (82%) benefited; median response duration was 9 months. The median OS was 32 months in responders vs 16.3 months in non-responders. Decitabine is a viable therapeutic option for patients with MPN-AML, MP-AP and high-risk PMF. Prospective clinical studies combining decitabine with other clinically active agents are needed to improve overall outcome. PMID:26183878

  5. Greater responsiveness to donepezil in Alzheimer patients with higher levels of acetylcholinesterase based on attention task scores and a donepezil PET study.

    PubMed

    Kasuya, Masashi; Meguro, Kenichi; Okamura, Nobuyuki; Funaki, Yoshihito; Ishikawa, Hiroyasu; Tanaka, Naofumi; Iwata, Ren; Yanai, Kazuhiko

    2012-01-01

    The aim of the study was to predict donepezil responders among patients with Alzheimer disease (AD) based on cognitive tests and positron emission tomography. The Mini-Mental State Examination, Digit Symbol subtest (DigSm) of Wechsler Adult Intelligence Scale Revised, and Trail-Making Test A were administered for 80 patients with AD to assess global function, attention, and executive function, respectively. The same tests and the Clinical Global Impression (CGI) scale were conducted after treatment with oral donepezil (5 mg/d) for 6 months (study 1). [C]-Donepezil positron emission tomography examinations were conducted before and after treatment for 30 randomly selected patients. The distribution volume (DV), which indicates the density of donepezil-binding sites, was calculated using Logan graphical analysis (study 2). In study 1, 35 patients were identified as responders based on the CGI and Mini-Mental State Examination changes. These patients had higher baseline DigSm scores compared with nonresponders. In study 2, 15 patients were responders. DigSm correlated with DV at baseline. DV at baseline and %DV change in responders were higher than in nonresponders, and these variables correlated with ΔDigSm and CGI scores. Higher baseline attention may predict responsiveness to donepezil in patients with AD, and higher acetylcholinesterase levels result in a greater clinical effect.

  6. Long-term safety and efficacy of dalfampridine for walking impairment in patients with multiple sclerosis: Results of open-label extensions of two Phase 3 clinical trials

    PubMed Central

    Goodman, Andrew D; Bethoux, Francois; Brown, Theodore R; Schapiro, Randall T; Cohen, Ron; Marinucci, Lawrence N; Henney, Herbert R

    2015-01-01

    Background: In Phase 3 double-blind trials (MS-F203 and MS-F204), dalfampridine extended release tablets 10 mg twice daily (dalfampridine-ER; prolonged-release fampridine in Europe; fampridine modified or sustained release elsewhere) improved walking speed relative to placebo in patients with multiple sclerosis (MS). Objectives: Evaluation of long-term safety and efficacy of dalfampridine-ER in open-label extensions (MS-F203EXT, MS-F204EXT). Methods: Patients received dalfampridine-ER 10 mg twice daily; and had Timed 25-Foot Walk (T25FW) assessments at 2, 14 and 26 weeks, and then every 6 months. Subjects were categorized as dalfampridine-ER responders or non-responders, based on their treatment response in the double-blind parent trials that assessed T25FW. Results: We had 269 patients enter MS-F203EXT and 154 patients complete it; for a maximum exposure of 5 years. We had 214 patients enter MS-F204EXT and 146 complete it; for a maximum exposure of 3.3 years. No new safety signals emerged and dalfampridine-ER tolerability was consistent with the double-blind phase. Improvements in walking speed were lost after dalfampridine-ER was discontinued in the parent trial, but returned by the 2-week assessment after re-initiation of the drug. Throughout the extensions, mean improvement in walking speed declined, but remained improved, among the double-blind responders as compared with non-responders. Conclusions: The dalfamipridine-ER safety profile was consistent with the parent trials. Although walking speed decreased over time, dalfampridine-ER responders continued to show improved walking speed, which was sustained compared with non-responders. PMID:25583832

  7. Changes in the Temperament and Character Inventory dimensions after paroxetine treatment in patients with major depressive disorder.

    PubMed

    Tomita, Tetsu; Kaneda, Ayako; Nakagami, Taku; Kaneko, Sunao; Yasui-Furukori, Norio

    2015-09-01

    Previous studies have reported changes in the dimensions of the Temperament and Character Inventory (TCI) after patients with major depressive disorder are treated. We aimed to investigate the changes in the TCI dimensions after paroxetine treatment in patients with major depressive disorder. Forty-eight patients were enrolled in this study and were treated with 10-40 mg/day of paroxetine for 6 weeks. The TCI was completed twice, at weeks 0 and 6. We used the Montgomery-Asberg Depression Rating Scale (MADRS) to evaluate patients. The participants were divided into three groups (responders, non-responders, and early responders) based on treatment response. The scores of each dimension of the TCI were compared before and after treatment using repeated-measures two-way analyses of variance. In the responders group (n = 24), no TCI dimension scores changed significantly during treatment, but the interaction between sex and MADRS score change was significantly associated with the results. In the non-responders group (n = 15), the self-directedness score increased significantly during the treatment period (p = 0.000), and the change in MADRS score significantly affected the results. In the early responders group (n = 9), no TCI dimension scores changed significantly during treatment. The results of the present study may reveal a possible correlation between paroxetine treatment and changes in personality traits.

  8. Phenotypic differences of CD4(+) T cells in response to red blood cell immunization in transfused sickle cell disease patients.

    PubMed

    Vingert, Benoît; Tamagne, Marie; Habibi, Anoosha; Pakdaman, Sadaf; Ripa, Julie; Elayeb, Rahma; Galacteros, Frédéric; Bierling, Philippe; Ansart-Pirenne, Hélène; Bartolucci, Pablo; Noizat-Pirenne, France

    2015-06-01

    Alloimmunization against red blood cells (RBCs) is the main immunological risk associated with transfusion in patients with sickle cell disease (SCD). However, about 50-70% of SCD patients never get immunized despite frequent transfusion. In murine models, CD4(+) T cells play a key role in RBC alloimmunization. We therefore explored and compared the CD4(+) T-cell phenotypes and functions between a group of SCD patients (n = 11) who never became immunized despite a high transfusion regimen and a group of SCD patients (n = 10) who had become immunized (at least against Kidd antigen b) after a low transfusion regimen. We studied markers of CD4(+) T-cell function, including TLR, that directly control lymphocyte function, and their spontaneous cytokine production. We also tested responders for the cytokine profile in response to Kidd antigen b peptides. Low TLR2/TLR3 expression and, unexpectedly, strong expression of CD40 on CD4(+) T cells were associated with the nonresponder status, whereas spontaneous expression of IL-10 by CD4(+) T cells and weak Tbet expression were associated with the responder status. A Th17 profile was predominant in responders when stimulated by Jb(k) . These findings implicate CD4(+) T cells in alloimmunization in humans and suggest that they may be exploited to differentiate responders from nonresponders.

  9. Stroke volume variation fail to predict fluid responsiveness in patients undergoing pulmonary lobectomy with one-lung ventilation using thoracotomy.

    PubMed

    Fu, Qiang; Zhao, Feng; Mi, Weidong; Zhang, Hong

    2014-02-01

    The purpose of this study was to investigate the ability of stroke volume variation (SVV) to predict fluid responsiveness in patients undergoing pulmonary lobectomy with one lung ventilation (OLV). Thirty patients intubated with double-lumen tube were scheduled for a pulmonary lobectomy requiring OLV for at least 1 hour under general anesthesia. Hemodynamic variables including heart rate, mean arterial pressure, cardiac index (CI), stroke volume index (SVI), central venous pressure (CVP) and SVV were measured before and after volume expansion (VE) (8 mL/kg of 6% hydroxyethyl starch). Fluid responsiveness was defined as an increase in CI ≥ 10% after VE. Of the 30 patients, 16 (53%) were responders and 14 (47%) were nonresponders to intravascular VE. There were significant increases of CI, SVI in responders after VE (p < 0.01), but there were no significant changes in SVV in responders and nonresponders (p > 0.05). The baseline value of SVV, CVP, CI and SVI did not correlate significantly with ΔCI (p > 0.05). The area under the Receiver Operating Characteristic (ROC) curve were 0.507 for SVV (95% confidence interval, 0.294-0.720) and 0.556 for CVP (95% confidence interval, 0.339-0.773), neither was able to predict fluid responsiveness with sufficient statistical power. SVV measured by the Vigileo-FloTrac system was not able to predict fluid responsiveness in patients undergoing pulmonary lobectomy with OLV after thoractomy.

  10. Interferon-alpha reduces insulin resistance and beta-cell secretion in responders among patients with chronic hepatitis B and C.

    PubMed

    Tai, T-Y; Lu, J-Y; Chen, C-L; Lai, M-Y; Chen, P-J; Kao, J-H; Lee, C-Z; Lee, H-S; Chuang, L-M; Jeng, Y-M

    2003-09-01

    This study aimed at elucidating the effects of interferon (IFN)-alpha on glucose metabolism in patients with chronic hepatitis B and C infections. Twenty-eight biopsy-proven patients with chronic hepatitis B (ten cases) and hepatitis C (18 cases) were given IFN-alpha for a total of 24 weeks. The patients received a 75 g oral glucose tolerance test (OGTT), glucagon stimulation test, tests for type 1 diabetes-related autoantibodies and an insulin suppression test before and after IFN-alpha therapy. Ten of the 28 patients responded to IFN-alpha therapy. Steady-state plasma glucose of the insulin suppression test decreased significantly in responders (13.32+/-1.48 (S.E.M.) vs 11.33+/-1.19 mmol/l, P=0.0501) but not in non-responders (12.29+/-1.24 vs 11.11+/-0.99 mmol/l, P=0.2110) immediately after completion of IFN-alpha treatment. In the oral glucose tolerance test, no significant difference was observed in plasma glucose in either responders (10.17+/-0.23 vs 10.03+/-0.22 mmol/l) or non-responders (10.11+/-0.22 vs 9.97+/-0.21 mmol/l) 3 Months after completion of IFN-alpha treatment. However, significant differences were noted in C-peptide in both responders (2.90+/-0.13 vs 2.20+/-0.09 nmol/l, P=0.0040) and non-responders (2.45+/-0.11 vs 2.22+/-0.08 nmol/l, P=0.0287) before vs after treatment. The changes of C-peptide in an OGTT between responders and non-responders were also significantly different (P=0.0028), with responders reporting a greater reduction in C-peptide. No case developed autoantibodies during the treatment. In patients who were successfully treated with IFN-alpha, insulin sensitivity improved and their plasma glucose stayed at the same level without secreting as much insulin from islet beta-cells.

  11. Analysis of potentially predictive factors of efficacy of adjunct extended-release quetiapine fumarate in patients with major depressive disorder.

    PubMed

    Bauer, Michael; Thase, Michael E; Liu, Sherry; Earley, Willie; Eriksson, Hans

    2015-05-01

    Identification of predictors of treatment response in patients with major depressive disorder (MDD) may facilitate improved disease management. Data were pooled from two 6-week, double-blind, placebo-controlled studies of extended-release quetiapine (quetiapine XR; 150 or 300 mg/day) as adjunct to ongoing antidepressant therapy. Effects of psychiatric history and baseline demographic and disease characteristics on efficacy outcomes (Week 6 Montgomery Åsberg Depression Rating Scale [MADRS] total score reduction) were evaluated in population subgroups (quetiapine XR both doses pooled, n = 616; placebo, n = 303). Baseline Clinical Global Impressions-Severity (CGI-S) score and previous depressive episodes on Week 6 MADRS total score change, and baseline MADRS individual item scores on Week 6 change in CGI-Improvement score, were also evaluated. No major differences between responders and non-responders to quetiapine XR were observed for patient characteristics or demographic and disease characteristics. No suggestion of a predictive association was found between baseline CGI-S score, number of depressive episodes, and baseline MADRS item scores and efficacy outcomes. These analyses showed no major differences between responders and non-responders, and no predictive association between the parameters assessed and efficacy outcomes for adjunct quetiapine XR in patients with MDD and an inadequate response to prior antidepressant therapy.

  12. Ten-day decitabine as initial therapy for newly diagnosed patients with acute myeloid leukemia unfit for intensive chemotherapy.

    PubMed

    Bhatnagar, Bhavana; Duong, Vu H; Gourdin, Theodore S; Tidwell, Michael L; Chen, Ching; Ning, Yi; Emadi, Ashkan; Sausville, Edward A; Baer, Maria R

    2014-07-01

    We retrospectively reviewed outcomes in 45 previously untreated patients with acute myeloid leukemia (AML) considered unfit for chemotherapy who were treated with 10-day courses of decitabine 20 mg/m(2) daily outside of a clinical trial, with no cut-offs for organ function or performance status (PS). Nineteen had Eastern Cooperative Group performance status (ECOG PS) ≥ 2, and 39 had ≥ 2 comorbidities. Fourteen patients (31%) achieved complete remission (CR) and five (11%) CR with incomplete count recovery, for an overall response rate of 42%, after a median of 2 (range, 1-4) courses. The only pretreatment characteristic that differed significantly between responders and non-responders was percent marrow blasts (median 42% vs. 65%; p = 0.01). Median overall survival was 9.0 months; it was 19.4 and 2.3 months for responders and non-responders, respectively (p < 0.001). Thus 10-day decitabine therapy has efficacy in patients with AML considered unfit for chemotherapy, and may serve as a backbone for the addition of other novel agents. PMID:24144313

  13. Early sorafenib-related adverse events predict therapy response of TACE plus sorafenib: A multicenter clinical study of 606 HCC patients.

    PubMed

    Zhao, Yan; Li, Hailiang; Bai, Wei; Liu, Jueshi; Lv, Weifu; Sahu, Sonia; Guan, Sheng; Qin, Xiao; Wang, Wenhui; Ren, Weixin; Mu, Wei; Guo, Weidong; Gu, Shanzhi; Ma, Yilong; Yin, Zhanxin; Guo, Wengang; Wang, Wenjun; Wang, Yongji; Duran, Rafael; Fan, Daiming; Zhang, Zhuoli; Han, Guohong

    2016-08-15

    The purpose of our study was to test the hypothesis that sorafenib-related dermatologic adverse events (AEs) as an early biomarker can predict the long-term outcomes following the combination therapy of transarterial chemoembolization (TACE) plus sorafenib (TACE-S). The intermediate-stage hepatocellular carcinoma patients who received either TACE-S or TACE-alone treatment were consecutively included into analysis. In the TACE-S group, patients with ≥ grade 2 dermatologic AEs within the first month of sorafenib initiation were defined as responders; whereas those with < grade 2 were defined as nonresponders. In the TACE-S group, the median overall survival (OS) of the responders was significantly longer than that of nonresponders (28.9 months vs. 16.8 months, respectively; p = 0.004). Multivariate analysis demonstrated that nonresponders were significantly associated with an increased risk of death compared with responders (HR = 1.9; 95% confidence Interval-CI: 1.3-2.7; p = 0.001). The survival analysis showed that the median OS was 27.9 months (95% CI: 25.0-30.8) among responders treated with TACE-S vs.18.3 months (95% CI: 14.5-22.1) among those who received TACE-alone (p = 0.046). The median time to progression was 13.1 months (95% CI: 4.4-21.8) in the TACE-S group, a duration that was significantly longer than that in the TACE-alone group [5 months (95% CI: 6.4-13.3), p = 0.014]. This study demonstrated that sorafenib-related dermatologic AEs are clinical biomarkers to identify responders from all of the patients for TACE-S therapy. Sorafenib-related dermatologic AEs, clinical biomarkers, can predict the efficacy of TACE-S in future randomized controlled trials.

  14. Patient preference compared with random allocation in short-term psychodynamic supportive psychotherapy with indicated addition of pharmacotherapy for depression.

    PubMed

    Van, Henricus L; Dekker, Jack; Koelen, Jurrijn; Kool, Simone; van Aalst, Gerda; Hendriksen, Marielle; Peen, Jaap; Schoevers, Robert

    2009-03-01

    Depressed patients randomized to psychotherapy were compared with those who had been chosen for psychotherapy in a treatment algorithm, including addition of an antidepressant in case of early nonresponse. There were no differences between randomized and by-preference patients at baseline in adherence and outcome. About half of the early nonresponders refused the additional medication. However, no clear effect of medication addition on ultimate outcome could be demonstrated. In total, 37% of the patients achieved remission. The study suggested that randomization of patients does not induce a great influence on outcome. It might be warranted to continue an initially ineffective psychotherapy for depression, because a considerable number of patients do have a pattern of delayed response.

  15. Potential biomarkers for monitoring therapeutic response in patients with CIDP.

    PubMed

    Dalakas, Marinos C

    2011-06-01

    Although the majority of patients with CIDP variably respond to intravenous immunoglobulin (IVIg), steroids, or plasmapheresis, 30% of them are unresponsive or insufficiently responsive to these therapies. The heterogeneity in therapeutic responses necessitates the need to search for biomarkers to determine the most suitable therapy from the outset and explore the best means for monitoring disease activity. The ICE study, which led to the first FDA-approved indication for IVIg in CIDP, has shown that maintenance therapy prevents relapses and axonal loss. In this paper, the multiple actions exerted by IVIg on the immunoregulatory network of CIDP are discussed as potential predictors of response to therapies. Emerging molecular markers, promising in identifying responders to IVIg from non-responders, include modulation of FcγRIIB receptors on monocytes and genome-wide transcription studies related to inflammatory mediators, demyelination, or axonal degeneration. Skin biopsies, Peripheral Blood Lymhocytes, CSF, and sera are accessible surrogate tissues for further exploring these molecules during therapies.

  16. Decitabine treatment could ameliorate primary iron-overload in myelodysplastic syndrome patients.

    PubMed

    Shucheng, Gu; Chunkang, Chang; Youshan, Zhao; Juan, Guo; Chengming, Fei; Xi, Zhang; Chao, Xiao; Xiao, Li

    2015-04-01

    In order to research how does hypomethylating agents ameliorate iron metabolism in myelodysplastic syndrome (MDS), we performed methylation-specific, polymerase chain reaction (MSP), bisulfate genomic sequencing polymerase chain reaction (BSP), quantitative real-time PCR and western blot of hemojuvelin (HJV) and ELISA assay for hepcidin before and after demethylating therapy (decitabine) to determine whether the change of HJV methylation status would have an influence on hepcidin expression. Eleven of 22 MDS patients achieved CR or PR according to IWG criteria (50%). HJV mRNA was induced in decitabine responders (p = .006 comparing pre/post decitabine treatment) but not in non-responders (p = .121). Similarly, hepcidin serum expression increased from 320.77 ± 34.8 μg/L to 366.77 ± 21.90 μg/L (p = .012) in responders but did not significantly change in non-responders (p = .058), while no difference of adjusted serum ferritin (ASF) was found. In conclusion, hypermethylation of HJV promoter region could silence the gene expression and demethylating therapy might ameliorate iron-overload through HJV demethylation.

  17. Usefulness of ultrasonographic measurement of the diameter of the inferior vena cava to predict responsiveness to intravascular fluid administration in patients with cancer

    PubMed Central

    Arredondo-Armenta, Juan M.; Guevara-García, Humberto; Barragán-Dessavre, Mireya; García-Guillén, Francisco J.; Sánchez-Hurtado, Luis A.; Córdova-Sánchez, Bertha; Bautista-Ocampo, Andoreni R.; Herrera-Gómez, Angel; Meneses-García, Abelardo

    2016-01-01

    We conducted an observational, longitudinal prospective study in which we measured the diameters of the inferior vena cava (IVC) of 47 patients using ultrasonography. The aim of our study was to assess the state of blood volume and to determine the percentage of patients who responded to intravascular volume expansion. Only 17 patients (36%) responded to fluid management. A higher number of responding patients had cardiovascular failure compared with nonresponders (82% vs. 50%, P = 0.03). Among the patients with cardiovascular failure, the probability of finding responders was 4.6 times higher than that of not finding responders (odds ratio, 4.66; 95% confidence interval, 1.10–19.6; P = 0.04). No significant difference was observed in the mortality rate between the two groups (11% vs. 23%, P = 0.46). In conclusion, responding to intravascular volume expansion had no impact on patient survival in the intensive care unit. PMID:27695165

  18. Usefulness of ultrasonographic measurement of the diameter of the inferior vena cava to predict responsiveness to intravascular fluid administration in patients with cancer

    PubMed Central

    Arredondo-Armenta, Juan M.; Guevara-García, Humberto; Barragán-Dessavre, Mireya; García-Guillén, Francisco J.; Sánchez-Hurtado, Luis A.; Córdova-Sánchez, Bertha; Bautista-Ocampo, Andoreni R.; Herrera-Gómez, Angel; Meneses-García, Abelardo

    2016-01-01

    We conducted an observational, longitudinal prospective study in which we measured the diameters of the inferior vena cava (IVC) of 47 patients using ultrasonography. The aim of our study was to assess the state of blood volume and to determine the percentage of patients who responded to intravascular volume expansion. Only 17 patients (36%) responded to fluid management. A higher number of responding patients had cardiovascular failure compared with nonresponders (82% vs. 50%, P = 0.03). Among the patients with cardiovascular failure, the probability of finding responders was 4.6 times higher than that of not finding responders (odds ratio, 4.66; 95% confidence interval, 1.10–19.6; P = 0.04). No significant difference was observed in the mortality rate between the two groups (11% vs. 23%, P = 0.46). In conclusion, responding to intravascular volume expansion had no impact on patient survival in the intensive care unit.

  19. Factors affecting response to medical management in patients of filarial chyluria: A prospective study

    PubMed Central

    Goyal, Neeraj Kumar; Goel, Apul; Sankhwar, Satyanarayan; Singh, Vishwajeet; Ali, Wahid; Natu, S. M.; Singh, Bhupendra Pal; Sinha, Rahul Janak; Dalela, Divakar

    2014-01-01

    Introduction: Filarial chyluria is a common problem in filarial endemic countries. Its management begins with medical therapy but some patients progress to require surgery. The present study aimed to determine factors affecting response to medical management in patients of filarial chyluria. Materials and Methods: This prospective study conducted between August 2008 and November 2012, included conservatively managed patients of chyluria. Demographic profile, clinical presentation, treatment history and urinary triglycerides (TGs) and cholesterol levels at baseline were compared between the responders and non-responders. Apart from the clinical grade of chyluria, hematuria was evaluated as an independent risk factor. Results: Out of the 222 patients (mean age, 37.99 ± 13.29 years, 129 males), 31 patients failed to respond while 35 had a recurrence after initial response; the overall success rate being 70.3% at a mean follow-up of 25 months. No difference was observed in demographics, clinical presentation, presence of hematuria, disease duration and mean urinary TGs loss between responders and non-responders. On multivariate analysis, patients with treatment failure were found to have a higher-grade disease (14.3% Grade-I, 36.6% Grades-II and 60% Grade-III), higher number of pretreatment courses (1.59 ± 1.08 vs. 1.02 ± 0.79) and heavier cholesterol (26.54 ± 23.46 vs. 8.81 ± 8.55 mg/dl) loss at baseline compared with responders (P < 0.05). Conclusion: Conservative management has a success rate in excess of 70%, not affected by the disease chronicity, previous episodes and recurrent nature. However, higher-grade disease, extensive pre-treatment with drugs and higher urinary cholesterol loss at baseline are the predictors of poor response. Hematuria is not an independent poor risk factor for conservative management. PMID:24497677

  20. Changes in bone marrow lesions in response to weight-loss in obese knee osteoarthritis patients: a prospective cohort study

    PubMed Central

    2013-01-01

    Background Patients are susceptible for knee osteoarthritis (KOA) with increasing age and obesity and KOA is expected to become a major disabling disease in the future. An important feature of KOA on magnetic resonance imaging (MRI) is changes in the subchondral bone, bone marrow lesions (BMLs), which are related to the future degeneration of the knee joint as well as prevalent clinical symptoms. The aim of this study was to investigate the changes in BMLs after a 16-week weight-loss period in obese subjects with KOA and relate changes in BMLs to the effects of weight-loss on clinical symptoms. Methods This prospective cohort study included patients with a body mass index ≥ 30 kg/m2, an age ≥ 50 years and primary KOA. Patients underwent a 16 weeks supervised diet program which included formula products and dietetic counselling (ClinicalTrials.gov: NCT00655941). BMLs in tibia and femur were assessed on MRI before and after the weight-loss using the Boston-Leeds Osteoarthritis Knee Score. Response to weight-loss in BML scores was dichotomised to patients experiencing a decrease in BML scores (responders) and patients who did not (non-responders). The association of BMLs to weight-loss was assessed by logistic regressions and correlation analyses. Results 39 patients (23%) were classified as responders in the sum of all BML size scores whereas 130 patients (77%) deteriorated or remained stable and were categorized as non-responders. Logistic regression analyses revealed no association between weight-loss < or ≥ 10% and response in BMLs in the most affected compartment (OR 1.86 [CI 0.66 to 5.26, p=0.24]). There was no association between weight-loss and response in maximum BML score (OR 1.13 [CI 0.39 to 3.28, p=0.81]). The relationship between changes in BMLs and clinical symptoms revealed that an equal proportion of patients classified as BML responders and non-responders experienced an OMERACT-OARSI response (69 vs. 71%, p=0.86). Conclusions Weight-loss did not

  1. Utility of bortezomib retreatment in relapsed or refractory multiple myeloma patients: a multicenter case series.

    PubMed

    Wolf, Jeffrey; Richardson, Paul G; Schuster, Michael; LeBlanc, Annette; Walters, Ian B; Battleman, David S

    2008-10-01

    Bortezomib therapy has become an important part of the standard of care for patients with relapsed multiple myeloma, and preliminary clinical evidence suggests that bortezomib retreatment in patients previously treated with the drug may prolong disease control. This retrospective study was designed to clarify the utility of bortezomib as a repeat therapy. We reviewed records from 3 major cancer centers that had participated in the phase II (SUMMIT or CREST) or phase III (APEX) registration studies to identify patients who were subsequently retreated off protocol with bortezomib-based therapy. We found 22 patients who received bortezomib retreatment following a 60 or more day gap between bortezomib treatments. Twelve patients had intervening therapy between initial bortezomib treatment and bortezomib retreatment. During retreatment, 14 of 22 patients received bortezomib in combination with another antineoplastic agent. The overall response rate for bortezomib retreatment was 50% (9% complete responses). The median length of retreatment was 5.1 months in responding patients and 2.4 months in nonresponding patients. Therapy was terminated due to unmanageable toxicity in 2 patients during retreatment, compared with 6 patients during initial treatment. During retreatment, no patients required dose reduction due to peripheral neuropathy, compared to 4 patients during their initial treatment. Thus, bortezomib retreatment appears to be safe and effective. Favorable observed response rates with bortezomib retreatment suggest that it may be a viable option for relapsed or refractory multiple myeloma, even in patients previously exposed to bortezomib.

  2. Interleukin-15 receptor α expression in inflammatory bowel disease patients before and after normalization of inflammation with infliximab

    PubMed Central

    Perrier, Clémentine; Arijs, Ingrid; Staelens, Dominiek; Breynaert, Christine; Cleynen, Isabelle; Covens, Kris; Ferrante, Marc; Assche, Gert; Vermeire, Séverine; Hertogh, Gert; Schuit, Frans; Rutgeerts, Paul; Ceuppens, Jan L

    2013-01-01

    Interleukin-15 (IL-15) is a pro-inflammatory cytokine thought to contribute to the inflammation in inflammatory bowel diseases (IBD). The specific receptor chain IL-15Rα can be expressed as a transmembranous signalling receptor, or can be cleaved by a disintegrin and metalloprotease domain 17 (ADAM17) into a neutralizing, soluble receptor (sIL-15Rα). The aim of this study is to evaluate the expression of IL-15Rα in ulcerative colitis (UC) and Crohn's disease (CD) patients before and after infliximab (IFX) therapy. Gene expression of IL-15Rα, IL-15 and ADAM17 was measured at the mRNA level by quantitative reverse transcription-PCR in mucosal biopsies harvested before and after first IFX therapy. Concentrations of sIL-15Rα were measured in sera of patients by ELISA and IL-15Rα protein was localized in the gut by immunohistochemistry and immunofluorescence. Mucosal expression of IL-15Rα is increased in UC and CD patients compared with controls and it remains elevated after IFX therapy in both responder and non-responder patients. The concentration of sIL-15Rα in serum is also increased in UC patients when compared with controls and does not differ between responders and non-responders either before or after IFX. CD patients have levels of sIL-15Rα comparable to healthy controls before and after therapy. In mucosal tissues, IL-15Rα+ cells closely resemble activated memory B cells with a pre-plasmablastic phenotype. To conclude, IBD patients have an increased expression of IL-15Rα mRNA in the mucosa. Expression is localized in B cells, suggesting that IL-15 regulates B-cell functions during bowel inflammation. No change in release of sIL-15Rα is observed in patients treated with IFX. PMID:23039249

  3. Variability of residual platelet function despite clopidogrel treatment in patients with peripheral arterial occlusive disease.

    PubMed

    Linnemann, Birgit; Schwonberg, Jan; Toennes, Stefan W; Mani, Helen; Lindhoff-Last, Edelgard

    2010-04-01

    Residual platelet function despite treatment with clopidogrel may predict an unfavourable cardiovascular outcome. The majority of studies have investigated the effects of clopidogrel administration in conjunction with aspirin in patients undergoing percutaneous coronary intervention. The primary objective of the present study was to assess the platelet response to clopidogrel in the absence of aspirin in patients with peripheral arterial occlusive disease (PAOD) and to investigate whether non-responsiveness to clopidogrel is reproducible during long-term follow-up. Fifty-four clinically stable PAOD patients on a maintenance dose of 75 mg/d clopidogrel were enrolled in this study. Platelet function was assessed at baseline and after a median follow-up of 18 months using light transmittance aggregometry (LTA) with 2 microM ADP as an agonist. HPLC-coupled mass spectrometry was used to detect clopidogrel and clopidogrel carboxylic acid, the main metabolite of clopidogrel. Residual platelet function, as defined by late aggregation values within the reference range (i.e., >43%), was observed in 35.2% of patients at baseline and 17.6% during follow-up. During the observation period, 26.5% had switched from responder to non-responder status or vice versa. Among non-responders, either clopidogrel or its metabolite was detected in 89.5% and 83.3% of patients at baseline and at follow-up, respectively. We conclude that non-responsiveness to clopidogrel as determined by ADP-induced LTA is not stable over time. This phenomenon cannot be attributed to non-compliance alone. PMID:20153859

  4. The role of IL-28, IFN-γ, and TNF-α in predicting response to pegylated interferon/ribavirin in chronic HCV patients.

    PubMed

    Abdou, Asmaa Gaber; Asaad, Nancy Youssef; Ehsan, Nermin; Eltahmody, Mohammad; El-Sabaawy, Maha Mohamed; Elkholy, Shimaa; Elnaidany, Nada Farag

    2015-01-01

    The primary goal of HCV therapy is to achieve a sustained virological response (SVR). Many host and viral factors influence the treatment response. Cytokines play an important role in the defense against viral infections, where successful treatment of hepatitis C depends on a complex balance between pro- and anti-inflammatory responses. In the present study, we investigated the relationship between the presence and percentage of some cytokines (IL-28, IFN-γ, and TNF-α) regarding different clinicopathological parameters including response to therapy in chronic HCV patients using immunohistochemical technique. This study was carried out on 64 chronic HCV patients (34 responders and 30 non-responders). Of cases, 54% showed IL-28 expression, which was associated with low AST (p = 0.002) and low HAI score (p = 0.006). Of cases, 67 and 45% showed IFN-γ and TNF-α expression, respectively, where the median percentage of TNF-α expression was higher in grade II spotty necrosis compared to grade I. Some inflammatory cytokines expressed by intrahepatic inflammatory cells in chronic HCV patients promote inflammation and injury (pro-inflammatory) such as TNF-α. Other cytokines aid in resolving inflammation and injury (anti-inflammatory) such as IL-28. The balance between these cytokines will determine the degree of inflammatory state. None of the investigated cytokines proved its clear cut role in affecting response to therapy, however, their levels varied between responders and non-responders for further investigations to clarify. PMID:25131720

  5. 10% Tumor Diameter Shrinkage on the First Follow-Up Computed Tomography Predicts Clinical Outcome in Patients With Advanced Renal Cell Carcinoma Treated With Angiogenesis Inhibitors: A Follow-Up Validation Study

    PubMed Central

    Franchetti, Yoko; Nishino, Mizuki; Fay, André P.; Ramaiya, Nikhil; Van den Abbeele, Annick D.; Choueiri, Toni K.

    2014-01-01

    Background. Vascular endothelial growth factor (VEGF)-targeted agents are standard therapies for metastatic renal cell carcinoma (mRCC), associated with variable tumor shrinkage. Response Evaluation Criteria in Solid Tumors (RECIST) is of limited utility in this setting, and other imaging changes are sought to reliably predict outcome early. We aim to validate 10% tumor shrinkage as the best early indicator of outcome. Methods. In this institutional review board-approved, Health Insurance Portability and Accountability Act-compliant study, 66 mRCC patients with 165 lesions on clinical trials of VEGF-targeted agents underwent thoracic and abdominal computed tomography at baseline and at first follow-up after therapy. Measurements were performed according to RECIST and tumor shrinkage of ≥10% decrease in sum of the longest diameter (−10%SLD). Correlation with time-to-treatment failure (TTF) and overall survival (OS) were compared and stratified by response to the radiologic criteria. Receiver-operating characteristics (ROC) analysis yielded the optimal threshold change in SLD, defining patients with prolonged survival. Results. More than −10%SLD significantly differentiated responders from nonresponders (median TTF 8.4 vs. 4.1 months, p = .001), whereas partial response by RECIST did not (median TTF 6.9 vs. 5.5 months in responders vs. nonresponders, p = .34). −10%SLD was also significantly predictive of OS (median OS 35.1 vs. 15.0 months in responders vs. nonresponders, p = .003). ROC curve analysis yielded −9.3% in SLD as the optimal threshold for response/no response. Conclusion. Ten percent tumor shrinkage is validated as a reliable early predictor of outcome in mRCC patients receiving VEGF-targeted therapies and may provide a practical measure to guide therapeutic decisions. PMID:24755461

  6. Retrospective evaluation of biopsychosocial determinants and treatment response in patients receiving devil's claw extract (doloteffin).

    PubMed

    Thanner, J; Kohlmann, Th; Künzel, O; Chrubasik, S

    2009-05-01

    In a retrospective evaluation of patients taking part for 2 months in a postmarketing surveillance study on the effectiveness and safety of Harpagophytum procumbens, associations were found to known explanators of pain, disability and depression. Therefore, treatment non-responders might best be referred to a multimodal pain relief program that deals with fear avoidance beliefs, enhances experiences that decrease perceptions linking disability and pain and forces the patients to rethink the way they deal with the problem. However, during treatment with the aqueous Harpagophytum extract, this decision might reasonably be postponed to the end of month 4, since it has been shown that the maximum pain relief occurs after 3-4 months. PMID:19107732

  7. Can hydroxyurea serve as a free radical scavenger and reduce iron overload in β-thalassemia patients?

    PubMed

    Italia, Khushnooma; Chandrakala, S; Ghosh, Kanjaksha; Colah, Roshan

    2016-09-01

    In this study, we hypothesize that hydroxyurea could provide an additional benefit as a free radical scavenger and/or iron chelator in β-thalassemia patients with iron overload. Twenty-one β-thalassemia intermedia patients who presented between 3 and 17 years but later required regular blood transfusions were enrolled for hydroxyurea therapy for a year. Fourteen patients responded to the therapy with hemoglobin levels maintained above 7.5 g/dl without transfusions. Hydroxyurea was discontinued after 6 months in seven patients who did not respond to the therapy and had to be continued on regular blood transfusions. We observed a statistically significant decrease in serum ferritin levels from 4194 ± 4850 ng/ml to 2129 ± 2380 ng/ml among the responders and from 2955 ± 2909 ng/ml to 2040 ± 2432 ng/ml among the non-responders and statistically significant decrease in labile iron pool from 18678.7 ± 10067.4 mean fluorescence intensity (MFI) to 14888.5 ± 5284.0 MFI among responders and from 17986.3 ± 9079.8 MFI to 15634.8 ± 8976.9 MFI among the non-responders after therapy. Phosphatidylserine externalization also showed a statistically significant decrease from 44.2 ± 22.2 MFI to 16.6 ± 6.7 MFI among the responders and from 46.9 ± 33.1 MFI to 39.8 ± 7.4 MFI among the non-responders along with a statistically significant decrease in the levels of reactive oxygen species from 72.8 ± 35.5 MFI to 29.0 ± 8.3 MFI among the responders and from 80.9 ± 41.4 MFI to 40.5 ± 15.8 MFI among the non-responders after therapy. A statistically significant increase in reduced glutathione levels was also observed from 430.8 ± 201.1 MFI to 715.5 ± 292.4 MFI among the responders and from 359.6 ± 165.6 MFI to 450.3 ± 279.5 MFI among the non-responders after therapy. This suggests the possible additional role of hydroxyurea as a free radical scavenger and

  8. CTLA-4 blockade enhances polyfunctional NY-ESO-1 specific T cell responses in metastatic melanoma patients with clinical benefit.

    PubMed

    Yuan, Jianda; Gnjatic, Sacha; Li, Hao; Powel, Sarah; Gallardo, Humilidad F; Ritter, Erika; Ku, Geoffrey Y; Jungbluth, Achim A; Segal, Neil H; Rasalan, Teresa S; Manukian, Gregor; Xu, Yinyan; Roman, Ruth-Ann; Terzulli, Stephanie L; Heywood, Melanie; Pogoriler, Evelina; Ritter, Gerd; Old, Lloyd J; Allison, James P; Wolchok, Jedd D

    2008-12-23

    Blockade of inhibitory signals mediated by cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) has been shown to enhance T cell responses and induce durable clinical responses in patients with metastatic melanoma. The functional impact of anti-CTLA-4 therapy on human immune responses is still unclear. To explore this, we analyzed immune-related adverse events and immune responses in metastatic melanoma patients treated with ipilimumab, a fully human anti-CTLA-4 monoclonal antibody. Fifteen patients were selected on the basis of availability of suitable specimens for immunologic monitoring, and eight of these showed evidence of clinical benefit. Five of the eight patients with evidence of clinical benefit had NY-ESO-1 antibody, whereas none of seven clinical non-responders was seropositive for NY-ESO-1. All five NY-ESO-1 seropositive patients had clearly detectable CD4(+) and CD8(+) T cells against NY-ESO-1 following treatment with ipilimumab. One NY-ESO-1 seronegative clinical responder also had a NY-ESO-1 CD4(+) and CD8(+) T cell response, possibly related to prior vaccination with NY-ESO-1. Among five clinical non-responders analyzed, only one had a NY-ESO-1 CD4(+) T cell response and this patient did not have detectable anti-NY-ESO-1 antibody. Overall, NY-ESO-1-specific T cell responses increased in frequency and functionality during anti-CTLA-4 treatment, revealing a polyfunctional response pattern of IFN-gamma, MIP-1beta and TNF-alpha. We therefore suggest that CTLA-4 blockade enhanced NY-ESO-1 antigen-specific B cell and T cell immune responses in patients with durable objective clinical responses and stable disease. These data provide an immunologic rationale for the efficacy of anti-CTLA-4 therapy and call for immunotherapeutic designs that combine NY-ESO-1 vaccination with CTLA-4 blockade.

  9. Cytokine profile of autologous platelet-derived eye drops in patients with ocular chronic graft-versus-host disease.

    PubMed

    Valentini, C G; Nuzzolo, E R; Orlando, N; Metafuni, E; Bianchi, M; Chiusolo, P; Zini, G; Teofili, L

    2016-02-01

    Ocular chronic GVHD is efficaciously treated with autologous platelet-derived eye drops. We investigated the cytokine content of eye drops produced using a non-gelified lysate obtained from autologous platelet-rich plasma in six patients with ocular GVHD. In both the responding (n = 4) and the resistant (n = 2) patients, the eye drops were significantly enriched with various growth factors, in amounts proportional with the platelet counts. In contrast, chemokine ligand and interleukin levels were similar to those of plasma. The non-responding patients showed the highest levels of chemokine (C-X-C motif) ligand (CXCL)10. These findings provide possible explanations for beneficial or detrimental effects of eye drops. PMID:26383050

  10. Identification and characterization of HPA-axis reactivity endophenotypes in a cohort of female PTSD patients.

    PubMed

    Zaba, Monika; Kirmeier, Thomas; Ionescu, Irina A; Wollweber, Bastian; Buell, Dominik R; Gall-Kleebach, Dominique J; Schubert, Christine F; Novak, Bozidar; Huber, Christine; Köhler, Katharina; Holsboer, Florian; Pütz, Benno; Müller-Myhsok, Bertram; Höhne, Nina; Uhr, Manfred; Ising, Marcus; Herrmann, Leonie; Schmidt, Ulrike

    2015-05-01

    Analysis of the function of the hypothalamic-pituitary-adrenal (HPA)-axis in patients suffering from posttraumatic stress disorder (PTSD) has hitherto produced inconsistent findings, inter alia in the Trier Social Stress Test (TSST). To address these inconsistencies, we compared a sample of 23 female PTSD patients with either early life trauma (ELT) or adult trauma (AT) or combined ELT and AT to 18 age-matched non-traumatized female healthy controls in the TSST which was preceded by intensive baseline assessments. During the TSST, we determined a variety of clinical, psychological, endocrine and cardiovascular parameters as well as expression levels of four HPA-axis related genes. Using a previously reported definition of HPA-axis responsive versus non-responsive phenotypes, we identified for the first time two clinically and biologically distinct HPA-axis reactivity subgroups of PTSD. One subgroup ("non-responders") showed a blunted HPA-axis response and distinct clinical and biological characteristics such as a higher prevalence of trauma-related dissociative symptoms and of combined AT and ELT as well as alterations in the expression kinetics of the genes encoding for the mineralocorticoid receptor (MR) and for FK506 binding protein 51 (FKBP51). Interestingly, this non-responder subgroup largely drove the relatively diminished HPA axis response of the total cohort of PTSD patients. These findings are limited by the facts that the majority of patients was medicated, by the lack of traumatized controls and by the relatively small sample size. The here for the first time identified and characterized HPA-axis reactivity endophenotypes offer an explanation for the inconsistent reports on HPA-axis function in PTSD and, moreover, suggest that most likely other factors than HPA-axis reactivity play a decisive role in determination of PTSD core symptom severity.

  11. Protein kinase expression as a predictive factor for interferon response in chronic hepatitis C patients.

    PubMed

    Mohamed, Amal A; Amin, Magdi A; Ragab, Mai M; Ismail, Soheir A; Baki, Amin Abdel M

    2014-01-01

    Egypt has the highest prevalence of hepatitis C virus (HCV) worldwide. Currently, combined pegylated interferon and ribavirin therapy are the standard treatment. The biological activity of interferon (IFN) is mediated by the induction of intracellular antiviral proteins, such as 2'-5' oligoadenylate synthetase, and dsRNA-activated protein kinase. IFN-inducible double-stranded RNA-activated protein kinase (PKR) is thought to play a key antiviral role against HCV. Some studies observed that PKR expression was higher in sustained viral responders compared with the non-responders. The PKR is considered as antiviral toward HCV and responsible for IFN's effect against HCV while others have showed that, there were kinetic results indicate that HCV infection is not altered by reduced levels of PKR, indicating that HCV is resistant to the translational inhibitory effects of the phosphorylated forms of PKR. This study was conducted on 50 consecutive patients with chronic HCV infection (CHC) and 20 healthy controls. All the patients were subjected to clinical and laboratory assessment, abdominal ultrasound, and liver biopsy. Determination of PKR gene quantity by using a real time PCR was done at the baseline and at the end of treatment for all patients and controls. Pre-treatment levels of protein kinase gene were significantly higher in responders in comparison with non-responders (P < 0.001). It was found that 97.06% of patients who were responding to treatment had the expression of protein kinase gene greater than 2(6) cycle threshold. PMID:25685478

  12. Protein kinase expression as a predictive factor for interferon response in chronic hepatitis C patients

    PubMed Central

    Mohamed, Amal A.; Amin, Magdi A.; Ragab, Mai M.; Ismail, Soheir A.; Baki, Amin Abdel M.

    2013-01-01

    Egypt has the highest prevalence of hepatitis C virus (HCV) worldwide. Currently, combined pegylated interferon and ribavirin therapy are the standard treatment. The biological activity of interferon (IFN) is mediated by the induction of intracellular antiviral proteins, such as 2′–5′ oligoadenylate synthetase, and dsRNA-activated protein kinase. IFN-inducible double-stranded RNA-activated protein kinase (PKR) is thought to play a key antiviral role against HCV. Some studies observed that PKR expression was higher in sustained viral responders compared with the non-responders. The PKR is considered as antiviral toward HCV and responsible for IFN’s effect against HCV while others have showed that, there were kinetic results indicate that HCV infection is not altered by reduced levels of PKR, indicating that HCV is resistant to the translational inhibitory effects of the phosphorylated forms of PKR. This study was conducted on 50 consecutive patients with chronic HCV infection (CHC) and 20 healthy controls. All the patients were subjected to clinical and laboratory assessment, abdominal ultrasound, and liver biopsy. Determination of PKR gene quantity by using a real time PCR was done at the baseline and at the end of treatment for all patients and controls. Pre-treatment levels of protein kinase gene were significantly higher in responders in comparison with non-responders (P < 0.001). It was found that 97.06% of patients who were responding to treatment had the expression of protein kinase gene greater than 26 cycle threshold. PMID:25685478

  13. Identification and characterization of HPA-axis reactivity endophenotypes in a cohort of female PTSD patients.

    PubMed

    Zaba, Monika; Kirmeier, Thomas; Ionescu, Irina A; Wollweber, Bastian; Buell, Dominik R; Gall-Kleebach, Dominique J; Schubert, Christine F; Novak, Bozidar; Huber, Christine; Köhler, Katharina; Holsboer, Florian; Pütz, Benno; Müller-Myhsok, Bertram; Höhne, Nina; Uhr, Manfred; Ising, Marcus; Herrmann, Leonie; Schmidt, Ulrike

    2015-05-01

    Analysis of the function of the hypothalamic-pituitary-adrenal (HPA)-axis in patients suffering from posttraumatic stress disorder (PTSD) has hitherto produced inconsistent findings, inter alia in the Trier Social Stress Test (TSST). To address these inconsistencies, we compared a sample of 23 female PTSD patients with either early life trauma (ELT) or adult trauma (AT) or combined ELT and AT to 18 age-matched non-traumatized female healthy controls in the TSST which was preceded by intensive baseline assessments. During the TSST, we determined a variety of clinical, psychological, endocrine and cardiovascular parameters as well as expression levels of four HPA-axis related genes. Using a previously reported definition of HPA-axis responsive versus non-responsive phenotypes, we identified for the first time two clinically and biologically distinct HPA-axis reactivity subgroups of PTSD. One subgroup ("non-responders") showed a blunted HPA-axis response and distinct clinical and biological characteristics such as a higher prevalence of trauma-related dissociative symptoms and of combined AT and ELT as well as alterations in the expression kinetics of the genes encoding for the mineralocorticoid receptor (MR) and for FK506 binding protein 51 (FKBP51). Interestingly, this non-responder subgroup largely drove the relatively diminished HPA axis response of the total cohort of PTSD patients. These findings are limited by the facts that the majority of patients was medicated, by the lack of traumatized controls and by the relatively small sample size. The here for the first time identified and characterized HPA-axis reactivity endophenotypes offer an explanation for the inconsistent reports on HPA-axis function in PTSD and, moreover, suggest that most likely other factors than HPA-axis reactivity play a decisive role in determination of PTSD core symptom severity. PMID:25745955

  14. Outcome of patients with high risk Myelodysplastic Syndrome (MDS) and advanced Chronic Myelomonocytic Leukemia (CMML) treated with decitabine after azacitidine failure.

    PubMed

    Harel, Stéphanie; Cherait, Amina; Berthon, Céline; Willekens, Christophe; Park, Sophie; Rigal, Marthe; Brechignac, Sabine; Thépot, Sylvain; Quesnel, Bruno; Gardin, Claude; Adès, Lionel; Fenaux, Pierre; Braun, Thorsten

    2015-05-01

    Outcome of patients with high risk MDS and CMML who failed treatment with azacitidine remains poor with a median survival of 6 months, without established therapy available except allogeneic hematopoietic stem cell transplantation. The objective of our study was to evaluate efficacy of decitabine after azacitidine failure in a relatively large patient cohort based on conflicting results with 0-28% response rates (RR) in this setting in small patient series. Thirty-six consecutive high risk MDS and CMML patients who received decitabine after azacitidine failure were retrospectively reviewed. Response was based on IWG 2006 criteria for MDS and CMML with WBC<13G/l and also included for proliferative CMML the evolution of WBC, splenomegaly (SMG) and extramedullary disease (EMD). Patients received a median number of 3 (range 1-27) cycles of decitabine and 12 patients received at least 6 cycles. Seven (19.4%) patients were responders including 3 marrow CR (mCR), 2 stable disease (SD) with HI-E, 1 SD with HI-N and HI-P and 1 SD with HI-N. In a CMML patient with SD, specific skin lesions resolved with decitabine. Responses were generally short lived (2-5 months) except 1 responder currently ongoing with +11 months follow up. Two non-responders had prolonged SD (without HI) of 21 and 27 months duration respectively. Median OS from onset of decitabine was 7.3 months, without significant difference between responders and non-responders. Treatment with decitabine after azacitidine failure yielded modest ORR (19.4%) with short response duration and poor OS. Thus, use of decitabine in such patients who failed or progressed after azacitidine cannot be recommended, underscoring the need for novel strategies in this setting.

  15. HLA-C and KIR combined genotype as new response marker for HBeAg-positive chronic hepatitis B patients treated with interferon-based combination therapy.

    PubMed

    Stelma, F; Jansen, L; Sinnige, M J; van Dort, K A; Takkenberg, R B; Janssen, H L A; Reesink, H W; Kootstra, N A

    2016-08-01

    Current treatment for chronic hepatitis B infection (CHB) consists of interferon-based therapy. However, for unknown reasons, a large proportion of patients with CHB do not respond to this treatment. Hence, there is a pressing need to establish response markers to select patients who will benefit from therapy and to spare potential nonresponders from unnecessary side effects of antiviral therapy. Here, we assessed whether HLA-C and KIR genotypes were associated with treatment outcome for CHB. Twelve SNPs in or near the HLA-C gene were genotyped in 86 CHB patients (41 HBeAg positive; 45 HBeAg negative) treated with peginterferon alfa-2a + adefovir. Genotyping of killer immunoglobin-like receptors (KIRs) was performed by SSP-PCR. One SNP in HLA-C (rs2308557) was significantly associated with combined response in HBeAg-positive CHB patients (P = 0.003). This SNP is linked to the HLA-C group C1 or C2 classification, which controls KIR binding. The combination of KIR2DL1 with its ligand HLA-C2 was observed significantly more often in HBeAg-positive patients with a combined response (13/14) than in nonresponders (11/27, P = 0.001). Patients with the KIR2DL1/C2 genotype had significantly higher baseline ALT levels (136 vs 50 U/L, P = 0.002) than patients without this combination. Furthermore, KIR2DL1-C2 predicted response independent of HBV genotype and ALT at baseline. HLA-C and KIR genotype is strongly associated with response in HBeAg-positive CHB patients treated with interferon-based therapy. In combination with other known response markers, HLA-C/KIR genotype could enable the selection of patients more likely to respond to interferon-based therapy. PMID:26945896

  16. Tics Moderate Sertraline, but Not Cognitive-Behavior Therapy Response in Pediatric Obsessive-Compulsive Disorder Patients Who Do Not Respond to Cognitive-Behavior Therapy

    PubMed Central

    Compton, Scott; Thomsen, Per Hove; Weidle, Bernhard; Dahl, Kitty; Nissen, Judith Becker; Torp, Nor Christian; Hybel, Katja; Melin, Karin Holmgren; Valderhaug, Robert; Wentzel-Larsen, Tore; Ivarsson, Tord

    2015-01-01

    Abstract Objective: The purpose of this study was to investigate whether the presence of tic disorder is negatively associated with sertraline (SRT) outcomes, but not with continued cognitive-behavioral therapy (CBT), in a sample of youth who were unresponsive to an initial full course of CBT. Methods: In the Nordic Long-Term OCD Study, children and adolescents with OCD who were rated as nonresponders to 14 weeks of open-label CBT were randomized to continued CBT (n=28) or SRT treatment (n=22) for an additional 16 weeks of treatment. We investigated whether the presence or absence of comorbid tic disorder moderated treatment outcomes on the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). Results: Twelve out of 50 (24.0%) participants were diagnosed with comorbid tic disorder, with 7 receiving continued CBT and 5 receiving SRT, respectively. In patients without tic disorder, results showed no significant between-group differences on average CY-BOCS scores. However, in patients with comorbid tic disorder, those who received SRT had significantly lower average CY-BOCS scores than those who received continued CBT. Conclusions: Children and adolescents with OCD and comorbid tic disorder, who are nonresponders to an initial 14 week course of CBT, may benefit more from a serotonin reuptake inhibitor (SRI) than from continued CBT. PMID:26091197

  17. Cardiometabolic comorbidities and the approach to patients with psoriasis.

    PubMed

    Gisondi, P; Girolomoni, G

    2009-12-01

    Psoriasis is a chronic inflammatory, immune-mediated skin disease, which may cause significant deterioration in the quality of life. Recent evidence indicates that psoriasis and psoriatic arthritis are frequently associated with cardiometabolic diseases including myocardial infarction, stroke, diabetes, obesity, dyslipidemia and non-alcoholic fatty liver disease. Although the causal relationship between cardiometabolic comorbidities and psoriasis has not yet been completely proven, it appears that obesity is a relevant risk factor for the development of psoriasis and metabolic syndrome. In addition, moderate to severe psoriasis itself is a risk factor for cardiovascular disease and the metabolic syndrome. Some common genetic traits as well as inflammatory mechanisms may underlie the development of psoriasis and cardiometabolic comorbidities. The presence of comorbidities has important implications in the global approach to patients with psoriasis. Traditional systemic anti-psoriatic agents could negatively affect cardiometabolic comorbidities, and may have important interactions with drugs commonly used by psoriasis patients. In contrast, the recent findings that the risk of myocardial infarction is markedly reduced in rheumatoid arthritis patients who respond to anti-TNF-alpha therapy compared with non-responders supports the hypothesis that the anti-inflammatory effect of TNF-alpha blockers might potentially reduce the cardiovascular risk also in psoriasis patients. Finally, patients with moderate to severe psoriasis should be treated promptly and effectively, should also be encouraged to drastically correct their modifiable cardiovascular risk factors, in particular obesity and smoking habit. PMID:20096157

  18. NLRP3 inflammasome is associated with the response to IFN-β in patients with multiple sclerosis

    PubMed Central

    Malhotra, Sunny; Río, Jordi; Urcelay, Elena; Nurtdinov, Ramil; Bustamante, Marta F; Fernández, Oscar; Oliver, Begoña; Zettl, Uwe; Brassat, David; Killestein, Joep; Lechner-Scott, Jeannette; Drulovic, Jelena; Chan, Andrew; Martinelli-Boneschi, Filippo; García-Merino, Antonio; Montalban, Xavier

    2015-01-01

    Evidence exists for a potential modulation of inflammasome activity by interferon beta. Here, we investigated the roles of inflammasomes [absent in melanoma 2 (AIM2); NLR family, CARD domain containing 4 (NLRC4); NLR family, pyrin domain containing 1 and 3 (NLRP1 and NLRP3)] and related cytokines (IL1B, IL10, IL18) in the response to interferon beta in patients with relapsing-remitting multiple sclerosis. Ninety-seven patients treated with interferon beta were classified into responders and non-responders according to clinical criteria after 24 months and clinical-radiological criteria after 12 months of treatment. Messenger RNA expression levels of inflammasomes and cytokines were determined by real-time polymerase chain reaction in peripheral blood mononuclear cells collected before treatment with interferon beta. In a subgroup of patients, NLRP3 and IL1B expression was also determined after 3 months (n = 32) and 12 months (n = 20) of interferon beta treatment. A polymorphism located in the NLRP3 gene, rs35829419, was genotyped in 789 multiple sclerosis patients treated with interferon beta. Baseline mRNA expression levels for NLRP3 and IL1B were increased in peripheral blood mononuclear cells from non-responders compared to responders classified according to clinical criteria after 24 months (P = 0.02 and P = 0.001, respectively). No significant differences were observed for other inflammasomes and related cytokines. Differences in NLRP3 and IL1B expression remained significant following a clinical-radiological classification after 12 months (P = 0.007 and P = 0.02, respectively). After treatment with interferon beta, NLRP3 and IL1B expression was increased in responders but unchanged in non-responders. A trend for association was observed between rs35829419 and interferon beta response (pM-H = 0.08). These results point to a role of the NLRP3 inflammasome and its related cytokine IL1B in the response to interferon beta in patients with relapsing

  19. Molecular epidemiology, genotype-phenotype correlation and BH4 responsiveness in Spanish patients with phenylketonuria.

    PubMed

    Aldámiz-Echevarría, Luis; Llarena, Marta; Bueno, María A; Dalmau, Jaime; Vitoria, Isidro; Fernández-Marmiesse, Ana; Andrade, Fernando; Blasco, Javier; Alcalde, Carlos; Gil, David; García, María C; González-Lamuño, Domingo; Ruiz, Mónica; Ruiz, María A; Peña-Quintana, Luis; González, David; Sánchez-Valverde, Felix; Desviat, Lourdes R; Pérez, Belen; Couce, María L

    2016-08-01

    Phenylketonuria (PKU), the most common inborn error of amino acid metabolism, is caused by mutations in the phenylalanine-4-hydroxylase (PAH) gene. This study aimed to assess the genotype-phenotype correlation in the PKU Spanish population and the usefulness in establishing genotype-based predictions of BH4 responsiveness in our population. It involved the molecular characterization of 411 Spanish PKU patients: mild hyperphenylalaninemia non-treated (mild HPA-NT) (34%), mild HPA (8.8%), mild-moderate (20.7%) and classic (36.5%) PKU. BH4 responsiveness was evaluated using a 6R-BH4 loading test. We assessed genotype-phenotype associations and genotype-BH4 responsiveness in our population according to literature and classification of the mutations. The mutational spectrum analysis showed 116 distinct mutations, most missense (70.7%) and located in the catalytic domain (62.9%). The most prevalent mutations were c.1066-11G>A (9.7%), p.Val388Met (6.6%) and p.Arg261Gln (6.3%). Three novel mutations (c.61-13del9, p.Ile283Val and p.Gly148Val) were reported. Although good genotype-phenotype correlation was observed, there was no exact correlation for some genotypes. Among the patients monitored for the 6R-BH4 loading test: 102 were responders (87, carried either one or two BH4-responsive alleles) and 194 non-responders (50, had two non-responsive mutations). More discrepancies were observed in non-responders. Our data reveal a great genetic heterogeneity in our population. Genotype is quite a good predictor of phenotype and BH4 responsiveness, which is relevant for patient management, treatment and follow-up.

  20. Efficacy and Factors Affecting Outcome of Gemcitabine Concurrent Chemoradiotherapy in Patients With Locally Advanced Pancreatic Cancer

    SciTech Connect

    Huang, P.-I.; Chao, Yee; Li, C.-P.; Lee, R.-C.; Chi, K.-H.; Shiau, C.-Y.; Wang, L.-W.; Yen, S.-H.

    2009-01-01

    Purpose: To evaluate the efficacy and prognostic factors of gemcitabine (GEM) concurrent chemoradiotherapy (CCRT) in patients with locally advanced pancreatic cancer. Methods and Materials: Between January 2002 and December 2005, 55 patients with locally advanced pancreatic cancer treated with GEM (400 mg/m{sup 2}/wk) concurrently with radiotherapy (median dose, 50.4 Gy; range, 26-61.2) at Taipei Veterans General Hospital were enrolled. GEM (1,000 mg/m{sup 2}) was continued after CCRT as maintenance therapy once weekly for 3 weeks and repeated every 4 weeks. The response, survival, toxicity, and prognostic factors were evaluated. Results: With a median follow-up of 10.8 months, the 1- and 2-year survival rate was 52% and 19%, respectively. The median overall survival (OS) and median time to progression (TTP) was 12.4 and 5.9 months, respectively. The response rate was 42% (2 complete responses and 21 partial responses). The major Grade 3-4 toxicities were neutropenia (22%) and anorexia (19%). The median OS and TTP was 15.8 and 9.5 months in the GEM CCRT responders compared with 7.5 and 3.5 months in the nonresponders, respectively (both p < 0.001). The responders had a better Karnofsky performance status (KPS) (86 {+-} 2 vs. 77 {+-} 2, p = 0.002) and had received a greater GEM dose intensity (347 {+-} 13 mg/m{sup 2}/wk vs. 296 {+-} 15 mg/m{sup 2}/wk, p = 0.02) than the nonresponders. KPS and serum carbohydrate antigen 19-9 were the most significant prognostic factors of OS and TTP. Conclusion: The results of our study have shown that GEM CCRT is effective and tolerable for patients with locally advanced pancreatic cancer. The KPS and GEM dose correlated with response. Also, the KPS and CA 19-9 level were the most important factors affecting OS and TTP.

  1. Angina Relief by Ranolazine Identifies False-Negative SPECT Myocardial Perfusion Scans in Patients with Coronary Disease Demonstrated by Coronary Angiography

    PubMed Central

    Murray, Gary L.

    2014-01-01

    Normal myocardial perfusion imaging (MPI) reduces intermediate- or high-risk pretest probability patients to low- or intermediate-risk posttest probability, respectively, for coronary disease (CD). Since ranolazine (RAN) relieves only angina, anginal patients with normal MPI whose angina is relieved by RAN present a significant dilemma. The purpose of this retrospective chart review was to confirm the impression that coronary angiography (CA) is indicated in patients whose class 3 to 4 angina is relieved by RAN, but have normal myocardial single-photon emission computed tomography (SPECT) MPIs. Charts of patients with stable class 3 to 4 angina (typical and atypical) and normal MPIs (left ventricular ejection fraction [LVEF] ≥50% and segmental score = 0) were reviewed. CA was done on all the patients with complete angina relief taking RAN, as well as nonresponders whose anginal etiology could not be explained. Stenoses were considered flow-restrictive when more than 70% diameter stenosis is observed by quantitative CA, or, when 50 to 70%, fractional flow reserve (FFR) measured ≤0.80. RAN relieved angina in 36 of 54 (67%) patients. Of the known cases, 25 of these 36 (69%) had 43 stenoses ≥50% (mean = 66%): 15 (60%) had 1 vessel disease; 9 (36%) had multivessel disease; 18 (72%) had left anterior descending (LAD) disease; 1 (4%) had left main disease. Twenty one of 43 (49%) stenosis were > 70%; 22 (51%) stenoses were 50 to 70% and required FFR measurement. Twenty nine of 43 stenoses (67%) were considered flow-restrictive in 18 of these 25 (72%) patients. Eight RAN nonresponders with no explanation for angina had no CD at CA. RAN angina relief is invaluable in identifying falsely negative SPECT MPI, and 50% of these patients have flow-restrictive stenoses. PMID:25317027

  2. Identification of Endogenous HLA-A2–Restricted Reactivity Against Shared Melanoma Antigens in Patients Using the Quantitative Real-Time Polymerase Chain Reaction

    PubMed Central

    Thurber, Stacy E.; Khong, Hung T.; Kammula, Udai S.; Rosenberg, Steven A.

    2008-01-01

    Summary This study was conducted to determine whether reactivity to melanoma cells of pretreatment peripheral blood mononuclear cells (PBMCs) from patients with metastatic melanoma correlated with subsequent response to treatment with interleukin-2 (IL-2). The sensitivity of the quantitative real-time polymerase chain reaction (PCR) assay was optimized, including the total number of cells used (3 × 106 in 1 mL), the responder-to-stimulator cell ratio (5:1), the optimal time to incubate PBMCs with tumor (2 h), the appropriate tumor stimulators (melanoma cell lines differing only in the expression of histocompatibility leukocyte antigen [HLA-A2]), the duration of recovery in the culture of PBMCs after cryopreservation (18–24 h), and the medium used (Iscove, 10% human AB serum). Using this optimized assay to detect HLA-A2–restricted antitumor reactivity in the pretreatment PBMCs from patients with melanoma, positive reactive responses were detected in 7 of 28 patients with an objective clinical response to IL-2 therapy compared with 6 of 21 positive reactive responses in nonresponding patients. None of 12 healthy donors were positive in this study. Thus, there was no significant difference in the reactivity of pretreatment PBMCs when responders were compared with nonresponders, although the melanoma patients had an increased incidence of response compared with healthy donors (p = 0.05). The PBMCs from 11 of the 13 melanoma patients with pretreatment HLA-A2–restricted antimelanoma reactivity were tested against a panel of transfectants expressing known shared melanoma antigens. Anti–MART-1 reactivity was detected in the pretreatment PBMCs of three patients. It thus appears that some melanoma patients are immunologically primed to antigens expressed on the tumor surface, although the HLA-A2–restricted antimelanoma activity detected in this real-time PCR assay was not predictive of patients’ responses to IL-2 therapy. PMID:11924911

  3. Higher Strength Lanthanum Carbonate Provides Serum Phosphorus Control With a Low Tablet Burden and Is Preferred by Patients and Physicians: A Multicenter Study

    PubMed Central

    Mehrotra, Rajnish; Martin, Kevin J.; Fishbane, Steven; Sprague, Stuart M.; Zeig, Steven; Anger, Michael

    2008-01-01

    Background and objectives: Management of hyperphosphatemia, a predictor of mortality in chronic kidney disease, is challenging. Nonadherence to dietary phosphate binders, in part, contributes to uncontrolled serum phosphorus levels. This phase IIIb trial assessed the efficacy of increased dosages (3000 to 4500 mg/d) of reformulated lanthanum carbonate (500-, 750-, and 1000-mg tablets) in nonresponders to dosages of up to 3000 mg/d. Design, setting, participants, & measurements: This 8-wk study with a 4-mo open-label extension enrolled 513 patients who were undergoing maintenance hemodialysis. Patients who achieved serum phosphorus control at week 4 with ≤3000 mg/d lanthanum carbonate entered cohort A; nonresponders were randomly assigned to receive 3000, 3750, or 4500 mg/d (cohort B). The primary outcome measure was the control rate for predialysis serum phosphorus levels at the end of week 8, among patients in cohort B. Results: At the end of week 4, 54% of patients achieved serum phosphorus control at dosages ≤3000 mg/d administered as one tablet per meal. Among patients who entered cohort B, control rates of 25, 38, and 32% for patients who were randomly assigned to 3000, 3750, or 4500 mg/d lanthanum carbonate, respectively, were achieved, with no increase in adverse events. Patients and physicians reported significantly higher levels of satisfaction with reformulated lanthanum carbonate compared with previous phosphate binders, partly because of reduced tablet burden with higher dosage strengths. Physicians and patients also expressed a preference for lanthanum carbonate over previous medication. Conclusions: Reformulated lanthanum carbonate is an effective phosphate binder that may reduce daily tablet burden. PMID:18579668

  4. Genetic polymorphism in the serotonin transporter gene-linked polymorphic region and response to serotonin reuptake inhibitors in patients with premature ejaculation

    PubMed Central

    Ozbek, Emin; Otunctemur, Alper; Simsek, Abdulmuttalip; Polat, Emre Can; Ozcan, Levent; Köse, Osman; Cekmen, Mustafa

    2014-01-01

    OBJECTIVES: Serotonin plays a central role in ejaculation and selective serotonin reuptake inhibitors have been successfully used to treat premature ejaculation. Here, we evaluated the relationship between a polymorphism in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the response of patients with premature ejaculation to SSRI medication. METHODS: Sixty-nine premature ejaculation patients were treated with 20 mg/d paroxetine for three months. The Intravaginal Ejaculatory Latency Time and International Index of Erectile Function scores were compared with baseline values. The patients were scored as having responded to therapy when a 2-fold or greater increase was observed in Intravaginal Ejaculatory Latency Time compared with baseline values after three months. Three genotypes of 5-HTTLPR were studied: LL, LS and SS. The appropriateness of the allele frequencies in 5-HTTLPR were analyzed according to Hardy-Weinberg equilibrium using the χ2-test. RESULTS: The short (S) allele of 5-HTTLPR was significantly more frequent in responders than in nonresponders (p<0.05). Out of the 69 total PE patients, 41 patients (59%) responded to therapy. There was no significant difference in the International Index of Erectile Function score at the end of therapy between the responder and nonresponder groups. The frequencies of the L allele and S allele were 20% and 39%, respectively, in the responder group (p<0.05). CONCLUSION: We conclude that premature ejaculation patients with the SS genotype respond well to selective serotonin reuptake inhibitor therapy. Further studies with large patient groups are necessary to confirm this conclusion. PMID:25518026

  5. Using 18F Fluorodeoxyglucose Positron Emission Tomography (FDG PET) to Monitor Clinical Outcomes in Patients Treated with Neoadjuvant Chemo-Radiotherapy for Locally Advanced Pancreatic Cancer

    PubMed Central

    Choi, Minsig; Heilbrun, Lance K.; Venkatramanamoorthy, Raghu; Lawhorn-Crews, Jawana M.; Zalupski, Mark M.; Shields, Anthony F.

    2013-01-01

    BACKGROUND Pancreatic cancer ranks as the fourth leading cause of cancer death in the United States with five year survival ranging from 1-5%. Positron emission tomography (PET) is a metabolic imaging system that is widely used for the initial staging of cancer and detecting residual disease after treatment. There are limited data, however, on the use of this molecular imaging technique to assess early tumor response after treatment in pancreatic cancer. METHODS The objective of the study was to explore the relationship of early treatment response using the 18 F- fluorodeoxyglucose (FDG) PET with surgical outcome and overall survival in patients with locally advanced pancreatic cancer. FDG-PET measurements of maximum standardized uptake value (SUV) and kinetic parameters were compared to the clinical outcome. RESULTS Twenty patients were enrolled in the study evaluating neoadjuvant induction chemotherapy followed by concurrent chemoradiotherapy (chemo-RT) for locally advanced pancreatic cancer. All twenty patients had pre-study PET scans and a total of fifty PET scans were performed. Among patients who were PET responders (≥50% decrease in SUV after cycle 1), 100% (2/2) had complete surgical resection. Only 6% (1/16) had surgical resection in the PET non-responders (<50% decrease). Two patients did not have the second PET scan due to clinical progression or treatment toxicity. Mean survival was 23.2 months for PET responders and 11.3 months for non-responders (p=0.234). Similar differences in survival were also noted when response was measured using Patlak analysis. CONCLUSION FDG-PET can aid in monitoring the clinical outcome of patients with locally advanced pancreatic cancer treated with neoadjuvant chemo-RT. FDG-PET may be used to aid patients who could have complete surgical resection as well as prognosticate patients’ survival. PMID:19806035

  6. Experience of Varied Presentation of Chronic Progressive Disseminated Histoplasmosis in Immunocompetent Patients: A Diagnostic Conundrum

    PubMed Central

    Ghosh, Roumi; Mishra, Pranshu; Sen, Sumit; Maiti, Prasanta Kumar; Chatterjee, Govinda

    2016-01-01

    We report two cases of chronic progressive disseminated histoplasmosis with unusual and rare clinical picture in a patient with no underlying risk factor. One 50-year-old male, presented with hoarseness of voice, chronic cough, with a history of nonresponding anti-tubercular therapy, revealed mucocutaneous lesions on examination. Fungating vocal cord lesions were visualized on bronchoscopy, raised suspicion of carcinoma. The second case, a 22-year-old female, referred to hospital with suspected vasculitis, with complaints of “off and on” fever with decreased oral intake, arthralgia, who later developed generalized nodular skin eruptions. On investigation, human immunodeficiency virus test was found to be negative in both the cases. Histopathological findings of skin biopsy, adrenal and bone marrow aspirates raised suspicion, whereas fungal cultures confirmed Histoplasma infection. Although diagnosis was delayed, but both of them were successfully treated with amphotericin B.

  7. Experience of Varied Presentation of Chronic Progressive Disseminated Histoplasmosis in Immunocompetent Patients: A Diagnostic Conundrum

    PubMed Central

    Ghosh, Roumi; Mishra, Pranshu; Sen, Sumit; Maiti, Prasanta Kumar; Chatterjee, Govinda

    2016-01-01

    We report two cases of chronic progressive disseminated histoplasmosis with unusual and rare clinical picture in a patient with no underlying risk factor. One 50-year-old male, presented with hoarseness of voice, chronic cough, with a history of nonresponding anti-tubercular therapy, revealed mucocutaneous lesions on examination. Fungating vocal cord lesions were visualized on bronchoscopy, raised suspicion of carcinoma. The second case, a 22-year-old female, referred to hospital with suspected vasculitis, with complaints of “off and on” fever with decreased oral intake, arthralgia, who later developed generalized nodular skin eruptions. On investigation, human immunodeficiency virus test was found to be negative in both the cases. Histopathological findings of skin biopsy, adrenal and bone marrow aspirates raised suspicion, whereas fungal cultures confirmed Histoplasma infection. Although diagnosis was delayed, but both of them were successfully treated with amphotericin B. PMID:27688460

  8. Experience of Varied Presentation of Chronic Progressive Disseminated Histoplasmosis in Immunocompetent Patients: A Diagnostic Conundrum.

    PubMed

    Ghosh, Roumi; Mishra, Pranshu; Sen, Sumit; Maiti, Prasanta Kumar; Chatterjee, Govinda

    2016-01-01

    We report two cases of chronic progressive disseminated histoplasmosis with unusual and rare clinical picture in a patient with no underlying risk factor. One 50-year-old male, presented with hoarseness of voice, chronic cough, with a history of nonresponding anti-tubercular therapy, revealed mucocutaneous lesions on examination. Fungating vocal cord lesions were visualized on bronchoscopy, raised suspicion of carcinoma. The second case, a 22-year-old female, referred to hospital with suspected vasculitis, with complaints of "off and on" fever with decreased oral intake, arthralgia, who later developed generalized nodular skin eruptions. On investigation, human immunodeficiency virus test was found to be negative in both the cases. Histopathological findings of skin biopsy, adrenal and bone marrow aspirates raised suspicion, whereas fungal cultures confirmed Histoplasma infection. Although diagnosis was delayed, but both of them were successfully treated with amphotericin B. PMID:27688460

  9. [Influence of out-patient training on locus of control and health-relevant attitudes in hypertensive patients].

    PubMed

    Pötz, Hermann; Kurz, Robert W; Pirker, Hans; Dörrscheidt, Waltraud; Uhlir, Heinz

    2002-01-01

    Therapy of essential hypertension needs a comprehensive and broad assessment that includes somatic as well as psychological aims. We examined the effects of out-patient training for hypertensive patients on somatic parameters as well as locus of control and different relevant attitudes of patients. Psychological results are described in this paper. Out of the 50 patients analysis of somatic data distinguish so-called "responders" with clear improvement that permitted reduction of drugs from another group, called "non-responders", for which no reduction of drugs was possible. Analyses of psychological data show that "responders" develop a higher awareness of their body, a more positive attitude towards health, a freer attitude towards pleasure of life, sexuality, play and creativity. Their will to work and produce becomes less important. Internal locus of control (conviction that one is able to influence illness by oneself) is higher in "responders". Furthermore social external locus of control (conviction that following the suggestions of therapists is helpful) rises. Remnants of these effects were found in a follow up 18 months later.

  10. Serum microRNA-199a/b-3p as a predictive biomarker for treatment response in patients with hepatocellular carcinoma undergoing transarterial chemoembolization

    PubMed Central

    Luo, Zelong; Feng, Chao; Hu, Peng; Chen, Yong; He, Xiao-feng; Li, Yanhao; Zhao, Jianbo

    2016-01-01

    Objective The aim of this study was to investigate whether the level of serum microRNA-199a/b-3p (miR-199a/b-3p) can serve as a predictor of treatment response to transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). Methods Serum miR-199a/b-3p expression level was measured in 132 patients with HCC before TACE (t1) and 3–5 days after TACE (t2). Additionally, 126 patients of these 132 patients had levels measured 4 weeks after TACE (t3) and 3–5 days after second TACE (t4). Serum miR-199a/b-3p expression levels were compared with those of 50 healthy controls. Correlations between miR-199a/b-3p expression levels and clinicopathologic factors and tumor responsiveness were analyzed. The modified Response Evaluation Criteria in Solid Tumors assessment was conducted at t3. Results A lower mean baseline miR-199a/b-3p expression level was observed in patients with HCC compared with healthy controls (0.68±0.81 vs 2.50±2.16, P<0.001). A negative correlation between baseline miR-199a/b-3p expression levels and tumor size (P<0.001) was observed. The nonresponder group had significantly lower miR-199a/b-3p expression levels than the responder group at t1 (0.77±1.09 vs 1.96±1.32, P<0.001). In addition, the decrease in miR-199a/b-3p at t2 was greater in the responder group than in the nonresponder group (P=0.011). A higher proportion of the responder group achieved a >25% decrease in serum miR-199a/b-3p expression levels compared with the nonresponder group (64% vs 39%). Conclusion Serum miR-199a/b-3p may represent a novel biomarker for predicting efficacy of TACE in patients with HCC. PMID:27226729

  11. Discordant responses to cART in HIV-1 patients in the era of high potency antiretroviral drugs: clinical evaluation, classification, management prospects.

    PubMed

    Cenderello, Giovanni; De Maria, Andrea

    2016-01-01

    The goal of antiretroviral treatment (ART) in HIV-1 patients is immune reconstitution following control of viral replication. CD4+ cell number/proportions are a crude but essential correlate of immune reconstitution. Despite suppression of HIV replication, a fraction of ART-treated patients still fails to fully reconstitute CD4+ T cell numbers (immunological nonresponders, INRs). New drugs, regimens and treatment strategies led to increased efficacy, lower side effects and higher virological success rates in clinical practice. The multitude of described immune defects and clinical events accompanying INR opposed to the marginal effect of antiretroviral intensification or immunotherapy trials underline the need for continuing efforts at understanding the mechanisms that underlie INR. Here, we reassess INR definition, frequency, and the achievements of active clinical and translational research suggesting a shared definition for insufficient, partial and complete CD4+ cell number recovery thus improving homogeneity in patient selection and mechanism identification.

  12. Outer Segment Thickness Predicts Visual Field Response to QLT091001 in Patients with RPE65 or LRAT Mutations

    PubMed Central

    Wen, Yuquan; Birch, David G.

    2015-01-01

    Purpose To determine whether the degree of change in Goldmann visual fields (GVFs) following oral administration of QLT091001 was related to baseline measures of retinal structure. Methods Oral QLT091001 was administered once daily for 7 days in all study patients. Comprehensive ophthalmic testing, including spectral-domain optical coherence tomography (SD-OCT), was conducted in 14 patients with Leber congenital amaurosis (LCA) and 18 patients with retinitis pigmentosa (RP) at seven international sites. Average thickness of the outer segment (OS) layer was calculated over central 20°. Both eyes of each subject were evaluated separately. Results Nineteen of 28 eyes (68%) with LCA and 13 of 36 eyes (36%) with RP responded to QLT091001. Among these responders, the average baseline thickness of the OS layer (central 20°) was 13.5 μm in the LCA cohort and 11.7 μm in the RP cohort. Nonresponders had average baseline OS thickness of less than 4.6 μm in both cohorts. The OS thickness in the central 20° was significantly shorter in nonresponders than responders in the LCA cohort (P = 0.01, t-test) and in the RP cohort (P = 0.02, Wilcoxon rank sum test). The OS thickness in the central 20° did not change significantly from baseline during the first 2 months (P = 0.09, t-test, paired). Conclusions The present findings suggest that there is a close parallel between the thickness of the photoreceptor layer and the potential for functional improvement in these patients. Translational Relevance SD-OCT thickness in the central retina may be useful for predicting the visual field response in the peripheral retina to QLT091001. (https://clinicaltrials.gov/ct2/show/NCT01014052 number, NCT01014052) PMID:26448901

  13. Hepatitis B Vaccination in End-Stage Pulmonary Disease Patients Evaluated for Lung Transplantation: A Retrospective Single-Center Evaluation.

    PubMed

    Wald, Alexandra; Deterding, Lea; Maier, Melanie; Liebert, Uwe G; Berg, Thomas; Wirtz, Hubert; Wiegand, Johannes

    2016-06-14

    BACKGROUND In times of limited organs for transplantation, anti-HBc-positive organs can be accepted for lung transplantation to increase the number of donors. Transplant recipients should be vaccinated against hepatitis B to prevent HBV infection. However, response after HBV vaccination has only been poorly evaluated in patients with end-stage pulmonary disease. MATERIAL AND METHODS Anti-HBs titers of 40 anti-HBc negative patients with end-stage pulmonary disease evaluated for lung transplantation were analyzed with the Architect® system (Abbott, Germany). Responders, partial responders, or non-responders after HBV vaccination were defined by anti-HBs titers >100 IU/L, 10-100 IU/L, and <10 IU/L, respectively. RESULTS There were 34/40 individuals (85%) vaccinated against hepatitis B, and 6 were not vaccinated. Response, partial response, and non-response after vaccination were observed in 10/34 (29.4%), 11/34 (32.4%), and 13/34 (38.2%) of patients, respectively. Response to vaccination did not correlate with sex, pulmonary disease, comorbidities, immunosuppressive therapy, or smoking status. CONCLUSIONS Although 85% of patients evaluated for lung transplantation were vaccinated against hepatitis B, 38.2% did not show an anti-HBs titer >10 IU/L. Thus, anti-HBs titers should be regularly monitored. Nonresponders should be considered for booster vaccinations, alternative vaccination schedules, or prophylactic treatment with a nucleos(t)ide analogue in case of transplantation of an anti-HBc-positive organ.

  14. Response as a predictor of survival in patients with recurrent glioblastoma treated with bevacizumab

    PubMed Central

    Prados, Michael; Cloughesy, Timothy; Samant, Meghna; Fang, Liang; Wen, Patrick Y.; Mikkelsen, Tom; Schiff, David; Abrey, Lauren E.; Yung, W.K. Alfred; Paleologos, Nina; Nicholas, Martin K.; Jensen, Randy; Vredenburgh, James; Das, Asha; Friedman, Henry S.

    2011-01-01

    Development of effective therapies for recurrent glioblastoma multiforme (GBM) and reliable, timely evaluation of their benefit are needed. Understanding the relationship between objective response (OR) and survival is important for determining whether OR can provide an early signal of treatment activity in clinical trials. We performed a landmark analysis to evaluate the association between OR and survival at 9, 18, and 26 weeks for 167 patients with recurrent GBM who participated in BRAIN, a phase II trial that evaluated efficacy of bevacizumab alone or in combination with irinotecan, using the Cox regression models adjusted for age, baseline Karnofsky performance score, first vs second relapse, and treatment arm. Hazard ratios (HRs) and P-values for survival between responders and nonresponders were calculated. Additional analyses were performed to test robustness, validity, fit, and accuracy of the models. The relationships between progression-free survival (PFS) and survival and between OR and PFS were also explored. There were 55 responders and 112 nonresponders across the 2 treatment arms in BRAIN. OR status at 9, 18, and 26 weeks was a statistically significant predictor of survival (HR ≤ 0.52, P < .01). PFS was also a statistically significant predictor of survival at each landmark (HR ≤ 0.25, P < .0001). The association between OR and PFS was not statistically significant, likely due to inadequate statistical power for the analysis. Clarifying the relationship of OR and survival is important for determining whether OR can be a reliable predictor of the benefit of a therapeutic agent in patients with recurrent GBM. PMID:21084434

  15. Could the depression of obese patients suffering from chronic hepatitis C be temporarily improved?

    PubMed

    Tarantino, G; Basile, V; Conca, P; Ariello, M; Di Minno, M N D; Romano, A; Gentile, A; Capone, D

    2008-09-01

    Depression is an usual finding in patients suffering from chronic hepatitis C. Development of moderate to severe depressive symptoms occurs frequently during pegylated interferon/ribavirin treatment and is generally predicted by baseline depression scores. Furthermore, the obese patients have been found to be twice as likely to suffer from anxiety, impaired social interaction, and depression when compared with the no obese population. In order to evaluate the efficacy of a pharmacological treatment of depression, 68 obese patients with chronic hepatitis C, under or not antiviral therapy, were selected and enrolled into this open, controlled pilot study. Our population was divided in two groups: 'on Selective Serotonin Reuptake Inhibitors plus support', with individual titration of medication to adequate side-effects, including thirty seven patients, and 'on only support', involving thirty one patients. Both groups were well balanced for gender, age and antiviral treatment. The selected patients had, at entry, a Beck Depression Inventory score of 24.5 +/- 8.1 (mean +/- SD). Therapeutic successful outcomes (a decreased score of >or= 10 units compared to the baseline) were statistically more frequent in antidepressant drug-treated group (P = 0.005); they were well predicted by dose of Selective Serotonin Reuptake Inhibitors. Thirty five percent of patients were non-responder to Selective Serotonin Reuptake Inhibitors. The drug tolerability was good. Nearly twenty percent of patients were responder to only support.

  16. [Antiviral therapy for patients with chronic hepatitis B with multi-drug resistance to nucleoside analogues].

    PubMed

    Ozeki, Itaru; Hige, Shuhei; Karino, Yoshiyasu; Kimura, Mutsuumi; Arakawa, Tomohiro; Nakajima, Tomoaki; Kuwata, Yasuaki; Ohmura, Takumi; Sato, Takahiro; Toyota, Joji

    2013-01-01

    In 18 of 547 patients who had received nucleoside analogue preparations for 1 year or more, multi-drug resistance was detected, after a median follow-up of 53 months. No patient showed liver failure related to multi-drug resistance acquisition. Multi-drug resistance was associated with entecavir (ETV) therapy in 7 lamivudine (LAM) -resistant patients, combination therapy with adefovir dipivoxil (ADV) in 8 LAM-resistant patients, LAM switching to ETV in 2 patients, and initial ETV administration in 1. For treatment, combination therapy with LAM and ADV was performed. In non-responders, combination therapy with ADV and ETV was employed. In all LAM- and ADV-resistant patients, and the HBV DNA level decreased to 3.0LC/ml or less. However, a similar decrease was noted in 7 (58.3%) of 12 LAM- and ETV-resistant patients. Of the 18 patients, 1 did not respond to combination therapy with ADV and ETV. Therapy with tenofovir disoproxil fumarate (TDF) was required.

  17. Real Response to Therapy in Chronic Hepatitis C Virus Patients: A Study From Iran

    PubMed Central

    Namazee, Najmeh; Sali, Shahnaz; Asadi, Sorour; Shafiei, Mostafa; Behnava, Bita; Alavian, Seyed Moayed

    2012-01-01

    Background Despite significant advances in the treatment of chronic hepatitis C in the past decades, factors which can affect response rates to combination therapy; peginterferon and ribavirin, are still under study and reaching sustained virological response (SVR) is affected by several different factors. Objectives To investigate predictor factors contributing to SVR in Iranian patients. Patients and Methods The present non-randomized, clinical trial was conducted on 100 patients referred to the Tehran Hepatitis Center in 2009-2011. The patients were administered combined peginterferon α-2a-ribavirin treatment, based on the standard protocol of the Iranian Ministry of Health. At the end of the treatment, the SVR rate and predictors were evaluated. Results The mean age of the patients was 42 and 78% were male. Genotype 1a was the most common (70%) and 55% of patients were treatment naïve. The outcomes showed that 12%, 16% and 22% patients were; non-responders, breakthroughs and relapsers, respectively, while 50% of the patients reached SVR. Patients reaching SVR were aged 40 years or lower, they were less likely to have been a non-responder in prior treatments, more likely to have a non-1a genotype and a higher number had an HCV RNA of less than 600 000 IU/ml. The multivariate analysis showed that an age of 40 or lower (OR = 3.74, CI95% = 1.52-9.22), a non-1a genotype (OR = 3.71, CI 95% = 1.40-9.81) and an HCV RNA less than 600 000 IU/ml (OR = 2.52, CI 95% = 1.03-6.15) may be useful SVR predictors. Conclusions The findings of the present study showed that half of the patients reached SVR through combined peginterferon α-2a and ribavirin treatment, the majority of whom had genotype 3a and a minority had genotype 1a. In addition, an age of 40 or lower, non-1a genotype and a viral load less than 600 000 IU/ml were strong SVR predictors. PMID:23087759

  18. Association of rs1568885, rs1813443 and rs4411591 polymorphisms with anti-TNF medication response in Greek patients with Crohn’s disease

    PubMed Central

    Thomas, Diamantis; Gazouli, Maria; Karantanos, Theodoros; Rigoglou, Stella; Karamanolis, Georgios; Bramis, Konstantinos; Zografos, George; Theodoropoulos, George E

    2014-01-01

    AIM: To investigate the correlation between rs1568885, rs1813443 and rs4411591 polymorphisms and response to infliximab in a cohort of Greek patients with Crohn’s disease (CD). METHODS: One hundred and twenty-six patients diagnosed with CD based on standard clinical, endoscopic, radiological, and pathological criteria were enrolled in this study at the Gastroenterology Unit of the 2nd Department of Surgery and at the Colorectal Unit of the 1st Department of Propaedeutic Surgery. Infliximab at a dose of 5 mg/kg was administered intravenously at weeks 0, 2, 6 and then every 8 wk. Clinical and serological responses were assessed using the Harvey-Bradshaw Index and serum C-reactive protein (CRP) levels, respectively, and the endoscopic response was evaluated by ileocolonoscopy performed at baseline and after 12-20 wk of therapy. The changes in endoscopic appearance compared to baseline were classified into four categories, and patients were classified as responders and non-responders. Genomic DNA from whole peripheral blood was extracted and genotyping was performed by allele-specific polymerase chain reactions. χ2 test with Yate’s correction based on the S-Plus was used to compare the genotype frequencies. RESULTS: Eighty patients (63.49%) were classified as complete and 32 (25.39%) as partial responders to infliximab, while 14 (11.11%) were primary non-responders. No correlation was found between response to infliximab and patients’ characteristics such as age, gender and disease duration. There was consistency between Harvey-Bradshaw index scores and serum CRP levels. The TT genotype of the rs1568885 polymorphism was significantly related to partial response (P = 0.024) and resistance to infliximab (P = 0.007) while the AT genotype was more frequent in partial responders (P = 0.035) and in primary non-responders (P = 0.032). Regarding rs1813443, the CC genotype was found to be associated with partial response (P = 0.005) and primary resistance (P = 0.002) to

  19. Estimating the monetary value of the annual productivity gained in patients with early rheumatoid arthritis receiving etanercept plus methotrexate: interim results from the PRIZE study

    PubMed Central

    Zhang, Wei; Bansback, Nick; Sun, Huiying; Pedersen, Ronald; Kotak, Sameer; Anis, Aslam H

    2015-01-01

    Objective To measure and value the impact of combined etanercept (ETN) and methotrexate (MTX) therapy on work productivity in patients with early rheumatoid arthritis (RA) over 52 weeks. Methods MTX- and biological-naïve patients with RA (symptom onset ≤12 months; Disease Activity Score based on a 28-joint count (DAS28) >3.2) received open-label ETN50/MTX for 52 weeks. The Valuation of Lost Productivity (VOLP) questionnaire, measuring paid and unpaid work productivity impacts, was completed approximately every 13 weeks. Bootstrapping methods were used to test changes in VOLP outcomes over time. One-year productivity impacts were compared between responders (DAS28 ≤3.2) at week 13 and non-responders using zero-inflated models for time loss and two-part models for total costs of lost productivity. Results 196 patients were employed at baseline and had ≥1 follow-up with VOLP. Compared with baseline, at week 52, patients gained 33.4 h per 3 months in paid work and 4.2 h per week in unpaid work. Total monetary productivity gains were €1322 per 3 months. Over the 1-year period, responders gained paid (231 h) and unpaid work loss (122 h) compared with non-responders, which amounted to a gain of €3670 for responders. Conclusions This is the first clinical trial to measure and value the impact of biological treatment on all the labour input components that affect overall productivity. Combination therapy with ETN50/MTX was associated with a significant productivity gain for patients with early RA who were still observed at week 52. Over the 1-year treatment period, responders at week 13 suffered significantly less productivity loss than non-responders suggesting this gain was related to treatment response. Trial registration number ClinicalTrials.gov number NCT00913458 PMID:26535135

  20. The effectiveness of cardiac resynchronization therapy for patients with New York Heart Association class IV non-ambulatory heart failure

    PubMed Central

    Yamashita, Soichiro; Fukuzawa, Koji; Yoshida, Akihiro; Itoh, Mitsuaki; Imamura, Kimitake; Fujiwara, Ryudo; Suzuki, Atsushi; Nakanishi, Tomoyuki; Matsumoto, Akinori; Kanda, Gaku; Kiuchi, Kunihiko; Shimane, Akira; Okajima, Katsunori; Tanaka, Hidekazu; Hirata, Ken-ichi

    2015-01-01

    Background We reviewed the effectiveness and safety of cardiac resynchronization therapy (CRT) for patients with New York Heart Association (NYHA) class IV non-ambulatory heart failure (NAHF). Methods From 2006 to 2011, 310 patients underwent CRT at Kobe University Hospital and Himeji Cardiovascular Center because of heart failure. Of these, 29 NAHF patients were retrospectively analyzed. The control group comprised 21 age- and ejection fraction-matched patients with NAHF who did not undergo CRT from the ICU database of Kobe University Hospital. The primary endpoint was all-cause death and hospitalization for heart failure. Response was defined as a >15% reduction in left ventricular end-systolic volume (LVESV). Results CRT was performed successfully without serious complications in all patients. Twenty-three patients (79%) were discharged 19±15 days after CRT implantation, while 6 (21%) died during their hospital stay due to progressive heart failure. Compared with the control group, patients in the CRT group showed significant improvements in the primary endpoint (log-rank p=0.04). Six patients (21%) were defined as responders and the Kaplan–Meier curve showed that responders experienced a better outcome than non-responders (log-rank p=0.029). LV dyssynchrony before implantation was significantly related to the occurrence of the primary endpoint (p=0.02). Conclusions CRT can be safely used in patients with NAHF and can improve long-term patient outcomes, especially in treatment responders. PMID:26336563

  1. Differential viral kinetics in treated genotype 4 chronic hepatitis C patients according to ethnicity.

    PubMed

    Elefsiniotis, I S; Pavlidis, C; Dimitroulopoulos, D; Vezali, E; Mihas, C; Mariolis-Sapsakos, T; Koutsounas, S; Paraskevas, E; Saroglou, G

    2009-10-01

    Data concerning the efficacy of PEG-IFN alpha 2a plus ribavirin treatment in treatment-naive, genotype 4-infected chronic hepatitis C (CHC) patients from Europe are limited. Hence the aim of this study was to investigate the viral kinetics as well as the sustained virological response (SVR) rates and their predictors, in these patients. One hundred and twenty-three patients were retrospectively analysed. Early (EVR) and late virological response (LVR) was confirmed by undetectable (<50 IU/mL) serum HCV-RNA at week 12 and week 24 of treatment, respectively. SVR was confirmed by undetectable serum HCV-RNA at the end of treatment as well as 6 months later. Overall, 43.5% of patients exhibited SVR, 42.6% were nonresponders and 13.9% were relapsers. EVR was observed in 40.74% and LVR in 59.25% of them. The positive predictive values of EVR and LVR were 72.97% and 86.27% whereas their negative predictive values were 64.29% and 92.85%, respectively. EVR independently predicted SVR in Caucasian patients (P < 0.001) but not in Egyptian patients (P = 0.613), in whom the only independent predictor of SVR was the absence of cirrhosis (P = 0.004). LVR seems to be a better predictor of SVR than EVR in the vast majority of genotype 4-infected CHC patients, irrespective of ethnicity and all the other baseline parameters. PMID:19413697

  2. Is Response to Radiotherapy in Patients Related to the Severity of Pretreatment Pain?

    SciTech Connect

    Kirou-Mauro, Andrea; Hird, Amanda; Wong, Jennifer; Sinclair, Emily; Barnes, Elizabeth A.; Tsao, May; Danjoux, Cyril; Chow, Edward

    2008-07-15

    Purpose: The primary objective of this study was to determine whether there is a relationship between the severity of pretreatment pain and response to palliative radiotherapy (RT) for painful bone metastases. Methods and Materials: The database for patients with bone metastases seen at the Rapid Response Radiotherapy Program at the Odette Cancer Center from 1999 to 2006 was analyzed. The proportion of patients with mild (scores 1-4), moderate (scores 5-6), or severe (scores 7-10) pain at baseline who experienced a complete response, partial response, stable response, or progressive response after palliative RT was determined according to International Bone Metastases Consensus definitions. Results: During the 7-year study period 1,053 patients received palliative radiation for bone metastases. The median age was 68 years and the median Karnofsky performance status was 70. Of the patients, 53% had a complete or partial response at 1 month, 52% at 2 months, and 54% at 3 months post-RT. Conclusions: There was no significant difference in terms of the proportion of responders (patients with complete or partial response) and nonresponders in terms of painful bone metastases among patients presenting with mild, moderate, or severe pain. Patients with moderate pain should be referred for palliative RT.

  3. Longitudinal Liver Stiffness Assessment in Patients with Chronic Hepatitis C Undergoing Antiviral Therapy

    PubMed Central

    Martinez, Stella M.; Foucher, Juliette; Combis, Jean-Marc; Métivier, Sophie; Brunetto, Maurizia; Capron, Dominique; Bourlière, Marc; Bronowicki, Jean-Pierre; Dao, Thong; Maynard-Muet, Marianne; Lucidarme, Damien; Merrouche, Wassil; Forns, Xavier; de Lédinghen, Victor

    2012-01-01

    Background/Aims Liver stiffness (LS) measurement by means of transient elastography (TE) is accurate to predict fibrosis stage. The effect of antiviral treatment and virologic response on LS was assessed and compared with untreated patients with chronic hepatitis C (CHC). Methods TE was performed at baseline, and at weeks 24, 48, and 72 in 515 patients with CHC. Results 323 treated (62.7%) and 192 untreated patients (37.3%) were assessed. LS experienced a significant decline in treated patients and remained stable in untreated patients at the end of study (P<0.0001). The decline was significant for patients with baseline LS ≥ 7.1 kPa (P<0.0001 and P 0.03, for LS ≥9.5 and ≥7.1 kPa vs lower values, respectively). Sustained virological responders and relapsers had a significant LS improvement whereas a trend was observed in nonresponders (mean percent change −16%, −10% and −2%, for SVR, RR and NR, respectively, P 0.03 for SVR vs NR). In multivariate analysis, high baseline LS (P<0.0001) and ALT levels, antiviral therapy and non-1 genotype were independent predictors of LS improvement. Conclusions LS decreases during and after antiviral treatment in patients with CHC. The decrease is significant in sustained responders and relapsers (particularly in those with high baseline LS) and suggests an improvement in liver damage. PMID:23082200

  4. Plasma Derived From Human Umbilical Cord Blood Modulates Mitogen-Induced Proliferation of Mononuclear Cells Isolated From the Peripheral Blood of ALS Patients.

    PubMed

    Eve, David J; Ehrhart, Jared; Zesiewicz, Theresa; Jahan, Israt; Kuzmin-Nichols, Nicole; Sanberg, Cyndy Davis; Gooch, Clifton; Sanberg, Paul R; Garbuzova-Davis, Svitlana

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by degeneration of motor neurons in the spinal cord and brain. This disease clinically manifests as gradual muscular weakness and atrophy leading to paralysis and death by respiratory failure. While multiple interdependent factors may contribute to the pathogenesis of ALS, increasing evidence shows the possible presence of autoimmune mechanisms that promote disease progression. The potential use of plasma derived from human umbilical cord blood (hUCB) as a therapeutic tool is currently in its infancy. The hUCB plasma is rich in cytokines and growth factors that are required for growth and survival of cells during hematopoiesis. In this study, we investigated the effects of hUCB plasma on the mitogen-induced proliferation of mononuclear cells (MNCs) isolated from the peripheral blood of ALS patients and apoptotic activity by detection of caspase 3/7 expression of the isolated MNCs in vitro. Three distinct responses to phytohemagglutinin (PHA)-induced proliferation of MNCs were observed, which were independent of age, disease duration, and the ALS rating scale: Group I responded normally to PHA, Group II showed no response to PHA, while Group III showed a hyperactive response to PHA. hUCB plasma attenuated the hyperactive response (Group III) and potentiated the normal response in Group I ALS patients, but did not alter that of the nonresponders to PHA (Group II). The elevated activity of caspase 3/7 observed in the MNCs from ALS patients was significantly reduced by hUCB plasma treatment. Thus, study results showing different cell responses to mitogen suggest alteration in lymphocyte functionality in ALS patients that may be a sign of immune deficiency in the nonresponders and autoimmunity alterations in the hyperactive responders. The ability of hUCB plasma to modulate the mitogen cell response and reduce caspase activity suggests that the use of hUCB plasma alone, or with

  5. Outcomes and Costs of Treating Hepatitis C Patients in the Era of First Generation Protease Inhibitors – Results from the PAN Study

    PubMed Central

    Bert, Florian; Böker, Klaus H. W.; Bruch, Harald-Robert; Eisenbach, Christoph; Link, Ralph; John, Christine; Mauss, Stefan; Heyne, Renate; Schott, Eckart; Pfeiffer-Vornkahl, Heike; Hüppe, Dietrich; Krauth, Christian

    2016-01-01

    1. Objective Chronic hepatitis C virus infections (HCV) cause a significant public health burden. Introduction of telaprevir (TVR) and boceprevir (BOC) has increased sustained virologic response rates (SVR) in genotype 1 patients but were accompanied by higher treatment costs and more side effects. Aim of the study was to assess outcomes and costs of treating HCV with TVR or BOC in routine care. 2. Material and Methods Data was obtained from a non-interventional study. This analysis relates on a subset of 1,786 patients for whom resource utilisation was documented. Sociodemografic and clinical parameters as well as resource utilisation were collected using a web-based data recording system. Costs were calculated using official remuneration schemes. 3. Results Mean age of patients was 49.2 years, 58.6% were male. In treatment-naive patients SVR-rates of 62.2% and 55.7% for TVR and BOC were observed (prior relapser: 68.5% for TVR and 63.5% for BOC; prior non-responder: 45.6% for TVR and 39.1% for BOC). Treatment costs are dominated by costs for pharmaceuticals and range between €39,081 and €53,491. We calculated average costs per SVR of €81,347 (TVR) and €70,163 (BOC) in treatment-naive patients (prior relapser: 78,089 €/SVR for TVR and 82,077 €/SVR for BOC; prior non-responder: 116,509 €/SVR for TVR and 110,156 €/SVR for BOC). Quality of life data showed a considerable decrease during treatment. 4. Conclusion Our study is one of few investigating both, outcomes and costs, of treating HCV in a real-life setting. Data can serve as a reference in the discussion of increasing costs in recently introduced agents. PMID:27467772

  6. The relationship between mucosal immunoresponse and clinical outcome in patients with recurrent upper respiratory tract infections treated with a mechanical bacterial lysate.

    PubMed

    Braido, F; Schenone, G; Pallestrini, E; Reggiardo, G; Cangemi, G; Canonica, G W; Melioli, G

    2011-01-01

    This open prospective study aims to evaluate whether a therapy with a polyvalent mechanical bacterial lysate (PMBL) could be associated to the enhancement of the locoregional immunoresponse in patients with recurrent upper respiratory tract infections. Forty patients (23 females and 17 males) were enrolled, 33 of whom concluded the study. The duration of the study was six months and each patient was visited five times. Twenty-six patients had an objective improvement in clinical and medical locoregional conditions, while in seven patients the treatment did not result in an objective amelioration. Twenty-five out of 27 patients with clinical response were characterized by an increase of specific antibodies against PMBL antigens in salivary fluids. Only two patients, with a non-significant clinical result, had a slight increase in the concentration of salivary specific IgA. The association between PMBLspecific immunoglobulin titers and clinical results was significant for IgG and IgA, but not significant for IgM. Th1 switch was detected only in patients with clinical amelioration, while the Th0 phenotype was observed in three responder and four non-responder patients. Weak Th2 polarization was also observed in one clinical responsive patient. The capacity of effectively opsonizing living bacteria was detected in samples derived from responder patients. These results suggest that PMBL treatment was able to trigger an efficient and well-targeted immune-response resulting in positive clinical outcome of the patients treated. PMID:22023774

  7. Clinical and treatment effects on /sup 3/H-clonidine and /sup 3/H-imipramine binding in elderly depressed patients

    SciTech Connect

    Georgotas, A.; Schweitzer, J.; McCue, R.E.; Armour, M.; Friedhoff, A.J.

    1987-06-01

    /sup 3/H-clonidine and /sup 3/H-imipramine binding were measured in depressed patients, 55 years and older. There was no significant difference in either /sup 3/H-clonidine or /sup 3/H-imipramine binding between depressed patients and age- and sex-matched controls. There was no significant correlation between /sup 3/H-clonidine or /sup 3/H-imipramine binding and severity of depression before treatment. There was a significant negative correlation between the K/sub D/ of /sup 3/H-imipramine binding sites and Hamilton score over seven weeks of antidepressant treatment. There was no significant difference between receptor data of responders and nonresponders to antidepressant treatment. 19 references, 2 tables.

  8. Overall Response Rate, Progression-Free Survival, and Overall Survival With Targeted and Standard Therapies in Advanced Non–Small-Cell Lung Cancer: US Food and Drug Administration Trial-Level and Patient-Level Analyses

    PubMed Central

    Blumenthal, Gideon M.; Karuri, Stella W.; Zhang, Hui; Zhang, Lijun; Khozin, Sean; Kazandjian, Dickran; Tang, Shenghui; Sridhara, Rajeshwari; Keegan, Patricia; Pazdur, Richard

    2015-01-01

    Purpose To conduct analyses exploring trial-level and patient-level associations between overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in advanced non–small-cell lung cancer (NSCLC) trials. Methods We identified 14 trials (N = 12,567) submitted to US Food and Drug Administration since 2003 of treatments for advanced NSCLC. Only randomized, active-controlled trials with more than 150 patients were included. Associations between trial-level PFS hazard ratio (HR), OS HR, and ORR odds ratio were analyzed using a weighted linear regression model. Patient-level responder analyses comparing PFS and OS between patients with and without an objective response were performed using pooled data from all studies. Results In the trial-level analysis, the association between PFS and ORR was strong (R2 = 0.89; 95% CI, 0.80 to 0.98). There was no association between OS and ORR (R2 = 0.09; 95% CI, 0 to 0.33) and OS and PFS (R2 = 0.08; 95% CI, 0 to 0.31). In the patient-level responder analyses, patients who achieved a response had better PFS and OS compared with nonresponders (PFS: HR, 0.40; 95% CI, 0.38 to 0.42; OS: HR, 0.40; 95% CI, 0.38 to 0.43). Conclusion On a trial level, there is a strong association between ORR and PFS. An association between ORR and OS and between PFS and OS was not established, possibly because of cross-over and longer survival after progression in the targeted therapy and first-line trials. The patient-level analysis showed that responders have a better PFS and OS compared with nonresponders. A therapy in advanced NSCLC with a large magnitude of effect on ORR may have a large PFS effect. PMID:25667291

  9. Management of headache disorders: design of a randomised clinical trial screening for prognostic patient characteristics

    PubMed Central

    De Hertogh, Willem J; Vaes, Peter H; Devroey, Dirk; Truijen, Steven; Duquet, William; Oostendorp, Rob

    2007-01-01

    Background Treatment of headache disorders is not always optimal. Patients are treated in multiple ways, and the lack of scientific arguments for referral and the insufficient implementation of guidelines result in unclear treatment strategies. The coexistence of headache and neck pain can lead to the referral to a musculoskeletal physiotherapist. This treatment can only be successful if an underlying cervical segmental dysfunction is present. In such cases a physical treatment can be a valuable option that should be considered. The aim of this study is to identify prognostic therapeutic patient characteristics and to increase the number of correct physiotherapy referrals. Methods/design This trial is designed to identify patient characteristics which can influence the prognosis of the patient. Patients with recurrent headache and co-existent neck pain are recruited via a multicenter setup. After screening for eligibility, subjects are tested at baseline and randomly allocated to one of two treatment groups. Testing includes the administering of questionnaires (a Headache Diagnosis Questionnaire, Headache Inventory List and the Headache Impact Test (HIT-6)) and physical tests (Thermal Stimuli, Manual Cervical Spine Examination and Pressure Algometry). Treatment groups are a usual care group (UC) administered by the General Practitioner (GP) and a usual care plus musculoskeletal physiotherapy treatment group (UCMT). UC is based on the Dutch GP Guideline for Headache. UCMT consists of the UC plus a combination of exercises and spinal cervical mobilisations. Follow-up measurements consist of the completion of the Headache Inventory List, the HIT-6 and scoring of the global perceived effect (GPE). The latter allowing the distinction between responders (positive effect) and non-responders (no effect or worse). Logistic regression analysis will be used to identify the specific patient characteristics of the responders and the non-responders. The additional value of the

  10. Physical function improvements and relief from fatigue and pain are associated with increased productivity at work and at home in rheumatoid arthritis patients treated with certolizumab pegol

    PubMed Central

    Taylor, Peter; Strand, Vibeke; Purcaru, Oana; Coteur, Geoffroy; Mease, Philip

    2010-01-01

    Objectives. To evaluate the association between improvements in physical function, fatigue and pain and improvements in productivity at work and at home in patients treated with certolizumab pegol (CZP) in combination with MTX. Methods. Physical function, fatigue and pain were assessed in two CZP clinical trials (Rheumatoid Arthritis PreventIon of structural Damage 1 and 2) using the HAQ-Disability Index (HAQ-DI), Fatigue Assessment Scale (FAS) and Patient Assessment of Pain, with minimal clinically important differences (MCIDs) defined as ≥0.22, ≥1 and ≥10 points, respectively. Work and home productivity were evaluated using the RA-specific Work Productivity Survey (WPS-RA). The odds of achieving an HAQ-DI, FAS or pain ‘response’ at Week 12, defined as improvements ≥MCID, were compared between CZP and control groups. Improvements in productivity at Week 12 were compared between CZP-treated HAQ-DI, FAS or pain responders and non-responders. Results. The odds of achieving improvements ≥MCID were five times higher for pain, and two to three times higher for physical function and fatigue, in patients receiving CZP vs control. Per month, responders reported significantly greater improvements in productivity at work and reduced interference of RA with their work productivity than non-responders. Responders also reported significantly greater improvements in productivity at home and participation in family, social and leisure activities. Conclusions. This study demonstrated a clear association between patient-reported improvements in physical function, fatigue and pain, and improvements in productivity both at work and home. PMID:20547658

  11. Immunocytochemical assessment of bone marrow aspirates for monitoring response to chemotherapy in small-cell lung cancer patients

    PubMed Central

    Pelosi, G; Pasini, F; Ottensmeier, C; Pavanel, F; Bresaola, E; Bonetti, A; Fraggetta, F; Terzi, A; Iannucci, A; Cetto, G L

    1999-01-01

    Recent reports have suggested that tumour cell immunodetection in bone marrow of small-cell lung cancer patients is by far more frequent than found cytohistologically and may have clinical relevance. This study evaluates primarily the efficacy of chemotherapy as method of in vivo purging, but also the relationship of marrow involvement with survival. A total of 112 bone marrow aspirates from 30 chemo-naïve patients were stained twice using anti-NCAM antibodies, first at diagnosis and then after chemotherapy (24 patients) or at disease progression (six patients). Marrow contamination was associated with lower survival (P = 0.002), and was also detected in 7/17 patients conventionally staged as having limited disease. At multivariate analysis, marrow involvement was an independent factor of unfavourable prognosis (P = 0.033). The amount of tumour contamination, before and after chemotherapy, remained unchanged also in responders and even in the subset of patients with apparent limited disease. Following chemotherapy, bone marrow became tumour negative only in 25% of initially positive responders and in none of non-responders. Our results indicate that (i) chemotherapy is not effective in purging bone marrow even in chemo-responsive patients and (ii) a subset of patients with limited disease and negative bone marrow aspirates might have a more favourable prognosis. © 1999 Cancer Research Campaign PMID:10584884

  12. Prediction of Treatment Outcome in Patients with Obsessive-Compulsive Disorder with Low-Resolution Brain Electromagnetic Tomography: A Prospective EEG Study.

    PubMed

    Krause, Daniela; Folkerts, Malte; Karch, Susanne; Keeser, Daniel; Chrobok, Agnieszka I; Zaudig, Michael; Hegerl, Ulrich; Juckel, Georg; Pogarell, Oliver

    2015-01-01

    The issue of predicting treatment response and identifying, in advance, which patient will profit from treating obsessive-compulsive disorder (OCD) seems to be an elusive goal. This prospective study investigated brain electric activity [using Low-Resolution Brain Electromagnetic Tomography (LORETA)] for the purpose of predicting response to treatment. Forty-one unmedicated patients with a DSM-IV diagnosis of OCD were included. A resting 32-channel EEG was obtained from each participant before and after 10 weeks of standardized treatment with sertraline and behavioral therapy. LORETA was used to localize the sources of brain electrical activity. At week 10, patients were divided into responders and non-responders (according to a reduction of symptom severity >50% on the Y-BOCS). LORETA analysis revealed that at baseline responders showed compared to non-responders a significantly lower brain electric activity within the beta 1 (t = 2.86, p < 0.05), 2 (t = 2.81, p < 0.05), and 3 (t = 2.76, p < 0.05) frequency bands and ROI analysis confirmed a reduced activity in alpha 2 (t = 2.06, p < 0.05) in the anterior cingulate cortex (ACC). When baseline LORETA data were compared to follow-up data, the analysis showed in the responder group a significantly lower brain electrical resting activity in the beta 1 (t = 3.17. p < 0.05) and beta 3 (t = 3.11. p < 0.05) frequency bands and equally for the ROI analysis of the orbitofrontal cortex (OFC) in the alpha 2 (t = 2.15. p < 0.05) frequency band. In the group of non-responders the opposite results were found. In addition, a positive correlation between frequency alpha 2 (rho = 0.40, p = 0.010), beta 3 (rho = 0.42, p = 0.006), delta (rho = 0.33, p = 0.038), theta (rho = 0.34, p = 0.031), alpha 1 (rho = 0.38, p = 0.015), and beta1 (rho = 0.34, p = 0.028) of the OFC and the bands delta (rho = 0.33, p = 0.035), alpha 1 (rho = 0.36, p = 0.019), alpha 2 (rho = 0.34, p = 0.031), and beta 3 (rho = 0.38, p = 0.015) of the ACC with a

  13. Prediction of Treatment Outcome in Patients with Obsessive-Compulsive Disorder with Low-Resolution Brain Electromagnetic Tomography: A Prospective EEG Study

    PubMed Central

    Krause, Daniela; Folkerts, Malte; Karch, Susanne; Keeser, Daniel; Chrobok, Agnieszka I.; Zaudig, Michael; Hegerl, Ulrich; Juckel, Georg; Pogarell, Oliver

    2016-01-01

    The issue of predicting treatment response and identifying, in advance, which patient will profit from treating obsessive-compulsive disorder (OCD) seems to be an elusive goal. This prospective study investigated brain electric activity [using Low-Resolution Brain Electromagnetic Tomography (LORETA)] for the purpose of predicting response to treatment. Forty-one unmedicated patients with a DSM-IV diagnosis of OCD were included. A resting 32-channel EEG was obtained from each participant before and after 10 weeks of standardized treatment with sertraline and behavioral therapy. LORETA was used to localize the sources of brain electrical activity. At week 10, patients were divided into responders and non-responders (according to a reduction of symptom severity >50% on the Y-BOCS). LORETA analysis revealed that at baseline responders showed compared to non-responders a significantly lower brain electric activity within the beta 1 (t = 2.86, p < 0.05), 2 (t = 2.81, p < 0.05), and 3 (t = 2.76, p < 0.05) frequency bands and ROI analysis confirmed a reduced activity in alpha 2 (t = 2.06, p < 0.05) in the anterior cingulate cortex (ACC). When baseline LORETA data were compared to follow-up data, the analysis showed in the responder group a significantly lower brain electrical resting activity in the beta 1 (t = 3.17. p < 0.05) and beta 3 (t = 3.11. p < 0.05) frequency bands and equally for the ROI analysis of the orbitofrontal cortex (OFC) in the alpha 2 (t = 2.15. p < 0.05) frequency band. In the group of non-responders the opposite results were found. In addition, a positive correlation between frequency alpha 2 (rho = 0.40, p = 0.010), beta 3 (rho = 0.42, p = 0.006), delta (rho = 0.33, p = 0.038), theta (rho = 0.34, p = 0.031), alpha 1 (rho = 0.38, p = 0.015), and beta1 (rho = 0.34, p = 0.028) of the OFC and the bands delta (rho = 0.33, p = 0.035), alpha 1 (rho = 0.36, p = 0.019), alpha 2 (rho = 0.34, p = 0.031), and beta 3 (rho = 0.38, p = 0.015) of the ACC with a

  14. Successful treatment of chronic hepatitis C with pegylated interferon in combination with ribavirin in a methadone maintenance treatment program

    PubMed Central

    Litwin, Alain H.; Harris, Kenneth A.; Nahvi, Shadi; Zamor, Philippe J.; Soloway, Irene J.; Tenore, Peter L.; Kaswan, Daniel; Gourevitch, Marc. N.; Arnsten, Julia H.

    2009-01-01

    Injection drug users constitute 60% of the more than 4 million people in the United States with hepatitis C virus (HCV), including many methadone maintenance patients. Few data exist describing clinical outcomes for patients receiving HCV treatment on-site in a methadone maintenance settings. In this retrospective study, we describe clinical outcomes for 73 patients receiving HCV treatment on-site in a methadone maintenance treatment program. Fifty-five percent of patients achieved end-of-treatment response, and 45% achieved sustained viral response. These treatment response rates are nearly equivalent to previously published HCV treatment response rates, despite high prevalences of ongoing drug use (49%), psychiatric comorbidity (67%), and HIV coinfection (32%). These data show that on-site HCV treatment with pegylated interferon and ribavirin is effective in methadone-maintained patients, many of whom are active drug users, psychiatrically ill, or HIV coinfected, and that methadone maintenance treatment programs represent an opportunity to safely treat chronic hepatitis C. PMID:19038524

  15. Response Assessment and Prediction in Esophageal Cancer Patients via F-18 FDG PET/CT Scans

    NASA Astrophysics Data System (ADS)

    Higgins, Kyle J.

    Purpose: The purpose of this study is to utilize F-18 FDG PET/CT scans to determine an indicator for the response of esophageal cancer patients during radiation therapy. There is a need for such an indicator since local failures are quite common in esophageal cancer patients despite modern treatment techniques. If an indicator is found, a patient's treatment strategy may be altered to possibly improve the outcome. This is investigated with various standard uptake volume (SUV) metrics along with image texture features. The metrics and features showing the most promise and indicating response are used in logistic regression analysis to find an equation for the prediction of response. Materials and Methods: 28 patients underwent F-18 FDG PET/CT scans prior to the start of radiation therapy (RT). A second PET/CT scan was administered following the delivery of ~32 Gray (Gy) of dose. A physician contoured gross tumor volume (GTV) was used to delineate a PET based GTV (GTV-pre-PET) based on a threshold of >40% and >20% of the maximum SUV value in the GTV. Deformable registration was used in VelocityAI software to register the pre-treatment and intra-treatment CT scans so that the GTV-pre-PET contours could be transferred from the pre to intra scans (GTV-intra-PET). The fractional decrease in the maximum, mean, volume to the highest intensity 10%-90%, and combination SUV metrics of the significant previous SUV metrics were compared to post-treatment pathologic response for an indication of response. Next for the >40% threshold, texture features based on a neighborhood gray-tone dimension matrix (NGTDM) were analyzed. The fractional decrease in coarseness, contrast, busyness, complexity, and texture strength were compared to the pathologic response of the patients. From these previous two types of analysis, SUV and texture features, the two most significant results were used in logistic regression analysis to find an equation to predict the probability of a non-responder

  16. Pasireotide: a novel treatment for patients with acromegaly

    PubMed Central

    Cuevas-Ramos, Daniel; Fleseriu, Maria

    2016-01-01

    Morbidity and mortality rates in patients with active acromegaly are higher than the general population. Adequate biochemical control restores mortality to normal rates. Now, medical therapy has an increasingly important role in the treatment of patients with acromegaly. Somatostatin receptor ligands (SRLs) are considered the standard medical therapy, either after surgery or as a first-line therapy when surgery is deemed ineffective or is contraindicated. Overall, octreotide and lanreotide are first-generation SRLs and are effective in ~20%–70% of patients. Pegvisomant, a growth hormone receptor antagonist, controls insulin-like growth factor 1 in 65%–90% of cases. Consequently, a subset of patients (nonresponders) requires other treatment options. Drug combination therapy offers the potential for more efficacious disease control. However, the development of new medical therapies remains essential. Here, emphasis is placed on new medical therapies to control acromegaly. There is a focus on pasireotide long-acting release (LAR) (Signifor LAR®), which was approved in 2014 by the US Food and Drug Administration and the European Medicine Agency for the treatment of acromegaly. Pasireotide LAR is a long-acting somatostatin multireceptor ligand. In a Phase III clinical trial in patients with acromegaly (naïve to medical therapy or uncontrolled on a maximum dose of first-generation SRLs), 40 and 60 mg of intramuscular pasireotide LAR achieved better biochemical disease control than octreotide LAR, and tumor shrinkage was noted in both pasireotide groups. Pasireotide LAR tolerability was similar to other SRLs, except for a greater frequency and degree of hyperglycemia and diabetes mellitus. Baseline glucose may predict hyperglycemia occurrence after treatment, and careful monitoring of glycemic status and appropriate treatment is required. A precise definition of patients with acromegaly who will derive the greatest therapeutic benefit from pasireotide LAR remains to

  17. Pasireotide: a novel treatment for patients with acromegaly.

    PubMed

    Cuevas-Ramos, Daniel; Fleseriu, Maria

    2016-01-01

    Morbidity and mortality rates in patients with active acromegaly are higher than the general population. Adequate biochemical control restores mortality to normal rates. Now, medical therapy has an increasingly important role in the treatment of patients with acromegaly. Somatostatin receptor ligands (SRLs) are considered the standard medical therapy, either after surgery or as a first-line therapy when surgery is deemed ineffective or is contraindicated. Overall, octreotide and lanreotide are first-generation SRLs and are effective in ~20%-70% of patients. Pegvisomant, a growth hormone receptor antagonist, controls insulin-like growth factor 1 in 65%-90% of cases. Consequently, a subset of patients (nonresponders) requires other treatment options. Drug combination therapy offers the potential for more efficacious disease control. However, the development of new medical therapies remains essential. Here, emphasis is placed on new medical therapies to control acromegaly. There is a focus on pasireotide long-acting release (LAR) (Signifor LAR®), which was approved in 2014 by the US Food and Drug Administration and the European Medicine Agency for the treatment of acromegaly. Pasireotide LAR is a long-acting somatostatin multireceptor ligand. In a Phase III clinical trial in patients with acromegaly (naïve to medical therapy or uncontrolled on a maximum dose of first-generation SRLs), 40 and 60 mg of intramuscular pasireotide LAR achieved better biochemical disease control than octreotide LAR, and tumor shrinkage was noted in both pasireotide groups. Pasireotide LAR tolerability was similar to other SRLs, except for a greater frequency and degree of hyperglycemia and diabetes mellitus. Baseline glucose may predict hyperglycemia occurrence after treatment, and careful monitoring of glycemic status and appropriate treatment is required. A precise definition of patients with acromegaly who will derive the greatest therapeutic benefit from pasireotide LAR remains to be

  18. Pasireotide: a novel treatment for patients with acromegaly.

    PubMed

    Cuevas-Ramos, Daniel; Fleseriu, Maria

    2016-01-01

    Morbidity and mortality rates in patients with active acromegaly are higher than the general population. Adequate biochemical control restores mortality to normal rates. Now, medical therapy has an increasingly important role in the treatment of patients with acromegaly. Somatostatin receptor ligands (SRLs) are considered the standard medical therapy, either after surgery or as a first-line therapy when surgery is deemed ineffective or is contraindicated. Overall, octreotide and lanreotide are first-generation SRLs and are effective in ~20%-70% of patients. Pegvisomant, a growth hormone receptor antagonist, controls insulin-like growth factor 1 in 65%-90% of cases. Consequently, a subset of patients (nonresponders) requires other treatment options. Drug combination therapy offers the potential for more efficacious disease control. However, the development of new medical therapies remains essential. Here, emphasis is placed on new medical therapies to control acromegaly. There is a focus on pasireotide long-acting release (LAR) (Signifor LAR®), which was approved in 2014 by the US Food and Drug Administration and the European Medicine Agency for the treatment of acromegaly. Pasireotide LAR is a long-acting somatostatin multireceptor ligand. In a Phase III clinical trial in patients with acromegaly (naïve to medical therapy or uncontrolled on a maximum dose of first-generation SRLs), 40 and 60 mg of intramuscular pasireotide LAR achieved better biochemical disease control than octreotide LAR, and tumor shrinkage was noted in both pasireotide groups. Pasireotide LAR tolerability was similar to other SRLs, except for a greater frequency and degree of hyperglycemia and diabetes mellitus. Baseline glucose may predict hyperglycemia occurrence after treatment, and careful monitoring of glycemic status and appropriate treatment is required. A precise definition of patients with acromegaly who will derive the greatest therapeutic benefit from pasireotide LAR remains to be

  19. Clopidogrel Responsiveness in Patients Undergoing Peripheral Angioplasty

    SciTech Connect

    Pastromas, Georgios Spiliopoulos, Stavros Katsanos, Konstantinos Diamantopoulos, Athanasios Kitrou, Panagiotis Karnabatidis, Dimitrios Siablis, Dimitrios

    2013-12-15

    Purpose: To investigate the incidence and clinical significance of platelet responsiveness in patients receiving clopidogrel after peripheral angioplasty procedures. Materials and Methods: This prospective study included patients receiving antiplatelet therapy with clopidogrel 75 mg after infrainguinal angioplasty or stenting and who presented to our department during routine follow-up. Clopidogrel responsiveness was tested using the VerifyNow P2Y12 Assay. Patients with residual platelet reactivity units (PRU) {>=} 235 were considered as nonresponders (NR group NR), whereas patients with PRU < 235 were considered as normal (responders [group R]). Primary end points were incidence of resistance to clopidogrel and target limb reintervention (TLR)-free survival, whereas secondary end points included limb salvage rates and the identification of any independent predictors influencing clinical outcomes. Results: In total, 113 consecutive patients (mean age 69 {+-} 8 years) with 139 limbs were enrolled. After clopidogrel responsiveness analysis, 61 patients (53.9 %) with 73 limbs (52.5 %) were assigned to group R and 52 patients (46.1 %) with 66 limbs (47.5 %) to group NR. Mean follow-up interval was 27.7 {+-} 22.9 months (range 3-95). Diabetes mellitus, critical limb ischemia, and renal disease were associated with clopidogrel resistance (Fisher's exact test; p < 0.05). According to Kaplan-Meier analysis, TLR-free survival was significantly superior in group R compared with group NR (20.7 vs. 1.9 %, respectively, at 7-year follow-up; p = 0.001), whereas resistance to clopidogrel was identified as the only independent predictor of decreased TLR-free survival (hazard rate 0.536, 95 % confidence interval 0.31-0.90; p = 0.01). Cumulative TLR rate was significantly increased in group NR compared with group R (71.2 % [52 of 73] vs. 31.8 % [21 of 66], respectively; p < 0.001). Limb salvage was similar in both groups. Conclusion: Clopidogrel resistance was related with

  20. Pharmacokinetics and Pharmacodynamics with Extended Dosing of CC-486 in Patients with Hematologic Malignancies

    PubMed Central

    Garcia-Manero, Guillermo; Cogle, Christopher R.; Gore, Steven D.; Hetzer, Joel; Kumar, Keshava; Skikne, Barry; MacBeth, Kyle J.

    2015-01-01

    CC-486 (oral azacitidine) is an epigenetic modifier in development for patients with myelodysplastic syndromes and acute myeloid leukemia. In part 1 of this two-part study, a 7-day CC-486 dosing schedule showed clinical activity, was generally well tolerated, and reduced DNA methylation. Extending dosing of CC-486 beyond 7 days would increase duration of azacitidine exposure. We hypothesized that extended dosing would therefore provide more sustained epigenetic activity. Reported here are the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of CC-486 extended dosing schedules in patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) or acute myeloid leukemia (AML) from part 2 of this study. PK and/or PD data were available for 59 patients who were sequentially assigned to 1 of 4 extended CC-486 dosing schedules: 300mg once-daily or 200mg twice-daily for 14 or 21 days per 28-day cycle. Both 300mg once-daily schedules and the 200mg twice-daily 21-day schedule significantly (all P < .05) reduced global DNA methylation in whole blood at all measured time points (days 15, 22, and 28 of the treatment cycle), with sustained hypomethylation at cycle end compared with baseline. CC-486 exposures and reduced DNA methylation were significantly correlated. Patients who had a hematologic response had significantly greater methylation reductions than non-responding patients. These data demonstrate that extended dosing of CC-486 sustains epigenetic effects through the treatment cycle. Trial Registration ClinicalTrials.gov NCT00528983 PMID:26296092

  1. CDKAL1 gene variants affect the anti-TNF response among Psoriasis patients.

    PubMed

    Coto-Segura, Pablo; Batalla, Ana; González-Fernández, Daniel; Gómez, Juan; Santos-Juanes, Jorge; Queiro, Rubén; Alonso, Belén; Iglesias, Sara; Coto, Eliecer

    2015-12-01

    The heterogeneous response to anti-TNF biological drugs among Psoriasis (Psor) patients might be explained by gene variants linked to the risk for Psor. Common variants in the CDKAL1 gene have been associated with the risk of developing Psor. Our hypothesis was that these variants could also influence the response to anti-TNFs among Psor-patients. A reduction of at least 75% in the Psoriasis area and severity index (PASI 75) at week 24 was considered a positive response to treatment. A total of 116 patients (78 responders and 38 non-responders) were genotyped for the CDKAL1 rs6908425, rs4712523, rs111739077, and rs77152992 (p.P409L) single nucleotide polymorphisms. Allele and genotype frequencies differed between the two response groups, with the highest difference for the rs6908425: CC homozygotes were significantly more common among responders (72% vs. 45%; p=0.005; OR=3.14, 95%CI=1.40-7.05). In conclusion, our data suggested that CDKAL1 gene variants have a significant effect on the response to anti-TNF therapies among Psor patients. If confirmed on other large cohorts of patients, the genotyping of these variants might help to predict the biological response. PMID:26563541

  2. CDKAL1 gene variants affect the anti-TNF response among Psoriasis patients.

    PubMed

    Coto-Segura, Pablo; Batalla, Ana; González-Fernández, Daniel; Gómez, Juan; Santos-Juanes, Jorge; Queiro, Rubén; Alonso, Belén; Iglesias, Sara; Coto, Eliecer

    2015-12-01

    The heterogeneous response to anti-TNF biological drugs among Psoriasis (Psor) patients might be explained by gene variants linked to the risk for Psor. Common variants in the CDKAL1 gene have been associated with the risk of developing Psor. Our hypothesis was that these variants could also influence the response to anti-TNFs among Psor-patients. A reduction of at least 75% in the Psoriasis area and severity index (PASI 75) at week 24 was considered a positive response to treatment. A total of 116 patients (78 responders and 38 non-responders) were genotyped for the CDKAL1 rs6908425, rs4712523, rs111739077, and rs77152992 (p.P409L) single nucleotide polymorphisms. Allele and genotype frequencies differed between the two response groups, with the highest difference for the rs6908425: CC homozygotes were significantly more common among responders (72% vs. 45%; p=0.005; OR=3.14, 95%CI=1.40-7.05). In conclusion, our data suggested that CDKAL1 gene variants have a significant effect on the response to anti-TNF therapies among Psor patients. If confirmed on other large cohorts of patients, the genotyping of these variants might help to predict the biological response.

  3. Pegylated IFN-α 2b added to ongoing lamivudine therapy in patients with lamivudine-resistant chronic hepatitis B

    PubMed Central

    Vassiliadis, Themistoklis; Patsiaoura, Kalliopi; Tziomalos, Konstantinos; Gkiourtzis, Theodoros; Giouleme, Olga; Grammatikos, Nikolaos; Rizopoulou, Despoina; Nikolaidis, Nikolaos; Katsinelos, Panagiotis; Orfanou-Koumerkeridou, Eleni; Eugenidis, Nikolaos

    2006-01-01

    AIM: To investigate the role of pegylated-interferon (IFN) α-2b in the management of patients with lamivudine-resistant chronic hepatitis B. METHODS: Twenty consecutive anti-HBe positive patients were treated with pegylated IFN α-2b (100 μg sc once weekly) for 12 mo. There was no interruption in lamivudine therapy. Hematology, liver biochemistry, serum HBV DNA levels were detected by PCR, and vital signs were also assessed. Liver histology was assessed in some patients at entry and at wk 52 for comparison. RESULTS: Nine patients (45%) had a partial virological end-treatment response; seven patients (35%) showed complete virological end-treatment response. Eight patients (40%) showed biochemical end-treatment response. There was a trend for higher virological response rates in patients who had previously responded to IFN and relapsed compared to IFN non-responders (four out of seven patients vs none out of six patients, respectively; P = 0.1). Patients without virological end-treatment response showed significant worsening of fibrosis [median score 2 (range, 1 to 3) vs median score 3 (range, 1 to 4)], in the first and second biopsy respectively (P = 0.014), whereas necroinflammatory activity was not significantly affected. Patients with complete or partial virological end-treatment response did not show any significant changes in histological findings, possibly due to the small number of patients with paired biopsies (n = 5). Nevertheless, after 12 mo of follow-up, only one patient (5%) showed sustained virological response and only 2 patients (10%) showed sustained biochemical response. Two patients (10%) discontinued pegylated IFN both after 6 mo of treatment due to flu-like symptoms. CONCLUSION: Pegylated IFNα-2b, when added to ongoing lamivudine therapy in patients with lamivudine-resistant chronic hepatitis B, induces sustained responses only in a small minority of cases. PMID:16688836

  4. Serum Autotaxin is a Marker of the Severity of Liver Injury and Overall Survival in Patients with Cholestatic Liver Diseases.

    PubMed

    Wunsch, Ewa; Krawczyk, Marcin; Milkiewicz, Malgorzata; Trottier, Jocelyn; Barbier, Olivier; Neurath, Markus F; Lammert, Frank; Kremer, Andreas E; Milkiewicz, Piotr

    2016-01-01

    Autotaxin (ATX) is involved in the synthesis of lysophosphatidic acid. Both have recently been linked to cholestatic pruritus and liver injury. We aimed to investigate whether ATX is an indicator of cholestatic liver injury, health-related quality of life (HRQoL) and prognosis based on a group of 233 patients, 118 with primary biliary cholangitis (PBC) and 115 with primary sclerosing cholangitis (PSC). Patients were followed for 1-60 months, cumulative survival rates were calculated. ATX activity was significantly higher in both groups than in the 103 controls, particularly in patients with cirrhosis and in patients with longer disease duration. Ursodeoxycholic acid (UDCA) non-responders with PBC exhibited increased ATX activity. ATX activity was correlated with liver biochemistry, MELD, Mayo Risk scores and was associated with worse disease-specific HRQoL aspects. In both groups, Cox model analysis indicated that ATX was a negative predictor of survival. Increased ATX levels were associated with a 4-fold higher risk of death/liver transplantation in patients with PBC and a 2.6-fold higher risk in patients with PSC. We conclude that in patients with cholestatic conditions, ATX is not only associated with pruritus but also indicates impairment of other HRQoL aspects, liver dysfunction, and can serve as a predictor of survival. PMID:27506882

  5. Serum Autotaxin is a Marker of the Severity of Liver Injury and Overall Survival in Patients with Cholestatic Liver Diseases

    PubMed Central

    Wunsch, Ewa; Krawczyk, Marcin; Milkiewicz, Malgorzata; Trottier, Jocelyn; Barbier, Olivier; Neurath, Markus F.; Lammert, Frank; Kremer, Andreas E.; Milkiewicz, Piotr

    2016-01-01

    Autotaxin (ATX) is involved in the synthesis of lysophosphatidic acid. Both have recently been linked to cholestatic pruritus and liver injury. We aimed to investigate whether ATX is an indicator of cholestatic liver injury, health-related quality of life (HRQoL) and prognosis based on a group of 233 patients, 118 with primary biliary cholangitis (PBC) and 115 with primary sclerosing cholangitis (PSC). Patients were followed for 1–60 months, cumulative survival rates were calculated. ATX activity was significantly higher in both groups than in the 103 controls, particularly in patients with cirrhosis and in patients with longer disease duration. Ursodeoxycholic acid (UDCA) non-responders with PBC exhibited increased ATX activity. ATX activity was correlated with liver biochemistry, MELD, Mayo Risk scores and was associated with worse disease-specific HRQoL aspects. In both groups, Cox model analysis indicated that ATX was a negative predictor of survival. Increased ATX levels were associated with a 4-fold higher risk of death/liver transplantation in patients with PBC and a 2.6-fold higher risk in patients with PSC. We conclude that in patients with cholestatic conditions, ATX is not only associated with pruritus but also indicates impairment of other HRQoL aspects, liver dysfunction, and can serve as a predictor of survival. PMID:27506882

  6. The rationale for patient-reported outcomes surveillance in cancer and a reproducible method for achieving it.

    PubMed

    Smith, Tenbroeck G; Castro, Kathleen M; Troeschel, Alyssa N; Arora, Neeraj K; Lipscomb, Joseph; Jones, Shelton M; Treiman, Katherine A; Hobbs, Connie; McCabe, Ryan M; Clauser, Steven B

    2016-02-01

    Patient-reported outcomes (PROs) measure quality of life, symptoms, patient functioning, and patient perceptions of care; they are essential for gaining a full understanding of cancer care and the impact of cancer on people's lives. Repeatedly captured facility-level and/or population-level PROs (PRO surveillance) could play an important role in quality monitoring and improvement, benchmarking, advocacy, policy making, and research. This article describes the rationale for PRO surveillance and the methods of the Patient Reported Outcomes Symptoms and Side Effects Study (PROSSES), which is the first PRO study to use the American College of Surgeons Commission on Cancer's Rapid Quality Reporting System to identify patients and manage study data flow. The American Cancer Society, the National Cancer Institute, the Commission on Cancer, and RTI International collaborated on PROSSES. PROSSES was conducted at 17 cancer programs that participated in the National Cancer Institute Community Cancer Centers Program among patients diagnosed with locoregional breast or colon cancer. The methods piloted in PROSSES were successful as demonstrated by high eligibility (93%) and response (61%) rates. Differences in clinical and demographic characteristics between respondents and nonrespondents were mostly negligible, with the exception that non-white individuals were somewhat less likely to respond. These methods were consistent across cancer centers and reproducible over time. If repeated and expanded, they could provide PRO surveillance data from patients with cancer on a national scale.

  7. Hepatic compartmentalization of exhausted and regulatory cells in HIV/HCV-coinfected patients.

    PubMed

    Barrett, L; Trehanpati, N; Poonia, S; Daigh, L; Sarin, S Kumar; Masur, H; Kottilil, S

    2015-03-01

    Accelerated intrahepatic hepatitis C virus (HCV) pathogenesis is likely the result of dysregulation within both the innate and adaptive immune compartments, but the exact contribution of peripheral blood and liver lymphocyte subsets remains unclear. Prolonged activation and expansion of immunoregulatory cells have been thought to play a role. We determined immune cell subset frequency in contemporaneous liver and peripheral blood samples from chronic HCV-infected and HIV/HCV-coinfected individuals. Peripheral blood mononuclear cells (PBMC) and biopsy-derived liver-infiltrating lymphocytes from 26 HIV/HCV-coinfected, 10 chronic HCV-infected and 10 HIV-infected individuals were assessed for various subsets of T and B lymphocytes, dendritic cell, natural killer (NK) cell and NK T-cell frequency by flow cytometry. CD8(+) T cells expressing the exhaustion marker PD-1 were increased in HCV-infected individuals compared with uninfected individuals (P = 0.02), and HIV coinfection enhanced this effect (P = 0.005). In the liver, regulatory CD4(+) CD25(+) Foxp3(+) T cells, as well as CD4(+) CD25(+) PD1(+) T cells, were more frequent in HIV/HCV-coinfected than in HCV-monoinfected samples (P < 0.001). HCV was associated with increased regulatory T cells, PD-1(+) T cells and decreased memory B cells, regardless of HIV infection (P ≤ 0.005 for all). Low CD8(+) expression was observed only in PD-1(+) CD8(+) T cells from HCV-infected individuals and healthy controls (P = 0.002) and was associated with enhanced expansion of exhausted CD8(+) T cells when exposed in vitro to PHA or CMV peptides. In conclusion, in HIV/HCV coinfection, ongoing HCV replication is associated with increased regulatory and exhausted T cells in the periphery and liver that may impact control of HCV. Simultaneous characterization of liver and peripheral blood highlights the disproportionate intrahepatic compartmentalization of immunoregulatory T cells, which may contribute to establishment of chronicity and

  8. TRAIL and TRAIL receptors splice variants during long-term interferon β treatment of patients with multiple sclerosis: evaluation as biomarkers for therapeutic response

    PubMed Central

    López-Gómez, Carlos; Oliver-Martos, Begoña; Pinto-Medel, María-Jesús; Suardiaz, Margarita; Reyes-Garrido, Virginia; Urbaneja, Patricia; Fernández, Óscar; Leyva, Laura

    2016-01-01

    Objective We aimed to assess the effects of interferon β (IFNβ) treatment on the expression of the splice variants of the Tumour necrosis factor-Related Apoptosis Inducing Ligand (TRAIL) and its receptors in different cell subpopulations (CD14+, CD4+ and CD8+) from patients with multiple sclerosis (MS), and to determine whether this expression discriminated responders from non-responders to IFNβ therapy. Methods We examined mRNA expression of the TRAIL and TRAIL receptors variants in patients with MS, at baseline and after one year of IFNβ therapy, according to responsiveness to this drug. Results Long-term therapy with IFNβ increased the expression of TRAIL-α in T cell subsets exclusively from responders and decreased the expression of the isoform 2 of TRAILR-2 in monocytes from responders as well as non-responders. Lower expression of TRAIL-α, and higher expression of TRAIL-β in monocytes and T cells, was found before the onset of IFNβ therapy in patients who will subsequently become responders. Baseline expression of TRAILR-1 was also significantly higher in monocytes and CD4+ T cells from responders. Conclusions The present study shows that long-term IFNβ treatment has a direct influence on TRAIL-α and TRAILR-2 isoform 2 expression. Besides, receiver operating characteristic analysis revealed that the baseline expression of TRAIL-α in monocytes and T cells, and that of TRAILR-1 in monocytes and CD4+ T cells, showed a predictive value of the clinical response to IFNβ therapy, pointing to a role of TRAIL system in the mechanism of action of IFNβ in MS that will need further investigation. PMID:25736057

  9. Tophus burden reduction with pegloticase: results from phase 3 randomized trials and open-label extension in patients with chronic gout refractory to conventional therapy

    PubMed Central

    2013-01-01

    Introduction Two replicate randomized, placebo-controlled six-month trials (RCTs) and an open-label treatment extension (OLE) comprised the pegloticase development program in patients with gout refractory to conventional therapy. In the RCTs, approximately 40% of patients treated with the approved dose saw complete response (CR) of at least one tophus. Here we describe the temporal course of tophus resolution, total tophus burden in patients with multiple tophi, tophus size at baseline, and the relationship between tophus response and urate-lowering efficacy. Methods Baseline subcutaneous tophi were analyzed quantitatively using computer-assisted digital images in patients receiving pegloticase (8 mg biweekly or monthly) or placebo in the RCTs, and pegloticase in the OLE. Tophus response, a secondary endpoint in the trials, was evaluated two ways. Overall tophus CR was the proportion of patients achieving a best response of CR (without any new/enlarging tophi) and target tophus complete response (TT-CR) was the proportion of all tophi with CR. Results Among 212 patients randomized in the RCTs, 155 (73%) had ≥1 tophus and 547 visible tophi were recorded at baseline. Overall tophus CR was recorded in 45% of patients in the biweekly group (P = 0.002 versus placebo), 26% in the monthly group, and 8% in the placebo group after six months of RCT therapy. TT-CR rates at six months were 28%, 19%, and 2% of tophi, respectively. Patients meeting the primary endpoint of sustained urate-lowering response to therapy (responders) were more likely than nonresponders to have an overall tophus CR at six months (54% vs 20%, respectively and 8% with placebo). Both overall tophus CR and TT-CRs increased with treatment duration in the OLE, reaching 70% (39/56) of patients and 55% (132/238) of target tophi after one year of treatment in patients receiving pegloticase during both the RCTs and OLE. At that time point, more tophi had resolved in responders (102/145 or 70% of tophi) than

  10. Patient Preferences Regarding Rheumatoid Arthritis Therapies: A Conjoint Analysis

    PubMed Central

    Louder, Anthony M.; Singh, Amitabh; Saverno, Kim; Cappelleri, Joseph C.; Aten, Aaron J.; Koenig, Andrew S.; Pasquale, Margaret K.

    2016-01-01

    Background Tofacitinib, an oral Janus kinase inhibitor approved for the treatment of rheumatoid arthritis (RA), provides patients with an alternative to subcutaneously or intravenously administered biologic disease-modifying antirheumatic drugs (DMARDs). Little is known about patient preference for novel RA treatments. Objective To investigate patient preferences for attributes associated with RA treatments. Methods A choice-based conjoint survey was mailed to 1400 randomly selected commercially insured patients (aged 21–80 years) diagnosed with RA, who were continuously enrolled from May 1, 2012, through April 30, 2013, and had ≥2 medical claims for International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code 714.0 and no previous biologic DMARD use. Treatment attributes included route of administration; monthly out-of-pocket cost; frequency of administration; ability to reduce daily joint pain and swelling; likelihood of serious adverse events; improvement in the ability to perform daily tasks; and medication burden. Mean attribute importance scores were calculated after adjusting for patient demographics (eg, age, sex, years since diagnosis) using a hierarchical Bayes model. Patient preferences for each treatment attribute were ranked by the importance score. Part-worth utilities (ie, preference scores) were used to perform a conjoint market simulation. Results A total of 380 patients (response rate, 27.1%) returned the survey. Their mean age (± standard deviation) was 54.9 (± 9.3) years. Nonrespondents were 2 years younger (mean, 52.9 years; P = .002) but did not differ significantly from respondents in known clinical characteristics. After adjustment for demographic characteristics, mean patients' ranking of treatment attribute importance, in decreasing order, was route of administration, 34.1 (± 15.5); frequency of administration, 16.4 (± 6.8); serious adverse events, 12.0 (± 9.3); cost, 10.1 (± 6.2); medication

  11. 5-HTR1A and 5-HTR2A genetic polymorphisms and SSRI antidepressant response in depressive Chinese patients

    PubMed Central

    Dong, Zai-Quan; Li, Xi-Rong; He, Lin; He, Guang; Yu, Tao; Sun, Xue-Li

    2016-01-01

    Objective Genetic variabilities within the serotoninergic system may predict response or remission to antidepressant drugs. Several serotonin receptor (5-HTR) gene polymorphisms have been associated with susceptibility to psychiatric diseases. In this study, we analyzed the correlation between 5-HTR1A and 5-HTR2A polymorphisms and response or remission to selective serotonin reuptake inhibitors (SSRIs) drugs. Methods Two hundred and ninety patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depressive disorder were involved in this study. SSRIs (fluoxetine, paroxetine, citalopram, or sertraline) were selected randomly for treatment. The Hamilton Rating Scale for Depression was used to evaluate the antidepressant effect. To assess 5-HTR gene variabilities, two single-nucleotide polymorphisms in 5-HTR1A (rs1364043 and rs10042486) and three in 5-HTR2A (rs6311, rs6313, and rs17289304) were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using the Sequenom MassARRAY Analyzer 4 system. Results There were 220 responders and 70 nonresponders (120 remissioners and 170 nonremissioners) after 6 weeks of treatment. We found no association between any of the five 5-HTR1A and 5-HTR2A gene polymorphisms and antidepressant drug response or remission (P>0.05). It is worth mentioning that TT genotype frequency of rs10042486 was significantly different from the CT genotype frequency between responders and nonresponders, although the significance was not maintained after correcting for multiple testing. Conclusion Thus, 5-HTR1A and 5-HTR2A gene polymorphisms may not play an important role in antidepressant drug response or remission. PMID:27445478

  12. Glycyrrhizin in patients who failed previous interferon alpha-based therapies: biochemical and histological effects after 52 weeks.

    PubMed

    Manns, M P; Wedemeyer, H; Singer, A; Khomutjanskaja, N; Dienes, H P; Roskams, T; Goldin, R; Hehnke, U; Inoue, H

    2012-08-01

    Chronic hepatitis C patients often fail to respond to interferon-based therapies. This phase III study aimed at confirming the efficacy and safety of glycyrrhizin in interferon + ribavirin-based therapy non-responders. A randomised, double-blind, placebo-controlled, comparison of glycyrrhizin, administered intravenously 5×/or 3×/week, and 5×/week placebo for 12 weeks to 379 patients, was followed by a randomised, open comparison of glycyrrhizin i.v. 5×/versus 3×/week for 40 weeks. Primary endpoints were: (1) the proportion of patients with ≥50% ALT (alanine aminotransferase) reduction after 12 weeks double-blind phase, and (2) the proportion of patients with improvement of necro-inflammation after 52 weeks as compared with baseline. The proportion of patients with ALT reduction ≥50% after 12 weeks was significantly higher with 5×/week glycyrrhizin (28.7%, P < 0.0001) and 3×/week glycyrrhizin (29.0%, P < 0.0001) compared with placebo (7.0%). The proportion of patients with improvement in necro-inflammation after 52 weeks was 44.9% with 5×/week and 46.0% with 3×/week, respectively. Glycyrrhizin exhibited a significantly higher ALT reduction compared to placebo after 12 weeks of therapy and an improvement of necro-inflammation and fibrosis after 52-weeks treatment. Generally, glycyrrhizin treatment was well tolerated.

  13. Elevation in Peripheral Blood Circulating Tumor Cell Number Correlates with Macroscopic Progression in UICC Stage IV Colorectal Cancer Patients

    PubMed Central

    Molnar, Bela; Floro, Lajos; Sipos, Ferenc; Toth, Bernadett; Sreter, Lydia; Tulassay, Zsolt

    2008-01-01

    Aims: Cytokeratin(CK) based real-time RT-PCR assays (QRT-PCR) are now available for peripheral blood circulating tumor cell (CTC) evaluations in colorectal cancer(CRC) patients. Results are non-existent for the application of these techniques to the determination of progression and therapy response in Dukes stage D CRC patients. Patients and methods: Each month 30 ml peripheral blood of 30 Dukes D patients (17 with progression) were drawn. CEA, CA19-9, CA72-A and TPA-M determinations were made. CK20, thymidilate synthase(TS) QRT-PCR was performed, as well. Buffy coat was used for immunmagnetic cancer cell isolation and CTC counting. Correlation between elevated CTC and macroscopic progression within 3 months was determined by Chi2 test. Results: Microscopic CTC single cell, doublet, cluster number were found in correlation with CK20 QRT-PCR results (p < 0.01). There was a significant increase in microscopic CTC number, CK20 and decrease in TS QRT-PCR levels (p < 0.05) in the peripheral blood of the non-responder as compared to responder patients. Elevation of the CTC was in significant correlation with macroscopic progression of the disease in 3 months (p < 0.01). Conclusions: CTC number reflects the chemotherapeutic sensitivity of CRC patients. Elevation of circulating tumor cell number in peripheral blood is in correlation with macroscopic progression. PMID:18334735

  14. SPLENIC VOLUME CHANGE AND THERAPUETIC RESPONSE IN PATIENTS TREATED WITH RADIOMMUNOCONJUGATES

    SciTech Connect

    Shen, S; DeNardo, G L; Yuan, A; Siantar, C H; O'Donnell, R T; DeNardo, S J

    2005-04-06

    Splenomegaly is frequently found in non-Hodgkin's lymphoma (NHL) patients. This study evaluated the implications of splenic volume change in response to radioimmunotherapy (RIT). Twenty-nine NHL patients treated with radiolabeled-Lym-1 and 9 breast cancer patients (reference group) treated with radiolabeled-ChL6, BrE-3 or m170 were analyzed using CT splenic images obtained before and after RIT. Patient-specific radiation doses to spleen were determined using actual splenic volume determined by CT and body weight. In 13 of 29 NHL patients who had splenic volume {le} 310 ml, there was no or small change (-23 to 15 mL) in splenic volume, despite splenic doses as high as 14.4 Gy. Similarly, in a reference group of 9 breast cancer patients, there was no or small change (-5 to 13 mL), despite splenic doses as high as 11.4 Gy. In contrast, 13 of 29 NHL patients who had splenic volume 380-1400 mL, splenic volume decreased by 68 to 548 mL despite splenic doses as low as 1.40 Gy. Ten of 29 NHL patients with greater than a 15% decrease in splenic volume after RIT had nodal tumor regression (5 CR, 5 PR). In the remaining 19 NHL patients with less than a 15% decrease in splenic volume after RIT, there were 7 non-responders (5 CR and 7 PR). Splenic volume changes were found in NHL patients with splenomegaly. These splenic volume changes is likely due to therapeutic effect on malignant lymphocytes associated with splenomegaly. Nodal tumor response was more likely when splenomegaly decreased after RIT.

  15. The Relationship between Leishmaniasis and AIDS: the Second 10 Years

    PubMed Central

    Alvar, Jorge; Aparicio, Pilar; Aseffa, Abraham; Den Boer, Margriet; Cañavate, Carmen; Dedet, Jean-Pierre; Gradoni, Luigi; Ter Horst, Rachel; López-Vélez, Rogelio; Moreno, Javier

    2008-01-01

    Summary: To date, most Leishmania and human immunodeficiency virus (HIV) coinfection cases reported to WHO come from Southern Europe. Up to the year 2001, nearly 2,000 cases of coinfection were identified, of which 90% were from Spain, Italy, France, and Portugal. However, these figures are misleading because they do not account for the large proportion of cases in many African and Asian countries that are missed due to a lack of diagnostic facilities and poor reporting systems. Most cases of coinfection in the Americas are reported in Brazil, where the incidence of leishmaniasis has spread in recent years due to overlap with major areas of HIV transmission. In some areas of Africa, the number of coinfection cases has increased dramatically due to social phenomena such as mass migration and wars. In northwest Ethiopia, up to 30% of all visceral leishmaniasis patients are also infected with HIV. In Asia, coinfections are increasingly being reported in India, which also has the highest global burden of leishmaniasis and a high rate of resistance to antimonial drugs. Based on the previous experience of 20 years of coinfection in Europe, this review focuses on the management of Leishmania-HIV-coinfected patients in low-income countries where leishmaniasis is endemic. PMID:18400800

  16. Patient-reported outcome measures in arthroplasty registries

    PubMed Central

    Bohm, Eric; Franklin, Patricia; Lyman, Stephen; Denissen, Geke; Dawson, Jill; Dunn, Jennifer; Eresian Chenok, Kate; Dunbar, Michael; Overgaard, Søren; Garellick, Göran; Lübbeke, Anne

    2016-01-01

    Abstract — The International Society of Arthroplasty Registries (ISAR) Patient-Reported Outcome Measures (PROMs) Working Group have evaluated and recommended best practices in the selection, administration, and interpretation of PROMs for hip and knee arthroplasty registries. The 2 generic PROMs in common use are the Short Form health surveys (SF-36 or SF-12) and EuroQol 5-dimension (EQ-5D). The Working Group recommends that registries should choose specific PROMs that have been appropriately developed with good measurement properties for arthroplasty patients. The Working Group recommend the use of a 1-item pain question (“During the past 4 weeks, how would you describe the pain you usually have in your [right/left] [hip/knee]?”; response: none, very mild, mild, moderate, or severe) and a single-item satisfaction outcome (“How satisfied are you with your [right/left] [hip/knee] replacement?”; response: very unsatisfied, dissatisfied, neutral, satisfied, or very satisfied). Survey logistics include patient instructions, paper- and electronic-based data collection, reminders for follow-up, centralized as opposed to hospital-based follow-up, sample size, patient- or joint-specific evaluation, collection intervals, frequency of response, missing values, and factors in establishing a PROMs registry program. The Working Group recommends including age, sex, diagnosis at joint, general health status preoperatively, and joint pain and function score in case-mix adjustment models. Interpretation and statistical analysis should consider the absolute level of pain, function, and general health status as well as improvement, missing data, approaches to analysis and case-mix adjustment, minimal clinically important difference, and minimal detectable change. The Working Group recommends data collection immediately before and 1 year after surgery, a threshold of 60% for acceptable frequency of response, documentation of non-responders, and documentation of incomplete or

  17. Health service utilization patterns of primary care patients with osteoarthritis

    PubMed Central

    Rosemann, Thomas; Joos, Stefanie; Szecsenyi, Joachim; Laux, Gunter; Wensing, Michel

    2007-01-01

    Background To assess factors associated with visits to GPs, orthopaedists, and non-physician practitioners of complementary medicine (alternative practitioners) by primary care patients with osteoarthritis (OA). Methods Cross-sectional survey among 1250 consecutively addressed patients from 75 primary care practices in Germany. All patients suffered from OA of the knee or hip according to ACR criteria. They received questionnaires collecting sociodemographic data, data about health service utilisation, prescriptions, comorbidities. They also included established instruments as the Arthritis Impact Measurement Scale (AIMS2-SF) to assess disease-specific quality of life and the Patient Health Questionnaire (PHQ-9) to assess depression. Hierarchical stepwise multiple linear regression models were used to reveal significant factors influencing health service utilization. Results 1021 of 1250 (81.6%) questionnaires were returned. Nonrespondents did not differ from participants. Factors associated with health service use (HSU) varied between providers of care. Not being in a partnership, achieving a high score on the PHQ-9, increased pain severity reflected in the “symptom” scale of the AIMS2-SF, and an increased number of drug prescriptions predicted a high frequency of GP visits. The PHQ-9 score was also a predictor for visits to orthopaedists, as were previous GP contacts, a high score in the "symptom" scale as well as a high score in the "lower limb scale" of the AIMS2-SF. Regarding visits to alternative practitioners, a high score in the AIMS -"social" scale was a positive predictor as older people were less likely to visit them. Conclusion Our results emphasize the need for awareness of psychological factors contributing to the use of health care providers. Addressing the revealed factors associated with HSU appropriately may lead to decreased health care utilization. But further research is needed to assess how this can be done successfully. PMID:17956605

  18. Assessment of Treatment Response by Total Tumor Volume and Global Apparent Diffusion Coefficient Using Diffusion-Weighted MRI in Patients with Metastatic Bone Disease: A Feasibility Study

    PubMed Central

    Blackledge, Matthew D.; Collins, David J.; Tunariu, Nina; Orton, Matthew R.; Padhani, Anwar R.; Leach, Martin O.; Koh, Dow-Mu

    2014-01-01

    We describe our semi-automatic segmentation of whole-body diffusion-weighted MRI (WBDWI) using a Markov random field (MRF) model to derive tumor total diffusion volume (tDV) and associated global apparent diffusion coefficient (gADC); and demonstrate the feasibility of using these indices for assessing tumor burden and response to treatment in patients with bone metastases. WBDWI was performed on eleven patients diagnosed with bone metastases from breast and prostate cancers before and after anti-cancer therapies. Semi-automatic segmentation incorporating a MRF model was performed in all patients below the C4 vertebra by an experienced radiologist with over eight years of clinical experience in body DWI. Changes in tDV and gADC distributions were compared with overall response determined by all imaging, tumor markers and clinical findings at serial follow up. The segmentation technique was possible in all patients although erroneous volumes of interest were generated in one patient because of poor fat suppression in the pelvis, requiring manual correction. Responding patients showed a larger increase in gADC (median change = +0.18, range = −0.07 to +0.78×10−3 mm2/s) after treatment compared to non-responding patients (median change = −0.02, range = −0.10 to +0.05×10−3 mm2/s, p = 0.05, Mann-Whitney test), whereas non-responding patients showed a significantly larger increase in tDV (median change = +26%, range = +3 to +284%) compared to responding patients (median change = −50%, range = −85 to +27%, p = 0.02, Mann-Whitney test). Semi-automatic segmentation of WBDWI is feasible for metastatic bone disease in this pilot cohort of 11 patients, and could be used to quantify tumor total diffusion volume and median global ADC for assessing response to treatment. PMID:24710083

  19. Reduced effect of percutaneous renal denervation on blood pressure in patients with isolated systolic hypertension.

    PubMed

    Ewen, Sebastian; Ukena, Christian; Linz, Dominik; Kindermann, Ingrid; Cremers, Bodo; Laufs, Ulrich; Wagenpfeil, Stefan; Schmieder, Roland E; Böhm, Michael; Mahfoud, Felix

    2015-01-01

    Renal denervation can reduce blood pressure in certain patients with resistant hypertension. The effect in patients with isolated systolic hypertension (ISH, ≥140/<90 mm Hg) is unknown. This study investigated the effects of renal denervation in 126 patients divided into 63 patients with ISH and 63 patients with combined hypertension (CH, ≥140/≥90 mm Hg) defined as baseline office systolic blood pressure (SBP) ≥140 mm Hg despite treatment with ≥3 antihypertensive agents. Renal denervation significantly reduced office SBP and diastolic blood pressure (DBP) at 3, 6, and 12 months by 17/18/17 and 5/4/4 mm Hg in ISH and by 28/27/30 and 13/16/18 mm Hg in CH, respectively. The reduction in SBP and DBP in ISH was lower compared with patients with CH at all observed time points (P<0.05 for SBP/DBP intergroup comparison). The nonresponder rate (change in office SBP <10 mm Hg) after 6 months was 37% in ISH and 21% in CH (P<0.001). Mean 24-hour ambulatory SBP and DBP after 3, 6, and 12 months were significantly reduced by 10/13/15 and 6/6/9 mm Hg in CH, respectively. In patients with ISH the reduction in systolic ambulatory blood pressure was 4/8/7 mm Hg (P=0.032/P<0.001/P=0.009) and 3/4/2 mm Hg (P=0.08/P<0.001/P=0.130) in diastolic ambulatory blood pressure after 3, 6, and 12 months, respectively. The ambulatory blood pressure reduction was significantly lower after 3 and 12 months in SBP and after 12 months in ambulatory DBP, respectively. In conclusion, renal denervation reduces office and ambulatory blood pressure in patients with ISH. However, this reduction is less pronounced compared with patients with CH.

  20. Impact of ATM and SLC22A1 Polymorphisms on Therapeutic Response to Metformin in Iranian Diabetic Patients

    PubMed Central

    Shokri, Fazlollah; Ghaedi, Hamid; Ghafouri Fard, Soudeh; Movafagh, Abolfazl; Abediankenari, Saeid; Mahrooz, Abdolkarim; Kashi, Zahra; Omrani, Mir Davood

    2016-01-01

    Metabolic syndrome and its pathological sequel, type 2 diabetes are considered as important global health problems. Metformin is the most common drug prescribed for patients with this disorder. Consequently, understanding the genetic pathways involved in pharmacokinetics and pharmacodynamics of this drug can have a considerable effect on the personalized treatment of type 2 diabetes. In this study, we evaluated the association between rs11212617 polymorphism of ATM gene and rs628031 of SLC22A1 gene with response to treatment in newly diagnosed type 2 diabetes patients. We genotyped rs11212617 and rs628031 polymorphism by PCR based restriction fragment length polymorphism (RFLP) and assessed the role of this polymorphisms on response to treatment in 140 patients who have been recently diagnosed with type 2 diabetes and were under monotherapy with metformin for 6 months. Response to metformin was defined by HbA1c and fasting blood sugar (FBS) values. Based on such evaluations, patients were divided into two groups: responders (n= 63) and non-responders (n= 77). No significant association was found between these polymorphisms and response to treatment (OR= 0.86, [95% CI 0.52–1.41], P= 0.32) for rs11212617 and (OR= 0.45, [95% CI 0.64–1.76], P= 0.45) for rs 628031. The reported gene variants in ATM and SLC22A1 are not significantly associated with metformin treatment response in type 2 diabetic patients in an Iranian population. PMID:27386433

  1. Agomelatine Increases BDNF Serum Levels in Depressed Patients in Correlation with the Improvement of Depressive Symptoms

    PubMed Central

    Pettorruso, Mauro; De Berardis, Domenico; Varasano, Paola Annunziata; Lucidi Pressanti, Gabriella; De Remigis, Valeria; Valchera, Alessandro; Ricci, Valerio; Di Nicola, Marco; Janiri, Luigi; Biggio, Giovanni; Di Giannantonio, Massimo

    2016-01-01

    Background: Agomelatine modulates brain-derived neurotrophic factor expression via its interaction with melatonergic and serotonergic receptors and has shown promising results in terms of brain-derived neurotrophic factor increase in animal models. Methods: Twenty-seven patients were started on agomelatine (25mg/d). Venous blood was collected and brain-derived neurotrophic factor serum levels were measured at baseline and after 2 and 8 weeks along with a clinical assessment, including Hamilton Depression Rating Scale and Snaith-Hamilton Pleasure Scale. Results: Brain-derived neurotrophic factor serum concentration increased after agomelatine treatment. Responders showed a significant increase in brain-derived neurotrophic factor levels after 2 weeks of agomelatine treatment; no difference was observed in nonresponders. Linear regression analysis showed that more prominent brain-derived neurotrophic factor level variation was associated with lower baseline BDNF levels and greater anhedonic features at baseline. Conclusions: Patients affected by depressive disorders showed an increase of brain-derived neurotrophic factor serum concentration after a 2-week treatment with agomelatine. The increase of brain-derived neurotrophic factor levels was found to be greater in patients with lower brain-derived neurotrophic factor levels and marked anhedonia at baseline. PMID:26775293

  2. Predictive and Prognostic Significance of Glutathione Levels and DNA Damage in Cervix Cancer Patients Undergoing Radiotherapy

    SciTech Connect

    Vidyasagar, Mamidipudi Srinivasa; Kodali, Maheedhar; Prakash Saxena, Pu

    2010-10-01

    Purpose: To assess the predictive significance of serum glutathione (GSH) and tumor tissue DNA damage in the treatment of cervical cancer patients undergoing chemoradiotherapy. Methods and Materials: This study included subjects undergoing hysterectomy (for normal cervix tissue) and cervical cancer patients who underwent conventional concurrent chemoradiotherapy (cisplatin once per week for 5 weeks with concurrent external radiotherapy of 2 Gy per fraction for 5 weeks, followed by two applications of intracavitary brachytherapy once per week after 2 weeks' rest). Blood was collected after two fractions, whereas both blood and tissues were collected after five fractions of radiotherapy in separate groups of subjects. Serum for total GSH content and tissues were processed for single-cell gel electrophoresis (SCGE) assay for DNA damage analysis. Clinical tumor radioresponse was assessed 2 months after the completion of treatment as complete responders (CR) (100% shrinkage), partial responders (PR) (>50%), and nonresponders (NR) (<50%). Results: Serum GSH content depleted significantly after a total dose of 4 Gy and 10 Gy of radiotherapy with a single dose of cisplatin, which was significantly lesser in NR than of CR patients. Similarly, Olive Tail Moment, the index of DNA damage, indicated significantly higher values in the fifth fraction of radiotherapy (5-RT) than in pretreatment. The DNA damage after 5-RT in the NR subgroup was significantly lower than that of CR. Conclusions: Serum GSH analysis and tumor tissue SCGE assay found to be useful parameters for predicting chemoradioresponse prior to and also at an early stage of treatment of cervical cancers.

  3. Early response evaluation and prediction in neoadjuvant-treated patients with esophageal cancer

    PubMed Central

    Theisen, Joerg; Krause, Bernd; Peschel, Christian; Schmid, Roland; Geinitz, Hans; Friess, Helmut

    2009-01-01

    Since the introduction of multimodal therapy regimens, the prognosis of esophageal cancer has improved. There is undoubtedly true for patients with surgically resected tumors in the case of a response to neoadjuvant chemotherapy or chemoradiation. Important conclusions can be drawn from this regarding the indication for perioperative therapies, the radicality of surgery, or the surgical indications. Thus, most of the current research in this field is aimed at the early identification of this subset of patients, at the beginning of, or even before, neoadjuvant treatment. Conventional staging tools have failed to predict responses to neoadjuvant therapy. However, molecular imaging methods, e.g. positron emission tomography (PET)-scans, have shown promising results in the early selection of responders and non-responders during the course of neoadjuvant therapy, allowing physicians to alter the treatment plan accordingly. Even more desirable is the identification of potential responders before the start of neoadjuvant therapy. Preliminary molecular data on biopsy specimens demonstrate the possibility of early response prediction in these patients. We present the current knowledge on response evaluation and prediction in esophageal cancer and draw conclusions for future clinical practice and studies in this review. PMID:21160793

  4. MATE1 regulates cellular uptake and sensitivity to imatinib in CML patients

    PubMed Central

    Harrach, S; Schmidt-Lauber, C; Pap, T; Pavenstädt, H; Schlatter, E; Schmidt, E; Berdel, W E; Schulze, U; Edemir, B; Jeromin, S; Haferlach, T; Ciarimboli, G; Bertrand, J

    2016-01-01

    Although imatinib is highly effective in the treatment of chronic myeloid leukemia (CML), 25–30% patients do not respond or relapse after initial response. Imatinib uptake into targeted cells is crucial for its molecular response and clinical effectiveness. The organic cation transporter 1 (OCT1) has been proposed to be responsible for this process, but its relevance has been discussed controversially in recent times. Here we found that the multidrug and toxin extrusion protein 1 (MATE1) transports imatinib with a manifold higher affinity. MATE1 mainly mediates the cellular uptake of imatinib into targeted cells and thereby controls the intracellular effectiveness of imatinib. Importantly, MATE1 but not OCT1 expression is reduced in total bone marrow cells of imatinib-non-responding CML patients compared with imatinib-responding patients, indicating that MATE1 but not OCT1 determines the therapeutic success of imatinib. We thus propose that imatinib non-responders could be identified early before starting therapy by measuring MATE1 expression levels. PMID:27635733

  5. Low-density lipoprotein receptor genetic polymorphism in chronic hepatitis C virus Egyptian patients affects treatment response

    PubMed Central

    Naga, Mazen; Amin, Mona; Algendy, Dina; Elbadry, Ahmed; Fawzi, May; Foda, Ayman; Esmat, Serag; Sabry, Dina; Rashed, Laila; Gabal, Samia; Kamal, Manal

    2015-01-01

    AIM: To correlate a genetic polymorphism of the low-density lipoprotein (LDL) receptor with antiviral responses in Egyptian chronic hepatitis C virus (HCV) patients. METHODS: Our study included 657 HCV-infected patients with genotype 4 who received interferon-based combination therapy. Patients were divided into two groups based on their response to therapy: 356 were responders, and 301 were non-responders. Patients were compared to 160 healthy controls. All patients and controls underwent a thorough physical examination, measurement of body mass index (BMI) and the following laboratory tests: serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, albumin, total bilirubin, direct bilirubin, prothrombin time, prothrombin concentration, INR, complete blood count, serum creatinine, fasting blood sugar, HCV antibody, and hepatitis B surface antigen. All HCV patients were further subjected to the following laboratory tests: HCV-RNA using quantitative polymerase chain reaction (PCR), antinuclear antibodies, thyroid-stimulating hormone, an LDL receptor (LDLR) genotype study of LDLR exon8c.1171G>A and exon10c.1413G>A using real-time PCR-based assays, abdominal ultrasonography, ultrasonographic-guided liver biopsy, and histopathological examination of liver biopsies. Correlations of LDL receptor polymorphisms with HAI, METAVIR score, presence of steatosis, and BMI were performed in all cases. RESULTS: There were no statistically significant differences in response rates between the different types of interferon used or LDLR exon10c.1413G>A. However, there was a significant difference in the frequency of the LDL receptor exon8c.1171G>A genotype between cases (AA: 25.9%, GA: 22.2%, GG: 51.9%) and controls (AA: 3.8%, GA: 53.1% and GG: 43.1%) (P < 0.001). There was a statistically significant difference in the frequency of the LDLR exon 8C:1171 G>A polymorphism between responders (AA: 3.6%, GA: 15.2%, GG: 81.2%) and non-responders (AA: 52.2%, GA: 30

  6. A phase-II sequential case-series study of all patients presenting to four plasma exchange centres with presumed relapsed/refractory thrombotic thrombocytopenic purpura treated with rituximab.

    PubMed

    Clark, William F; Rock, Gail; Barth, David; Arnold, Donald M; Webert, Kathyrn E; Yenson, Paul R; Kelton, John G; Li, Lihua; Foley, Steven R

    2015-07-01

    The primary objective of this phase II study was to evaluate the efficacy of rituximab in the management of adult patients with physician-diagnosed presumed thrombotic thrombocytopenic purpura (TTP); relapsed or refractory. We conducted a multicentre study in four Canadian hospital-based apheresis units. Forty patients with presumed TTP (20 refractory and 20 relapsing) were sequentially enrolled and all received rituximab in a standardized manner. A complete response was documented in 14 of 19 refractory patients by week 8 and 15/16 were alive and in remission at 52 weeks (one patient was lost to follow-up, one was a non-responder, and three died). Among relapsing patients, 16/18 had a complete response at week 8 and 18/18 at week 52 (one patient lost to follow-up and one withdrew). At 1 year, all relapsing and 85% of refractory patients survived. Of 38/40 patients who had ADMATS13 testing at study entry, 13/19 refractory and 10/19 relapsing patients had ADAMTS13 < 10% (typical TTP); whereas 6/19 refractory and 9/19 relapsing cases had ADAMTS13 > 10% (other thrombotic microangiopathy; TMA). Refractory-typical TTP in contrast to refractory-other TMA and all relapsing patients treated with plasma exchange and rituximab, were less likely to be responsive and more likely to die or relapse. PMID:25855259

  7. Bendamustine in heavily pre-treated multiple myeloma patients: Results of a retrospective analysis from the Korean Multiple Myeloma Working Party

    PubMed Central

    Kim, Seok Jin; Bang, Soo-Mee; Choi, Yoon Seok; Jo, Deog-Yeon; Kim, Jin Seok; Lee, Hyewon; Eom, Hyeon Seok; Yoon, Dok Hyun; Suh, Cheolwon; Lee, Je-Jung; Hong, Junshik; Lee, Jae Hoon; Koh, Youngil; Kim, Kihyun

    2016-01-01

    Background Bendamustine may be a potential treatment option for patients with myeloma, but little is known about the utility of bendamustine as a salvage treatment, especially in Asian patients. Methods We performed a multicenter retrospective study of patients with relapsed or refractory myeloma who received bendamustine and prednisone. Results The records of 65 heavily pre-treated patients, who had undergone bortezomib and lenalidomide treatment (median number of previous treatments: 5), were analyzed. The median time from diagnosis to bendamustine treatment was 3.8 years, and the median patient age was 63 years (range, 38‒77 yr). The responses to the last treatment before bendamustine were refractory disease (N=52, 80%) or disease progression from partial response (N=13, 20%). Twenty-three patients responded to the treatment, with an overall response rate of 35% (23/65), and the median number of bendamustine treatment cycles was two (range, 1‒5 cycles). The median overall survival after bendamustine treatment was 5.5 months and the overall survival rate in responders to bendamustine was significantly better than that in non-responders (P=0.036). Conclusion Bendamustine may be a potential salvage treatment to extend survival in a select group of heavily pre-treated patients with relapsed or refractory myeloma. PMID:27722131

  8. Racial diversity in mortality and morbidity in urban patients with hepatitis C.

    PubMed

    Stubbs, A; Naylor, P; Ravindran, K; Benjaram, S; Reddy, N; Mutchnick, S; May, E; Ehrinpreis, M; Mutchnick, M

    2016-06-01

    Defining mortality for Caucasians and African American patients with chronic hepatitis C with respect to racial diversity is critical for counselling patients on therapy options. The objective of this study was to define racial diversity influence on mortality and morbidity of 3724 consecutive hepatitis C virus (HCV)-infected patients seen in an urban clinic between 1995 and 2008. Mortality, as of 2011, was defined using the SSA National Death Index and correlated with early visit medical information. The HCV chronically infected patient population consisted of 2879 African Americans (AA), 758 Caucasians and 87 other, and the majority were not treated for their infection prior to 2011. The average time to death from first visit was 5 years, the average age at death was 55 years, and despite racial diversity, AA were just as likely to be reported dead as Caucasians (23% AA vs 22% Caucasians). Cirrhosis and fibrosis (liver biopsy, AST Platelet Ratio Index or Fibrosis-4) at first visit as well as low albumin, diabetes, renal impairment and cardiac symptoms were associated with increased mortality. Treated patients who cleared the virus (sustained viral response (SVR); AA = 59; Caucasians = 40) had lower mortality than patients who were not treated (AA: 5% vs 27%; Caucasians 5% vs 26%). Hence, we find that race is not a factor in the early mortality of patients with chronic HCV infection and achieving a SVR reduced mortality. Unexpectedly, nonresponding AA also benefited by a lower mortality. African American patients with kidney disease and low albumin were at highest risk and should be treated as soon as identified. PMID:26818494

  9. Antiplatelet Effect of Sequential Administration of Cilostazol in Patients with Acetylsalycilic Acid Resistance

    PubMed Central

    Cakmak, Muzaffer; Demircelik, Bora; Cetin, Mustafa; Cetin, Zehra; Isık, Serhat; Cıcekcıoglu, Hulya; Ulusoy, Feridun Vasfi; Eryonucu, Beyhan

    2016-01-01

    Background Acetylsalicylic acid (ASA) resistance in patients with coronary artery disease is an important medical problem that can affect treatment decision-making and outcomes. Cilostazol has been investigated to determine its effectiveness in patients with acetylsalicylic acid resistance. The aim of this study was to evaluate the antiplatelet efficacy of sequential administration of CLZ in patients with ASA resistance. Methods A total of 180 patients were enrolled in our study. Patients with stable coronary artery disease were first given orally ASA 100 for 10 days, followed by collagen/epinephrine induced closure time (CTCEPI) measurements. Those who were found to be resistant to orally 100 mg of ASA were given orally 300 mg of ASA for an additional 10 days after which we repeated CTCEPI measurements. Those patients with resistance to orally 300 mg ASA were then given CLZ at a daily dose of orally 200 mg for 10 days followed by a final CTCEPI measurement. Results The rate of resistance to 100 mg ASA was 81/180 (45%) compared to a rate of 35/81 (43.2%) with 300 mg ASA. Of the 35 patients found to be resistant to 300 mg ASA, 22 (62.9%) also failed to respond to CLZ treatment. Overall, sequential administration of 300 mg ASA and 200 mg CLZ resulted in a reduction in the number of non-responders from 45% to 12.2%. Conclusions Initiation of CLZ could be of benefit in some patients with ASA-resistance for whom an effective anti-aggregant effect is of clinical importance. PMID:27274173

  10. HCV Infection and Interferon-Based Treatment Induce p53 Gene Transcription in Chronic Hepatitis C Patients.

    PubMed

    Świątek-Kościelna, Bogna; Kałużna, Ewelina Maria; Januszkiewicz-Lewandowska, Danuta; Rembowska, Jolanta; Mozer-Lisewska, Iwona; Bereszyńska, Iwona; Czubała, Katarzyna; Dziechciowska, Katarzyna; Wysocka-Leszczyńska, Joanna; Barcińska, Dominika; Wysocki, Jacek; Nowak, Jerzy Stanisław

    2015-10-01

    It is suggested that the tumor suppressor p53 gene, classified as an interferon-stimulated gene, is implicated in the interferon (IFN)-mediated innate immunity against viruses. This study aimed to examine the transcriptional response of the p53 gene to hepatitis C virus (HCV) infection and IFN-based therapy in chronic hepatitis C (CHC) patients. The study included 65 CHC patients (HCV genotype 1), treated with pegylated IFN-α and ribavirin, and 51 healthy individuals. p53 gene expression was quantified by real-time polymerase chain reaction in peripheral blood mononuclear cells (PBMCs). Analyses were performed before and at weeks 4 and 12 of treatment. p53 gene expression was significantly upregulated in CHC patients compared with healthy controls and at week 4 of therapy. No significant differences in p53 mRNA expression between rapid virologic responders, complete early virologic responders, and nonresponders were observed. No significant correlation was found between p53 gene expression and viral load. The results obtained indicate that HCV infection and IFN-based treatment induces p53 gene transcription in PBMCs. The p53 gene may therefore play a role in HCV infection but is not directly involved in treatment-induced HCV elimination. Moreover, variations in p53 gene expression do not determine on-treatment response in patients with chronic HCV genotype 1 infection.

  11. Liver Gene Expression Profiles Correlate with Virus Infection and Response to Interferon Therapy in Chronic Hepatitis B Patients.

    PubMed

    Wu, Hui-Lin; Hsiao, Tzu-Hung; Chen, Pei-Jer; Wong, Siao-Han; Kao, Jia-Horng; Chen, Ding-Shinn; Lu, Jo-Yang; Lu, Tzu-Pin; Chen, Yidong; Chuang, Eric Y; Tu, Hui-Chu; Liu, Chun-Jen

    2016-01-01

    The natural course of chronic hepatitis B (CHB) infection and treatment response are determined mainly by the genomic characteristics of the individual. We investigated liver gene expression profiles to reveal the molecular basis associated with chronic hepatitis B and IFN-alpha (IFNα) treatment response in CHB patients. Expression profiles were compared between seven paired liver biopsy samples taken before and 6 months after successful IFNα treatment or between pretreatment biopsy samples of 11 IFNα responders and 11 non-responders. A total of 132 differentially up-regulated and 39 down-regulated genes were identified in the pretreated livers of CHB patients. The up-regulated genes were mainly related to cell proliferation and immune response, with IFNγ and B cell signatures significantly enriched. Lower intrahepatic HBV pregenomic RNA levels and 25 predictive genes were identified in IFNα responders. The predictive gene set in responders significantly overlapped with the up-regulated genes associated with the pretreated livers of CHB patients. The mechanisms responsible for IFNα treatment responses are different between HBV and HCV patients. HBV infection evokes significant immune responses even in chronic infection. The up-regulated genes are predictive of responsiveness to IFNα therapy, as are lower intrahepatic levels of HBV pregenomic RNA and pre-activated host immune responses. PMID:27546197

  12. Liver Gene Expression Profiles Correlate with Virus Infection and Response to Interferon Therapy in Chronic Hepatitis B Patients

    PubMed Central

    Wu, Hui-Lin; Hsiao, Tzu-Hung; Chen, Pei-Jer; Wong, Siao-Han; Kao, Jia-Horng; Chen, Ding-Shinn; Lu, Jo-Yang; Lu, Tzu-Pin; Chen, Yidong; Chuang, Eric Y.; Tu, Hui-Chu; Liu, Chun-Jen

    2016-01-01

    The natural course of chronic hepatitis B (CHB) infection and treatment response are determined mainly by the genomic characteristics of the individual. We investigated liver gene expression profiles to reveal the molecular basis associated with chronic hepatitis B and IFN-alpha (IFNα) treatment response in CHB patients. Expression profiles were compared between seven paired liver biopsy samples taken before and 6 months after successful IFNα treatment or between pretreatment biopsy samples of 11 IFNα responders and 11 non-responders. A total of 132 differentially up-regulated and 39 down-regulated genes were identified in the pretreated livers of CHB patients. The up-regulated genes were mainly related to cell proliferation and immune response, with IFNγ and B cell signatures significantly enriched. Lower intrahepatic HBV pregenomic RNA levels and 25 predictive genes were identified in IFNα responders. The predictive gene set in responders significantly overlapped with the up-regulated genes associated with the pretreated livers of CHB patients. The mechanisms responsible for IFNα treatment responses are different between HBV and HCV patients. HBV infection evokes significant immune responses even in chronic infection. The up-regulated genes are predictive of responsiveness to IFNα therapy, as are lower intrahepatic levels of HBV pregenomic RNA and pre-activated host immune responses. PMID:27546197

  13. Noninvasive Transcutaneous Monitoring in Long-Term Follow-Up of Patients With Thromboangiitis Obliterans Treated With Intravenous Iloprost.

    PubMed

    Melillo, Elio; Grigoratos, Chrysanthos; Sanctis, Francesco De; Spontoni, Paolo; Nuti, Marco; Dell'Omodarme, Matteo; Ferrari, Mauro; Balbarini, Alberto

    2015-07-01

    We evaluated the effectiveness of intravenous iloprost (IVI) in outpatients with thromboangiitis obliterans (TAO) and lower limb noninvasive transcutaneous monitoring (TCM) at follow-up (FU). Ten consecutive patients with TAO underwent IVI therapy. Transcutaneous oxygen (TcPo 2) and carbon dioxide (TcPco 2) determination and laser Doppler flowmetry (LDF) were performed before and after IVI at 3, 6, and 12 months of FU. Clinical response was positive in 7 patients, whereas 3 nonresponders underwent a second IVI cycle with 1 showing a late positive clinical response. After 12 months of FU, all patients were alive without amputations. Supine and dependent TcP2 levels significantly improved (P < .005). Hallux LDF values showed significant change with the maximal hyperemic test at 44°C (P < .005). Forefoot maximal hyperemic test at 44°C LDF (P < .005) and improved venous arterial reflex (P < .05) showed statistically significant time evolution. We demonstrated some degree of IVI effectiveness and evaluated TCM in patients with TAO.

  14. Accelerated Intermittent Theta Burst Stimulation for Suicide Risk in Therapy-Resistant Depressed Patients: A Randomized, Sham-Controlled Trial

    PubMed Central

    Desmyter, Stefanie; Duprat, Romain; Baeken, Chris; Van Autreve, Sara; Audenaert, Kurt; van Heeringen, Kees

    2016-01-01

    Objectives: We aimed to examine the effects and safety of accelerated intermittent Theta Burst Stimulation (iTBS) on suicide risk in a group of treatment-resistant unipolar depressed patients, using an extensive suicide assessment scale. Methods: In 50 therapy-resistant, antidepressant-free depressed patients, an intensive protocol of accelerated iTBS was applied over the left dorsolateral prefrontal cortex (DLPFC) in a randomized, sham-controlled crossover design. Patients received 20 iTBS sessions over 4 days. Suicide risk was assessed using the Beck Scale of Suicide ideation (BSI). Results: The iTBS protocol was safe and well tolerated. We observed a significant decrease of the BSI score over time, unrelated to active or sham stimulation and unrelated to depression-response. No worsening of suicidal ideation was observed. The effects of accelerated iTBS on mood and depression severity are reported in Duprat et al. (2016). The decrease in suicide risk lasted up to 1 month after baseline, even in depression non-responders. Conclusions: This accelerated iTBS protocol was safe. The observed significant decrease in suicide risk was unrelated to active or sham stimulation and unrelated to depression response. Further sham-controlled research in suicidal depressed patients is necessary. (Clinicaltrials.gov identifier: NCT01832805). PMID:27729854

  15. Long-term Outcome of Lupus Nephritis Class II in Argentine Patients

    PubMed Central

    Collado, Maria Victoria; Dorado, Enrique; Rausch, Silvia; Gomez, Graciela; Khoury, Marina; Zazzetti, Federico; Gargiulo, María; Suarez, Lorena; Chaparro, Rafael; Paira, Sergio; Galvan, Laura; Juarez, Vicente; Pisoni, Cecilia; Garcia, Mercedes; Martinez, Liliana; Alvarez, Analia; Alvarez, Clarisa; Barreira, Juan; Sarano, Judith

    2016-01-01

    Background There is controversy in medical literature over the outcome of patients with lupus nephritis (LN) class II. The aim of this study was to explore the risk of histological transformation (HT) and possible factors related to negative response to treatment in patients with mesangial LN class II. Methods A retrospective and multicenter study was carried out that includes patients who had received a diagnosis of LN class II on their first renal biopsy. Creatinine, urine sediment, and proteinuria were recorded at the time of the first biopsy, 6 months, and 1, 2, and 5 years after the first biopsy. Response to treatment, HT, and long-term outcome were evaluated. Results Forty-one patients were included. The manifestation at first biopsy was proteinuria greater than 0.5 g/d in 28 patients (68.29%; 8 [28.57%] of 28 patients had nephrotic syndrome), hematuria in 18 patients (43.90%), and deterioration of renal function in 3 patients (7.31%). During the follow-up (median, 8 years; range, 1–35 years), a new biopsy was performed in 18 patients (43.90%), and in 17 patients (17/18 [94.44%]), there was HT. Median time at rebiopsy was 32 months (range, 11–305 months). Of the 18 patients who had a second biopsy, 10 (55.55%) were on hydroxychloroquine versus 100% (19/19) of patients who did not undergo the procedure (P = 0.001). A year after the first renal biopsy, there are data available from 34 patients; of them, 24 patients (70.58%) had achieved response, and 10 patients (29.41%) had no response (NR) (missing data in 7). A higher 24-hour urinary protein at 6 months was predictor of worse outcome at 1 year, with statistical significance difference for the nonresponder group (median proteinuria, 2.3 g/d [range, 0–4.7 g/d]) compared with responders (median proteinuria, 0.28 g/d [range, 0–1.7 g/d]) (P = 0.0133). In the long-term follow-up (5 years), HT was the main cause of unfavorable outcome and was measured in 78.57% of patients (11/14 patients). Conclusions This

  16. Absolute Measurements of Macrophage Migration Inhibitory Factor and Interleukin-1-β mRNA Levels Accurately Predict Treatment Response in Depressed Patients

    PubMed Central

    Ferrari, Clarissa; Uher, Rudolf; Bocchio-Chiavetto, Luisella; Riva, Marco Andrea; Pariante, Carmine M.

    2016-01-01

    Background: Increased levels of inflammation have been associated with a poorer response to antidepressants in several clinical samples, but these findings have had been limited by low reproducibility of biomarker assays across laboratories, difficulty in predicting response probability on an individual basis, and unclear molecular mechanisms. Methods: Here we measured absolute mRNA values (a reliable quantitation of number of molecules) of Macrophage Migration Inhibitory Factor and interleukin-1β in a previously published sample from a randomized controlled trial comparing escitalopram vs nortriptyline (GENDEP) as well as in an independent, naturalistic replication sample. We then used linear discriminant analysis to calculate mRNA values cutoffs that best discriminated between responders and nonresponders after 12 weeks of antidepressants. As Macrophage Migration Inhibitory Factor and interleukin-1β might be involved in different pathways, we constructed a protein-protein interaction network by the Search Tool for the Retrieval of Interacting Genes/Proteins. Results: We identified cutoff values for the absolute mRNA measures that accurately predicted response probability on an individual basis, with positive predictive values and specificity for nonresponders of 100% in both samples (negative predictive value=82% to 85%, sensitivity=52% to 61%). Using network analysis, we identified different clusters of targets for these 2 cytokines, with Macrophage Migration Inhibitory Factor interacting predominantly with pathways involved in neurogenesis, neuroplasticity, and cell proliferation, and interleukin-1β interacting predominantly with pathways involved in the inflammasome complex, oxidative stress, and neurodegeneration. Conclusion: We believe that these data provide a clinically suitable approach to the personalization of antidepressant therapy: patients who have absolute mRNA values above the suggested cutoffs could be directed toward earlier access to more

  17. Cost-effectiveness of sofosbuvir for the treatment of chronic hepatitis C-infected patients.

    PubMed

    Cure, S; Guerra, I; Dusheiko, G

    2015-11-01

    The efficacy of treatment for hepatitis C genotype 1 infection has significantly improved with the introduction of first-generation protease inhibitors. However, there remains a need for effective treatments for patients infected with other genotypes, for nonresponders and patients unsuitable for interferon. Sofosbuvir is the first nucleotide polymerase inhibitor with pan-genotypic activity. Sofosbuvir-based regimens have resulted in >90% sustained virological response across treatment-naïve genotype 1-6 patients in five phase III clinical trials of sofosbuvir administered with ribavirin or pegylated interferon and ribavirin. This analysis evaluates the cost-effectiveness of sofosbuvir within the current licensed indication, for genotype 1-6 in the UK. A Markov model followed a cohort of 10 000 patients over lifetime, with approximately 20% initiating treatment for compensated cirrhosis. Sofosbuvir-regimens were compared to telaprevir, boceprevir, pegylated interferon and ribavirin, or no treatment. Costs and outcomes were discounted at 3.5%. The cost perspective utilized costs applicable to the National Health Service in the UK. Sofosbuvir proved to be cost-effective in most patient populations with incremental cost-effectiveness ratios (ICERs) at £11 836/QALY and £7292/QALY against telaprevir and boceprevir, respectively. In genotype 3, sofosbuvir had a weighted ICER of £18 761/QALY. Sofosbuvir-based regimens are a cost-effective option for the majority of hepatitis C-infected patients in the United Kingdom although the incremental cost-effectiveness varies by genotype and regimen. Sofosbuvir and ribavirin is an alternative regimen for patients unsuitable for interferon.

  18. Bendamustine with or without rituximab for the treatment of heavily pretreated non-Hodgkin's lymphoma patients : A multicenter retrospective study on behalf of the Italian Lymphoma Foundation (FIL).

    PubMed

    Rigacci, Luigi; Puccini, Benedetta; Cortelazzo, Sergio; Gaidano, Gianluca; Piccin, Andrea; D'Arco, Alfonso; Freilone, Roberto; Storti, Sergio; Orciuolo, Enrico; Zinzani, Pier Luigi; Zaja, Francesco; Bongarzoni, Velia; Balzarotti, Monica; Rota-Scalabrini, Delia; Patti, Caterina; Gobbi, Marco; Carpaneto, Andrea; Liberati, Anna Marina; Bosi, Alberto; Iannitto, Emilio

    2012-07-01

    Bendamustine is an alkylating agent with a nitrogen mustard group and a purine-like benzimidazole group. The aim of this study was to collect all the Italian experiences with this drug in order to evaluate the results in term of response to therapy and toxicities. We analyzed lymphoma patients treated in 24 Italian haematological centres with bendamustine alone or in combination with anti-CD20 antibody. One hundred seventy-five relapsed or refractory lymphoma patients were enrolled. The median age was 69 years (range 26-87). Seventy-nine patients were relapsed, 35 were refractory and 61 presented a progressive disease after partial response. The diagnoses were 60 indolent non-follicular lymphomas, 34 diffuse large B-cell lymphomas, 48 follicular lymphomas, 30 mantle cell lymphomas and three peripheral T-cell lymphomas. All patients were evaluable for response: 52 (29%) with complete remission, 72 (43%) with partial response with an overall response rate of 71%, and 51 non-responders. With a median observation period of 10 months (1-43), 70% of patients are alive. In summary, this retrospective study shows that treatment with bendamustine alone or in combination with rituximab is a safe and effective regimen in a subset of multi-resistant patients.

  19. Effectiveness of Pooled Platelet Transfusion in Concordant and Discordant Groups among Dengue Patients

    PubMed Central

    Chowdappa, Vijaya; Masamatti, Smita Surendra

    2016-01-01

    Introduction Dengue affects more than 50 million people per year and is one of the most common causes of severe thrombocytopaenia. Thrombocytopaenia is a common complication of dengue and other viral fevers apart from malaria, typhoid, leptospirosis, leukaemia and megaloblastic anaemia. A platelet count of <20,000/μl is characteristically seen in dengue haemorrhagic fever and dengue fever. It results from immune complex mediated platelet destruction or bone marrow suppression. Severe thrombocytopaenia <10,000/μl is one of the indications for prophylactic platelet transfusion therapy to prevent haemorrhage. Aim To evaluate the effectiveness of transfusion of ABO compatible and ABO incompatible pooled platelet units in severe thrombocytopaenia cases. Materials and Methods In this study ABO compatible and incompatible pooled platelet units were transfused to serologically confirmed dengue cases having thrombocytopaenia with or without bleeding manifestations. Each of the adult patients received 4-6 units of pooled platelet concentrates prepared from random donor whole blood suspended in plasma for severe thrombocytopaenia. Pre and post transfusion platelet counts were compared. Children aged less than 12 years, pregnant women and patients with splenomegaly those on ayurvedic and homeopathic therapy, recipients of packed red cells on the same day of platelet transfusion and recipients of multiple platelet transfusions within 24 hours were excluded from the study. Results The median post transfusion platelet increments (PPI) and corrected count increments (CCI) at 4hour post transfusion were 25,000/μL (5,000-80,000/μL) and 18,000/μL (range 8,000/μL- 47,500/μL) respectively among the responders. Median PPI and CCI at 24 hours were 45,000/μL and 28,863/μL among the responders. The median CCI at 4 hour post transfusion among the non-responders was 850/μL and at 24hours was 1,425/μL. At 24 hours responders showed significantly higher PPI as compared to non

  20. Effectiveness of Pooled Platelet Transfusion in Concordant and Discordant Groups among Dengue Patients

    PubMed Central

    Chowdappa, Vijaya; Masamatti, Smita Surendra

    2016-01-01

    Introduction Dengue affects more than 50 million people per year and is one of the most common causes of severe thrombocytopaenia. Thrombocytopaenia is a common complication of dengue and other viral fevers apart from malaria, typhoid, leptospirosis, leukaemia and megaloblastic anaemia. A platelet count of <20,000/μl is characteristically seen in dengue haemorrhagic fever and dengue fever. It results from immune complex mediated platelet destruction or bone marrow suppression. Severe thrombocytopaenia <10,000/μl is one of the indications for prophylactic platelet transfusion therapy to prevent haemorrhage. Aim To evaluate the effectiveness of transfusion of ABO compatible and ABO incompatible pooled platelet units in severe thrombocytopaenia cases. Materials and Methods In this study ABO compatible and incompatible pooled platelet units were transfused to serologically confirmed dengue cases having thrombocytopaenia with or without bleeding manifestations. Each of the adult patients received 4-6 units of pooled platelet concentrates prepared from random donor whole blood suspended in plasma for severe thrombocytopaenia. Pre and post transfusion platelet counts were compared. Children aged less than 12 years, pregnant women and patients with splenomegaly those on ayurvedic and homeopathic therapy, recipients of packed red cells on the same day of platelet transfusion and recipients of multiple platelet transfusions within 24 hours were excluded from the study. Results The median post transfusion platelet increments (PPI) and corrected count increments (CCI) at 4hour post transfusion were 25,000/μL (5,000-80,000/μL) and 18,000/μL (range 8,000/μL- 47,500/μL) respectively among the responders. Median PPI and CCI at 24 hours were 45,000/μL and 28,863/μL among the responders. The median CCI at 4 hour post transfusion among the non-responders was 850/μL and at 24hours was 1,425/μL. At 24 hours responders showed significantly higher PPI as compared to non

  1. Patients' experiences and satisfaction with health care: results of a questionnaire study of specific aspects of care

    PubMed Central

    Jenkinson, C; Coulter, A; Bruster, S; Richards, N; Chandola, T

    2002-01-01

    Objective: To determine what aspects of healthcare provision are most likely to influence satisfaction with care and willingness to recommend hospital services to others and, secondly, to explore the extent to which satisfaction is a meaningful indicator of patient experience of healthcare services. Design: Postal survey of a sample of patients who underwent a period of inpatient care. Patients were asked to evaluate their overall experience of this episode of care and to complete the Picker Inpatient Survey questionnaire on specific aspects of their care. Sample: Patients aged 18 and over presenting at five hospitals within one NHS trust in Scotland. Method: 3592 questionnaires were mailed to patients' homes within 1 month of discharge from hospital during a 12 month period. Two reminders were sent to non-responders; 2249 (65%) questionnaires were returned. Results: Almost 90% of respondents indicated that they were satisfied with their period of inpatient care. Age and overall self-assessed health were only weakly associated with satisfaction. A multiple linear regression indicated that the major determinants of patient satisfaction were physical comfort, emotional support, and respect for patient preferences. However, many patients who reported their satisfaction with the care they received also indicated problems with their inpatient care as measured on the Picker Inpatient Survey; 55% of respondents who rated their inpatient episode as "excellent" indicated problems on 10% of the issues measured on the Picker questionnaire. Discussion: The evidence suggests that patient satisfaction scores present a limited and optimistic picture. Detailed questions about specific aspects of patients' experiences are likely to be more useful for monitoring the performance of various hospital departments and wards and could point to ways in which delivery of health care could be improved. PMID:12468693

  2. Reduced Activity of Double-Strand Break Repair Genes in Prostate Cancer Patients With Late Normal Tissue Radiation Toxicity

    SciTech Connect

    Oorschot, Bregje van; Hovingh, Suzanne E.; Moerland, Perry D.; Medema, Jan Paul; Stalpers, Lukas J.A.; Vrieling, Harry; Franken, Nicolaas A.P.

    2014-03-01

    Purpose: To investigate clinical parameters and DNA damage response as possible risk factors for radiation toxicity in the setting of prostate cancer. Methods and Materials: Clinical parameters of 61 prostate cancer patients, 34 with (overresponding, OR) and 27 without (non-responding, NR) severe late radiation toxicity were assembled. In addition, for a matched subset the DNA damage repair kinetics (γ-H2AX assay) and expression profiles of DNA repair genes were determined in ex vivo irradiated lymphocytes. Results: Examination of clinical data indicated none of the considered clinical parameters to be correlated with the susceptibility of patients to develop late radiation toxicity. Although frequencies of γ-H2AX foci induced immediately after irradiation were similar (P=.32), significantly higher numbers of γ-H2AX foci were found 24 hours after irradiation in OR compared with NR patients (P=.03). Patient-specific γ-H2AX foci decay ratios were significantly higher in NR patients than in OR patients (P<.0001). Consequently, NR patients seem to repair DNA double-strand breaks (DSBs) more efficiently than OR patients. Moreover, gene expression analysis indicated several genes of the homologous recombination pathway to be stronger induced in NR compared with OR patients (P<.05). A similar trend was observed in genes of the nonhomologous end-joining repair pathway (P=.09). This is congruent with more proficient repair of DNA DSBs in patients without late radiation toxicity. Conclusions: Both gene expression profiling and DNA DSB repair kinetics data imply that less-efficient repair of radiation-induced DSBs may contribute to the development of late normal tissue damage. Induction levels of DSB repair genes (eg, RAD51) may potentially be used to assess the risk for late radiation toxicity.

  3. CYP2C19 polymorphisms in the Thai population and the clinical response to clopidogrel in patients with atherothrombotic-risk factors

    PubMed Central

    Sukasem, Chonlaphat; Tunthong, Ramaimon; Chamnanphon, Montri; Santon, Siwalee; Jantararoungtong, Thawinee; Koomdee, Napatrupron; Prommas, Santirhat; Puangpetch, Apichaya; Vathesatogkit, Prin

    2013-01-01

    Genetic variation in the cytochrome P450 2C19 (CYP2C19) gene has been documented gradually as the determinant conversion and variability in the antiplatelet effect of clopidogrel. The aims of this study were to determine the prevalence of clinically relevant allele variants (CYP2C19*2, CYP2C19*3, and CYP2C19*17) in a Thai study population, and finally determine whether the allele distributes and predicts metabolic phenotypes in clopidogrel treated patients. A total of 1,051 Thai patients participated in this study. Genotypes for CYP2C19 polymorphisms were detected by the microarray-based technique. Furthermore, results of genotyping and platelet aggregation in 96 cardiovascular disease patients on 75 mg clopidogrel maintenance daily dose therapy also were analyzed. Among 1,051 samples, the allele frequencies of CYP2C19 *1/*1, *1/*2, *1/*3, *2/*2, *2/*3, and *1/*17 were found in 428 (40.72%), 369 (35.10%), 72 (6.85%), 77 (7.32%), 59 (5.61%), and 45 (4.30%) of the patients, respectively. Homozygous CYP2C19 *3/*3 was found in one patient (0.10%). Therefore, 40.72% of the patients were predicted as extensive metabolizers, 41.95% as intermediate metabolizers, 13.03% as poor metabolizers, and 4.30% as ultra-rapid metabolizers. Among 96 patients, the frequency of poor metabolizers was significantly higher in the clopidogrel non-responder group than in the responder group (36.0% and 15.5%, respectively, P = 0.03). CYP2C19*1/*17 was observed in responders (n = 2; 2.8%). As a result, CYP2C19 variants were associated with clopidogrel non-responders. However, there is a need for further elucidation of the clinical importance and use of this finding to make firm and cost-effective recommendations for drug treatment in the future. PMID:24019752

  4. Insights on GRACE (Gender, Race, And Clinical Experience) from the patient's perspective: GRACE participant survey.

    PubMed

    Squires, Kathleen; Feinberg, Judith; Bridge, Dawn Averitt; Currier, Judith; Ryan, Robert; Seyedkazemi, Setareh; Dayaram, Yaswant K; Mrus, Joseph

    2013-06-01

    The Gender, Race And Clinical Experience (GRACE) study was conducted between October 2006 and December 2008 to evaluate sex- and race-based differences in outcomes after treatment with a darunavir/ritonavir-based antiretroviral regimen. Between June 2010 and June 2011, former participants of the GRACE trial at participating sites were asked to complete a 40-item questionnaire as part of the GRACE Participant Survey study, with a primary objective of assessing patients' characteristics, experiences, and opinions about participation in GRACE. Of 243 potential survey respondents, 151 (62%) completed the survey. Respondents were representative of the overall GRACE population and were predominantly female (64%); fewer were black, and more reported recreational drug use compared with nonrespondents (55% vs. 62% and 17% vs. 10%, respectively). Access to treatment (41%) and too many blood draws (26%) were reported as the best and worst part of GRACE, respectively. Support from study site staff was reported as the most important factor in completing the study (47%). Factors associated with nonadherence, study discontinuation, and poor virologic response in univariate analyses were being the primary caregiver for children, unemployment, and transportation difficulties, respectively. Patients with these characteristics may be at risk of poor study outcomes and may benefit from additional adherence and retention strategies in future studies and routine clinical care.

  5. New Direct-Acting Antiviral Therapies for Treatment of Chronic Hepatitis C Virus Infection

    PubMed Central

    Ara, A. Kardashian

    2015-01-01

    The treatment of hepatitis C virus infection has been advancing at breakneck speeds over the past few years. This article provides an update on the newest drugs available and those currently in development, including newer-generation protease inhibitors, RNA-dependent RNA polymerase, and nonstructural component inhibitors. Also discussed in this article are the regimens developed and the genotypes they target. Treatment of cirrhotic patients and patients who have failed prior therapy is also addressed, as are special populations, such as patients with harder-to-treat genotypes, patients with HIV coinfection, patients who have undergone liver transplantation, and patients with chronic kidney disease. Future developments and economic considerations are also mentioned. PMID:27118941

  6. EEG and Neuronal Activity Topography analysis can predict effectiveness of shunt operation in idiopathic normal pressure hydrocephalus patients.

    PubMed

    Aoki, Yasunori; Kazui, Hiroaki; Tanaka, Toshihisa; Ishii, Ryouhei; Wada, Tamiki; Ikeda, Shunichiro; Hata, Masahiro; Canuet, Leonides; Musha, Toshimitsu; Matsuzaki, Haruyasu; Imajo, Kaoru; Yoshiyama, Kenji; Yoshida, Tetsuhiko; Shimizu, Yoshiro; Nomura, Keiko; Iwase, Masao; Takeda, Masatoshi

    2013-01-01

    Idiopathic normal pressure hydrocephalus (iNPH) is a neuropsychiatric syndrome characterized by gait disturbance, cognitive impairment and urinary incontinence that affect elderly individuals. These symptoms can potentially be reversed by cerebrospinal fluid (CSF) drainage or shunt operation. Prior to shunt operation, drainage of a small amount of CSF or "CSF tapping" is usually performed to ascertain the effect of the operation. Unfortunately, conventional neuroimaging methods such as single photon emission computed tomography (SPECT) and functional magnetic resonance imaging (fMRI), as well as electroencephalogram (EEG) power analysis seem to have failed to detect the effect of CSF tapping on brain function. In this work, we propose the use of Neuronal Activity Topography (NAT) analysis, which calculates normalized power variance (NPV) of EEG waves, to detect cortical functional changes induced by CSF tapping in iNPH. Based on clinical improvement by CSF tapping and shunt operation, we classified 24 iNPH patients into responders (N = 11) and nonresponders (N = 13), and performed both EEG power analysis and NAT analysis. We also assessed correlations between changes in NPV and changes in functional scores on gait and cognition scales before and after CSF tapping. NAT analysis showed that after CSF tapping there was a significant decrease in alpha NPV at the medial frontal cortex (FC) (Fz) in responders, while nonresponders exhibited an increase in alpha NPV at the right dorsolateral prefrontal cortex (DLPFC) (F8). Furthermore, we found correlations between cortical functional changes and clinical symptoms. In particular, delta and alpha NPV changes in the left-dorsal FC (F3) correlated with changes in gait status, while alpha and beta NPV changes in the right anterior prefrontal cortex (PFC) (Fp2) and left DLPFC (F7) as well as alpha NPV changes in the medial FC (Fz) correlated with changes in gait velocity. In addition, alpha NPV changes in the right DLPFC (F

  7. Role of Baroreflex Sensitivity in Predicting Tilt Training Response in Patients with Neurally Mediated Syncope

    PubMed Central

    Chun, Kwang Jin; Yim, Hye Ran; Park, Jungwae; Park, Seung-Jung; Park, Kyoung-Min; On, Young Keun

    2016-01-01

    Purpose An association between baroreflex sensitivity (BRS) and the response to tilt training has not been reported in patients with neurally mediated syncope (NMS). This study sought to investigate the role of BRS in predicting the response to tilt training in patients with NMS. Materials and Methods We analyzed 57 patients who underwent tilt training at our hospital. A responder to tilt training was defined as a patient with three consecutive negative responses to the head-up tilt test (HUT) during tilt training. Results After tilt training, 52 patients (91.2%) achieved three consecutive negative responses to the HUT. In the supine position before upright posture during the first session of tilt training for responders and non-responders, the mean BRS was 18.17±10.09 ms/mm Hg and 7.99±5.84 ms/mm Hg (p=0.008), respectively, and the frequency of BRS ≥8.945 ms/mm Hg was 45 (86.5%) and 1 (20.0%; p=0.004), respectively. Age, male gender, frequency of syncopal events before HUT, type of NMS, phase of positive HUT, total number of tilt training sessions, and mean time of tilt training did not differ between the study groups. In the multivariate analysis, BRS <8.945 ms/mm Hg in the supine position (odds ratio 23.10; 95% CI 1.20-443.59; p=0.037) was significantly and independently associated with non-response to tilt training. Conclusion The BRS value in the supine position could be a predictor for determining the response to tilt training in patients with NMS who are being considered for inpatient tilt training. PMID:26847281

  8. Efficacy and Safety of Escalation of Adalimumab Therapy to Weekly Dosing in Pediatric Patients with Crohn's Disease

    PubMed Central

    Rosh, Joel; Faubion, William A.; Kierkus, Jaroslaw; Ruemmele, Frank; Hyams, Jeffrey S.; Eichner, Samantha; Li, Yao; Huang, Bidan; Mostafa, Nael M.; Lazar, Andreas; Thakkar, Roopal B.

    2016-01-01

    Background: The efficacy of adalimumab in inducing and maintaining remission in children with moderately to severely active Crohn's disease was shown in the IMAgINE 1 trial (NCT00409682). As per protocol, nonresponders or patients experiencing flare(s) on every other week (EOW) maintenance dosing could escalate to weekly dosing; we aimed to determine the therapeutic benefits of weekly dose escalation in this subpopulation. Methods: Week 52 remission and response rates were assessed in patients who escalated to weekly dosing from their previous EOW schedule, which was according to randomized treatment dose (higher dose [HD] adalimumab [≥40 kg, 40 mg EOW; <40 kg, 20 mg EOW] or lower dose [LD; ≥40 kg, 20 mg EOW; <40 kg, 10 mg EOW]). Adverse events were reported for patients remaining on EOW dosing and patients receiving weekly dosing. Results: Escalation to weekly dosing occurred in 48/95 (50.5%) patients randomized to LD and 35/93 (37.6%) patients randomized to HD adalimumab (P = 0.076). Week 52 remission and response rates were 18.8% and 47.9% for patients receiving LD adalimumab weekly and 31.4% and 57.1% for patients receiving HD adalimumab weekly, respectively (LD versus HD, P = 0.19 for remission; P = 0.41 for response). Adverse event rates were similar for patients receiving EOW and weekly adalimumab. Conclusions: Weekly adalimumab dosing was clinically beneficial for children with Crohn's disease who experienced nonresponse or flare on EOW dosing. No increased safety risks were observed with weekly dosing. PMID:26950307

  9. Comparative Effectiveness of Biosimilar, Reference Product and Other Erythropoiesis-Stimulating Agents (ESAs) Still Covered by Patent in Chronic Kidney Disease and Cancer Patients: An Italian Population-Based Study

    PubMed Central

    2016-01-01

    Background Since 2007 biosimilars of erythropoiesis-stimulating agents (ESAs) are available on the Italian market. Very limited post-marketing data exist on the comparative effectiveness of biosimilar and originator ESAs. Aim This population-based study was aimed to compare the effects of biosimilars, reference product and other ESAs still covered by patent on hemoglobinemia in chronic kidney disease (CKD) and cancer patients in a Local Health Unit (LHU) from Northern Italy. Methods A retrospective cohort study was conducted during the years 2009–2014 using data from Treviso LHU administrative database. Incident ESA users (no ESA dispensing within 6 months prior to treatment start, i.e. index date (ID)) with at least one hemoglobin measurement within one month prior to ID (baseline Hb value) and another measurement between 2nd and 3rd month after ID (follow-up Hb value) were identified. The strength of the consumption (as total number of defined daily dose (DDD) dispensed during the follow-up divided by days of follow-up) and the difference between follow-up and baseline Hb values [delta Hb (ΔHb)] were evaluated. Based on Hb changes, ESA users were classified as non-responders (ΔHb≤0 g/dl), responders (0<ΔHb≤2 g/dl), and highly responders (ΔHb>2 g/dl). A multivariate ordinal logistic regression model to identify predictors for responsiveness to treatment was performed. All analyses were stratified by indication for use and type of dispensed ESA at ID. Results Overall, 1,003 incident ESA users (reference product: 252, 25.1%; other ESAs covered by patent: 303, 30.2%; biosimilars: 448, 44.7%) with CKD or cancer were eligible for the study. No statistically significant difference in the amount of dose dispensed during the follow-up among biosimilars, reference product and other ESAs covered by patent was found in both CKD and cancer. After three months from treatment start, all ESAs increased Hb values on average by 2g/dl. No differences in ΔHb as well as in

  10. Patient satisfaction.

    PubMed

    Prakash, Bhanu

    2010-09-01

    Patient satisfaction is an important and commonly used indicator for measuring the quality in health care. Patient satisfaction affects clinical outcomes, patient retention, and medical malpractice claims. It affects the timely, efficient, and patient-centered delivery of quality health care. Patient satisfaction is thus a proxy but a very effective indicator to measure the success of doctors and hospitals. This article discusses as to how to ensure patient satisfaction in dermatological practice. PMID:21430827

  11. Patient satisfaction.

    PubMed

    Prakash, Bhanu

    2010-09-01

    Patient satisfaction is an important and commonly used indicator for measuring the quality in health care. Patient satisfaction affects clinical outcomes, patient retention, and medical malpractice claims. It affects the timely, efficient, and patient-centered delivery of quality health care. Patient satisfaction is thus a proxy but a very effective indicator to measure the success of doctors and hospitals. This article discusses as to how to ensure patient satisfaction in dermatological practice.

  12. Computerised brain electrical activity findings of parkinson patients suffering from hyperkinetic side effects (hypersensitive dopamine syndrome) and a review of possible sources.

    PubMed

    Fünfgeld, E W

    1995-01-01

    Among 2,000 Park. pat. hospitalised during the years 1988 till 1990 we found 61 pat. with hyperkinetic side-effects in the sequence of a long-term L-dopa treatment. 43 (mean age 64y.) had a complete clinical data set and hyperkinesia ratings (AIMS scale). Compared to the system's data base--none of these patients showed a strickly normal CEEG. Our standard parkinson treatment was established in 1986: L-dopa as low as possible, dopamine agonists low, amantadines as high as necessary, L-deprenyl till 10 mg and anticholinergics--no, if possible. Our pat. group got initially a mean of 508 mg L-dopa, at the end of the study 296 mg. Conventional EEG (Picker-Schwarzer) and CEEG data were recorded (Dynamic Brain Mapping, Itil). Clinical and CEEG follow-up investigations were done after 2 weeks and 2 years. At follow-up, a reduction of the hyperkinesias was found in 43 patients (AIMS scale). 28 pat. received an additional treatment with nootropic drugs, 15 pat. were without this additional therapy. The visually evaluated CEEG at the latter group showed an acceleration ("response") in 33%, but among the patients with nootropic drugs the acceleration was seen in 66%. In patients without nootropics the mean delta power increased, patients additionally treated showed a reduction of delta. In cases of high L-dopa dosage--associated with severe hyperkinetic side effects--more slow waves were registered. The non-nootropic treated patients were divided into two groups--non-responders and the responders: a) Non-responders (n = 10) showed a significant reduction of alpha and a significant increase of delta and theta, b) Responders (5 pat.) without nootropics had a significant reduction of theta and a increase of alpha, but the acceleration is less pronounced than in the responder group with nootropics. Without co-medication a high L-dopa dosage may provoke/facilitate an organic cerebral dysfunction. The nootropic-treated but non-responder group showed no significant changes (n = 13

  13. An ANOCEF genomic and transcriptomic microarray study of the response to radiotherapy or to alkylating first-line chemotherapy in glioblastoma patients

    PubMed Central

    2010-01-01

    Background The molecular characteristics associated with the response to treatment in glioblastomas (GBMs) remain largely unknown. We performed a retrospective study to assess the genomic characteristics associated with the response of GBMs to either first-line chemotherapy or radiation therapy. The gene expression (n = 56) and genomic profiles (n = 67) of responders and non-responders to first-line chemotherapy or radiation therapy alone were compared on Affymetrix Plus 2 gene expression arrays and BAC CGH arrays. Results According to Verhaak et al.'s classification system, mesenchymal GBMs were more likely to respond to radiotherapy than to first-line chemotherapy, whereas classical GBMs were more likely to respond to first-line chemotherapy than to radiotherapy. In patients treated with radiation therapy alone, the response was associated with differential expression of microenvironment-associated genes; the expression of hypoxia-related genes was associated with short-term progression-free survival (< 5 months), whereas the expression of immune genes was associated with prolonged progression-free survival (> 10 months). Consistently, infiltration of the tumor by both CD3 and CD68 cells was significantly more frequent in responders to radiotherapy than in non-responders. In patients treated with first-line chemotherapy, the expression of stem-cell genes was associated with resistance to chemotherapy, and there was a significant association between response to treatment and p16 locus deletions. Consistently, in an independent data set of patients treated with either radiotherapy alone or with both radiotherapy and adjuvant chemotherapy, we found that patients with the p16 deletion benefited from adjuvant chemotherapy regardless of their MGMT promoter methylation status, whereas in patients without the p16 deletion, this benefit was only observed in patients with a methylated MGMT promoter. Conclusion Differential expression of microenvironment genes and p16 locus

  14. The addition of arsenic trioxide to low-dose Ara-C in older patients with AML does not improve outcome.

    PubMed

    Burnett, A K; Hills, R K; Hunter, A; Milligan, D; Kell, J; Wheatley, K; Yin, J; McMullin, M-F; Cahalin, P; Craig, J; Bowen, D; Russell, N

    2011-07-01

    Most patients with acute myeloid leukaemia (AML) are older, with many unsuitable for conventional chemotherapy. Low-dose Ara-C (LDAC) is superior to best supportive care but is still inadequate. The combination of arsenic trioxide (ATO) and LDAC showed promise in an unrandomised study. We report a randomised trial of LDAC versus LDAC+ATO. Patients with AML according to WHO criteria or myelodysplastic syndrome with >10% blasts, considered as unfit for conventional chemotherapy, were randomised between subcutaneous Ara-C (20 mg b.d. for 10 days) and the same LDAC schedule with ATO (0.25 mg/kg) on days 1-5, 9 and 11, for at least four courses every 4 to 6 weeks. Overall 166 patients were entered; the trial was terminated on the advice of the DMC, as the projected benefit was not observed. Overall 14% of patients achieved complete remission (CR) and 7% CRi. Median survival was 5.5 months and 19 months for responders (CR: not reached; CRi: 14 months; non-responders: 4 months). There were no differences in response or survival between the arms. Grade 3/4 cardiac and liver toxicity, and supportive care requirements were greater in the ATO arm. This randomised comparison demonstrates that adding ATO to LDAC provides no benefit for older patients with AML.

  15. Association of the FCGR3A-158F/V gene polymorphism with the response to rituximab treatment in Spanish systemic autoimmune disease patients.

    PubMed

    Robledo, Gema; Márquez, Ana; Dávila-Fajardo, Cristina Lucía; Ortego-Centeno, Norberto; Rubio, José Luis Callejas; Garrido, Enrique de Ramón; Sánchez-Román, Julio; García-Hernández, Francisco J; Ríos-Fernández, Raquel; González-Escribano, Maria Francisca; García, Maria Teresa Camps; Palma, Maria Jesús Castillo; Ayala, Maria Del Mar; Martín, Javier

    2012-12-01

    Rituximab is being used as treatment for systemic autoimmune diseases. The objective of this study was to determine whether the genetic variant in the Fc gamma-receptor III a (FCGR3A) gene, 158F/V, contributes to the observed variation in response to rituximab in patients with systemic autoimmune diseases. DNA samples from 132 Spanish patients with different systemic autoimmune diseases receiving rituximab were genotyped for FCGR3A-158F/V (rs396991) gene polymorphism using the TaqMan(®) allelic discrimination technology. Six months after infusion with rituximab we evaluated the response to the drug: 61% of the patients showed a complete response, partial 27% and 12% did not respond to the treatment. A statistically significant difference was observed in V allele frequency between responder (38%) and nonresponder (16%) patients (p=0.01; odds ratio [OR]=3.24, 95% confidence interval [CI] 1.17-11.1). Rituximab was also more effective in V allele carriers (94%) than in homozygous FF patients (81%): p=0.02; OR=3.96, 95% CI 1.10-17.68. These results suggest that FCGR3A-158F/V (rs396991) gene polymorphism play a role in the response to rituximab in autoimmune diseases. Validation of these findings in independent cohorts is warranted.

  16. Patient-specific electromechanical models of the heart for the prediction of pacing acute effects in CRT: a preliminary clinical validation.

    PubMed

    Sermesant, M; Chabiniok, R; Chinchapatnam, P; Mansi, T; Billet, F; Moireau, P; Peyrat, J M; Wong, K; Relan, J; Rhode, K; Ginks, M; Lambiase, P; Delingette, H; Sorine, M; Rinaldi, C A; Chapelle, D; Razavi, R; Ayache, N

    2012-01-01

    Cardiac resynchronisation therapy (CRT) is an effective treatment for patients with congestive heart failure and a wide QRS complex. However, up to 30% of patients are non-responders to therapy in terms of exercise capacity or left ventricular reverse remodelling. A number of controversies still remain surrounding patient selection, targeted lead implantation and optimisation of this important treatment. The development of biophysical models to predict the response to CRT represents a potential strategy to address these issues. In this article, we present how the personalisation of an electromechanical model of the myocardium can predict the acute haemodynamic changes associated with CRT. In order to introduce such an approach as a clinical application, we needed to design models that can be individualised from images and electrophysiological mapping of the left ventricle. In this paper the personalisation of the anatomy, the electrophysiology, the kinematics and the mechanics are described. The acute effects of pacing on pressure development were predicted with the in silico model for several pacing conditions on two patients, achieving good agreement with invasive haemodynamic measurements: the mean error on dP/dt(max) is 47.5±35mmHgs(-1), less than 5% error. These promising results demonstrate the potential of physiological models personalised from images and electrophysiology signals to improve patient selection and plan CRT. PMID:21920797

  17. Exploring the genes associated with the response to intravenous immunoglobulin in patients with Kawasaki disease using DNA microarray analysis.

    PubMed

    Xing, Yanlin; Wang, Hong; Liu, Xiaomei; Yu, Xianyi; Chen, Rui; Wang, Ce; Yu, Xuexin; Sun, Le

    2015-02-01

    In this study we aimed to screen genes associated with intravenous immunoglobulin (IVIG) responding in patients with Kawasaki disease (KD) and thus explore the underlying molecular mechanism of IVIG resistance. The differentially expressed genes (DEGs) were identified by samr package in R. Then, protein-protein interaction (PPI) networks were constructed by STRING software. We further collected the regulatory data from TRANSFAC database, followed by regulatory interaction network construction. A total 194 of DEGs, including 185 up- and 9 down-regulated DEGs, were identified between IVIG-responding and non-responding patients with KD at acute stage. In contrast, no DEGs were found at convalescent stage. PPI networks and regulatory networks were constructed based on the 185 up-regulated genes at acute stage. The degrees of TFRC (transferrin receptor protein 1) and GADD45A (growth arrest and DNA-damage-inducible alpha) were higher than other genes, and meanwhile MYC (V-Myc Myelocytomatosis Viral Oncogene Homolog) and E2F1 (E2F Transcription Factor 1) were found to be two TFs (transcription factors) with the highest degrees. In conclusions, the response to IVIG in Kawasaki disease patients may be involved in the expression of TFRC, GADD45A, MYC and E2F1. PMID:25449331

  18. Association between early promoter-specific DNA methylation changes and outcome in older acute myeloid leukemia patients.

    PubMed

    Achille, Nicholas J; Othus, Megan; Phelan, Kathleen; Zhang, Shubin; Cooper, Kathrine; Godwin, John E; Appelbaum, Frederick R; Radich, Jerald P; Erba, Harry P; Nand, Sucha; Zeleznik-Le, Nancy J

    2016-03-01

    Treatment options for older patients with acute myeloid leukemia (AML) range from supportive care alone to full-dose chemotherapy. Identifying factors that predict response to therapy may help increase efficacy and avoid toxicity. The phase II SWOG S0703 study investigated the use of hydroxyurea and azacitidine with gemtuzumab ozogamicin in the elderly AML population and found survival rates similar to those expected with standard AML regimens, with less toxicity. As part of this study, global DNA methylation along with promoter DNA methylation and expression analysis of six candidate genes (CDKN2A, CDKN2B, HIC1, RARB, CDH1 and APAF1) were determined before and during therapy to investigate whether very early changes are prognostic for clinical response. Global DNA methylation was not associated with a clinical response. Samples after 3 or 4 days of treatment with azacitidine showed significantly decreased CDKN2A promoter DNA methylation in patients achieving complete remission (CR) compared to those who did not. Samples from day 7 of treatment showed significantly decreased RARB, CDKN2B and CDH1 promoter DNA methylation in responders compared to nonresponders. Gene-specific DNA methylation analysis of peripheral blood samples may help early identification of those older AML patients most likely to benefit from demethylating agent therapy.

  19. Prolactin-induced protein as a potential therapy response marker of adjuvant chemotherapy in breast cancer patients

    PubMed Central

    Jablonska, Karolina; Grzegrzolka, Jedrzej; Podhorska-Okolow, Marzenna; Stasiolek, Mariusz; Pula, Bartosz; Olbromski, Mateusz; Gomulkiewicz, Agnieszka; Piotrowska, Aleksandra; Rys, Janusz; Ambicka, Aleksandra; Ong, Siew Hwa; Zabel, Maciej; Dziegiel, Piotr

    2016-01-01

    Many studies are dedicated to exploring the molecular mechanisms of chemotherapy-resistance in breast cancer (BC). Some of them are focused on searching for candidate genes responsible for this process. The aim of this study was typing the candidate genes associated with the response to standard chemotherapy in the case of invasive ductal carcinoma. Frozen material from 28 biopsies obtained from IDC patients with different responses to chemotherapy were examined using gene expression microarray, Real-Time PCR (RT-PCR) and Western blot (WB). Based on the microarray results, further analysis of candidate gene expression was evaluated in 120 IDC cases by RT-PCR and in 224 IDC cases by immunohistochemistry (IHC). The results were correlated with clinical outcome and molecular subtype of the BC. Gene expression microarray revealed Prolactin-Induced Peptide (PIP) as a single gene differentially expressed in BC therapy responder or non-responder patients (p <0.05). The level of PIP expression was significantly higher in the BC therapy responder group than in the non-responder group at mRNA (p=0.0092) and protein level (p=0.0256). Expression of PIP mRNA was the highest in estrogen receptor positive (ER+) BC cases (p=0.0254) and it was the lowest in triple negative breast cancer (TNBC) (p=0.0336). Higher PIP mRNA expression was characterized by significantly longer disease free survival (DFS, p=0.0093), as well as metastasis free survival (MFS, p=0.0144). Additionally, PIP mRNA and PIP protein expression levels were significantly higher in luminal A than in other molecular subtypes and TNBC. Moreover significantly higher PIP expression was observed in G1, G2 vs. G3 cases (p=0.0027 and p=0.0013, respectively). Microarray analysis characterized PIP gene as a candidate for BC standard chemotherapy response marker. Analysis of clinical data suggests that PIP may be a good prognostic and predictive marker in IDC patients. Higher levels of PIP were related to longer DFS and MFS

  20. Achieving high treatment success for multidrug-resistant TB in Africa: initiation and scale-up of MDR TB care in Ethiopia—an observational cohort study

    PubMed Central

    Meressa, Daniel; Hurtado, Rocío M; Andrews, Jason R; Diro, Ermias; Abato, Kassim; Daniel, Tewodros; Prasad, Paritosh; Prasad, Rebekah; Fekade, Bekele; Tedla, Yared; Yusuf, Hanan; Tadesse, Melaku; Tefera, Dawit; Ashenafi, Abraham; Desta, Girma; Aderaye, Getachew; Olson, Kristian; Thim, Sok; Goldfeld, Anne E

    2015-01-01

    Background In Africa, fewer than half of patients receiving therapy for multidrug-resistant TB (MDR TB) are successfully treated, with poor outcomes reported for HIV-coinfected patients. Methods A standardised second-line drug (SLD) regimen was used in a non-governmental organisation–Ministry of Health (NGO-MOH) collaborative community and hospital-based programme in Ethiopia that included intensive side effect monitoring, adherence strategies and nutritional supplementation. Clinical outcomes for patients with at least 24 months of follow-up were reviewed and predictors of treatment failure or death were evaluated by Cox proportional hazards models. Results From February 2009 to December 2014, 1044 patients were initiated on SLD. 612 patients with confirmed or presumed MDR TB had ≥24 months of follow-up, 551 (90.0%) were confirmed and 61 (10.0%) were suspected MDR TB cases. 603 (98.5%) had prior TB treatment, 133 (21.7%) were HIV coinfected and median body mass index (BMI) was 16.6. Composite treatment success was 78.6% with 396 (64.7%) cured, 85 (13.9%) who completed treatment, 10 (1.6%) who failed, 85 (13.9%) who died and 36 (5.9%) who were lost to follow-up. HIV coinfection (adjusted HR (AHR): 2.60, p<0.001), BMI (AHR 0.88/kg/m2, p=0.006) and cor pulmonale (AHR 3.61, p=0.003) and confirmed MDR TB (AHR 0.50, p=0.026) were predictive of treatment failure or death. Conclusions We report from Ethiopia the highest MDR TB treatment success outcomes so far achieved in Africa, in a setting with severe resource constraints and patients with advanced disease. Intensive treatment of adverse effects, nutritional supplementation, adherence interventions and NGO-MOH collaboration were key strategies contributing to success. We argue these approaches should be routinely incorporated into programmes. PMID:26506854

  1. Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients

    PubMed Central

    Radvanyi, Laszlo G.; Bernatchez, Chantale; Zhang, Minying; Fox, Patricia S.; Miller, Priscilla; Chacon, Jessica; Wu, Richard; Lizee, Gregory; Mahoney, Sandy; Alvarado, Gladys; Glass, Michelle; Johnson, Valen E.; McMannis, John D.; Shpall, Elizabeth; Prieto, Victor; Papadopoulos, Nicholas; Kim, Kevin; Homsi, Jade; Bedikian, Agop; Hwu, Wen-Jen; Patel, Sapna; Ross, Merrick I.; Lee, Jeffrey E.; Gershenwald, Jeffrey E.; Lucci, Anthony; Royal, Richard; Cormier, Janice N.; Davies, Michael A.; Mansaray, Rahmatu; Fulbright, Orenthial J.; Toth, Christopher; Ramachandran, Renjith; Wardell, Seth; Gonzalez, Audrey; Hwu, Patrick

    2012-01-01

    Purpose Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) is a promising treatment for metastatic melanoma unresponsive to conventional therapies. We report here on the results of an ongoing Phase II clinical trial testing the efficacy of ACT using TIL in metastatic melanoma patients and the association of specific patient clinical characteristics and the phenotypic attributes of the infused TIL with clinical response. Experimental Design Altogether, 31 transiently lymphodepleted patients were treated with their expanded TIL followed by two cycles of high-dose (HD) IL-2 therapy. The effects of patient clinical features and the phenotypes of the T-cells infused on clinical response were determined. Results Overall, 15/31 (48.4%) patients had an objective clinical response using immune-related response criteria (irRC), with two patients (6.5%) having a complete response. Progression-free survival of >12 months was observed for 9/15 (60%) of the responding patients. Factors significantly associated with objective tumor regression included a higher number of TIL infused, a higher proportion of CD8+ T-cells in the infusion product, a more differentiated effector phenotype of the CD8+ population and a higher frequency of CD8+ T-cells co-expressing the negative costimulation molecule “B- and T-lymphocyte attenuator” (BTLA). No significant difference in telomere lengths of TIL between responders and non-responders was identified. Conclusion These results indicate that immunotherapy with expanded autologous TIL is capable of achieving durable clinical responses in metastatic melanoma patients and that CD8+ T-cells in the infused TIL, particularly differentiated effectors cells and cells expressing BTLA, are associated with tumor regression. PMID:23032743

  2. Functional Interference Clusters in Cancer Patients With Bone Metastases: A Secondary Analysis of RTOG 9714

    SciTech Connect

    Chow, Edward; James, Jennifer; Barsevick, Andrea; Hartsell, William; Ratcliffe, Sarah; Scarantino, Charles; Ivker, Robert; Roach, Mack; Suh, John; Petersen, Ivy; Konski, Andre; Demas, William; Bruner, Deborah

    2010-04-15

    Purpose: To explore the relationships (clusters) among the functional interference items in the Brief Pain Inventory (BPI) in patients with bone metastases. Methods: Patients enrolled in the Radiation Therapy Oncology Group (RTOG) 9714 bone metastases study were eligible. Patients were assessed at baseline and 4, 8, and 12 weeks after randomization for the palliative radiotherapy with the BPI, which consists of seven functional items: general activity, mood, walking ability, normal work, relations with others, sleep, and enjoyment of life. Principal component analysis with varimax rotation was used to determine the clusters between the functional items at baseline and the follow-up. Cronbach's alpha was used to determine the consistency and reliability of each cluster at baseline and follow-up. Results: There were 448 male and 461 female patients, with a median age of 67 years. There were two functional interference clusters at baseline, which accounted for 71% of the total variance. The first cluster (physical interference) included normal work and walking ability, which accounted for 58% of the total variance. The second cluster (psychosocial interference) included relations with others and sleep, which accounted for 13% of the total variance. The Cronbach's alpha statistics were 0.83 and 0.80, respectively. The functional clusters changed at week 12 in responders but persisted through week 12 in nonresponders. Conclusion: Palliative radiotherapy is effective in reducing bone pain. Functional interference component clusters exist in patients treated for bone metastases. These clusters changed over time in this study, possibly attributable to treatment. Further research is needed to examine these effects.

  3. Serum phosphate levels reflect responses to cardiac resynchronization therapy in chronic heart failure patients

    PubMed Central

    Kamiyama, Yoshiyuki; Suzuki, Hitoshi; Yamada, Shinya; Kaneshiro, Takashi; Takeishi, Yasuchika

    2014-01-01

    Background Recent studies have shown that high levels of serum phosphate are associated with adverse cardiovascular events. However, little is known about the relation between phosphate levels and improvement of cardiac function in chronic heart failure (CHF) patients who underwent cardiac resynchronization therapy (CRT). The purpose of this study was to examine whether serum phosphate levels were able to predict responders to CRT and adverse cardiac events. Methods The study population consisted of 30 CHF patients (24 males, mean age 65.7±8.5 years) who received CRT with defibrillator (CRT-D) implantation. Levels of serum phosphate were measured before, and 6 months after, CRT-D implantation. Left ventricular end-diastolic volume and end-systolic volume were assessed simultaneously by echocardiography. In addition, the rate of re-hospitalization due to worsening of heart failure was investigated. All patients were divided into 2 groups: responders (Group-R, n=18) and non-responders (Group-NR, n=12) to CRT-D. Responders were defined as patients who showed >15% reduction in left ventricular end-systolic volume. We compared these parameters between the 2 groups. Results Serum phosphate levels were significantly lower in Group-R than in Group-NR (3.3±0.2 vs. 3.7±0.4 mg/dL, p=0.01). The rate of re-hospitalization was lower in Group-R than in Group-NR (0% vs. 33%, p=0.018). Multivariate analysis showed that serum phosphate levels had a predictive power to determine responders to CRT (odds ratio 0.008, 95% confidence interval 0.000–0.348, p=0.015). Conclusions These results suggest that serum phosphate levels might predict both responders to CRT, and adverse cardiac events, in CHF patients with CRT-D. PMID:26336522

  4. Baseline MxA mRNA Expression Predicts Interferon Beta Response in Multiple Sclerosis Patients

    PubMed Central

    Matas, Elisabet; Bau, Laura; Martínez-Iniesta, María; Romero-Pinel, Lucía; Mañé, M. Alba; Cobo-Calvo, Álvaro; Martínez-Yélamos, Sergio

    2014-01-01

    Background Myxovirus resistance protein A (MxA) is a molecule induced after interferon-beta injection, mostly used to evaluate its bioactivity. There is little available data on clinical utility of baseline MxA mRNA status. The objective of the study is to investigate whether baseline MxA mRNA expression can predict relapse and disease progression in multiple sclerosis patients treated with interferon-beta. Methods Baseline blood samples were obtained before the first interferon-beta dose was administered to evaluate MxA mRNA expression using real-time polymerase chain reaction (PCR). Demographic and clinical variables were prospectively recorded to define treatment responder and non responder groups. Results 104 patients were included in the study. Baseline MxA mRNA expression was significantly lower in the group of patients who met the definition of responders (1.07 vs 1.95, Student t test, p<0.0001). A threshold of 1.096 was established using Receiver Operating Characteristic analysis to differentiate between responders and non-responders (sensitivity 73.9%, specificity 69.0%). Survival analysis using this threshold showed that time to next relapse (p<0.0001) and to EDSS progression (p = 0.01) were significantly higher in patients with lower MxA titers. Conclusion The results suggest that baseline MxA mRNA levels may be useful for predicting whether multiple sclerosis patients will respond or not to interferon-beta treatment. PMID:25396411

  5. Laparoscopic ovarian treatment in infertile patients with polycystic ovarian syndrome (PCOS): endocrine changes and clinical outcome.

    PubMed

    Liguori, G; Tolino, A; Moccia, G; Scognamiglio, G; Nappi, C

    1996-08-01

    During the years 1991-1994, 97 anovulatory infertile women with polycystic ovarian syndrome (PCOS) were treated with laparoscopic electrocautery of the ovarian surface after they had failed to ovulate under ovarian stimulation. To assess the endocrinological and clinical outcome and in an attempt to determine the mechanism of action, the serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), androstenedione, testosterone and dehydroepiandrosterone sulfate (DHEAS) were determined before and after laparoscopic ovarian cautery. Fifty regularly cycling women undergoing laparoscopy for investigation of infertility or tubal ligation served as controls. In patients with PCOS but not in controls, the reduction of androgen levels and normalization of cycle length were highly significant. In contrast, LH and FSH levels rose during the first 2 days after the operation. These results resemble those reported after ovarian wedge resection. Ovulation was obtained in 90% (81 of 90) and pregnancy in 81.1% (73 of 90) of the patients; that increased to 84.4%, including the non-responders (nine patients) treated with clomiphene citrate (CC), after electrocautery. The response to ovarian electrocautery was influenced by body weight, with an ovulation rate of 95-96% in the slim and moderately obese women, decreasing to 81-82% in the really obese ones. When ovulation was established, the pregnancy rate was independent of body weight. However, a striking relationship was detected between smoking habits and pregnancy rate subsequent to ovarian electrocautery, ranging from 24% in smokers to 92% in non-smoking couples. In 30 second-look operations, de novo adhesions were found in 23.3% of the patients (7 of 30). Therefore, ovarian electrocautery is an effective procedure to improve the intraovarian mechanism of selecting a dominant follicle for patients with PCOS in whom initial medical management fails, and it appears to be one of the possible treatments for this

  6. Cost-Effectiveness of Capsaicin 8% Patch Compared with Pregabalin for the Treatment of Patients with Peripheral Neuropathic Pain in Scotland.

    PubMed

    Mankowski, Colette; Patel, Sachin; Trueman, David; Bentley, Anthony; Poole, Chris

    2016-01-01

    We evaluated the cost-effectiveness of capsaicin 8% patch (QUTENZA™) versus pregabalin in patients with PNP from the perspective of the National Health Service (NHS) and Personal and Social Services in Scotland, UK. A decision-tree cost-effectiveness model was developed for non-diabetic patients with peripheral neuropathic pain (PNP) who were pregabalin-naïve and had not achieved adequate pain relief or tolerated conventional first- or second-line treatments. Patients entering the model received either a single application of capsaicin 8% patch or titrated daily dosing with pregabalin; after 8 weeks patients were classified as responders, non-responders, or were assumed to discontinue treatment due to intolerable adverse events. Responders continued to receive baseline treatment at intervals observed in clinical practice. Non-responders and those who discontinued treatment were assumed to receive last-line therapy (duloxetine). The base-case time horizon was 2 years. Model inputs for effectiveness, discontinuations and health-state utilities were taken from a head-to-head non-inferiority study (ELEVATE, NCT01713426). Other inputs were obtained from published sources or clinical expert opinion. Costs were expressed in GBP 2013/14. Results were presented as incremental cost-effectiveness ratios (ICER), i.e. cost per quality-adjusted life-year (QALY) gained. Model assumptions were tested with scenario analyses. Parameter uncertainty was tested using one-way and probabilistic sensitivity analyses. Compared with dose-optimized pregabalin, capsaicin 8% patch was the dominant treatment strategy (total cost difference, -£11; total QALY gain, 0.049). Capsaicin 8% patch was also the dominant treatment strategy versus pregabalin in 6 out of 7 scenario analyses. The model was most sensitive to variation in time to capsaicin 8% patch retreatment (maximum ICER, £7,951/QALY at lower-bound 95% confidence interval). At a willingness-to-pay threshold of £20,000/QALY, the

  7. Cost-Effectiveness of Capsaicin 8% Patch Compared with Pregabalin for the Treatment of Patients with Peripheral Neuropathic Pain in Scotland.

    PubMed

    Mankowski, Colette; Patel, Sachin; Trueman, David; Bentley, Anthony; Poole, Chris

    2016-01-01

    We evaluated the cost-effectiveness of capsaicin 8% patch (QUTENZA™) versus pregabalin in patients with PNP from the perspective of the National Health Service (NHS) and Personal and Social Services in Scotland, UK. A decision-tree cost-effectiveness model was developed for non-diabetic patients with peripheral neuropathic pain (PNP) who were pregabalin-naïve and had not achieved adequate pain relief or tolerated conventional first- or second-line treatments. Patients entering the model received either a single application of capsaicin 8% patch or titrated daily dosing with pregabalin; after 8 weeks patients were classified as responders, non-responders, or were assumed to discontinue treatment due to intolerable adverse events. Responders continued to receive baseline treatment at intervals observed in clinical practice. Non-responders and those who discontinued treatment were assumed to receive last-line therapy (duloxetine). The base-case time horizon was 2 years. Model inputs for effectiveness, discontinuations and health-state utilities were taken from a head-to-head non-inferiority study (ELEVATE, NCT01713426). Other inputs were obtained from published sources or clinical expert opinion. Costs were expressed in GBP 2013/14. Results were presented as incremental cost-effectiveness ratios (ICER), i.e. cost per quality-adjusted life-year (QALY) gained. Model assumptions were tested with scenario analyses. Parameter uncertainty was tested using one-way and probabilistic sensitivity analyses. Compared with dose-optimized pregabalin, capsaicin 8% patch was the dominant treatment strategy (total cost difference, -£11; total QALY gain, 0.049). Capsaicin 8% patch was also the dominant treatment strategy versus pregabalin in 6 out of 7 scenario analyses. The model was most sensitive to variation in time to capsaicin 8% patch retreatment (maximum ICER, £7,951/QALY at lower-bound 95% confidence interval). At a willingness-to-pay threshold of £20,000/QALY, the

  8. Mycobacterium tuberculosis transmission in a country with low tuberculosis incidence: role of immigration and HIV infection.

    PubMed

    Fenner, Lukas; Gagneux, Sebastien; Helbling, Peter; Battegay, Manuel; Rieder, Hans L; Pfyffer, Gaby E; Zwahlen, Marcel; Furrer, Hansjakob; Siegrist, Hans H; Fehr, Jan; Dolina, Marisa; Calmy, Alexandra; Stucki, David; Jaton, Katia; Janssens, Jean-Paul; Stalder, Jesica Mazza; Bodmer, Thomas; Ninet, Beatrice; Böttger, Erik C; Egger, Matthias

    2012-02-01

    Immigrants from high-burden countries and HIV-coinfected individuals are risk groups for tuberculosis (TB) in countries with low TB incidence. Therefore, we studied their role in transmission of Mycobacterium tuberculosis in Switzerland. We included all TB patients from the Swiss HIV Cohort and a sample of patients from the national TB registry. We identified molecular clusters by spoligotyping and mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) analysis and used weighted logistic regression adjusted for age and sex to identify risk factors for clustering, taking sampling proportions into account. In total, we analyzed 520 TB cases diagnosed between 2000 and 2008; 401 were foreign born, and 113 were HIV coinfected. The Euro-American M. tuberculosis lineage dominated throughout the study period (378 strains; 72.7%), with no evidence for another lineage, such as the Beijing genotype, emerging. We identified 35 molecular clusters with 90 patients, indicating recent transmission; 31 clusters involved foreign-born patients, and 15 involved HIV-infected patients. Birth origin was not associated with clustering (adjusted odds ratio [aOR], 1.58; 95% confidence interval [CI], 0.73 to 3.43; P = 0.25, comparing Swiss-born with foreign-born patients), but clustering was reduced in HIV-infected patients (aOR, 0.49; 95% CI, 0.26 to 0.93; P = 0.030). Cavitary disease, male sex, and younger age were all associated with molecular clustering. In conclusion, most TB patients in Switzerland were foreign born, but transmission of M. tuberculosis was not more common among immigrants and was reduced in HIV-infected patients followed up in the national HIV cohort study. Continued access to health services and clinical follow-up will be essential to control TB in this population.

  9. Improvements in clinical response between 12 and 24 weeks in patients with rheumatoid arthritis on etanercept therapy with or without methotrexate

    PubMed Central

    Kavanaugh, A; Klareskog, L; van der Heijde, D; Li, J; Freundlich, B; Hooper, M

    2008-01-01

    Background: Whereas many patients respond quickly to treatment with tumour necrosis factor (TNF) inhibitors, some patients may experience significant but delayed responses. Objective: To evaluate the clinical response between 12 and 24 weeks in subjects with rheumatoid arthritis from the Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes. Methods: Clinical response was assessed at 24 weeks in 12-week non-responders, according to American College of Rheumatology (ACR) response criteria. The proportion of subjects who successfully maintained response to 52 weeks was analysed, as were radiographic outcomes. Results: Data from 682 subjects were included in the analysis. Non and partial responders in all three groups (etanercept, methotrexate and etanercept plus methotrexate) at week 12 showed an improvement in responses at week 24. Over 80% of the week 24 ACR20/50/70 responders in the etanercept plus methotrexate arm sustained their response to 52 weeks. In the etanercept arms, a delayed clinical response was not associated with increased radiographic progression at week 52. Conclusion: A significant proportion of non and partial responders to etanercept with or without methotrexate therapy at week 12 achieved a good clinical response or improved their overall clinical response at week 24. Discontinuing TNF inhibitor therapy at 12 weeks may be premature in some rheumatoid arthritis patients. PMID:18535115

  10. Impact of IL28B gene polymorphisms rs8099917 and rs12980275 on response to pegylated interferon-α/ribavirin therapy in chronic hepatitis C genotype 4 patients

    PubMed Central

    Khattab, Mahmoud A; Abdelghany, Hend M; Ramzy, Maggie M; Khairy, Rasha M

    2016-01-01

    Abstract Host genetic factors may predict the outcome and treatment response in hepatitis C virus (HCV) infection. One of these factors is the single nucleotide polymorphisms of the interleukin 28B (IL28B) gene. We sought to evaluate the outcome of pegylated interferon and ribavirin therapy in association with IL-28B rs8099917 and rs12980275 in patients infected with HCV genotype 4. A total of 180 patients with chronic hepatitis C were selected from Egyptians who have received combined therapy with pegylated interferon and ribavirin for 6 months and their response was evaluated after follow-up at 0, 6, 12, 24 and 48 weeks from the beginning of the therapy. Blood samples were collected from responders and non-responders. Genomic DNA was extracted from whole blood and genotyping was carried out by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Our results showed that TT genotype of rs8099917 was associated with higher sustained viral response (SVR) rates and G allele represented a risk factor for failure of response (OR = 3.7, CI = 1.8:7.64) while rs12980275 was not significantly associated with SVR in genotype 4 Egyptian patients. The determination of IL-28B SNPs may be useful in enhancing correct prediction of SVR achievement in treating this group of genotype 4 patients.

  11. Pharmacogenetic analysis of cinacalcet response in secondary hyperparathyroidism patients

    PubMed Central

    Jeong, Sohyun; Kim, In-Wha; Oh, Kook-Hwan; Han, Nayoung; Joo, Kwon Wook; Kim, Hyo Jin; Oh, Jung Mi

    2016-01-01

    Background Secondary hyperparathyroidism (SHPT) is one of the major risk factors of morbidity and mortality in end-stage renal disease. Cinacalcet effectively controls SHPT without causing hypercalcemia and hyperphosphatemia. However, there is significant inter-individual response variance to cinacalcet treatment. Therefore, we aimed to evaluate the genetic effects related with parathyroid hormone regulation as factors for cinacalcet response variance. Methods Patients with a diagnosis of SHPT based on intact parathyroid hormone (iPTH) >300 pg/mL on dialysis were included in this study. They were over 18 years and have been treated by cinacalcet for more than 3 months. Responders and nonresponders were grouped by the serum iPTH changes. Twenty-four single nucleotide polymorphisms of CASR, VDR, FGFR1, KL, ALPL, RGS14, NR4A2, and PTHLH genes were selected for the pharmacogenetic analysis. Results After adjusting for age, sex, and calcium level, CASR rs1042636 (odds ratio [OR]: 0.066, P=0.027) and rs1802757 (OR: 10.532, P=0.042) were associated with cinacalcet response. The association of haplotypes of CASR rs1042636, rs10190, and rs1802757; GCC (OR: 0.355, P=0.015); and ATT (OR: 2.769, P=0.014) with cinacalcet response was also significant. Conclusion We obtained supporting information of the associations between cinacalcet response and CASR polymorphisms. CASR single nucleotide polymorphisms (SNPs) rs1802757, rs1042636, and haplotypes of rs1042636, rs10190, and rs1802757 were significantly associated with cinacalcet response variance. PMID:27468225

  12. A study into the genetic basis of aspirin resistance in Pakistani patients with coronary artery disease.

    PubMed

    Mukarram, Osama; Akhtar, Naveed; Junaid, Ayesha; Mohyuddin, Aisha

    2016-07-01

    Aspirin is a key player in the management and prevention of stroke and myocardial infarction in patients with atherothrombosis. About 12% of Pakistanis suffering from coronary artery disease are resistant to aspirin's effects. Clinical, biochemical and genetic factors are known to be responsible for this phenomenon. We conducted this study to investigate whether previously studied polymorphisms in COX-1, GPIIIa, GPIa and P2RYI genes could be the cause of aspirin resistance in our population. Blood samples were collected from 29 aspirin non-responders and 60 ethnically matched responders. Aspirin response assay was performed on IMPACT-R and DNA prepared from blood using the phenol: chloroform method. Genotyping was carried out for four SNPS including COX-1 C50T (rs3842787), GPIIIA PIA1/A2 polymorphism (rs5918), GPIA C807T (rs1126643) and p2RY1 C893T (rs1065776). No statistically significant differences were observed in the allele or genotype frequencies between the aspirin non responders and responders indicating the possible involvement of different genetic determinants of aspirin resistance in our population. This study paves the way for further research into the field of aspirin resistance in Pakistan. PMID:27393450

  13. A study into the genetic basis of aspirin resistance in Pakistani patients with coronary artery disease.

    PubMed

    Mukarram, Osama; Akhtar, Naveed; Junaid, Ayesha; Mohyuddin, Aisha

    2016-07-01

    Aspirin is a key player in the management and prevention of stroke and myocardial infarction in patients with atherothrombosis. About 12% of Pakistanis suffering from coronary artery disease are resistant to aspirin's effects. Clinical, biochemical and genetic factors are known to be responsible for this phenomenon. We conducted this study to investigate whether previously studied polymorphisms in COX-1, GPIIIa, GPIa and P2RYI genes could be the cause of aspirin resistance in our population. Blood samples were collected from 29 aspirin non-responders and 60 ethnically matched responders. Aspirin response assay was performed on IMPACT-R and DNA prepared from blood using the phenol: chloroform method. Genotyping was carried out for four SNPS including COX-1 C50T (rs3842787), GPIIIA PIA1/A2 polymorphism (rs5918), GPIA C807T (rs1126643) and p2RY1 C893T (rs1065776). No statistically significant differences were observed in the allele or genotype frequencies between the aspirin non responders and responders indicating the possible involvement of different genetic determinants of aspirin resistance in our population. This study paves the way for further research into the field of aspirin resistance in Pakistan.

  14. Geometrical Measures Obtained from Pretreatment Postcontrast T1 Weighted MRIs Predict Survival Benefits from Bevacizumab in Glioblastoma Patients

    PubMed Central

    Sepúlveda, Juan M.; Peralta, Sergi; Gil-Gil, Miguel J.; Reynes, Gaspar; Herrero, Ana; De Las Peñas, Ramón; Luque, Raquel; Capellades, Jaume

    2016-01-01

    Background Antiangiogenic therapies for glioblastoma (GBM) such as bevacizumab (BVZ), have been unable to extend survival in large patient cohorts. However, a subset of patients having angiogenesis-dependent tumors might benefit from these therapies. Currently, there are no biomarkers allowing to discriminate responders from non-responders before the start of the therapy. Methods 40 patients from the randomized GENOM009 study complied the inclusion criteria (quality of images, clinical data available). Of those, 23 patients received first line temozolomide (TMZ) for eight weeks and then concomitant radiotherapy and TMZ. 17 patients received BVZ+TMZ for seven weeks and then added radiotherapy to the treatment. Clinical variables were collected, tumors segmented and several geometrical measures computed including: Contrast enhancing (CE), necrotic, and total volumes; equivalent spherical CE width; several geometric measures of the CE ‘rim’ geometry and a set of image texture measures. The significance of the results was studied using Kaplan-Meier and Cox proportional hazards analysis. Correlations were assessed using Spearman correlation coefficients. Results Kaplan-Meier and Cox proportional hazards analysis showed that total, CE and inner volume (p = 0.019, HR = 4.258) and geometric heterogeneity of the CE areas (p = 0.011, HR = 3.931) were significant parameters identifying response to BVZ. The group of patients with either regular CE areas (small geometric heterogeneity, median difference survival 15.88 months, p = 0.011) or those with small necrotic volume (median survival difference 14.50 months, p = 0.047) benefited substantially from BVZ. Conclusion Imaging biomarkers related to the irregularity of contrast enhancing areas and the necrotic volume were able to discriminate GBM patients with a substantial survival benefit from BVZ. A prospective study is needed to validate our results. PMID:27557121

  15. Treatment approach in patients with hyperbilirubinemia secondary to liver metastases in gastrointestinal malignancies: a case series and review of literature

    PubMed Central

    Quidde, Julia; Azémar, Marc; Bokemeyer, Carsten; Arnold, Dirk; Stein, Alexander

    2016-01-01

    Background: Treatment of patients with severe liver dysfunction including hyperbilirubinemia secondary to liver metastases of gastrointestinal (GI) cancer is challenging. Regimen of oxaliplatin and fluoropyrimidine (FP)/folinic acid (FA) ± a monoclonal antibody (moAb), represents a feasible option considering the pharmacokinetics. Clinical data on the respective dosage and tolerability are limited and no recommendations are available. Methods: Consecutive patients with severe hyperbilirubinemia [>2 × upper limit of the normal range (ULN) and >2.4 mg/dl] due to liver metastases of GI cancer without options for drainage receiving oxaliplatin, FP/FA ± moAb were analyzed. To collect further data a review of the literature was performed. Results: A total of 12 patients were identified between 2011 and 2015. At treatment start, median bilirubin level was 6.1 mg/dl (>5 × ULN, range 2.7–13.6). The majority of patients (n = 11) received dose-reduced regimen with oxaliplatin (60–76%) and FP/FA (0–77%), rapidly escalating to full dose regimen. During treatment, bilirubin levels dropped more than 50% within 8 weeks or normalized within 12 weeks in 6 patients (responders). Median overall survival was 5.75 months (range 1.0–16.0 months) but was significantly prolonged in responders compared to nonresponders [9.7 and 3.0 months, p = 0.026 (two-sided test); 95% confidence interval (CI): 1.10–10.22]. In addition, case reports or series comprising a further 26 patients could be identified. Based on the obtained data a treatment algorithm was developed. Conclusion: Treatment with oxaliplatin, FP/FA ± moAb is feasible and may derive relevant benefits in patients with severe liver dysfunction caused by GI cancer liver metastases without further options of drainage. PMID:27239232

  16. Panobinostat as part of induction and maintenance for elderly patients with newly diagnosed acute myeloid leukemia: phase Ib/II panobidara study

    PubMed Central

    Ocio, Enrique M.; Herrera, Pilar; Olave, María-Teresa; Castro, Nerea; Pérez-Simón, José A.; Brunet, Salut; Oriol, Albert; Mateo, Marta; Sanz, Miguel-Ángel; López, Javier; Montesinos, Pau; Chillón, María-Carmen; Prieto-Conde, María-Isabel; Díez-Campelo, María; González, Marcos; Vidriales, María-Belén; Mateos, María-Victoria; San Miguel, Jesús F.

    2015-01-01

    This phase Ib/II trial combined the pan-deacetylase inhibitor panobinostat with chemotherapy followed by panobinostat maintenance in elderly patients with newly diagnosed acute myeloid leukemia. Patients with prior history of myelodysplastic syndrome were excluded and 38 evaluable patients were included in the study (median age: 71 years; range: 65–83). Study patients received an induction with idarubicin (8 mg/m2 iv days 1–3) plus cytarabine (100 mg/m2 iv days 1–7) plus panobinostat po at escalating doses (days 8, 10, 12, 15, 17 and 19) that could be repeated in non-responding patients. Patients achieving complete remission received a consolidation cycle with the same schema, followed by panobinostat maintenance (40 mg po 3 days/week) every other week until progression. Thirty-one patients were treated at the maximum tolerated dose of panobinostat in the combination (10 mg) with good tolerability. Complete remission rate was 64% with a time to relapse of 17.0 months (12.8–21.1). Median overall survival for the whole series was 17 months (5.5–28.4). Moreover, in 4 of 5 patients with persistent minimal residual disease before maintenance, panobinostat monotherapy reduced its levels, with complete negativization in two of them. Maintenance phase was well tolerated. The most frequent adverse events were thrombocytopenia (25% grades 3/4), and gastrointestinal toxicity, asthenia and anorexia (mainly grades 1/2). Five patients required dose reduction during this phase, but only one discontinued therapy due to toxicity. These results suggest that panobinostat is one of the first novel agents with activity in elderly acute myeloid leukemia patients, and suggest further investigation is warranted, particularly in the context of maintenance therapy. This trial is registered at clinicaltrials.gov identifier: 00840346. PMID:26160880

  17. Psychopathology and treatment responsiveness of patients with first-episode schizophrenia.

    PubMed

    Cesková, Eva; Prikryl, Radovan; Kaspárek, Tomás; Ondrusová, Marta

    2005-06-01

    One hundred and four male patients hospitalized for the first time with the diagnosis of first-episode schizophrenia were comprehensively assessed on admission and discharge. Psychopathology, treatment response, and remission rates were evaluated (based on the Positive and Negative Syndrome Scale (PANSS), severity of symptoms only). On admission, the most frequently observed symptoms were lack of judgment and insight (87.6%), suspiciousness/feelings of persecution (82.3%), delusions (77%), poor attention (70%), disturbance of volition (65.4%), conceptual disorganization (64.7%), and active social avoidance (64%). Except for delusions and hallucinations, the positive items of the PANSS correlated significantly with negative symptoms, and conceptual disorganization correlated with the greatest number of negative symptoms. Individual negative symptoms were present in about half the patients. At discharge, the most frequent symptoms were again lack of judgment and insight (in 55.7%), and for negative symptoms they were blunted affect (22.1%), emotional withdrawal (21.2%), and passive/apathetic social withdrawal (19.5%). The positive symptoms of suspiciousness/feelings of persecution and grandiosity persisted in 20.6% of patients. On average, all symptoms were significantly reduced 44 days after admission. The negative symptoms improved less, compared with the positive ones. At discharge there was a high rate of responders (response defined as minimal 30% reduction of total PANSS): 73% and 74% of patients fulfilled the criteria for remission. On admission, the responders (n = 76) had significantly higher scores of most symptoms, both positive and negative ones than nonresponders (n = 28). PMID:18568064

  18. Protease inhibitors partially overcome the interferon nonresponse phenotype in patients with chronic hepatitis C.

    PubMed

    Duarte-Rojo, A; Fischer, S E; Adeyi, O; Zita, D; Deneke, M G; Selzner, N; Chen, L; Malespin, M; Cotler, S J; McGilvray, I D; Feld, J J

    2016-05-01

    The outcome of triple therapy with protease inhibitors (PI) depends on the intrinsic response to interferon. Interferon-stimulated gene (ISG) expression differs by cell type in the liver and is a strong predictor of interferon responsiveness. Patients who respond well to interferon have low/absent ISG expression in hepatocytes but significant ISG expression in macrophages. Nonresponders (NRs) show the opposite pattern. We aimed to determine the association between cell-type-specific ISG staining and treatment outcome with PI-based triple therapy. Liver biopsy tissue from consecutive patients treated with boceprevir or telaprevir with peginterferon and ribavirin was stained for myxovirus A (MxA). Staining was scored 0-3 in macrophages (M-MxA) and hepatocytes (H-MxA), and IL28B genotyping was performed. Of 56 patients included 41 achieved SVR (73%) (sustained virological response), 2 (4%) relapsed, 10 (18%) were NRs, and 3 (5%) were lost to follow-up. Median M-MxA staining was stronger and H-MxA staining was weaker in patients who achieved SVR. MxA staining correlated with IL28B genotype and with the HCV RNA decline during lead-in phase. However, unlike with dual therapy, the negative predictive value (NPV) of absent or weak M-MxA staining was poor (42%), while the positive predictive value improved (93%). Although by multivariable logistic regression M-MxA staining was significantly associated with SVR (OR 4.35, 1.32-14.28, P = 0.012), the predictive ability was inadequate to withhold therapy. The interaction between macrophages and hepatocytes plays a critical role in interferon responsiveness; however, the addition of a PI at least partially overcomes the interferon nonresponse phenotype making the predictive ability of ISG staining less clinically useful. PMID:26710754

  19. Clinical response to chemotherapy in oesophageal adenocarcinoma patients is linked to defects in mitochondria.

    PubMed

    Aichler, Michaela; Elsner, Mareike; Ludyga, Natalie; Feuchtinger, Annette; Zangen, Verena; Maier, Stefan K; Balluff, Benjamin; Schöne, Cédrik; Hierber, Ludwig; Braselmann, Herbert; Meding, Stephan; Rauser, Sandra; Zischka, Hans; Aubele, Michaela; Schmitt, Manfred; Feith, Marcus; Hauck, Stefanie M; Ueffing, Marius; Langer, Rupert; Kuster, Bernhard; Zitzelsberger, Horst; Höfler, Heinz; Walch, Axel K

    2013-08-01

    Chemotherapeutic drugs kill cancer cells, but it is unclear why this happens in responding patients but not in non-responders. Proteomic profiles of patients with oesophageal adenocarcinoma may be helpful in predicting response and selecting more effective treatment strategies. In this study, pretherapeutic oesophageal adenocarcinoma biopsies were analysed for proteomic changes associated with response to chemotherapy by MALDI imaging mass spectrometry. Resulting candidate proteins were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and investigated for functional relevance in vitro. Clinical impact was validated in pretherapeutic biopsies from an independent patient cohort. Studies on the incidence of these defects in other solid tumours were included. We discovered that clinical response to cisplatin correlated with pre-existing defects in the mitochondrial respiratory chain complexes of cancer cells, caused by loss of specific cytochrome c oxidase (COX) subunits. Knockdown of a COX protein altered chemosensitivity in vitro, increasing the propensity of cancer cells to undergo cell death following cisplatin treatment. In an independent validation, patients with reduced COX protein expression prior to treatment exhibited favourable clinical outcomes to chemotherapy, whereas tumours with unchanged COX expression were chemoresistant. In conclusion, previously undiscovered pre-existing defects in mitochondrial respiratory complexes cause cancer cells to become chemosensitive: mitochondrial defects lower the cells' threshold for undergoing cell death in response to cisplatin. By contrast, cancer cells with intact mitochondrial respiratory complexes are chemoresistant and have a high threshold for cisplatin-induced cell death. This connection between mitochondrial respiration and chemosensitivity is relevant to anticancer therapeutics that target the mitochondrial electron transport chain.

  20. Evaluation of early weight loss thresholds for identifying non-responders to an intensive lifestyle intervention

    PubMed Central

    Unick, Jessica L.; Hogan, Patricia E.; Neiberg, Rebecca H.; Cheskin, Lawrence J.; Dutton, Gareth R.; Evans-Hudnall, Gina; Jeffery, Robert; Kitabchi, Abbas E.; Nelson, Julie A.; Pi-Sunyer, F. Xavier; West, Delia Smith; Wing, Rena R.

    2014-01-01

    Weight losses in lifestyle interventions are variable, yet prediction of long-term success is difficult. Objective We examined the utility of using various weight loss thresholds in the first 2 months of treatment for predicting 1-year outcomes. Design and Methods Participants included 2327 adults with type 2 diabetes (BMI:35.8±6.0) randomized to the intensive lifestyle intervention (ILI) of the Look AHEAD trial. ILI included weekly behavioral sessions designed to increase physical activity and reduce caloric intake. 1-month, 2-month, and 1-year weight changes were calculated. Results Participants failing to achieve a ≥2% weight loss at Month 1 were 5.6 (95% CI:4.5,7.0) times more likely to also not achieve a ≥10% weight loss at Year 1, compared to those losing ≥2% initially. These odds were increased to 11.6 (95% CI:8.6,15.6) when using a 3% weight loss threshold at Month 2. Only 15.2% and 8.2% of individuals failing to achieve the ≥2% and ≥3% thresholds at Months 1 and 2 respectively, go on to achieve a ≥10% weight loss at Year 1. Conclusions Given the association between initial and 1-year weight loss, the first few months of treatment may be an opportune time to identify those who are unsuccessful and utilize rescue efforts. PMID:24771618

  1. Intervention effects for students with comorbid forms of learning disability: understanding the needs of nonresponders.

    PubMed

    Fuchs, Lynn S; Fuchs, Douglas; Compton, Donald L

    2013-01-01

    In this article, we considered evidence from our intervention research programs on whether students with learning disability (LD) in reading and mathematics (comorbid LD) respond differently to intervention, compared to students with reading LD alone (RD) or to students with mathematics LD alone (MD). The goal was to gain insight into whether comorbid disorder represents an LD subtype distinct from RD or from MD, which requires differentiated forms of intervention. Our analysis suggested that students with comorbid LD respond differently than those with MD, depending on the nature of mathematics intervention, and may therefore represent a distinctive subtype. By contrast, students with RD appear to respond to intervention in similar ways, regardless of whether they experience RD alone or in combination with MD. Results also suggest that distinctions between comorbid and single-order LD may depend on whether LD is defined in terms of lower- versus higher-order academic skill. Recommendations for future study are provided. PMID:23232441

  2. Increased regulatory T cell counts in HIV-infected nonresponders to hepatitis B virus vaccine.

    PubMed

    del Pozo Balado, María del Mar; Leal, Manuel; Méndez Lagares, Gema; Mata, Rosario C; López-Cortés, Luis F; Viciana, Pompeyo; Pacheco, Yolanda M

    2010-08-15

    Hepatitis B virus (HBV) coinfection is a main cause of liver-related mortality in human immunodeficiency virus (HIV)-infected subjects. Unfortunately, HIV-infected subjects show a low rate of response to standard HBV vaccination (23%-56%), in contrast to rates >90% found in the general population, and the underlying causes (particularly cellular and molecular causes) are still unknown. We hypothesized that an increased frequency of regulatory T (T(reg)) cells could be involved in the low rate of seroconversion in HIV-infected subjects. Forty HIV-infected subjects were enrolled in the Assistance Vaccination Program against HBV of the Infectious Diseases Service from the Virgen del Rocío University Hospital, Seville, Spain. Freshly isolated peripheral blood mononuclear cells from baseline were immunophenotyped for T(reg) cells, CD4, and CD8 T cells in both naive and memory subpopulations and activation degree, as well as recent thymic emigrants. Baseline T(reg) cell frequency was found independently associated with the final nonresponse to HBV vaccine in HIV-infected subjects. Furthermore, a negative correlation between baseline frequency of T(reg) cells and antibody titers in the final response was found. These findings suggest an active role played by T(reg) cells on the immunization antigen-specific T and/or B cell responses with the final consequence of a B cell anti-HBs lower production.

  3. Bacterial phagocytosis by macrophages from lipopolysaccharide responder and nonresponder mouse strains.

    PubMed Central

    Cuffini, A; Carlone, N A; Forni, G

    1980-01-01

    The phagocytic capacity of macrophages from C3H/H3J mice was assessed against lipopolysaccharide-producing (Escherichia coli) and -nonproducing (Staphylococcus aureus) bacteria. Despite their gene-coded unresponsiveness to lipopolysaccharide endotoxin and lymphokines and their defective tumoricidal activity, proteose peptone-induced C3H/HeJ macrophages did not display a defective phagocytic capacity, but rather displayed an enhanced phagocytosis of both bacterial strains compared with macrophages from closely related C3H/HeN mice. Unstimulated peritoneal resident C3H/HeJ macrophages, on the other hand, displayed a normal phagocytic activity toward E. coli and enhanced phagocytosis toward S. aureus. PMID:6995321

  4. Intervention Effects for Students With Comorbid Forms of Learning Disability: Understanding the Needs of Nonresponders

    PubMed Central

    Fuchs, Lynn S.; Fuchs, Douglas; Compton, Donald L.

    2013-01-01

    In this article, we considered evidence from our intervention research programs on whether students with learning disability (LD) in reading and mathematics (comorbid LD) respond differently to intervention, compared to students with reading LD alone (RD) or to students with mathematics LD alone (MD). The goal was to gain insight into whether comorbid disorder represents an LD subtype distinct from RD or from MD, which requires differentiated forms of intervention. Our analysis suggested that students with comorbid LD respond differently than those with MD, depending on the nature of mathematics intervention, and may therefore represent a distinctive subtype. By contrast, students with RD appear to respond to intervention in similar ways, regardless of whether they experience RD alone or in combination with MD. Results also suggest that distinctions between comorbid and single-order LD may depend on whether LD is defined in terms of lower- versus higher-order academic skill. Recommendations for future study are provided. PMID:23232441

  5. Pretreatment Evaluation of Microcirculation by Dynamic Contrast-Enhanced Magnetic Resonance Imaging Predicts Survival in Primary Rectal Cancer Patients

    SciTech Connect

    DeVries, Alexander Friedrich; Piringer, Gudrun; Kremser, Christian; Judmaier, Werner; Saely, Christoph Hubert; Lukas, Peter; Öfner, Dietmar

    2014-12-01

    Purpose: To investigate the prognostic value of the perfusion index (PI), a microcirculatory parameter estimated from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), which integrates information on both flow and permeability, to predict overall survival and disease-free survival in patients with primary rectal cancer. Methods and Materials: A total of 83 patients with stage cT3 rectal cancer requiring neoadjuvant chemoradiation were investigated with DCE-MRI before start of therapy. Contrast-enhanced dynamic T{sub 1} mapping was obtained, and a simple data analysis strategy based on the calculation of the maximum slope of the tissue concentration–time curve divided by the maximum of the arterial input function was used as a measure of tumor microcirculation (PI), which integrates information on both flow and permeability. Results: In 39 patients (47.0%), T downstaging (ypT0-2) was observed. During a mean (±SD) follow-up period of 71 ± 29 months, 58 patients (69.9%) survived, and disease-free survival was achieved in 45 patients (54.2%). The mean PI (PImean) averaged over the group of nonresponders was significantly higher than for responders. Additionally, higher PImean in age- and gender-adjusted analyses was strongly predictive of therapy nonresponse. Most importantly, PImean strongly and significantly predicted disease-free survival (unadjusted hazard ratio [HR], 1.85 [ 95% confidence interval, 1.35-2.54; P<.001)]; HR adjusted for age and sex, 1.81 [1.30-2.51]; P<.001) as well as overall survival (unadjusted HR 1.42 [1.02-1.99], P=.040; HR adjusted for age and sex, 1.43 [1.03-1.98]; P=.034). Conclusions: This analysis identifies PImean as a novel biomarker that is predictive for therapy response, disease-free survival, and overall survival in patients with primary locally advanced rectal cancer.

  6. Scintigraphic detection of TNF-driven inflammation by radiolabelled certolizumab pegol in patients with rheumatoid arthritis and spondyloarthritis

    PubMed Central

    Carron, Philippe; Lambert, Bieke; Van Praet, Liesbet; De Vos, Filip; Varkas, Gaëlle; Jans, Lennart; Elewaut, Dirk; Van den Bosch, Filip

    2016-01-01

    Background Biologicals are the cornerstone for many treatment algorithms in inflammatory arthritis. While tumour necrosis factor (TNF) inhibitors may achieve important responses in ∼50% of patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA), a significant fraction of patients are partial or non-responders. We hypothesised that in vivo assessment of TNF by scintigraphy with 99mTc-radiolabelled certolizumab pegol (CZP) might lead to a more ‘evidence-based biological therapy’. Objectives Our goal was to perform a proof-of-concept study of in vivo detection of TNF by immunoscintigraphy of a radiolabelled TNF inhibitor in RA and SpA, and correlate this with clinical, imaging findings and therapeutic outcome. Methods CZP was conjugated with succinimidyl-6-hydrazino-nicotinamide and subsequently radiolabelled with Tc99m. Whole body and static images of hands, feet and sacroiliac joints of 20 patients (5 RA; 15 SpA) were acquired at 3 time points. Immunoscintigraphic findings were scored semiquantitatively. Subsequently, all patients were treated with CZP. Results In peripheral joints, clinically affected joints or abnormal ultrasound findings were observed more frequently (p<0.001) in the scintigraphic-positive group. In patients with axial SpA, bone marrow edema on MRI was detected more frequently (p<0.001) in quadrants with tracer uptake. At the patient level, the odds of a joint remaining tender despite 24 weeks of CZP treatment was significantly smaller in joints with clear tracer uptake as compared with those with no uptake (OR=0.42, p=0.04). Conclusions Immunoscintigraphy with radiolabelled CZP demonstrated both axial and peripheral inflammation, and displayed good correlation with clinical features, conventional imaging and therapy response. Trial registration number NCT01590966; Results. PMID:27403334

  7. U.S. survey of surgical capabilities and experience with surgical procedures in patients with congenital haemophilia with inhibitors.

    PubMed

    Shapiro, A; Cooper, D L

    2012-05-01

    General guidelines exist for the use of recombinant activated factor VII (rFVIIa) to maintain haemostasis during surgery in congenital haemophilia A and B patients with high responding inhibitors (CHwI). Individual surgical plans are required and based upon historical therapy response, adverse events and anticipated procedure. Surgical interventions are feasible, yet it remains unclear how many US hemophilia treatment centres (HTCs) perform procedures in this fragile population. To better understand the US HTC surgical experience in CHwI patients and the number/types of procedures performed, a 21-question survey was sent to 133 US HTCs, with follow-up for response clarification and to non-responders. 98/133 HTCs (74%) responded, with 87 currently treating CHwI patients. In the last decade, 76/85 HTCs performed 994 surgeries on CHwI patients. Sites were experienced in the following procedures: central line insertion/removal (73 HTCs), dental (58), orthopaedic (52), abdominal (23), cardiovascular (14) and otolaryngologic (11). Experience with orthopaedic surgeries included synovectomies - arthroscopic (23 HTCs), radioisotopic (22), and open (7); joint replacement (18); fracture repair (14); and arthrodesis (8). Treatment modalities included rFVIIa bolus (83 HTCs) or continuous infusions (9), plasma-derived activated prothrombin complex concentrate (pd-aPCC) (55), antifibrinolytics (51), topical haemostatic agents (29), factor VIII (16) and fibrin sealants (14). Protocols for bypassing agents were used by 31/92 (33%) HTCs. Most US HTCs surveyed care for CHwI patients (74%) and have experience in minor surgery; fewer HTCs reported complex orthopaedic surgical experience. Identification of best practices and surgical barriers is required to guide future initiatives to support these patients.

  8. Striatal D2/3 Binding Potential Values in Drug-Naïve First-Episode Schizophrenia Patients Correlate With Treatment Outcome

    PubMed Central

    Wulff, Sanne; Pinborg, Lars Hageman; Svarer, Claus; Jensen, Lars Thorbjørn; Nielsen, Mette Ødegaard; Allerup, Peter; Bak, Nikolaj; Rasmussen, Hans; Frandsen, Erik; Rostrup, Egill; Glenthøj, Birte Yding

    2015-01-01

    One of best validated findings in schizophrenia research is the association between blockade of dopamine D2 receptors and the effects of antipsychotics on positive psychotic symptoms. The aim of the present study was to examine correlations between baseline striatal D2/3 receptor binding potential (BPp) values and treatment outcome in a cohort of antipsychotic-naïve first-episode schizophrenia patients. Additionally, we wished to investigate associations between striatal dopamine D2/3 receptor blockade and alterations of negative symptoms as well as functioning and subjective well-being. Twenty-eight antipsychotic-naïve schizophrenia patients and 26 controls were included in the study. Single-photon emission computed tomography (SPECT) with [123I]iodobenzamide ([123I]-IBZM) was used to examine striatal D2/3 receptor BPp. Patients were examined before and after 6 weeks of treatment with the D2/3 receptor antagonist amisulpride. There was a significant negative correlation between striatal D2/3 receptor BPp at baseline and improvement of positive symptoms in the total group of patients. Comparing patients responding to treatment to nonresponders further showed significantly lower baseline BPp in the responders. At follow-up, the patients demonstrated a negative correlation between the blockade and functioning, whereas no associations between blockade and negative symptoms or subjective well-being were observed. The results show an association between striatal BPp of dopamine D2/3 receptors in antipsychotic-naïve first-episode patients with schizophrenia and treatment response. Patients with a low BPp have a better treatment response than patients with a high BPp. The results further suggest that functioning may decline at high levels of dopamine receptor blockade. PMID:25698711

  9. Striatal D(2/3) Binding Potential Values in Drug-Naïve First-Episode Schizophrenia Patients Correlate With Treatment Outcome.

    PubMed

    Wulff, Sanne; Pinborg, Lars Hageman; Svarer, Claus; Jensen, Lars Thorbjørn; Nielsen, Mette Ødegaard; Allerup, Peter; Bak, Nikolaj; Rasmussen, Hans; Frandsen, Erik; Rostrup, Egill; Glenthøj, Birte Yding

    2015-09-01

    One of best validated findings in schizophrenia research is the association between blockade of dopamine D2 receptors and the effects of antipsychotics on positive psychotic symptoms. The aim of the present study was to examine correlations between baseline striatal D(2/3) receptor binding potential (BP(p)) values and treatment outcome in a cohort of antipsychotic-naïve first-episode schizophrenia patients. Additionally, we wished to investigate associations between striatal dopamine D(2/3) receptor blockade and alterations of negative symptoms as well as functioning and subjective well-being. Twenty-eight antipsychotic-naïve schizophrenia patients and 26 controls were included in the study. Single-photon emission computed tomography (SPECT) with [(123)I]iodobenzamide ([(123)I]-IBZM) was used to examine striatal D(2/3) receptor BP(p). Patients were examined before and after 6 weeks of treatment with the D(2/3) receptor antagonist amisulpride. There was a significant negative correlation between striatal D(2/3) receptor BP(p) at baseline and improvement of positive symptoms in the total group of patients. Comparing patients responding to treatment to nonresponders further showed significantly lower baseline BP(p) in the responders. At follow-up, the patients demonstrated a negative correlation between the blockade and functioning, whereas no associations between blockade and negative symptoms or subjective well-being were observed. The results show an association between striatal BP(p) of dopamine D(2/3) receptors in antipsychotic-naïve first-episode patients with schizophrenia and treatment response. Patients with a low BP(p) have a better treatment response than patients with a high BP(p). The results further suggest that functioning may decline at high levels of dopamine receptor blockade.

  10. A Subset of Patients with Acute Myeloid Leukemia Has Leukemia Cells Characterized by Chemokine Responsiveness and Altered Expression of Transcriptional as well as Angiogenic Regulators

    PubMed Central

    Brenner, Annette K.; Reikvam, Håkon; Bruserud, Øystein

    2016-01-01

    Acute myeloid leukemia (AML) is an aggressive and heterogeneous bone marrow malignancy, the only curative treatment being intensive chemotherapy eventually in combination with allogeneic stem cell transplantation. Both the AML and their neighboring stromal cells show constitutive chemokine release, but chemokines seem to function as regulators of AML cell proliferation only for a subset of patients. Chemokine targeting is therefore considered not only for immunosuppression in allotransplanted patients but also as a possible antileukemic strategy in combination with intensive chemotherapy or as part of disease-stabilizing treatment at least for the subset of patients with chemokine-responsive AML cells. In this study, we characterized more in detail the leukemia cell phenotype of the chemokine-responsive patients. We investigated primary AML cells derived from 79 unselected patients. Standardized in vitro suspension cultures were used to investigate AML cell proliferation, and global gene expression profiles were compared for chemokine responders and non-responders identified through the proliferation assays. CCL28-induced growth modulation was used as marker of chemokine responsiveness, and 38 patients were then classified as chemokine-responsive. The effects of exogenous CCL28 (growth inhibition/enhancement/no effect) thus differed among patients and was also dependent on the presence of exogenous hematopoietic growth factors as well as constitutive AML cell cytokine release. The effect of CCR1 inhibition in the presence of chemokine-secreting mesenchymal stem cells also differed among patients. Chemokine-responsive AML cells showed altered expression of genes important for (i) epigenetic transcriptional regulation, particularly lysine acetylation; (ii) helicase activity, especially DExD/H RNA helicases; and (iii) angioregulatory proteins important for integrin binding. Thus, chemokine responsiveness is part of a complex AML cell phenotype with regard to

  11. Contribution of Genome-Wide HCV Genetic Differences to Outcome of Interferon-Based Therapy in Caucasian American and African American Patients

    PubMed Central

    Donlin, Maureen J.; Cannon, Nathan A.; Aurora, Rajeev; Li, Jia; Wahed, Abdus S.; Di Bisceglie, Adrian M.; Tavis, John E.

    2010-01-01

    Background Hepatitis C virus (HCV) has six major genotypes, and patients infected with genotype 1 respond less well to interferon-based therapy than other genotypes. African American patients respond to interferon α-based therapy at about half the rate of Caucasian Americans. The effect of HCV's genetic variation on treatment outcome in both racial groups is poorly understood. Methodology We determined the near full-length pre-therapy consensus sequences from 94 patients infected with HCV genotype 1a or 1b undergoing treatment with peginterferon α-2a and ribavirin through the Virahep-C study. The sequences were stratified by genotype, race and treatment outcome to identify HCV genetic differences associated with treatment efficacy. Principal Findings HCV sequences from patients who achieved sustained viral response were more diverse than sequences from non-responders. These inter-patient diversity differences were found primarily in the NS5A gene in genotype 1a and in core and NS2 in genotype 1b. These differences could not be explained by host selection pressures. Genotype 1b but not 1a African American patients had viral genetic differences that correlated with treatment outcome. Conclusions & Significance Higher inter-patient viral genetic diversity correlated with successful treatment, implying that there are HCV genotype 1 strains with intrinsic differences in sensitivity to therapy. Core, NS3 and NS5A have interferon-suppressive activities detectable through in vitro assays, and hence these activities also appear to function in human patients. Both preferential infection with relatively resistant HCV variants and host-specific factors appear to contribute to the unusually poor response to therapy in African American patients. PMID:20140258

  12. The treatment of 45 patients with cutaneous T-cell lymphoma with low doses of interferon-alpha 2a and etretinate.

    PubMed

    Dréno, B; Claudy, A; Meynadier, J; Verret, J L; Souteyrand, P; Ortonne, J P; Kalis, B; Godefroy, W Y; Beerblock, K; Thill, L

    1991-11-01

    Forty-five patients with cutaneous T-cell lymphomas (CTCL), 32 with mycosis fungoides (MF) and 13 with Sézary syndrome (SS), were treated with interferon-alpha 2a (IFN-alpha 2a) (6-9 x 10(6) IU daily) for 3 months. Those responding to treatment were then treated with interferon-alpha alone (6-9 x 10(6) IU three times weekly), and non-responders received a combination of etretinate (0.5 mg/kg/day) and IFN-alpha 2a in similar concentrations. After 12 months of treatment, 28/45 patients (62.2%) were in complete or partial (greater than 50%) remission. Of these, 17 (60.7%) were receiving IFN-alpha alone and 11 the combined interferon-retinoid therapy. Of the patients with MF stage I and II, 20/25 were responders (12 receiving IFN-alpha alone and eight on combined therapy), whereas only 8/20 with stage IV or SS responded to treatment (five receiving IFN-alpha 2a alone and three combined therapy). These results suggest that the association of etretinate with low-dose recombinant IFN-alpha 2a is an effective means of treating epidermotropic CTCL, particularly in the early stages.

  13. Hepatic expression levels of interferons and interferon-stimulated genes in patients with chronic hepatitis C: A phenotype-genotype correlation study.

    PubMed

    Noureddin, M; Rotman, Y; Zhang, F; Park, H; Rehermann, B; Thomas, E; Liang, T J

    2015-01-01

    IFNL4 is linked to hepatitis C virus treatment response and type III interferons (IFNs). We studied the functional associations among hepatic expressions of IFNs and IFN-stimulated genes (ISGs), and treatment response to peginterferon and ribavirin. Type I IFNs (IFNA1, IFNB1), type II (IFNG), type III (IFNL1, IFNL2/3), IFNL4 and ISG hepatic expressions were measured by qPCR from in 65 chronic hepatitis C (CHC) patients whose IFNL4-associated rs368234815 and IFNL3-associated rs12989760 genotype were determined. There was a robust correlation of hepatic expression within type I and type III IFNs and between type III IFNs and IFNL4 but no correlation between other IFN types. Expression of ISGs correlated with type III IFNs and IFNL4 but not with type I IFNs. Levels of ISGs and IFNL2/3 mRNAs were lower in IFNL3 rs12979860 CC patients compared with non-CC patients, and in treatment responders, compared with nonresponders. IFNL4-ΔG genotype was associated with high ISG levels and nonresponse. Hepatic levels of ISGs in CHC are associated with IFNL2/3 and IFNL4 expression, suggesting that IFNLs, not other types of IFNs, drive ISG expression. Hepatic IFNL2/3 expression is functionally linked to IFNL4 and IFNL3 polymorphisms, potentially explaining the tight association among ISG expression and treatment response.

  14. Ifosfamide plus etoposide combined with regional hyperthermia in patients with locally advanced sarcomas: a phase II study.

    PubMed

    Issels, R D; Prenninger, S W; Nagele, A; Boehm, E; Sauer, H; Jauch, K W; Denecke, H; Berger, H; Peter, K; Wilmanns, W

    1990-11-01

    20% (T20), 50% (T50), or 90% (T90) of measured tumor sites differed significantly between responders and nonresponders (T20, P = .003; T50, P = .006; and T90, P = .004; respectively). These data support activity for ifosfamide-etoposide combined with RHT in pretreated patients with advanced sarcomas.

  15. Transcriptome Analysis of Peripheral Blood in Chronic Inflammatory Demyelinating Polyradiculoneuropathy Patients Identifies TNFR1 and TLR Pathways in the IVIg Response

    PubMed Central

    Richard, Alexandra; Corvol, Jean-Christophe; Debs, Rabab; Reach, Pauline; Tahiri, Khadija; Carpentier, Wassila; Gueguen, Justine; Guillemot, Vincent; Labeyrie, Céline; Adams, David; Viala, Karine; Cohen Aubart, Fleur

    2016-01-01

    Abstract We have studied the response to intravenous immunoglobulins (IVIg) by a transcriptomic approach in 11 chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients (CIDP duration = 6 [0.83–6.5] years). RNA was extracted from cells in whole blood collected before and 3 weeks after IVIg treatment, and hybridized on Illumina chips. After RNA quality controls, gene expression was analyzed using statistical tests fitted for microarrays (R software, limma package), and a pathway analysis was performed using DAVID software. We identified 52 genes with expression that varied significantly after IVIg (fold change [FC] > 1.2, P < 0.001, false discovery rate [FDR] <0.05). Among these 52 genes, 7 were related to immunity, 3 were related to the tumor necrosis factor (TNF)-α receptor 1 (TNFR1) pathway (inhibitor of caspase-activated DNase (ICAD): FC = 1.8, P = 1.7E-7, FDR = 0.004; p21 protein-activated kinase 2 [PAK2]: FC = 1.66, P = 2.6E-5, FDR = 0.03; TNF-α-induced protein 8-like protein 1 [TNFAIP8L1]: P = 1.00E-05, FDR = 0.026), and 2 were related to Toll-like receptors (TLRs), especially TLRs 7 and 9, and were implicated in autoimmunity. These genes were UNC93B1 (FC = 1.6, P = 2E-5, FDR = 0.03), which transports TLRs 7 and 9 to the endolysosomes, and RNF216 (FC = 1.5, P = 1E-05, FDR = 0.03), which promotes TLR 9 degradation. Pathway analysis showed that the TNFR1 pathway was significantly lessened by IVIg (enrichment score = 24, Fischer exact test = 0.003). TNF-α gene expression was higher in responder patients than in nonresponders; however, it decreased after IVIg in responders (P = 0.04), but remained stable in nonresponders. Our data suggest the actions of IVIg on the TNFR1 pathway and an original mechanism involving innate immunity through TLRs in CIDP pathophysiology and the response to IVIg. We conclude that responder patients have stronger inflammatory activity

  16. Transcriptome Analysis of Peripheral Blood in Chronic Inflammatory Demyelinating Polyradiculoneuropathy Patients Identifies TNFR1 and TLR Pathways in the IVIg Response.

    PubMed

    Richard, Alexandra; Corvol, Jean-Christophe; Debs, Rabab; Reach, Pauline; Tahiri, Khadija; Carpentier, Wassila; Gueguen, Justine; Guillemot, Vincent; Labeyrie, Céline; Adams, David; Viala, Karine; Cohen Aubart, Fleur

    2016-05-01

    We have studied the response to intravenous immunoglobulins (IVIg) by a transcriptomic approach in 11 chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients (CIDP duration = 6 [0.83-6.5] years). RNA was extracted from cells in whole blood collected before and 3 weeks after IVIg treatment, and hybridized on Illumina chips. After RNA quality controls, gene expression was analyzed using statistical tests fitted for microarrays (R software, limma package), and a pathway analysis was performed using DAVID software. We identified 52 genes with expression that varied significantly after IVIg (fold change [FC] > 1.2, P < 0.001, false discovery rate [FDR] <0.05). Among these 52 genes, 7 were related to immunity, 3 were related to the tumor necrosis factor (TNF)-α receptor 1 (TNFR1) pathway (inhibitor of caspase-activated DNase (ICAD): FC = 1.8, P = 1.7E-7, FDR = 0.004; p21 protein-activated kinase 2 [PAK2]: FC = 1.66, P = 2.6E-5, FDR = 0.03; TNF-α-induced protein 8-like protein 1 [TNFAIP8L1]: P = 1.00E-05, FDR = 0.026), and 2 were related to Toll-like receptors (TLRs), especially TLRs 7 and 9, and were implicated in autoimmunity. These genes were UNC93B1 (FC = 1.6, P = 2E-5, FDR = 0.03), which transports TLRs 7 and 9 to the endolysosomes, and RNF216 (FC = 1.5, P = 1E-05, FDR = 0.03), which promotes TLR 9 degradation. Pathway analysis showed that the TNFR1 pathway was significantly lessened by IVIg (enrichment score = 24, Fischer exact test = 0.003). TNF-α gene expression was higher in responder patients than in nonresponders; however, it decreased after IVIg in responders (P = 0.04), but remained stable in nonresponders. Our data suggest the actions of IVIg on the TNFR1 pathway and an original mechanism involving innate immunity through TLRs in CIDP pathophysiology and the response to IVIg. We conclude that responder patients have stronger inflammatory activity that is

  17. Central modulation in cluster headache patients treated with occipital nerve stimulation: an FDG-PET study

    PubMed Central

    2011-01-01

    Background Occipital nerve stimulation (ONS) has raised new hope for drug-resistant chronic cluster headache (drCCH), a devastating condition. However its mode of action remains elusive. Since the long delay to meaningful effect suggests that ONS induces slow neuromodulation, we have searched for changes in central pain-control areas using metabolic neuroimaging. Methods Ten drCCH patients underwent an 18FDG-PET scan after ONS, at delays varying between 0 and 30 months. All were scanned with ongoing ONS (ON) and with the stimulator switched OFF. Results After 6-30 months of ONS, 3 patients were pain free and 4 had a ≥ 90% reduction of attack frequency (responders). In all patients compared to controls, several areas of the pain matrix showed hypermetabolism: ipsilateral hypothalamus, midbrain and ipsilateral lower pons. All normalized after ONS, except for the hypothalamus. Switching the stimulator ON or OFF had little influence on brain glucose metabolism. The perigenual anterior cingulate cortex (PACC) was hyperactive in ONS responders compared to non-responders. Conclusions Metabolic normalization in the pain neuromatrix and lack of short-term changes induced by the stimulation might support the hypothesis that ONS acts in drCCH through slow neuromodulatory processes. Selective activation in responders of PACC, a pivotal structure in the endogenous opioid system, suggests that ONS could restore balance within dysfunctioning pain control centres. That ONS is nothing but a symptomatic treatment might be illustrated by the persistent hypothalamic hypermetabolism, which could explain why autonomic attacks may persist despite pain relief and why cluster attacks recur shortly after stimulator arrest. PET studies on larger samples are warranted to confirm these first results. PMID:21349186

  18. Monitoring response to treatment in melanoma patients: potential of a serum glycomic marker.

    PubMed

    Selvan, Senthamil R; Dillman, Robert O; Fowler, Abner W; Carbonell, Denysha J; Ravindranath, Mepur H

    2008-03-15

    A mechanistic marker correlating with tumor progression and clinical response is useful for assessing therapeutic response and determining the course of therapy. Since serum-total-ganglioside (sTG) and antiganglioside-IgM antibody levels reflected tumor progression, the feasibility of utilizing sTG for assessing the response to immunotherapy of metastatic-melanoma was tested. Patients (n = 34) were immunized with dendritic cells cocultured with irradiated, IFN gamma-treated autologous tumor cells admixed with GM-CSF. Levels of sTG and antiganglioside-IgM antibody titers were measured in sera of vaccine recipients at 0, 4 and 24 weeks of treatment. Based on sTG-level, whether lower (L) or higher (H) than the mean + 1 SD of normal and healthy volunteers on weeks 0, 4 and 24, patients were categorized into cohorts-I (LLL, n = 16), II (HHL/HLL, n = 4), III (LLH/LHH/LHL, n = 7) and IV (HHH/HLH, n = 7). The cohorts were regrouped as sTG- downregulators (sTG-DR; n = 20) and upregulators (sTG-UR; n = 14). These two cohorts differed significantly in their overall (p < 0.012) and progression-free (p = 0.0001) survival post-treatment. 43% sTG-UR died within 39 months, with a median survival of 39 months, whereas 61% of the sTG-DR survived for 48 months. Both endogenous and vaccine-induced antiganglioside-IgM antibodies appeared to regulate sTG levels. Nonresponders had increased sTG with no or low IgM antibody response. The sTG level is regulated within 24 weeks post-treatment and therefore, may serve as an ideal biomarker for assessing therapeutic responses in patients. Clinical correlations of sTG indicate that sTG-downregulating therapy may be an effective treatment strategy for melanoma. PMID:17960619

  19. c-MYC expression sensitizes medulloblastoma cells to radio- and chemotherapy and has no impact on response in medulloblastoma patients

    PubMed Central

    2011-01-01

    Background To study whether and how c-MYC expression determines response to radio- and chemotherapy in childhood medulloblastoma (MB). Methods We used DAOY and UW228 human MB cells engineered to stably express different levels of c-MYC, and tested whether c-MYC expression has an effect on radio- and chemosensitivity using the colorimetric 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay, clonogenic survival, apoptosis assays, cell cycle analysis, and western blot assessment. In an effort to validate our results, we analyzed c-MYC mRNA expression in formalin-fixed paraffin-embedded tumor samples from well-documented patients with postoperative residual tumor and compared c-MYC mRNA expression with response to radio- and chemotherapy as examined by neuroradiological imaging. Results In DAOY - and to a lesser extent in UW228 - cells expressing high levels of c-MYC, the cytotoxicity of cisplatin, and etoposide was significantly higher when compared with DAOY/UW228 cells expressing low levels of c-MYC. Irradiation- and chemotherapy-induced apoptotic cell death was enhanced in DAOY cells expressing high levels of c-MYC. The response of 62 of 66 residual tumors was evaluable and response to postoperative radio- (14 responders (CR, PR) vs. 5 non-responders (SD, PD)) or chemotherapy (23 CR/PR vs. 20 SD/PD) was assessed. c-MYC mRNA expression was similar in primary MB samples of responders and non-responders (Mann-Whitney U test, p = 0.50, ratio 0.49, 95% CI 0.008-30.0 and p = 0.67, ratio 1.8, 95% CI 0.14-23.5, respectively). Conclusions c-MYC sensitizes MB cells to some anti-cancer treatments in vitro. As we failed to show evidence for such an effect on postoperative residual tumors when analyzed by imaging, additional investigations in xenografts and larger MB cohorts may help to define the exact function of c-MYC in modulating response to treatment. PMID:21324178

  20. Perceptions of HIV, AIDS and tuberculosis among patients on antiretroviral therapy in Bulawayo, Zimbabwe: implications for the provision of HIV and TB care services.

    PubMed

    Rödlach, Alexander; Dlodlo, Riitta A; Hwalima, Zanele E

    2012-06-01

    The objectives of the research were to explore perceptions of HIV, AIDS and tuberculosis (TB) among individuals enrolled in antiretroviral therapy (ART) at two municipal clinics in Bulawayo, Zimbabwe, and to assess the implications of these perceptions on the provision of HIV and TB care services. Data were collected using the freelist technique to elicit the elements of a cultural domain as well as open-ended interviews with ART clients, conducted during June and July 2009. Participants were recruited through non-probability convenience sampling. The freelist data were analysed using multidimensional scaling and hierarchical clustering, and the interview data were analysed using the grounded theory method. The results suggest that: 1) the participants had substantial knowledge about HIV, AIDS and TB; 2) the participants' perceptions of HIV, AIDS and TB constituted three distinct, though overlapping, cultural domains; 3) because of the availability of ART and TB treatment, a diagnosis of HIV infection or TB alone was generally perceived with hope that one would be able to live a normal life, while AIDS illness or TB/HIV coinfection were associated with notions of death and despair; and, 4) such perceptions may negatively impact the uptake of testing for HIV and TB, and thereby contribute to delayed start of the respective treatment. Health messages should build on these meanings which have the potential to either enhance or compromise available health programmes and their use by people living with HIV or TB.

  1. Ipilimumab-dependent cell-mediated cytotoxicity of regulatory T cells ex vivo by nonclassical monocytes in melanoma patients

    PubMed Central

    Romano, Emanuela; Kusio-Kobialka, Monika; Foukas, Periklis G.; Baumgaertner, Petra; Meyer, Christiane; Ballabeni, Pierluigi; Michielin, Olivier; Weide, Benjamin; Romero, Pedro; Speiser, Daniel E.

    2015-01-01

    Enhancing immune responses with immune-modulatory monoclonal antibodies directed to inhibitory immune receptors is a promising modality in cancer therapy. Clinical efficacy has been demonstrated with antibodies blocking inhibitory immune checkpoints such as cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) or PD-1/PD-L1. Treatment with ipilimumab, a fully human CTLA-4–specific mAb, showed durable clinical efficacy in metastatic melanoma; its mechanism of action is, however, only partially understood. This is a study of 29 patients with advanced cutaneous melanoma treated with ipilimumab. We analyzed peripheral blood mononuclear cells (PBMCs) and matched melanoma metastases from 15 patients responding and 14 not responding to ipilimumab by multicolor flow cytometry, antibody-dependent cell-mediated cytotoxicity (ADCC) assay, and immunohistochemistry. PBMCs and matched tumor biopsies were collected 24 h before (i.e., baseline) and up to 4 wk after ipilimumab. Our findings show, to our knowledge for the first time, that ipilimumab can engage ex vivo FcγRIIIA (CD16)-expressing, nonclassical monocytes resulting in ADCC-mediated lysis of regulatory T cells (Tregs). In contrast, classical CD14++CD16− monocytes are unable to do so. Moreover, we show that patients responding to ipilimumab display significantly higher baseline peripheral frequencies of nonclassical monocytes compared with nonresponder patients. In the tumor microenvironment, responders have higher CD68+/CD163+ macrophage ratios at baseline and show decreased Treg infiltration after treatment. Together, our results suggest that anti–CTLA-4 therapy may target Tregs in vivo. Larger translational studies are, however, warranted to substantiate this mechanism of action of ipilimumab in patients. PMID:25918390

  2. Patient Injuries?

    PubMed

    2015-01-01

    An injured patient may be the last thing dentists want to think about. However, in reality, patients can be injured during dental treatment or as the result of an incident such as a slip and fall in the office. Treatment-related injuries can run the gamut and include burns, lacerations, swallowed objects and allergic reactions, according to The Dentists Insurance Company.

  3. Hypomethylation and up-regulation of PD-1 in T cells by azacytidine in MDS/AML patients: A rationale for combined targeting of PD-1 and DNA methylation.

    PubMed

    Ørskov, Andreas D; Treppendahl, Marianne B; Skovbo, Anni; Holm, Mette S; Friis, Lone S; Hokland, Marianne; Grønbæk, Kirsten

    2015-04-20

    The hypomethylating agents (HMAs) are standard therapy for patients with higher-risk myelodysplastic syndrome (MDS); however, the majority of the patients will lose their response to HMAs over time due to unknown mechanisms. It has recently been shown that T cell expression of the immunoinhibitory receptor PD-1 is regulated by DNA methylation. In 12 of 27 patients (44%) PD-1 promoter demethylation was observed in sorted peripheral blood T cells isolated over consecutive cycles of treatment with 5-azacytidine (5-aza). The PD-1 promoter demethylation correlated with an increase in PD-1 expression. Moreover, demethylation of the PD-1 promoter correlated with a significantly worse overall response rate (8% vs. 60%, p = 0.014), and a trend towards a shorter overall survival (p = 0.11) was observed. A significantly higher baseline methylation level of the PD-1 promoter was observed in T cells of non-responding patients compared to healthy controls (p = 0.023). Accordingly, in addition to their beneficial function, HMAs induce PD-1 expression on T cells in the MDS microenvironment, thereby likely hampering the immune response against the MDS blasts. Thus, we suggest that activation of the PD-1 checkpoint during HMA treatment can be a possible resistance mechanism, which may be overcome by combination therapy with a PD-1 pathway inhibitor. PMID:25823822

  4. Long-Term Treatment Outcomes of Patients Infected With Hepatitis C Virus: A Systematic Review and Meta-analysis of the Survival Benefit of Achieving a Sustained Virological Response

    PubMed Central

    Simmons, Bryony; Saleem, Jawaad; Heath, Katherine; Cooke, Graham S.; Hill, Andrew

    2015-01-01

    Background. Achievement of a sustained virologic response (SVR) after treatment for Hepatitis C infection is associated with improved outcomes. This meta-analysis aimed to determine the impact of SVR on long-term mortality risk compared with nonresponders in a range of populations. Methods. An electronic search identified all studies assessing all-cause mortality in SVR and non-SVR patients. Eligible articles were stratified into general, cirrhotic, and populations coinfected with human immunodeficiency virus. The adjusted hazard ratio (95% confidence interval [CI]) for mortality in patients achieving SVR vs non-SVR, and pooled estimates for the 5-year mortality in each group were calculated. Results. 31 studies (n = 33 360) were identified as suitable for inclusion. Median follow-up time was 5.4 years (interquartile range, 4.9–7.5) across all studies. The adjusted hazard ratio of mortality for patients achieving SVR vs non-SVR was 0.50 (95% CI, .37–.67) in the general population, 0.26 (95% CI, .18–.74) in the cirrhotic group, and 0.21 (.10–.45) in the coinfected group. The pooled 5-year mortality rates were significantly lower for patients achieving SVR compared with non-SVR in all 3 populations. Conclusions. The results suggest that there is a significant survival benefit of achieving an SVR compared with unsuccessful treatment in a range of populations infected with hepatitis C virus. PMID:25987643

  5. Disproportionate Reduction of Serotonin Transporter May Predict the Response and Adherence to Antidepressants in Patients with Major Depressive Disorder: A Positron Emission Tomography Study with 4-[18F]-ADAM

    PubMed Central

    Yeh, Yi-Wei; Ho, Pei-Shen; Kuo, Shin-Chang; Chen, Chun-Yen; Liang, Chih-Sung; Yen, Che-Hung; Huang, Chang-Chih; Ma, Kuo-Hsing; Shiue, Chyng-Yann; Huang, Wen-Sheng; Shyu, Jia-Fwu; Wan, Fang-Jung; Lu, Ru-Band

    2015-01-01

    Background: Many lines of evidence suggest the role of serotonin transporter (SERT)-mediated reuptake of serotonin in the pathophysiology and treatment of major depressive disorder (MDD). This study aimed to examine whether the pretreatment of SERT binding potential or SERT binding ratio between terminal projection regions relative to the midbrain raphe nuclei was associated with treatment outcomes to SERT-targeted antidepressants. Methods: We recruited 39 antidepressant-naïve patients with MDD and 39 heathy controls. Positron emission tomography with N,N-dimethyl-2-(2-amino-4-[18F]fluorophenylthio)benzylamine (4-[18F]-ADAM) was used to measure in vivo SERT availability prior to antidepressant treatment. The 21-item Hamilton Depression Rating Scale (HDRS) was use to assess the severity of depression from baseline to week 6. All the patients with MDD had HDRS scores of 18 or more. Results: Pretreatment SERT binding in the thalamus and striatum positively correlated with an early reduction in HDRS scores at week 3. Nonresponders and dropout patients showed a proportionate reduction in SERT binding in the terminal projection regions and midbrain compared to healthy controls. In contrast, a disproportionate reduction in SERT binding in the terminal projection regions relative to midbrain was observed in responders. Conclusions: The results of this study suggested that a disproportionate reduction in SERT binding between terminal projection regions and midbrain may predict better treatment outcomes in patients with MDD. PMID:25568284

  6. DCE-MRI Perfusion and Permeability Parameters as predictors of tumor response to CCRT in Patients with locally advanced NSCLC

    PubMed Central

    Tao, Xiuli; Wang, Lvhua; Hui, Zhouguang; Liu, Li; Ye, Feng; Song, Ying; Tang, Yu; Men, Yu; Lambrou, Tryphon; Su, Zihua; Xu, Xiao; Ouyang, Han; Wu, Ning

    2016-01-01

    In this prospective study, 36 patients with stage III non-small cell lung cancers (NSCLC), who underwent dynamic contrast-enhanced MRI (DCE-MRI) before concurrent chemo-radiotherapy (CCRT) were enrolled. Pharmacokinetic analysis was carried out after non-rigid motion registration. The perfusion parameters [including Blood Flow (BF), Blood Volume (BV), Mean Transit Time (MTT)] and permeability parameters [including endothelial transfer constant (Ktrans), reflux rate (Kep), fractional extravascular extracellular space volume (Ve), fractional plasma volume (Vp)] were calculated, and their relationship with tumor regression was evaluated. The value of these parameters on predicting responders were calculated by receiver operating characteristic (ROC) curve. Multivariate logistic regression analysis was conducted to find the independent variables. Tumor regression rate is negatively correlated with Ve and its standard variation Ve_SD and positively correlated with Ktrans and Kep. Significant differences between responders and non-responders existed in Ktrans, Kep, Ve, Ve_SD, MTT, BV_SD and MTT_SD (P < 0.05). ROC indicated that Ve < 0.24 gave the largest area under curve of 0.865 to predict responders. Multivariate logistic regression analysis also showed Ve was a significant predictor. Baseline perfusion and permeability parameters calculated from DCE-MRI were seen to be a viable tool for predicting the early treatment response after CCRT of NSCLC. PMID:27762331

  7. [Glutamine synthetase-like protein, glutamate dehydrogenase, and cytochrome c-oxidase in platelets of patients with the first episode psychosis in the course of treatment].

    PubMed

    Burbaeva, G Sh; Boksha, I S; Kaleda, V G; Barkhatova, A N; Turishcheva, M S; Omel'chenko, M A; Tereshkina, E B; Savushkina, O K; Starodubtseva, L I; Prokhorova, T A; Vorob'eva, E A

    2011-01-01

    The authors searched for correlations between amounts of platelet proteins and results of psychometric tests in patients with the first episode psychosis (schizophrenia, schizoaffective psychosis) in the course of their combined antipsychotic treatment with haloperidol and clozapine. Psychometric evaluations (PANSS, BPRS) and analyses of platelet enzymes - glutamine synthetase-like protein (GSLP), glutamate dehydrogenase (GDH), and cytochrome c-oxidase (COX) - were carried out before, during, and after the treatment. These proteins were also analyzed in matched controls. All the parameters comprised a database, followed by statistical data processing using Statistica 6.0 (StatSoft) software, nonparametric statistics module. The patients before the treatment, when compared with controls, demonstrated significantly decreased COX activity (p=0,0000001) and increased GSLP amount (p=0,006) with a positive correlation between GSLP amount and PANSSneg (R=0,34, p<0,01). Those patients who displayed initially low COX activity (below median) demonstrated significant increase in COX activity after the treatment. Negative correlations were revealed between COX activity and PANSS, PANSSpsy scores during the treatment, i.e. the lower was COX activity, the more severe syndromes were observed. Negative correlations were found between the initial COX activity and PANSS, PANSSpsy, BPRS scores after the treatment, i.e., the higher was COX before the treatment, the less prominent syndromes were observed after the treatment. Significantly more "non-responders" by PANSSneg were found among the patients with low GSLP level (below median) than their calculated expected amount. The COX activity measured before the treatment was significantly lower in patients with schizophrenia than in patients with schizoaffective disorder (SAD) (p=0,038). In SAD patients, the initial COX activity was negatively correlated with PANSSpsy and BPRS scores after the treatment (R=-0,5, p=0,02), i.e. the lower

  8. Lumbosubarachnoid-lumboepidural shunting in patients with idiopathic normal-pressure hydrocephalus: surgical procedures and follow-up study of five cases.

    PubMed

    Takeuchi, Totaro; Fukushima, Shintaro; Misaki, Daigoro; Shibata, Satoshi

    2013-01-01

    The objective of the study is to introduce the surgical procedure of the lumbosubarachnoid-lumboepidural (L-L) shunting performed as treatment for idiopathic normal-pressure hydrocephalus (iNPH) and its follow-up. The subjects were five patients with probable iNPH (aged 78-85 years; mean age 81 years; four males and one female) who were judged to be at high risk from general or lumbar anesthesia due to their systemic complications and age. The L-L shunt operation was performed for all the patients under local anesthesia using Codman-Hakim Programmable Valve(®) (Codman & Shurtleff, Inc., Raynham, Massachusetts, USA). The initial pressure for all patients was set at 8 cmH2O. The evaluation of shunt efficacy and the lumbar epidural space cerebrospinal fluid (CSF) absorption test (injection of contrast media into epidural space) were performed both on the operation day and during follow-up period (9-12 months). The shunt operation was judged to be effective in four out of five patients (regarded as shunt responders), whereas no improvement in symptoms was seen in one patient (regarded as shunt nonresponder) where the shunting had no effect after the initial pressure was changed to 4 cmH2O. The lumbar epidural space CSF absorption test both on the operation day and during the follow-up period confirmed absorption in all patients. The L-L shunting is useful for patients with probable iNPH who are at high risk from general or lumbar anesthesia due to their systemic complications and age. CSF was continuously absorbed in the lumbar epidural space during postoperative follow-up period. A longer follow-up is required to establish this surgical procedure.

  9. Expression and activation of intracellular receptors TLR7, TLR8 and TLR9 in peripheral blood monocytes from HIV-infected patients

    PubMed Central

    Pinzón Herrera, Francisc; Cruz López, Juan J; Vera Gamboa, Ligia del Carmen; Pavía Ruiz, Norma; Santos Rivero, Adrián; Sánchez Lugo, Saulo; Puerto, Fernando

    2013-01-01

    Introduction: TLR´s play a role in host defense in HIV infection recognizing the viral DNA or RNA. Their activation induces a signaling pathway that includes the proteins MyD88, IRAK4, TRAF6 and the transcription factor NF-kBp65. Objective: To determine the expression of TLR7, TLR8 and TLR9, and activation of its signaling pathway in monocytes from patients infected with HIV. Methods. Expression of TLR7, TLR8 and TLR9 was determined in monocytes from HIV-infected patients (n= 13) and control subjects (n= 13), which were activated with specific ligands. The expression of MyD88 and NF-kBp65 were determined by flow cytometry; IRAK4 and TRAF6 were studied by immunoblotting. Results: No statistical difference was found in the expression of TLR7, 8 and 9 in monocytes from patients compared to controls, but we observed the non-significant increased expression of TLR9 in patients. The activation showed no significant difference in the expression of MyD88 and NF-kBp65 in patients when compared to controls, but were decreased in stimulated cells over non-stimulated cells. IRAK4 and TRAF6 were not detected. Conclusions: No statistical difference was observed in the expression of intracellular TLRs, MyD88 and NFkBp65 in monocytes from patients compared to controls. This was probably due to effective antiretroviral therapy being received at the time of study entry. Additional studies are needed under controlled conditions that include infected patients with and without ARVT, responders and non-responders, and work with different cell populations. PMID:24892454

  10. Anti-inflammatory effects of combined treatment with acetyl salicylic acid and atorvastatin in haemodialysis patients affected by Normal Weight Obese syndrome.

    PubMed

    Di Renzo, Laura; Noce, Annalisa; De Angelis, Sandro; Miani, Natascia; Di Daniele, Nicola; Tozzo, Carmela; De Lorenzo, Antonino

    2008-02-01

    Low-grade inflammation is a common feature of chronic kidney disease (CKD) and persistent systemic inflammation is thought to be a strong predictor of cardiovascular events. Inflammation plays a role in determining the serum albumin levels in haemodialysis patients (HD) independently of the nutritional status. Increased cardiovascular mortality in CKD has been associated with the increased incidence of obesity in uremic patients. Ingenbleek suggested a prognostic inflammation and nutritional index (PINI), based on serum albumin, pre-albumin, C-reactive protein, and alpha1 acid glycoprotein, to identify and to follow up acutely ill patients at risk of major complications. The aims of the present study were: to verify the incidence of Normal Weight Obese (NWO) syndrome; to evaluate by PINI the effect of 8 weeks acetyl salicylic (100 mg/die) and atorvastatin (10 mg/die) combined treatment on chronic inflammation in 52 selected HD patients. Laboratory evaluation, anthropometric and body composition measurements were detected. At baseline the 56.25% of non-obese, the 84.21% of pre-obese-obese, and the 41.17% of NWO women showed PINI values >1 (normal status PINI<1). After the pharmacological treatment, high significant (P<0.001) reduction in lipid profile, an elevated increase of HDL levels, and a significant reduction of inflammatory markers were obtained. Firstly, our results showed that ASA and atorvastatin combined treatment was effective in reducing inflammatory status in HD patients independently of body composition: at the end of the study only 7.49% of the patients exhibited PINI>1. Further studies will be necessary to understand the causes of inflammation in non-responder patients.

  11. Age and Bone Marrow Cellularity are Associated with Response to Eltrombopag in Japanese Adult Immune Thrombocytopenia Patients: A Retrospective Single-Center Study.

    PubMed

    Uto, Yui; Fujiwara, Shun; Arai, Nana; Kawaguchi, Yukiko; Kabasawa, Nobuyuki; Tsukamoto, Hiroyuki; Ariizumi, Hirotsugu; Hattori, Norimichi; Saito, Bungo; Yanagisawa, Kouji; Harada, Hiroshi; Mori, Hiraku; Shiozawa, Eisuke; Nakamaki, Tsuyoshi

    2015-05-01

    In the present retrospective single-center study, we examined the efficacy and safety of eltrombopag, a thrombopoietin (TPO) -receptor agonist (TPO-RA), and found clinical factors associated with its efficacy in Japanese patients with chronic immune thrombocytopenia (ITP). According to the definition of a response, which is to attain a platelet count of more than 50,000/μL at least once during eltrombopag treatment, 42 enrolled patients were divided into two groups: responders (29 patients, 69%) and non-responders (13 patients, 31%). In analyses of the clinical and laboratory data of these two groups, we extracted two factors that are significantly associated with a better response to eltrombopag, which have not been recognized previously, namely, (1) an older age of patients at eltrombopag initiation (≥ 70 years old) and (2) normal or decreased cellularity of iliac bone marrow (BM) biopsy at diagnosis. The significance of patient age contradicts previous findings from studies in which the Caucasian population was the major focus. However, factors such as changes of pharmacokinetics might modulate the effects of eltrombopag in older patients in Japan because East Asians show higher bioavailability of eltrombopag by as-yet-unknown mechanisms. BM cellularity in ITP may represent an impairment and/or lower responsiveness of pluripotent hematopoietic stem cells, not limited to the megakaryocyte (MgK) -platelet axis, to endogenous TPO, because recent evidence shows that TPO-RA can successfully restore hematopoiesis in aplastic anemia. These results should be useful for the therapeutic use of TPO-RA for ITP and also related thrombocytopenia in Japan.

  12. Patient-reported outcome measures in arthroplasty registries Report of the Patient-Reported Outcome Measures Working Group of the International Society of Arthroplasty Registries Part II. Recommendations for selection, administration, and analysis.

    PubMed

    Rolfson, Ola; Bohm, Eric; Franklin, Patricia; Lyman, Stephen; Denissen, Geke; Dawson, Jill; Dunn, Jennifer; Eresian Chenok, Kate; Dunbar, Michael; Overgaard, Søren; Garellick, Göran; Lübbeke, Anne

    2016-07-01

    - The International Society of Arthroplasty Registries (ISAR) Patient-Reported Outcome Measures (PROMs) Working Group have evaluated and recommended best practices in the selection, administration, and interpretation of PROMs for hip and knee arthroplasty registries. The 2 generic PROMs in common use are the Short Form health surveys (SF-36 or SF-12) and EuroQol 5-dimension (EQ-5D). The Working Group recommends that registries should choose specific PROMs that have been appropriately developed with good measurement properties for arthroplasty patients. The Working Group recommend the use of a 1-item pain question ("During the past 4 weeks, how would you describe the pain you usually have in your [right/left] [hip/knee]?"; response: none, very mild, mild, moderate, or severe) and a single-item satisfaction outcome ("How satisfied are you with your [right/left] [hip/knee] replacement?"; response: very unsatisfied, dissatisfied, neutral, satisfied, or very satisfied). Survey logistics include patient instructions, paper- and electronic-based data collection, reminders for follow-up, centralized as opposed to hospital-based follow-up, sample size, patient- or joint-specific evaluation, collection intervals, frequency of response, missing values, and factors in establishing a PROMs registry program. The Working Group recommends including age, sex, diagnosis at joint, general health status preoperatively, and joint pain and function score in case-mix adjustment models. Interpretation and statistical analysis should consider the absolute level of pain, function, and general health status as well as improvement, missing data, approaches to analysis and case-mix adjustment, minimal clinically important difference, and minimal detectable change. The Working Group recommends data collection immediately before and 1 year after surgery, a threshold of 60% for acceptable frequency of response, documentation of non-responders, and documentation of incomplete or missing data. PMID

  13. [The quality of life after chemotherapy in advanced non-small cell lung cancer patients].

    PubMed

    Słowik-Gabryelska, A; Szczepanik, A; Kalicka, A

    1999-01-01

    , neurological lesions, respiratory disorders, allergy, alopecia. It was established that, chemotherapy in the most patients improved the performance status and minimized cancer symptoms especially, after good response to treatment. After anticancer therapy more frequently severe infections and cardiac disorders, independently to results of treatment were seen. In non-responders, the cancer symptoms were intensified by side effects of antineoplastic-therapy. In this group of patients the severe side effects of therapy more frequently were seen.

  14. Reduced production of IFN-γ and LT-α is associated with successful prednisone therapy in patients with acquired hemophilia A: a pilot study.

    PubMed

    Kruse-Jarres, Rebecca; Fang, Jian; Leissinger, Cindy A; Ganapamo, Frédéric

    2011-11-01

    Glucocorticoids (GC) are a standard treatment for acquired hemophilia A (AH). Although the optimal treatment regimen and duration of GC's is unknown, measurement of sub-clinical immune responses may help direct therapeutic decision making. To study the helpfulness of this approach, three male patients diagnosed with AH were treated with prednisone. The therapy resulted in inhibitor elimination in two out of the three individuals. During the treatment, peripheral mononuclear cells were isolated at different time points and stimulated in vitro. The expression of IFN-γ and LT-α were monitored at both the protein and the mRNA levels. The amount of IFN-γ and LT-α were markedly reduced by the time of inhibitor disappearance in the patients responding to GC therapy but remained high in the non-responder until cyclophosphamide was added. This study suggests that the secretion level of IFN-γ and/or LT-α could be a predictive marker of prednisone responsiveness.

  15. Acute effects of transcutaneous electrical diaphragmatic stimulation on respiratory pattern in COPD patients: cross-sectional and comparative clinical trial

    PubMed Central

    Cancelliero-Gaiad, Karina M.; Ike, Daniela; Pantoni, Camila B. F.; Mendes, Renata G.; Borghi-Silva, Audrey; Costa, Dirceu

    2013-01-01

    Background Transcutaneous electrical diaphragmatic stimulation (TEDS) has been used to improve respiratory muscle strength in patients with respiratory muscle weakness. However, this physical therapy resource has not been studied in chronic obstructive pulmonary disease (COPD). Objective To evaluate the respiratory pattern during one session of TEDS in COPD patients. Method Fifteen COPD patients participated in one TEDS session for plethysmographic analysis and assessment of peripheral oxygen saturation (SpO2) and heart rate (HR). After the session, patients were divided into two groups: Responder (R; n=9) and Non-Responder (NR; n=6) to TEDS. Statistic analysis was performed using the Shapiro-Wilk normality test and two-way ANOVA. For the parameters that showed interaction, the Student t test was used (P<0.05). Results R group consisted mainly of men, with lower SpO2 and higher HR than NR group. When time (before and during) and groups (R and NR) were compared (interaction), there were differences in the parameters minute ventilation (Vent), inspiratory tidal volume (ViVol), expiratory tidal volume (VeVol), and respiratory rate (Br/M). In the intergroup comparison, differences were observed in the parameters Vent, ViVol, and VeVol. A significant effect was also observed for time in change in end-expiratory lung volume level (qDEEL), phase relation during inspiration (PhRIB); phase relation during expiration (PhREB); phase relation of entire breath (PhRTB), and phase angle (PhAng). During TEDS, there was an increase in SpO2 and a reduction in HR in both groups. Conclusions The most hypoxemic group with greater HR responded to TEDS and there was interaction between group and time of analysis for the pulmonary volumes. The time factor had an influence on the two groups with an increase in thoracoabdominal asynchrony. PMID:24271095

  16. Lymphocyte transformation assay for C neoformans antigen is not reliable for detecting cellular impairment in patients with Neurocryptococcosis

    PubMed Central

    2012-01-01

    Background Cryptococcus neoformans causes meningitis and disseminated infection in healthy individuals, but more commonly in hosts with defective immune responses. Cell-mediated immunity is an important component of the immune response to a great variety of infections, including yeast infections. We aimed to evaluate a specific lymphocyte transformation assay to Cryptococcus neoformans in order to identify immunodeficiency associated to neurocryptococcosis (NCC) as primary cause of the mycosis. Methods Healthy volunteers, poultry growers, and HIV-seronegative patients with neurocryptococcosis were tested for cellular immune response. Cryptococcal meningitis was diagnosed by India ink staining of cerebrospinal fluid and cryptococcal antigen test (Immunomycol-Inc, SP, Brazil). Isolated peripheral blood mononuclear cells were stimulated with C. neoformans antigen, C. albicans antigen, and pokeweed mitogen. The amount of 3H-thymidine incorporated was assessed, and the results were expressed as stimulation index (SI) and log SI, sensitivity, specificity, and cut-off value (receiver operating characteristics curve). We applied unpaired Student t tests to compare data and considered significant differences for p<0.05. Results The lymphotoxin alpha showed a low capacity with all the stimuli for classifying patients as responders and non-responders. Lymphotoxin alpha stimulated by heated-killed antigen from patients with neurocryptococcosis was not affected by TCD4+ cell count, and the intensity of response did not correlate with the clinical evolution of neurocryptococcosis. Conclusion Response to lymphocyte transformation assay should be analyzed based on a normal range and using more than one stimulator. The use of a cut-off value to classify patients with neurocryptococcosis is inadequate. Statistical analysis should be based on the log transformation of SI. A more purified antigen for evaluating specific response to C. neoformans is needed. PMID:23110700

  17. Does early improvement predict endpoint response in patients with generalized anxiety disorder (GAD) treated with pregabalin or venlafaxine XR?

    PubMed

    Baldwin, David S; Schweizer, Edward; Xu, Yikang; Lyndon, Gavin

    2012-02-01

    Many patients with generalized anxiety disorder (GAD) only respond to pharmacological treatment after a delay of some weeks, and approximately 35% of patients do not respond. Therefore, early identification of potential responders may have important implications for clinical decision-making. In order to identify early improvement criteria that optimally predict eventual response during short-term treatment of GAD with pregabalin or venlafaxine XR, data were pooled from four double-blind, placebo-controlled GAD treatment studies. A range of measures were analyzed using logistic regression models and receiver operator characteristic (ROC) curve analysis, to predict endpoint response. Results showed that early improvement (≥ 20% reduction from baseline score) on the Hamilton Anxiety Scale (HAM-A) was associated with a high probability of achieving an endpoint response at Weeks 1 and 2 among patients treated with pregabalin (~67%), and at Week 2 with venlafaxine XR (60%). A Clinical Global Impression - Improvement (CGI-I) score ≤ 3 at Week 2 was a reliable predictor of achieving endpoint response for pregabalin and venlafaxine XR (odds ratio [OR], 5.33 and 2.47, respectively) with high sensitivity (pregabalin, 0.91; venlafaxine XR, 0.86) and relatively low specificity (pregabalin, 0.33; venlafaxine XR, 0.29), indicating a high true positive rate, but relatively low true negative rate. These findings indicate that improvement by Week 2 on the single item CGI may be a simple and reliable way to predict treatment response with pregabalin or venlafaxine XR in patients with GAD, but a less reliable way to predict non-responders.

  18. Using an automated recruitment process to generate an unbiased study sample of multiple sclerosis patients.

    PubMed

    Miller, Deborah M; Fox, R; Atreja, A; Moore, S; Lee, J-C; Fu, A Z; Jain, A; Saupe, W; Chakraborty, S; Stadtler, M; Rudick, R A

    2010-01-01

    The objective of this study was to test the efficiency of an automated recruitment methodology developed as a component of a practical controlled trial to assess the benefits of a Web-based personal health site to guide self-management of multiple sclerosis symptoms called Mellen Center Care On-line. We describe the study's automated recruitment methodology using clinical and administrative databases and assess the comparability between subjects who completed informed consent (IC) forms, and individuals who were invited to participate but did not reply, designated as patient nonresponders (PNR). The IC and PNR groups were compared on demographics, number of physician or advanced practice nurse/physician assistant visits during the 12 months prior to the initial invitation, and level of disability as measured by the Charlson Comorbidity Index (CCI). Out of a total dynamic potential pool of 2,421 patients, 2,041 had been invited to participate, 309 had become ineligible to participate during the study, and 71 individuals remained in the pool at the end of recruitment. The IC group had a slightly greater proportion of females. Both groups were predominantly white with comparable marital status. The groups had comparable mean household income, education level, and commercial insurance. The computed mean CCI was similar between the groups. The only significant difference was that the PNR group had fewer clinic visits in the preceding 12 months. The subjects were highly representative of the target population, indicating that there was little bias in our selection process despite a constantly changing pool of eligible individuals. PMID:20064056

  19. Erectile dysfunction in uremic dialysis patients: diagnostic evaluation in the sildenafil era.

    PubMed

    Bellinghieri, G; Santoro, D; Lo Forti, B; Mallamace, A; De Santo, R M; Savica, V

    2001-10-01

    The two words that mean sexual dysfunction, impotence and erectile dysfunction (ED), express two different concepts. Impotence is a general male sexual dysfunction that includes libidinal, orgasmic, and ejaculatory dysfunction. ED is the inability to achieve or maintain an erection sufficient to allow satisfactory sexual intercourse and is part of the general male sexual dysfunction termed impotence that includes libidinal, orgasmic, and ejaculatory dysfunction. Uremic men of different ages report a variety of sexual problems, including sexual hormonal pattern alterations, reduction in or loss of libido, infertility, and impotence, conditioning their well-being status. In evaluating and treating sexual dysfunction, a nephrologist must consider factors involved in its pathogenesis, such as hypothalamic-pituitary-gonadal axis alterations, psychological problems related to chronic disease, secondary hyperparathyroidism, anemia, autonomic neuropathy, derangements in arterial supply or venous outflow, and the normal structure of cavernous body smooth muscle cells. The introduction of sildenafil to treat impotent patients has completely changed the approach to evaluating these subjects because this drug is considered an effective well-tolerated treatment for men with ED. In the past, we proposed an algorithm that gave the opportunity to explore the previously mentioned factors using such instrumental interventions as the nocturnal penile tumescence test, penile echo color Doppler, nervous conduction velocity, and cavernous body biopsy, addressed to prescribe needed surgical or medical interventions. The complexity of the proposed algorithm requires many diagnostic procedures and much time and economic resources to localize the pathological lesions responsible for ED. Because of the new oral drug sildenafil, we propose a new algorithm to test the possibility of obtaining an erection and classify patients as responders or nonresponders to the sildenafil test.

  20. Review of antifungal therapy, part II: treatment rationale, including specific patient populations.

    PubMed

    Baran, Robert; Hay, Rod J; Garduno, Javier I

    2008-01-01

    This portion of the antifungal review focuses on treatment rationale and suggestions, including special populations such as the elderly, children, and pregnant and immunocompromised individuals. In elderly individuals, the pathogen may be associated with certain comorbidities; treatment should begin with local treatments such as debridement (mechanical or chemical) and a topical. In children, the pathogen most commonly isolated is Trichophyton rubrum. Children should be examined for concomitant tinea and treatment options can begin with a chemical debridement (non-painful) and a topical, with non-responders being treated with combination therapy as in adults. It is suggested that blood tests are monitored at baseline and every 4-8 weeks in children on systemic therapy. Terbinafine is the only systemic in category B and local therapies should be the primary treatment modalities in pregnancy. Prevalence of onychomycosis is high in immunocompromised patients with higher relapse rates after treatment. The same fungal infections that are seen in healthy populations are usually represented in the immunocompromised host. There is a stepwise approach that is suggested in the treatment of onychomycosis. Before treatment, several factors should be determined, which include risk for failure and compliance issues. Strategies for therapy include monotherapy, combination therapy, supplemental therapy, and intermittent therapy. Topical monotherapy is effective in early distal nail disease and for the prevention of reinfection of the cured nail. Combination therapy is an appropriate progression of therapy for patients who failed monotherapy or are at risk for failure. Combined therapies are shown to increase cure rates. Mechanical interventions are essential in reducing fungal burdens to allow other modalities to penetrate, especially in dermatophytomas and onycholysis. PMID:18569273

  1. Patient Empowerment

    MedlinePlus

    ... cancer patient organization. Ask for this help. Your Responsibilities Keep Good Records Get in the habit of ... responsible for your follow-up. You should take responsibility for getting a follow-up scheduled and for ...

  2. Optimizing fluid management in patients with acute decompensated heart failure (ADHF): the emerging role of combined measurement of body hydration status and brain natriuretic peptide (BNP) levels.

    PubMed

    Valle, Roberto; Aspromonte, Nadia; Milani, Loredano; Peacock, Frank W; Maisel, Alan S; Santini, Massimo; Ronco, Claudio

    2011-11-01

    The study tests the hypothesis that in patients admitted with acutely decompensated heart failure (ADHF), achievement of adequate body hydration status with intensive medical therapy, modulated by combined bioelectrical vectorial impedance analysis (BIVA) and B-type natriuretic peptide (BNP) measurement, may contribute to optimize the timing of patient's discharge and to improve clinical outcomes. Three hundred patients admitted for ADHF underwent serial BIVA and BNP measurement. Therapy was titrated to reach a BNP value of <250 pg/ml, whenever possible. Patients were categorized as early responders (rapid BNP fall below 250 pg/ml); late responders (slow BNP fall below 250 pg/ml, after aggressive therapy); and non-responders (BNP persistently >250 pg/ml). Worsening of renal function (WRF) was evaluated during hospitalization. Death and rehospitalization were monitored with a 6-month follow-up. BNP value on discharge of ≤250 pg/ml led to a 25% event rate within 6 months (Group A: 17.4%; Group B: 21%, Chi2; n.s.), whereas a value >250 pg/ml (Group C) was associated with a far higher percentage (37%). At discharge, body hydration was 73.8 ± 3.2% in the total population and 73.2 ± 2.1, 73.5 ± 2.8, 74.1 ± 3.6% in the three groups, respectively. WRF was observed in 22.3% of the total. WRF occurred in 22% in Group A, 32% in Group B, and 20% in Group C (P = n.s.). Our study confirms the hypothesis that combined BNP/BIVA sequential measurements help to achieve adequate fluid balance status in patients with ADHF and can be used to drive a "tailored therapy," allowing clinicians to identify high-risk patients and possibly to reduce the incidence of complications secondary to fluid management strategies.

  3. Clinical Benefits of Systemic Chemotherapy for Patients with Metastatic Pheochromocytomas or Sympathetic Extra-Adrenal Paragangliomas: Insights from the Largest Single Institutional Experience

    PubMed Central

    Ayala-Ramirez, Montserrat; Feng, Lei; Habra, Mouhammed A.; Rich, Thereasa; Dickson, Paxton V.; Perrier, Nancy; Phan, Alexandria; Waguespack, Steven; Patel, Shreyaskumar; Jimenez, Camilo

    2013-01-01

    Background The purpose of this study was to evaluate the clinical benefits of systemic chemotherapy for patients with metastatic pheochromocytomas or sympathetic paragangliomas by assessing reduction in tumor size, blood pressure, and improvement in overall survival. Methods We retrospectively reviewed the medical records of patients with metastatic pheochromocytomas-sympathetic paragangliomas who had received chemotherapy at The University of Texas MD Anderson Cancer Center Results Clinical benefit and overall survival (OS) were assessed. Of fifty-four patients treated with chemotherapy, fifty-two were evaluable for response. Seventeen (33%) experienced a response, defined as decreased or normalized blood pressure/decreased number and dosage of antihypertensive medications and/or reduced tumor size after the first chemotherapy regimen. The median OS time was 6.4 years (95 confidence interval (CI): 5.2–16.4) for responders and 3.7 (95% CI: 3.0–7.5) years for non-responders. Of patients who had synchronous metastatic disease, a positive response at 1 year after the start of chemotherapy was associated with a trend toward a longer overall survival (log-rank test, P-value =0.095). In a multivariate Cox proportional hazards model, the effect of response to chemotherapy on overall survival was significant (hazard ratio=0.22, 95% confidence interval: 0.05–1.0; P-value = 0.05). All responders had been treated with dacarbazine and cyclophosphamide. Vincristine was included for 14 responders and doxorubicin was included for 12 responders. We could not identify clinical factors that predicted response to chemotherapy. Conclusion Chemotherapy may decrease tumor size and facilitate blood pressure control in about 33% of patients with metastatic pheochromocytoma-sympathetic paraganglioma. These patients exhibit a longer survival. PMID:22006217

  4. Serum level of hepatocyte growth factor is a novel marker of predicting the outcome and resistance to the treatment with trastuzumab in HER2-positive patients with metastatic gastric cancer

    PubMed Central

    Takahashi, Naoki; Furuta, Koh; Taniguchi, Hirokazu; Sasaki, Yusuke; Shoji, Hirokazu; Honma, Yoshitaka; Iwasa, Satoru; Okita, Natsuko; Takashima, Atsuo; Kato, Ken; Hamaguchi, Tetsuya; Shimada, Yasuhiro; Yamada, Yasuhide

    2016-01-01

    HER2-overexpression in tumor tissue is observed in 6 to 23% of advanced gastric cancer (GC) cases, and trastuzumab is an active molecular drug for these patients. There are no data available on whether serum levels of ligands are associated with the response and resistance to trastuzumab in HER2-positive patients with metastatic GC. HER2 screening of 502 patients with advanced gastric cancer was performed in our institution. Among these patients, 84 patients (16.8%) were diagnosed as HER2-positive, and those who were treated with trastuzumab and met the inclusion criteria were enrolled in the present study. Serum levels of ligands that affect the HER2 signal pathway were measured by an enzyme-linked immunosorbent assay. Forty-six HER2-positive patients were enrolled in this study, and 26 patients (56.5%) achieved a partial response to treatment with trastuzumab. Among several ligands, the serum level of hepatocyte growth factor (HGF) was significantly lower in responders compared with that in non-responders (p = 0.014). Multivariate analyses showed that a high level of serum HGF was a poor prognostic factor for overall survival (OS) compared with low levels of HGF (adjusted HR: 3.857, 95% CI: 1.309–11.361, p = 0.014). Among 25 patients without initial disease progression on the treatment with trastuzumab, the mean value of serum HGF at disease progression was significantly higher than that at pre-treatment (p = 0.041). As novel findings, our study indicated that serum level of HGF was associated with tumor shrinkage and time to progression of trastuzumab in HER2-positive patients with metastatic GC. PMID:26716644

  5. Zinc monotherapy is effective in Wilson’s disease patients with mild liver disease diagnosed in childhood: a retrospective study

    PubMed Central

    2014-01-01

    Background Wilson’s disease (WD) evolves rapidly and is fatal if untreated. The treatment of WD patients with mild liver disease is not clearly defined. To address this issue, we evaluated long-term outcomes of three treatment regimens (D-penicillamine, zinc or both) in patients diagnosed in childhood. Methods We retrospectively evaluated efficacy, compliance and reasons for treatment discontinuation in 42 WD patients (median age at diagnosis: 6 years; median follow-up: 12 years) with mild liver disease. Treatment duration for each treatment block until a medication change or completion of follow-up was analyzed. Events of change of treatment were evaluated using Kaplan-Meier analysis. Results Total discontinuations due to treatment failure or adverse events were more frequent in patients receiving D-penicillamine (45%) or combination (36%) therapy than in patients receiving zinc (12%) (P = .001 and P = .02, respectively). Treatment failure was more frequent on D-penicillamine (28%) and combination therapy (36%) than on zinc (12%); the difference was statistically significant only between zinc and combination therapy (P = .03). First-line zinc monotherapy controlled WD-related liver disease in 13/15 patients (87%); the two subjects that failed on zinc were poor adherent. Zinc was effective in 3/5 (60%) patients that failed on D-penicillamine and combination regimens. All 15 D-penicillamine responders that switched to zinc had good control of liver disease at a median follow-up of 13.1 years. Among 6 D-penicillamine non-responders that switched to zinc, 4 (67%) responded. At follow-up completion, only 5/42 (12%) patients failed. Adverse event-induced discontinuation was significantly more frequent in patients on D-penicillamine than in patients receiving zinc (P = .03). Conclusions Zinc monotherapy is effective in controlling WD-related liver disease both as first-line and as maintenance treatment in patients with mild liver disease diagnosed in

  6. Randomized Phase II Study of Docetaxel plus Personalized Peptide Vaccination versus Docetaxel plus Placebo for Patients with Previously Treated Advanced Wild Type EGFR Non-Small-Cell Lung Cancer.

    PubMed

    Takayama, Koichi; Sugawara, Shunichi; Saijo, Yasuo; Maemondo, Makoto; Sato, Atsushi; Takamori, Shinzo; Harada, Taishi; Sasada, Tetsuro; Kakuma, Tatsuyuki; Kishimoto, Junji; Yamada, Akira; Noguchi, Masanori; Itoh, Kyogo; Nakanishi, Yoichi

    2016-01-01

    Objectives. To evaluate the efficacy and safety of personalized peptide vaccination (PPV) combined with chemotherapy for patients with previously treated advanced non-small-cell lung cancer (NSCLC). Patients and Methods. Previously treated PS0-1 patients with IIIB/IV EGFR (epidermal growth factor receptor) wild genotype NSCLC were randomly assigned to docetaxel (60 mg/m(2) on Day 1) plus PPV based on preexisting host immunity or docetaxel plus placebo. Docetaxel administration was repeated every 3 weeks until disease progression. Personalized peptides or placebo was injected subcutaneously weekly in the first 8 weeks and biweekly in subsequent 16 weeks. The primary efficacy endpoint was progression-free survival (PFS). Results. PPV related toxicity was grade 2 or less skin reaction. The median PFS for placebo arm and PPV arm was 52 days and 59 days, respectively. There was no significant difference between two arms by log-rank test (p = 0.42). Interestingly, PFS and overall survival (OS) in humoral immunological responder were significantly longer than those in nonresponder. Conclusion. PPV did not improve the survival in combination with docetaxel for previously treated advanced NSCLC. However, PPV may be efficacious for the humoral immunological responders and a further clinical investigation is needed. PMID:27274999

  7. Interferon Stimulated Gene Expression in HIV/HCV Coinfected Patients Treated with Nitazoxanide/Peginterferon-Alfa-2a and Ribavirin.

    PubMed

    Petersen, Tess; Lee, Yu-Jin; Osinusi, Anu; Amorosa, Valerianna K; Wang, Crystal; Kang, Minhee; Matining, Roy; Zhang, Xiao; Dou, Diana; Umbleja, Triin; Kottilil, Shyam; Peters, Marion G

    2016-07-01

    A combination of nitazoxanide (NTZ), peginterferon (PegIFN), and ribavirin (RBV) may result in higher sustained virologic response (SVR) rates in hepatitis C virus (HCV) monoinfected patients. This study evaluated the effect of NTZ on interferon-stimulated gene (ISG) expression in vitro and in vivo among HIV/HCV genotype-1 (GT-1) treatment-naive patients. The ability of NTZ to enhance host response to interferon (IFN) signaling using the HCV cell culture system was initially evaluated. Second, ISG expression in 53 patients with treatment outcomes [21 SVR and 32 nonresponders (NR)] in the ACTG A5269 trial, a phase-II study (4-week lead in of NTZ 500 mg daily followed by 48 weeks of NTZ, PegIFN, and weight-based RBV), was assessed. The relative expression of 48 ISGs in peripheral blood mononuclear cells (PBMCs) was measured at baseline, week 4, and week 8 of treatment in a blinded manner. In vitro NTZ produced a direct and additive antiviral effect with IFN-alfa, with pretreatment of NTZ resulting in maximal HCV suppression. NTZ augmented IFN-mediated ISG induction in PBMCs from relapsers and SVRs (p < 0.05), but not NR. In ACTG A5269, baseline expression of most ISGs was similar between NR and SVR. NTZ minimally induced 17 genes in NR and 13 genes in SVR after 4 weeks of therapy. However, after initiation of PegIFN and RBV, ISG induction was predominantly observed in the SVR group and not NR group. NTZ treatment facilitates IFN-induced suppression of HCV replication. Inability to achieve SVR with IFN-based therapy in this clinical trial is associated with diminished ISG response to therapy that is refractory to NTZ. PMID:26974581

  8. A functional biological network centered on XRCC3: a new possible marker of chemoradiotherapy resistance in rectal cancer patients.

    PubMed

    Agostini, Marco; Zangrando, Andrea; Pastrello, Chiara; D'Angelo, Edoardo; Romano, Gabriele; Giovannoni, Roberto; Giordan, Marco; Maretto, Isacco; Bedin, Chiara; Zanon, Carlo; Digito, Maura; Esposito, Giovanni; Mescoli, Claudia; Lavitrano, Marialuisa; Rizzolio, Flavio; Jurisica, Igor; Giordano, Antonio; Pucciarelli, Salvatore; Nitti, Donato

    2015-01-01

    Preoperative chemoradiotherapy is widely used to improve local control of disease, sphincter preservation and to improve survival in patients with locally advanced rectal cancer. Patients enrolled in the present study underwent preoperative chemoradiotherapy, followed by surgical excision. Response to chemoradiotherapy was evaluated according to Mandard's Tumor Regression Grade (TRG). TRG 3, 4 and 5 were considered as partial or no response while TRG 1 and 2 as complete response. From pretherapeutic biopsies of 84 locally advanced rectal carcinomas available for the analysis, only 42 of them showed 70% cancer cellularity at least. By determining gene expression profiles, responders and non-responders showed significantly different expression levels for 19 genes (P < 0.001). We fitted a logistic model selected with a stepwise procedure optimizing the Akaike Information Criterion (AIC) and then validated by means of leave one out cross validation (LOOCV, accuracy = 95%). Four genes were retained in the achieved model: ZNF160, XRCC3, HFM1 and ASXL2. Real time PCR confirmed that XRCC3 is overexpressed in responders group and HFM1 and ASXL2 showed a positive trend. In vitro test on colon cancer resistant/susceptible to chemoradioterapy cells, finally prove that XRCC3 deregulation is extensively involved in the chemoresistance mechanisms. Protein-protein interactions (PPI) analysis involving the predictive classifier revealed a network of 45 interacting nodes (proteins) with TRAF6 gene playing a keystone role in the network. The present study confirmed the possibility that gene expression profiling combined with integrative computational biology is useful to predict complete responses to preoperative chemoradiotherapy in patients with advanced rectal cancer.

  9. Pretreatment Predictors of Response to PegIFN-RBV Therapy in Egyptian Patients with HCV Genotype 4

    PubMed Central

    Rizk, Hanan H.; Hamdy, Nadia M.; Al-Ansari, Nadia L.; El-Mesallamy, Hala O.

    2016-01-01

    Background Egypt has the highest prevalence of a difficult to treat chronic hepatitis C virus (HCV), genotype 4. Pretreatment factors could guide individualization of therapy which aids in treatment optimization and interleukin IL28B gene polymorphism has been shown to closely relate to HCV treatment response. Polymorphisms in genes encoding inhibitors of T-cell response, which have role in disease progression as Programmed Cell Death 1 (PD-1), and Cytotoxic T-Lymphocytes Antigen-4 (CTLA-4), could be candidate markers predicting treatment response. Methods This cohort study consisted of 200 chronic HCV genotype 4 infected patients treated with PegIFN α-2a and RBV in 2 hepatology centers. Genotyping of the polymorphisms in the IL28B gene region (rs12979860), PD1.3 (rs11568821) and CTLA-4 (rs231775) was performed on DNA collected from each patient using TaqMan® genotyping assay. Groups were classified according to response into sustained virological responders (SVR), or non-responders (NR). A multivariate logistic regression analysis was used to identify potential markers, host pretreatment clinical and viral predictive factors including viral load, insulin resistance, and alpha fetoprotein (AFP) related to treatment response. Results Our results showed that in a multivariate analyses IL28B C/C genotype was the most significant predictor for SVR (OR = 10.86; p<0.0001) followed by AFP (OR = 0.915; p = 0.001) then CTLA-4/G genotypes (OR = 1.948; p = 0.022). However, PD-1.3/A genotypes and platelets count were significantly related to response in univariate analysis only (OR = 1.973; p = 0.023; OR = 1.007; p = 0.009 respectively). Conclusion IL28B SNP, AFP level, and CTLA-4 SNP could be used in conjunction to predict treatment response in HCV genotype 4 infected Egyptian patients. PMID:27100663

  10. Prevalence and Characteristics of Hepatitis B Virus (HBV) Coinfection among HIV-Positive Women in South Africa and Botswana.

    PubMed

    Matthews, Philippa C; Beloukas, Apostolos; Malik, Amna; Carlson, Jonathan M; Jooste, Pieter; Ogwu, Anthony; Shapiro, Roger; Riddell, Lynn; Chen, Fabian; Luzzi, Graz; Jaggernath, Manjeetha; Jesuthasan, Gerald; Jeffery, Katie; Ndung'u, Thumbi; Goulder, Philip J R; Geretti, Anna Maria; Klenerman, Paul

    2015-01-01

    There is progressive concern about the evolving burden of morbidity and mortality caused by coinfection with HIV-1 and hepatitis B virus (HBV) in sub-Saharan Africa, but the epidemiology and impact of this problem are not well defined. We therefore set out to assimilate more information about the nature of HBV/HIV coinfection in this region by undertaking a retrospective observational study of southern African adult women. We used samples from previously recruited HIV-1 positive women attending antenatal clinics in three settings in South Africa and Botswana (n = 950) and added a small cohort of HIV-negative antenatal South African women for comparison (n = 72). We tested for HBsAg and followed up HBsAg-positive samples by testing for HBeAg, HBV DNA, HBV genotype, presence of drug-resistance associated mutations (RAMs) and HDV. We identified HBsAg in 72 individuals (7% of the whole cohort), of whom 27% were HBeAg-positive, and the majority HBV genotypes A1 and A2. We did not detect any HDV coinfection. HBV prevalence was significantly different between geographically distinct cohorts, but did not differ according to HIV status. Among adults from South Africa, HBV/HIV coinfected patients had lower CD4+ T cell counts compared to those with HIV-monoinfection (p = 0.02), but this finding was not replicated in the cohort from Botswana. Overall, these data provide a snapshot of the coinfection problem at the heart of the HIV/HBV co-epidemic, and are important to inform public health policy, resource allocation, education, surveillance and clinical care. PMID:26218239

  11. 1H-NMR-Based Metabolomic Study for Identifying Serum Profiles Associated with the Response to Etanercept in Patients with Rheumatoid Arthritis

    PubMed Central

    Valerio, Mariacristina; Scrivo, Rossana; Valesini, Guido; Manetti, Cesare

    2015-01-01

    Objective A considerable proportion of patients with rheumatoid arthritis (RA) do not have a satisfactory response to biological therapies. We investigated the use of metabolomics approach to identify biomarkers able to anticipate the response to biologics in RA patients. Methods Due to gender differences in metabolomic profiling, the analysis was restricted to female patients starting etanercept as the first biological treatment and having a minimum of six months’ follow-up. Each patient was evaluated by the same rheumatologist before and after six months of treatment. At this time, the clinical response (good, moderate, none) was determined according to the EUropean League Against Rheumatism (EULAR) criteria, based on both erythrocyte sedimentation rate (EULAR-ESR) and C-reactive protein (EULAR-CRP). Sera collected prior and after six months of etanercept were analyzed by 1H-nuclear magnetic resonance (NMR) spectroscopy in combination with multivariate data analysis. Results Twenty-seven patients were enrolled: 18 had a good/moderate response and 9 were non responders according to both EULAR-ESR and EULAR-CRP after six months of etanercept. Metabolomic analysis at baseline was able to discriminate good, moderate, and non-responders with a very good predictivity (Q2 = 0.68) and an excellent sensitivity, specificity, and accuracy (100%). In good responders, we found an increase in isoleucine, leucine, valine, alanine, glutamine, tyrosine, and glucose levels and a decrease in 3-hydroxybutyrate levels after six months of treatment with etanercept with respect to baseline. Conclusion Our study confirms the potential of metabolomic analysis to predict the response to biological agents. Changes in metabolic profiles during treatment may help elucidate their mechanism of action. PMID:26558759

  12. End-Tidal CO2 Tension Is Predictive of Effective Nocturnal Oxygen Therapy in Patients with Chronic Heart Failure and Central Sleep Apnea.

    PubMed

    Sugimura, Koichiro; Shinozaki, Tsuyoshi; Fukui, Shigefumi; Ogawa, Hiromasa; Shimokawa, Hiroaki

    2016-01-01

    Central sleep apnea (CSA) is characterized by recurring cycles of crescendo-decrescendo ventilation during sleep, and enhances sympathetic nerve activity. Thus CSA has a prognostic impact in patients with chronic heart failure (CHF). Although nocturnal oxygen (O2) therapy decreases frequency of CSA and improves functional exercise capacity, it is also known that some non-responders to the therapy exist. We thus aimed to identify predictors of responders to nocturnal O2 therapy in CHF patients with CSA. In 12 CHF patients with CSA hospitalized at our department, sleep study was performed at 2 consecutive nights. Patients nasally inhaled O2 at either the first or second night in a randomized manner. To predict the percentage reduction in apnea-hypopnea index (%ΔAHI) in response to the nocturnal O2 therapy, we performed multiple regression analysis with a stepwise method with variables including age, brain-natriuretic peptide, circulation time, baseline AHI, hypercapnic ventilatory response and end-tidal carbon dioxide tension (PETCO2). Nocturnal O2 therapy significantly decreased AHI (from 32 ± 13 /h to 12 ± 10 /h, P < 0.0001). Among the possible predictors, PETCO2 was the only variable that is predictive of % changes in AHI. Receiver operating characteristics analysis determined 4.25% as the optimal cutoff PETCO2 level to identify responder to nocturnal O2 therapy (> 50% reduction of AHI), with 88.9% of sensitivity and 66.7% of specificity. In conclusion, PETCO2 is useful to predict the efficacy of O2 therapy in CHF patients with CSA, providing important information to the current nocturnal O2 therapy.

  13. Interleukin-28b CC genotype predicts early treatment response and CT/TT genotypes predicts non-response in patients infected with HCV genotype 3.

    PubMed

    Gupta, Abhishak Chander; Trehanpati, Nirupma; Sukriti, Sukriti; Hissar, Syed; Midha, Vandana; Sood, Ajit; Sarin, Shiv K

    2014-04-01

    Response to antiviral therapy for hepatitis C virus (HCV) depends upon the genotype and host immune response. IL28b gene mutations have been shown to modulate host antiviral immune response against genotype 1. However, the predictive value of IL28b polymorphism in genotype 3 HCV patients is largely unknown. The association of IL28b polymorphism with virological response was studied in 356 patients with genotype 3 chronic HCV undergoing treatment with peg-interferon and ribavirin and was compared with matched controls. IL28b genotyping followed by DNA sequencing was performed to identify the CC, CT, or TT genotypes. Two log reduction of HCV RNA at Day 7 (Quick Viral Response, QVR) and HCV RNA negativity at Day 28 (Rapid Viral Response, RVR) were analyzed with CC and non-CC genotypes in addition to other predictors of response. The associations of alleles with the response patterns were predicted. Sustained viral response was seen in 250 (70.2%) patients and the IL28b genotype CC/CT/TT distribution was 61.1%; 30.5%; and 8.4%, respectively. The non-CC genotypes were significantly higher in non-responders when compared to responders (67.6% vs. 38.9%, P < 0.001). Interestingly, the rapid viral response in responders was observed in 72.7% with the CC genotype and in 27.2% with the non-CC genotype (P < 0.001). Multivariate analysis showed CC genotype as an independent factor predicting the sustained viral response in patients infected with HCV genotype 3. In conclusion, the IL28b CT/TT genotype strongly correlates with treatment non-response in patients infected with HCV genotype 3 and CC genotype of IL28b is associated with higher quick viral response.

  14. The association of clinical outcome and peripheral T-cell subsets in metastatic colorectal cancer patients receiving first-line FOLFIRI plus bevacizumab therapy.

    PubMed

    Roselli, Mario; Formica, Vincenzo; Cereda, Vittore; Jochems, Caroline; Richards, Jacob; Grenga, Italia; Orlandi, Augusto; Ferroni, Patrizia; Guadagni, Fiorella; Schlom, Jeffrey

    2016-07-01

    The first-line standard of care for patients with metastatic colorectal cancer (mCRC) is FOLFIRI (irinotecan, levo-leucovorin, 5-fluorouracil (5-FU)) plus bevacizumab. With the renewed interest in cancer immunotherapy with agents such as vaccines, checkpoint inhibitors and immune modulators, the possibility exists for the use of one or more of these immunotherapeutics in the first-line setting and thus in combination with the FOLFIRI and bevacizumab regimen. Studies were undertaken to study the effects of FOLFIRI and bevacizumab therapy on peripheral T-cell subsets, and to determine if there are any associations between these subsets and response to therapy. Peripheral blood mononuclear cell subsets of patients with mCRC (n = 23) were analyzed prior to and during therapy. While there were differences among patients, the majority of patients showed either a minimal change or an increase in CD4(+) T cell to regulatory T cell (Treg) ratios during therapy, as well as either minimal change or a decrease in Treg suppressive activity during therapy. There was also an association (p = 0.036) between a decrease in Treg frequency during FOLFIRI therapy and overall survival, and an association (p = 0.037) between the frequency of Tregs prior to therapy and progression-free survival. Responders to the chemotherapy by RECIST criteria also had a greater decrease in Tregs during therapy vs. pre-therapy (p = 0.0064) as compared to non-responders. While the number of mCRC patients undergoing chemotherapy in this study is relatively small, it provides the rationale for the use of immunotherapeutics in this first-line metastatic setting. PMID:27622042

  15. Dynamic of Mixed HCV Infection in Plasma and PBMC of HIV/HCV Patients Under Treatment With Peg-IFN/Ribavirin

    PubMed Central

    Bagaglio, Sabrina; Uberti-Foppa, Caterina; Di Serio, Clelia; Trentini, Filippo; Andolina, Andrea; Hasson, Hamid; Messina, Emanuela; Merli, Marco; Porrino, Lucy; Lazzarin, Adriano; Morsica, Giulia

    2015-01-01

    Abstract The extent of mixed hepatitis C virus (HCV) genotype in different compartments (plasma and peripheral blood mononuclear cell, PBMC) and possible association with treatment efficacy in HIV/HCV coinfected patients remains to be unknown. The objective of this study was to elucidate the frequency of mixed genotype infection (MG), its profile in different compartments during anti-HCV treatment, and the possible influence of different genotypes on the response rate. The compartmentalization of HCV population was investigated by next-generation sequencing in 19 HIV/HCV coinfected patients under anti-HCV treatment with peginterferon/ribavirin (P–R). Ten individuals were nonresponder (NR) or relapser (RE) to P–R treatment and 9 had a sustained virological response (SVR). Eleven/nineteen (58%) patients had MG in plasma compartment. Ten or 12 patients infected by a difficult to treat genotype (DTG) 1 or 4 as dominant strain, had an MG, whereas only 1/7 individuals infected by easy to treat genotype (ETG) harbored a mixed genotype, P = 0.006. HCV–RNA was more frequently detected in PBMC of NR (10/10) than in those of SVR (5/9), P = 0.032. Mixed genotype infection was detected in 6/15 (40%) PBMC-positive cases and was not associated with P–R treatment response. By multivariate analysis, MG in plasma samples was the most important viral factor affecting the treatment response (P = 0.0237). Detection of MG in plasma of HIV/HCV coinfected patients seems to represent the major determinant of response to P–R treatment. This finding may have important clinical implication in light of the new therapeutic approach in HIV/HCV coinfected individuals suggesting that combination treatment with direct acting antivirals could be less effective in MG. PMID:26512601

  16. Dynamic of Mixed HCV Infection in Plasma and PBMC of HIV/HCV Patients Under Treatment With Peg-IFN/Ribavirin.

    PubMed

    Bagaglio, Sabrina; Uberti-Foppa, Caterina; Di Serio, Clelia; Trentini, Filippo; Andolina, Andrea; Hasson, Hamid; Messina, Emanuela; Merli, Marco; Porrino, Lucy; Lazzarin, Adriano; Morsica, Giulia

    2015-10-01

    The extent of mixed hepatitis C virus (HCV) genotype in different compartments (plasma and peripheral blood mononuclear cell, PBMC) and possible association with treatment efficacy in HIV/HCV coinfected patients remains to be unknown.The objective of this study was to elucidate the frequency of mixed genotype infection (MG), its profile in different compartments during anti-HCV treatment, and the possible influence of different genotypes on the response rate.The compartmentalization of HCV population was investigated by next-generation sequencing in 19 HIV/HCV coinfected patients under anti-HCV treatment with peginterferon/ribavirin (P-R). Ten individuals were nonresponder (NR) or relapser (RE) to P-R treatment and 9 had a sustained virological response (SVR).Eleven/nineteen (58%) patients had MG in plasma compartment. Ten or 12 patients infected by a difficult to treat genotype (DTG) 1 or 4 as dominant strain, had an MG, whereas only 1/7 individuals infected by easy to treat genotype (ETG) harbored a mixed genotype, P = 0.006. HCV-RNA was more frequently detected in PBMC of NR (10/10) than in those of SVR (5/9), P = 0.032. Mixed genotype infection was detected in 6/15 (40%) PBMC-positive cases and was not associated with P-R treatment response. By multivariate analysis, MG in plasma samples was the most important viral factor affecting the treatment response (P = 0.0237).Detection of MG in plasma of HIV/HCV coinfected patients seems to represent the major determinant of response to P-R treatment. This finding may have important clinical implication in light of the new therapeutic approach in HIV/HCV coinfected individuals suggesting that combination treatment with direct acting antivirals could be less effective in MG.

  17. Milnacipran treatment and potential biomarkers in depressed patients following an initial SSRI treatment failure: a prospective, open-label, 24-week study

    PubMed Central

    Hashimoto, Tasuku; Sakurai, Daiji; Oda, Yasunori; Hasegawa, Tadashi; Kanahara, Nobuhisa; Sasaki, Tsuyoshi; Komatsu, Hideki; Takahashi, Junpei; Oiwa, Takahiro; Sekine, Yoshimoto; Watanabe, Hiroyuki; Iyo, Masaomi

    2015-01-01

    Background We assessed the effect of switching patients with major depressive disorder to milnacipran following an initial selective serotonin reuptake inhibitor treatment failure, and explored potential biomarkers in their blood. Methods We conducted a prospective, open-label, 24-week trial. Depression was assessed with the 17-item Hamilton Depression Rating Scale. Patients showing a ≥50% reduction in Hamilton Depression Rating Scale scores from baseline to final visit were considered responders. Regarding adverse effects (AEs), moderate-to-severe AEs were specifically identified as effects that required any medical treatment or that induced treatment withdrawals. We also measured blood levels of various molecules including inflammatory cytokines. Results Of the 30 participants who enrolled, 17 completed this study. The responder rate was 30% (n=10). Baseline serum levels of interleukin-6 (Z=−2.155; P=0.031) and interleukin-8 (Z=−2.616; P=0.009) were significantly higher when moderate-to-severe AEs were present (n=13 patients with moderate-to-severe AEs). Serum levels of macrophage inflammatory protein-1β showed a significant continuous decrease from the baseline level (Friedman’s test: χ2=23.9, df=4, P<0.001) only in non-responders. Conclusion These results demonstrate that serum levels of interleukin-6, interleukin-8, and macrophage inflammatory protein-1β as potential blood biomarkers could be utilized to identify the responsiveness of patients to serotonin and norepinephrine reuptake inhibitor like milnacipran, or to identify those patients who may experience AEs strong enough to warrant discontinuation of treatment. PMID:26677330

  18. Dynamic of Mixed HCV Infection in Plasma and PBMC of HIV/HCV Patients Under Treatment With Peg-IFN/Ribavirin.

    PubMed

    Bagaglio, Sabrina; Uberti-Foppa, Caterina; Di Serio, Clelia; Trentini, Filippo; Andolina, Andrea; Hasson, Hamid; Messina, Emanuela; Merli, Marco; Porrino, Lucy; Lazzarin, Adriano; Morsica, Giulia

    2015-10-01

    The extent of mixed hepatitis C virus (HCV) genotype in different compartments (plasma and peripheral blood mononuclear cell, PBMC) and possible association with treatment efficacy in HIV/HCV coinfected patients remains to be unknown.The objective of this study was to elucidate the frequency of mixed genotype infection (MG), its profile in different compartments during anti-HCV treatment, and the possible influence of different genotypes on the response rate.The compartmentalization of HCV population was investigated by next-generation sequencing in 19 HIV/HCV coinfected patients under anti-HCV treatment with peginterferon/ribavirin (P-R). Ten individuals were nonresponder (NR) or relapser (RE) to P-R treatment and 9 had a sustained virological response (SVR).Eleven/nineteen (58%) patients had MG in plasma compartment. Ten or 12 patients infected by a difficult to treat genotype (DTG) 1 or 4 as dominant strain, had an MG, whereas only 1/7 individuals infected by easy to treat genotype (ETG) harbored a mixed genotype, P = 0.006. HCV-RNA was more frequently detected in PBMC of NR (10/10) than in those of SVR (5/9), P = 0.032. Mixed genotype infection was detected in 6/15 (40%) PBMC-positive cases and was not associated with P-R treatment response. By multivariate analysis, MG in plasma samples was the most important viral factor affecting the treatment response (P = 0.0237).Detection of MG in plasma of HIV/HCV coinfected patients seems to represent the major determinant of response to P-R treatment. This finding may have important clinical implication in light of the new therapeutic approach in HIV/HCV coinfected individuals suggesting that combination treatment with direct acting antivirals could be less effective in MG. PMID:26512601

  19. Patient Monitoring

    NASA Technical Reports Server (NTRS)

    1978-01-01

    In photo above, the electrocardiogram of a hospitalized patient is being transmitted by telemetry. Widely employed in space operations, telemetry is a process wherein instrument data is converted to electrical signals and sent to a receiver where the signals are reconverted to usable information. In this instance, heart readings are picked up by the electrode attached to the patient's body and delivered by wire to the small box shown, which is a telemetry transmitter. The signals are relayed wirelessly to the console in the background, which converts them to EKG data. The data is displayed visually and recorded on a printout; at the same time, it is transmitted to a central control station (upper photo) where a nurse can monitor the condition of several patients simultaneously. The Patient Monitoring System was developed by SCI Systems, Inc., Huntsville, Alabama, in conjunction with Abbott Medical Electronics, Houston, Texas. In developing the system, SCI drew upon its extensive experience as a NASA contractor. The company applied telemetry technology developed for the Saturn launch vehicle and the Apollo spacecraft; instrumentation technology developed for heart, blood pressure and sleep monitoring of astronauts aboard NASA's Skylab long duration space station; and communications technology developed for the Space Shuttle.

  20. Patient Safety

    MedlinePlus

    You can help prevent medical errors by being an active member of your health care team. Research shows that patients who are more involved with their ... get better results. To reduce the risk of medical errors, you can Ask questions if you have doubts ...

  1. Refugee patients.

    PubMed

    Valeras, Aimee Burke

    2016-06-01

    This short story focuses on refugee patients. Family members talk about the horrific struggles of civil war, refugee camps, and promises of US resettlement. Their harsh reception into a brutal world includes unemployment, food scarcity, and isolation. (PsycINFO Database Record PMID:27270253

  2. Refugee patients.

    PubMed

    Valeras, Aimee Burke

    2016-06-01

    This short story focuses on refugee patients. Family members talk about the horrific struggles of civil war, refugee camps, and promises of US resettlement. Their harsh reception into a brutal world includes unemployment, food scarcity, and isolation. (PsycINFO Database Record

  3. Efficacy and Safety of Intensity-Modulated Radiotherapy Following Transarterial Chemoembolization in Patients With Unresectable Hepatocellular Carcinoma

    PubMed Central

    Zhang, Tao; Zhao, Yu-Ting; Wang, Zhi; Li, Cheng-Rui; Jin, Jing; Jia, Angela Y.; Wang, Shu-Lian; Song, Yong-Wen; Liu, Yue-Ping; Ren, Hua; Fang, Hui; Bao, Hui; Liu, Xin-Fan; Yu, Zi-Hao; Li, Ye-Xiong; Wang, Wei-Hu

    2016-01-01

    Abstract Three-dimensional conformal radiotherapy in combination with transarterial chemoembolization (TACE) has been beneficial in patients with unresectable hepatocellular carcinoma (HCC). There have been few clinical reports on the use of intensity-modulated radiotherapy (IMRT) in combination with TACE for these patients. The purpose of this study was to assess the efficacy and toxicity of IMRT following TACE in unresectable HCC. The medical records of consecutive patients with unresectable HCC, who underwent IMRT following TACE from January 2009 to June 2014, were retrospectively reviewed in order to assess the overall survival (OS), progression-free survival (PFS), tumor response, and treatment-associated toxicity. A total of 64 lesions in 54 patients were included in the analysis. IMRT was delivered at a median dose of 50 Gy (range 44–70 Gy) at 1.8 to 2.0 Gy per fraction. The overall response rate was achieved in 64.8% of patients with complete response in 20.4% of patients at 3 months after completion of IMRT. The median OS was 20.2 months (95% CI = 8.6–31.9), and the actuarial 1-, 2-, and 3-year OS rates were 84.6%, 49.7%, and 36.7%, respectively. The median PFS was 10.5 months (95% CI = 7.3–13.7) and the 1-, 2-, and 3-year PFS rates were 44.2%, 23.4%, and 14.6%, respectively. The responders had a significantly higher OS rate than the nonresponders (3-year OS 48.0% vs 14.4%, P = 0.001). During and the first month following IMRT, 10 (18.5%) patients developed grade 3 hematological toxicity, and 3 (5.6%) developed grade 3 hepatic toxicity. No patient experienced grade 4 or 5 toxicity. Radiation-induced liver disease was not observed. Our findings suggest that IMRT following TACE could be a favorable treatment option for both its safety profile and clinical benefit in patients with unresectable HCC. PMID:27227954

  4. Patient's perspective.

    PubMed

    Raffa, Robert B; Martin, Kathleen J

    2010-01-01

    An unknown, but significant subgroup (perhaps the majority), of patients who have undergone chemotherapy treatment for their cancer report a subsequent decline in cognitive performance (e.g., difficulty in balancing a checkbook; forgetting or mixing up names of friends or relatives, etc.). The condition has been termed chemo fog, chemo brain, or some similar term to reflect the fact that the symptoms are usually difficult to describe and involve domains of cognition such as attention, concentration, memory, speed of information processing, multitasking, or ability to organize information. The deficits are reported to persist. The magnitude of the negative impact on quality of life depends, as does the condition itself, on multiple and varied factors. This chapter relates the experience of one patient.

  5. Overwhelmed Patients

    PubMed Central

    Bohlen, Krista; Scoville, Elizabeth; Shippee, Nathan D.; May, Carl R.; Montori, Victor M.

    2012-01-01

    OBJECTIVE Patients with diabetes may experience high burden of treatment (BOT), including treatment-related effects and self-care demands. We examined whether patients with type 2 diabetes and their clinicians discuss BOT, the characteristics of their discussions, and their attempts to address BOT during visits. RESEARCH DESIGN AND METHODS Two coders independently reviewed videos of 46 primary care visits obtained during a practice-based trial and identified utterances concerning BOT, classifying them by topic and by whether BOT was addressed (i.e., whether statements emerged aimed at alleviating BOT). RESULTS Of the 46 visits, 43 (93.5%) contained BOT discussions. Both coders identified 83 discussions: 12 involving monitoring, 28 treatment administration, 19 access, and 24 treatment effects. BOT was unambiguously addressed only 30% of the time. CONCLUSIONS BOT discussions usually arise during visits but rarely beget problem-solving efforts. These discussions represent missed opportunities for reducing treatment-related disruptions in the lives of patients with diabetes, which may affect adherence and well-being. PMID:22100962

  6. Changes of tumor infiltrating lymphocyte subtypes before and after neoadjuvant endocrine therapy in estrogen receptor-positive breast cancer patients--an immunohistochemical study of Cd8+ and Foxp3+ using double immunostaining with correlation to the pathobiological response of the patients.

    PubMed

    Chan, Monica S M; Wang, Lin; Felizola, Saulo J A; Ueno, Takayuki; Toi, Masakazu; Loo, W; Chow, Louis W C; Suzuki, Takashi; Sasano, Hironobu

    2012-01-01

    Tumor-stromal interactions involve continuous crosstalk and interactions among different cell types and play pivotal roles in tumorigenesis, tumor development, disease progression, subsequent metastasis, and also tumor response to therapeutic agents. Tumor infiltrating lymphocytes (TILs) are important components of these tumor-stromal interactions. Specific TIL subtypes are known to be involved in the clinical course of individual patients. However, the status of TILs following endocrine therapy has not been studied in breast cancer patients. We evaluated the alterations of TIL subtypes in a cohort of East Asian patients with estrogen receptor-positive breast cancer during the course of neoadjuvant steroidal aromatase inhibitor (AI) therapy, using double immunohistochemical staining of CD8+ and T regulatory cells (Treg) or Foxp3+, yielding the CD8+/Treg ratio in individual patients. Changes in CD8+/Treg ratio before and after therapy were then correlated with pathobiological responses of individual patients based upon alterations of the Ki-67 labeling index (LI). A significant increase in the CD8+/Treg ratio was detected in responders (p=0.028) but not in non-responders, which may reflect the dynamic process in which the host immune response to tumor antigens changed in consequence of an interaction between tumor and stromal cells in its microenvironment following estrogen depletion caused by the AI. The CD8+/Treg ratio in breast cancer tissue can be a potential surrogate marker in surgical pathology specimens for predicting responses to neoadjuvant endocrine therapy, not only incorporating features of carcinoma cells as in Ki-67 LI but also those of adjacent stromal cells in the tumor microenvironment, especially in the early stage of treatment prior to any detectable clinical and/or histopathological changes. PMID:23280127

  7. Predicting subsequent bone density response to intermittent cyclical therapy with etidronate from initial density response in patients with osteoporosis.

    PubMed

    Crilly, R G; Sebaldt, R J; Hodsman, A B; Adachi, J D; Brown, J P; Goldsmith, C H; Hanley, D A; Olszynski, W O; Ste-Marie, L G; Stephenson, G F

    2000-01-01

    We investigated whether an increase in lumbar spine bone mineral density (LS BMD) at 6 months or at 12 months could predict the response to intermittent cyclical therapy (ICT) with etidronate, defined in one of two ways: (i) an increase in LS BMD at 24 months (improvement) or (ii) an increase in LS BMD > or = 0.028 g/cm2 (significant improvement). The latter is a precision term calculated from test-retest values for LS BMD in osteoporotic patients. Two hundred and forty-seven patients (32 men; 5 premenopausal and 210 postmenopausal women) were followed for 24 months by dual-energy X-ray absorptiometry (DXA) and were not taking estrogen, calcitonin or fluoride during treatment with ICT-etidronate. One hundred and fifty patients had a LS BMD measurement after 6 months of treatment with ICT-etidronate and 205 patients had one at 12 months. Baseline characteristics (mean;SD) were as follows: age, 66;11 years; years since menopause, 21;10; number of vertebral fractures at baseline, 0.87;1.26; LS BMD T-score, -2.8; 1.2. After 24 months of treatment with ICT-etidronate, 81% of the patients had an improvement, and 55% had a significant improvement at the LS. Only 6% significantly lost bone (loss of 0.028 g/cm2 or more). The mean percent change from baseline in LS BMD was 5.1% (95% confidence interval 4.2% to 6.0%). The results for men and postmenopausal women were similar to those for the entire group. Accuracy and sensitivity were marginally, but not significantly, higher when response was predicted using 12 month versus 6 month LS BMD measurements. The positive predictive values of improvement at 6 or 12 months were 89% and 90% respectively for improvement at 24 months, and 66% and 68% for significant improvement at 24 months. Identification of nonresponders was less successful and similar at 6 months and 12 months. Forty percent and 39% of the patients, who had no improvement at 6 or 12 months respectively, also had no improvement at 24 months, i.e., were true negatives

  8. The neutrophil to albumin ratio as a predictor of pathological complete response in rectal cancer patients following neoadjuvant chemoradiation.

    PubMed

    Tawfik, Bernard; Mokdad, Ali A; Patel, Prachi M; Li, Hsiao C; Huerta, Sergio

    2016-10-01

    Pathological complete response (pCR) following neoadjuvant chemoradiotherapy (nCRT) and total mesorectal excision (TME), in patients with locally advanced rectal cancer, occurs in 15-27% of patients. Because blood cell counts and albumin are a direct indicator of the host environment, a response to nCRT might be predicted by these markers. This study was carried out to determine whether the neutrophil to albumin ratio (NAR) was predictive of pCR in veteran patients. Ninety-eight patients with rectal cancer who underwent standard nCRT, followed by TME were analyzed. Pre-nCRT and post-nCRT hematologic data were collected. Univariate and multivariate analyses were carried out. Kaplan-Meier curves were constructed with our primary endpoint of pCR. Male patients (99%), age 62.4±9.1 years, BMI=27.4±5.9 kg/m, rectal cancer distance from anal verge=7.1±4.5 cm (SD), interval between nCRT and TME=8 weeks, 55% patients=low anterior resection, 95% received 5-fluorouracil, and all patients received radiation, with 15% achieving a pCR. Univariate analysis showed that pre-nCRT carcinoembryonic antigen (15.8±45.1 vs. 3.5±5.3 ng/dl; P=0.002) and the pre-nCRT NAR (16.4±4.8 vs. 14.2±1.6; P=0.002) were associated with pCR. On multivariate analysis, pre-nCRT carcinoembryonic antigen (odds ratio=0.41, 95% confidence interval 0.22-0.77) and pre-nCRT NAR (odds ratio=0.76, 95% confidence interval 0.60-0.97) remained independent predictors of pCR. Overall survival between nonresponders and pCR patients at 1, 5, and 10 years was 96, 62, and 44% versus 93, 85, and 61%, P=0.13, and disease-free survival was 95, 60, and 47% versus 93, 85, and 61%, P=0.17; respectively. Our study shows that the pre-nCRT NAR is an independent predictor of pCR. These findings should be applied to other cohorts to determine its validity and reliability for use as a potential predictor of pCR.

  9. The role of cytochromes p450 and aldo-keto reductases in prognosis of breast carcinoma patients.

    PubMed

    Hlaváč, Viktor; Brynychová, Veronika; Václavíková, Radka; Ehrlichová, Marie; Vrána, David; Pecha, Václav; Trnková, Markéta; Kodet, Roman; Mrhalová, Marcela; Kubáčková, Kateřina; Gatěk, Jiří; Vážan, Petr; Souček, Pavel

    2014-12-01

    Metabolism of anticancer drugs affects their antitumor effects. This study has investigated the associations of gene expression of enzymes metabolizing anticancer drugs with therapy response and survival of breast carcinoma patients. Gene expression of 13 aldo-keto reductases (AKRs), carbonyl reductase 1, and 10 cytochromes P450 (CYPs) was assessed using quantitative real-time polymerase chain reaction in tumors and paired adjacent nonneoplastic tissues from 68 posttreatment breast carcinoma patients. Eleven candidate genes were then evaluated in an independent series of 50 pretreatment patients. Protein expression of the most significant genes was confirmed by immunoblotting. AKR1A1 was significantly overexpressed and AKR1C1-4, KCNAB1, CYP2C19, CYP3A4, and CYP3A5 downregulated in tumors compared with control nonneoplastic tissues after correction for multiple testing. Significant association of CYP2B6 transcript levels in tumors with expression of hormonal receptors was found in the posttreatment set and replicated in the pretreatment set of patients. Significantly higher intratumoral levels of AKR1C1, AKR1C2, or CYP2W1 were found in responders to neoadjuvant chemotherapy compared with nonresponders. Patients with high AKR7A3 or CYP2B6 levels in the pretreatment set had significantly longer disease-free survival than patients with low levels. Protein products of AKR1C1, AKR1C2, AKR7A3, CYP3A4, and carbonyl reductase (CBR1) were found in tumors and those of AKR1C1, AKR7A3, and CBR1 correlated with their transcript levels. Small interfering RNA-directed knockdown of AKR1C2 or vector-mediated upregulation of CYP3A4 in MDA-MB-231 model cell line had no effect on cell proliferation after paclitaxel treatment in vitro. Prognostic and predictive roles of drug-metabolizing enzymes strikingly differ between posttreatment and pretreatment breast carcinoma patients. Mechanisms of action of AKR1C2, AKR7A3, CYP2B6, CYP3A4, and CBR1 should continue to be further followed in

  10. Effects of antihistamine on up-regulation of histamine H1 receptor mRNA in the nasal mucosa of patients with pollinosis induced by controlled cedar pollen challenge in an environmental exposure unit.

    PubMed

    Kitamura, Yoshiaki; Nakagawa, Hideyuki; Fujii, Tatsuya; Sakoda, Takema; Enomoto, Tadao; Mizuguchi, Hiroyuki; Fukui, Hiroyuki; Takeda, Noriaki

    2015-11-01

    In the present study, we examined the effects of antihistamine on the up-regulation of H1R mRNA in the nasal mucosa of patients with pollinosis induced by controlled exposure to pollen using an environmental exposure unit. Out of 20 patients, we designated 14 responders, whose levels of H1R mRNA in the nasal mucosa were increased after the first pollen exposure and excluded 6 non-responders. Accordingly, the first exposure to pollen without treatment significantly induced both nasal symptoms and the up-regulation of H1R mRNA in the nasal mucosa of the responders. Subsequently, prophylactic administration of antihistamine prior to the second pollen exposure significantly inhibited both of the above effects in the responders. Moreover, the nasal expression of H1R mRNA before the second pollen exposure in the responders pretreated with antihistamine was significantly decreased, as compared with that before the first pollen exposure without treatment. These findings suggest that antihistamines suppressed histamine-induced transcriptional activation of H1R gene in the nasal mucosa, in addition to their blocking effect against histamine on H1R, resulting in a decrease of nasal symptoms. These findings further suggest that by their inverse agonistic activity, antihistamines suppress the basal transcription of nasal H1R in the absence of histamine in responders.

  11. Four-Year Maintenance Treatment With Adalimumab in Patients with Moderately to Severely Active Ulcerative Colitis: Data from ULTRA 1, 2, and 3

    PubMed Central

    Colombel, Jean-Frederic; Sandborn, William J; Ghosh, Subrata; Wolf, Douglas C; Panaccione, Remo; Feagan, Brian; Reinisch, Walter; Robinson, Anne M; Lazar, Andreas; Kron, Martina; Huang, Bidan; Skup, Martha; Thakkar, Roopal B

    2014-01-01

    OBJECTIVES: The safety and efficacy of adalimumab for patients with moderately to severely active ulcerative colitis (UC) has been reported up to week 52 from the placebo-controlled trials ULTRA (Ulcerative Colitis Long-Term Remission and Maintenance with Adalimumab) 1 and 2. Up to 4 years of data for adalimumab-treated patients from ULTRA 1, 2, and the open-label extension ULTRA 3 are presented. METHODS: Remission per partial Mayo score, remission per Inflammatory Bowel Disease Questionnaire (IBDQ) score, and mucosal healing rates were assessed in adalimumab-randomized patients from ULTRA 1 and 2 up to week 208. Corticosteroid-free remission was assessed in adalimumab-randomized patients who used corticosteroids at lead-in study baseline. Maintenance of remission per partial Mayo score and mucosal healing was assessed in patients who entered ULTRA 3 in remission per full Mayo score and with mucosal healing, respectively. As observed, last observation carried forward (LOCF) and nonresponder imputation (NRI) were used to report efficacy. Adverse events were reported for any adalimumab-treated patient. RESULTS: A total of 600/1,094 patients enrolled in ULTRA 1 or 2 were randomized to receive adalimumab and included in the intent-to-treat analyses of the studies. Of these, 199 patients remained on adalimumab after 4 years of follow-up. Rates of remission per partial Mayo score, remission per IBDQ score, mucosal healing, and corticosteroid discontinuation at week 208 were 24.7%, 26.3%, 27.7% (NRI), and 59.2% (observed), respectively. Of the patients who were followed up in ULTRA 3 (588/1,094), a total of 360 patients remained on adalimumab 3 years later. Remission per partial Mayo score and mucosal healing after ULTRA 1 or 2 to year 3 of ULTRA 3 were maintained by 63.6% and 59.9% of patients, respectively (NRI). Adverse event rates were stable over time. CONCLUSIONS: Remission, mucosal healing, and improved quality of life were maintained in patients with moderately to

  12. Liver steatosis replaced with non-invasive viral and host parametars can serve as negative predictive model in patients with chronic hepatitis-C.

    PubMed

    Višnjić, Ana; Ostojić, Zvonimir; Hrstić, Irena; Corić, Marijana; Premuzić, Marina

    2014-09-01

    Almost 70% of chronic hepatitis C (CHC) patients will have concomitant hepatic steatosis (HS) usually determined with invasive method. HS serve as negative predictive factor for lower sustained viral response (SVR) in CHC patients treated with standard of care (SOC) (PEG-IFN and Rib). Retrospective analysis of biochemical, virological and histological data in CHC patients treated with PEG-IFN and Ribavarin. Statistical analysis was carried out by Biometriha Healthcare Research. Level of significance was set to 95% (p < 0.05). 72 patients (43 M; 29 F; median age 41 y) with CHC (60 G1; 12 G3) with no concomitant metabolic syndrome were analyzed. HS ranged from 5 to 30% (median 15%). Overall accuracy of prediction of SVR based on the levels of HS was AUC=0.71 (95% CI=0.58-0.84; p=0.005). When HS was split regarding cut-off value of 5% significant difference was found between responders and non-responders to treatment (chi2 = 10.025; df = 1; p = 0.002). Overall sensitivity was 48% and specificity 91%. Conventional predictive variables (gender, age, fibrosis and genotype) where combined with HS (>5%) and all together achieved Nagelherke R squared of 34.0% in prediction of SVR, with accuracy rate of 75.0%. Further, invasive variables (fibrosis and HS) where replaced with vire mia and body mass index (BMI). All noninvasive variables together achieved Nagelkerke R squared of 26.5% in prediction of SVR with 74% accuracy rate of the logistic regression model. Very low HS (<5%) is negative predictor of SVR and can be replaced with noninvasive variables (gender, age, viremia and BMI) with same accuracy rate of the logistic regres- sion model. PMID:25507366

  13. Lower pH values of weakly acidic refluxes as determinants of heartburn perception in gastroesophageal reflux disease patients with normal esophageal acid exposure.

    PubMed

    de Bortoli, N; Martinucci, I; Savarino, E; Franchi, R; Bertani, L; Russo, S; Ceccarelli, L; Costa, F; Bellini, M; Blandizzi, C; Savarino, V; Marchi, S

    2016-01-01

    Multichannel impedance pH monitoring has shown that weakly acidic refluxes are able to generate heartburn. However, data on the role of different pH values, ranging between 4 and 7, in the generation of them are lacking. The aim of this study was to evaluate whether different pH values of weakly acidic refluxes play a differential role in provoking reflux symptoms in endoscopy-negative patients with physiological esophageal acid exposure time and positive symptom index and symptom association probability for weakly acidic refluxes. One hundred and forty-three consecutive patients with gastroesophageal reflux disease, nonresponders to proton pump inhibitors (PPIs), were allowed a washout from PPIs before undergoing: upper endoscopy, esophageal manometry, and multichannel impedance pH monitoring. In patients with both symptom index and symptom association probability positive for weakly acidic reflux, each weakly acidic reflux was evaluated considering exact pH value, extension, physical characteristics, and correlation with heartburn. Forty-five patients with normal acid exposure time and positive symptom association probability for weakly acidic reflux were identified. The number of refluxes not heartburn related was higher than those heartburn related. In all distal and proximal liquid refluxes, as well as in distal mixed refluxes, the mean pH value of reflux events associated with heartburn was significantly lower than that not associated. This condition was not confirmed for proximal mixed refluxes. Overall, a low pH of weakly acidic reflux represents a determinant factor in provoking heartburn. This observation contributes to better understand the pathophysiology of symptoms generated by weakly acidic refluxes, paving the way toward the search for different therapeutic approaches to this peculiar condition of esophageal hypersensitivity.

  14. Changes in aortic blood flow induced by passive leg raising predict fluid responsiveness in critically ill patients

    PubMed Central

    Lafanechère, A; Pène, F; Goulenok, C; Delahaye, A; Mallet, V; Choukroun, G; Chiche, JD; Mira, JP; Cariou, A

    2006-01-01

    Introduction Esophageal Doppler provides a continuous and non-invasive estimate of descending aortic blood flow (ABF) and corrected left ventricular ejection time (LVETc). Considering passive leg raising (PLR) as a reversible volume expansion (VE), we compared the relative abilities of PLR-induced ABF variations, LVETc and respiratory pulsed pressure variations (ΔPP) to predict fluid responsiveness. Methods We studied 22 critically ill patients in acute circulatory failure in the supine position, during PLR, back to the supine position and after two consecutive VEs of 250 ml of saline. Responders were defined by an increase in ABF induced by 500 ml VE of more than 15%. Results Ten patients were responders and 12 were non-responders. In responders, the increase in ABF induced by PLR was similar to that induced by a 250 ml VE (16% versus 20%; p = 0.15). A PLR-induced increase in ABF of more than 8% predicted fluid responsiveness with a sensitivity of 90% and a specificity of 83%. Corresponding positive and negative predictive values (PPV and NPV, respectively) were 82% and 91%, respectively. A ΔPP threshold value of 12% predicted fluid responsiveness with a sensitivity of 70% and a specificity of 92%. Corresponding PPV and NPV were 87% and 78%, respectively. A LVETc of 245 ms or less predicted fluid responsiveness with a sensitivity of 70%, and a specificity of 67%. Corresponding PPV and NPV were 60% and 66%, respectively. Conclusion The PLR-induced increase in ABF and a ΔPP of more than 12% offer similar predictive values in predicting fluid responsiveness. An isolated basal LVETc value is not a reliable criterion for predicting response to fluid loading. PMID:16970817

  15. Role of the functional MNS16A VNTR-243 variant of the human telomerase reverse transcriptase gene in progression and response to therapy of patients with non-Hodgkin's B-cell lymphomas.

    PubMed

    Wysoczanska, B; Wrobel, T; Dobrzynska, O; Mazur, G; Bogunia-Kubik, K

    2015-04-01

    MNS16A is a functional polymorphic tandem repeat within the human telomerase reverse transcriptase (hTERT) gene. To investigate whether any of the MNS16A repeats represents a genetic risk factor for NHL susceptibility, progression of or response to therapy in 75 patients with non-Hodgkin's lymphomas (NHLs) and 126 healthy individuals were genotyped using the PCR-VNTR technique. A slightly higher frequency of the MNS16A VNTR-243 variant was detected among patients who did not respond to treatment (NR) as compared to patients with complete or partial remission (0.83 vs. 0.51, P = 0.055). NR patients more frequently developed aggressive than indolent type of the disease (0.92 vs. 0.41, P = 0.001). The VNTR-243 allele was more frequently detected among patients with an intermediate-high/high International Prognostic Index (IPI 3-4) score (P = 0.063), especially in patients with advanced age and IPI 3-4 (P = 0.040). In multivariate analysis, higher IPI 3-4 score (OR = 11.364, P = 0.051) and aggressive type of the disease (OR = 18.182, P = 0.012) were found to be independent genetic markers associated with nonresponse to treatment. Presence of the MNS16A VNTR-243 variant also strongly tended to affect the risk of a less favourable response to therapy and was more frequently present among nonresponders (OR = 5.848, P = 0.059). Genetic variation within the hTERT gene may affect the progression and treatment of lymphoproliferative disorders.

  16. Predictability of antitumor efficacy of cetuximab plus irinotecan based on skin rash severity according to observation period in patients with metastatic colorectal cancer following failure of fluorouracil, irinotecan and oxaliplatin

    PubMed Central

    HORIE, YOSHIKI; YAMAZAKI, KENTARO; FUNAKOSHI, TARO; HAMAUCHI, SATOSHI; TANIGUCHI, HIROYA; TSUSHIMA, TAKAHIRO; TODAKA, AKIKO; MACHIDA, NOZOMU; TAKU, KEISEI; FUKUTOMI, AKIRA; ONOZAWA, YUSUKE; YASUI, HIROFUMI; MIZUKAMI, TAKURO; IZAWA, NAOKI; HIRAKAWA, MAMI; TSUDA, TAKASHI; NAKAJIMA, TAKAKO; BOKU, NARIKAZU

    2015-01-01

    The efficacy of cetuximab correlates with the severity of skin toxicity, although its onset may vary. The AIM of this retrospective study was to investigate the optimal observation period for skin rash as a predictor of the efficacy of cetuximab plus irinotecan. The subjects comprised 33 patients with KRAS wild-type metastatic colorectal cancer (mCRC) who had received prior chemotherapy with fluorouracil, irinotecan and oxaliplatin. The response rate (RR), progression-free survival (PFS) and overall survival (OS) were compared according to the presence or absence of ≥grade 2 skin rash within 2, 4, 6, or 8 weeks following cetuximab initiation. The overall RR was 45% (15/33) and the median PFS and OS were 188 and 383 days, respectively. A total of 26 patients experienced ≥grade 2 skin rash within 8 weeks. The proportion of responders among patients who developed ≥grade 2 skin rash (severe group) decreased depending on the duration of the observation period (50% within 8 weeks), whereas the proportion of non-responders among patients with patients with an unfavorable prognosis (PFS <6 months, OS <1 year) in the mild group increased (86% for PFS and 71% for OS within 8 weeks), whereas the proportion of those with a favorable prognosis in the severe group remained stable (73% for PFS and 62% for OS within 8 weeks). Therefore, the absence of ≥grade 2 skin rash within 8 weeks may be predictive of unfavorable efficacy of cetuximab plus irinotecan in mCRC patients. PMID:26623045

  17. Association between IL28B rs12979860 single nucleotide polymorphism and the frequency of colonic Treg in chronically HCV-infected patients.

    PubMed

    Mehta, Minesh; Hetta, Helal F; Abdel-Hameed, Enass A; Rouster, Susan D; Hossain, MdMonir; Mekky, Mohamed A; Khalil, Nasr K; Mohamed, Wegdan A; El-Feky, Mohamed A; Ahmed, Shabaan H; Daef, Enas A; El-Mokhtar, Mohamed A; Abdelwahab, Sayed F; Medhat, Ahmed; Sherman, Kenneth E; Shata, Mohamed Tarek M

    2016-11-01

    The IL28B gene is associated with spontaneous or treatment-induced HCV viral clearance. However, the mechanism by which the IL28B single nucleotide polymorphism (SNP) affects the extra-hepatic HCV immune responses and its relationship to HCV pathogenesis have not been thoroughly investigated. To examine the mechanism by which IL28B affects HCV clearance. Forty Egyptian patients with chronic HCV infection receiving an Interferon/ribavirin treatment regimen were enrolled into this study. There were two groups: non-responders (NR; n = 20) and sustained virologic responders (SVR; n = 20). The initial plasma HCV viral loads prior to treatment and IL28B genotypes were determined by quantitative RT-PCR and sequencing, respectively. Liver biopsies were examined to determine the inflammatory score and the stage of fibrosis. Colonic regulatory T cell (Treg) frequency was estimated by immunohistochemistry. No significant association between IL28B genotypes and response to therapy was identified, despite an odds ratio of 3.4 to have the TT genotype in NR compared to SVR (95 % confidence interval 0.3-35.3, p = 0.3). Patients with the TT-IL28Brs12979860 genotype (unfavorable genotype) have significantly higher frequencies of colonic Treg compared to the CT (p = 0.04) and CC (p = 0.03) genotypes. The frequency of colonic Treg cells in HCV-infected patients had a strong association with the IL-28B genotype and may have a significant impact on HCV clearance.

  18. Distinct patterns of angiogenic factor expression as a predictive factor of response to chemotherapy in stage IIIA non-small-cell lung cancer patients

    PubMed Central

    Koufos, Nikolaos; Syrios, John; Michailidou, Despina; Xynos, Ioannis D.; Lazaris, Andreas; Kavantzas, Nicolaos; Tomos, Periclis; Kakaris, Stamatis; Kosmas, Christos; Tsavaris, Nikolas

    2016-01-01

    The expression of various angiogenic factors was assessed in tumour samples of patients with stage III non-small-cell lung cancer (NSCLC) and further evaluated in terms of response to induction paclitaxel-ifosfamide-cisplatin chemotherapy. Freshly isolated lung tumour specimens obtained by bronchoscopy from 70 stage IIIA NSCLC chemotherapy-naïve patients were sampled and analysed for vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2 and VEGFR-3. Microvessel density was assessed through evaluating the angiogenic markers CD34 and CD105. Immunostaining scores were calculated by multiplying the percentage of labeled cells by the intensity of staining for each examined parameter. The overall mean immunostaining score value from all NSCLC samples was 7.83, 5.56 and 15.86 for VEGFR-1, VEGFR-2 and VEGFR-3, respectively. The overall mean value of the endothelial antigen CD34 was 16.29, whereas the expression of the CD105 antigen in endothelial cells yielded a multivariate distribution. Patients who responded to chemotherapy expressed significantly higher VEGFR-1 and VEGFR-3 mean values compared with non-responders (P<0.001). No significant difference was noted in VEGFR-2 mean values between these two groups (P=0.06). The CD34 mean value was significantly higher in responders (P<0.001), whereas there was no significant difference in CD105 expression between the two groups (P=0.07). Angiogenic marker expression proved to be a potential predictive factor of response to chemotherapy in stage III NSCLC. which merits further investigation.

  19. Optical Coherence Tomographic and Visual Results at Six Months after Transitioning to Aflibercept for Patients on Prior Ranibizumab or Bevacizumab Treatment for Exudative Age-Related Macular Degeneration (An American Ophthalmological Society Thesis)

    PubMed Central

    Chan, Clement K.; Jain, Atul; Sadda, Srinivas; Varshney, Neeta

    2014-01-01

    Purpose: To study optical coherence tomographic (OCT) results and vision at 6 months after transition (post-Tx) from intravitreal bevacizumab and/or ranibizumab to aflibercept for treatment of neovascular age-related macular degeneration (nAMD). The null hypothesis was the lack of improvements in OCT metrics and vision outcome in study eyes at 6 months after transitioning from bevacizumab or ranibizumab to aflibercept. Methods: This retrospective study assessed 6 monthly OCT (Cirrus) data after transitioning to aflibercept for eyes on prior Legacy-ranibizumab, Legacy-bevacizumab, or mixed treatment for nAMD. Outcome measures were subretinal fluid (SRF), cystoid macular edema (CME), pigment epithelial detachment (PED) heights and volumes, central 1- and 3-mm subfield, Macular Volume, and best spectacle and pinhole visual acuity (VA). A single masked investigator performed all OCT measurements. Results: One hundred eighty-nine eyes in 172 patients in Legacy-bevacizumab (95 eyes), Legacy-ranibizumab (84 eyes), or Mixed Group(10 eyes) were switched to aflibercept and followed for 6 months. Significant post-Tx reductions were noted in SRF/CME heights and volumes (all P<.001). Similar findings were noted for PED heights (122.8 μm vs 79.4 μm) and PED volumes (all P<.001). Post-Tx VA was better (20/43 vs 20/51, P<.001). There were no differences between Legacy-bevacizumab and Legacy-ranibizumab groups in OCT and VA changes. Post-Tx VA, SRF/CME, and PED heights and volumes were improved for Nonresponders (suboptimal response to bevacizumab/ranibizumab) (P=.001 to <.001), but not Responders (good responses to same). The only adverse event was a retinal pigment epithelial tear in one eye. Conclusions: Significant improvements in vision and OCT metrics developed in Nonresponders but not in Responders. Post-Tx VA and OCT measures were similar for eyes on prior bevacizumab or ranibizumab. Post-Tx adverse events were uncommon. PMID:25646034

  20. Patient Advocate Foundation

    MedlinePlus

    ... Board Members Annual Reports & Financials Annual Patient Data Analysis Report About PAF's Patient Services Job & Volunteer Opportunities ... 06.16.2016 « PAF’s Releases 2015 Patient Data Analysis Report Illuminating Common Patient Issues 05.27.2016 « ...

  1. Outcomes in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with isolated deletion 5q treated with lenalidomide: a subset analysis from the MDS-004 study

    PubMed Central

    Giagounidis, Aristoteles; Mufti, Ghulam J; Mittelman, Moshe; Sanz, Guillermo; Platzbecker, Uwe; Muus, Petra; Selleslag, Dominik; Beyne-Rauzy, Odile; te Boekhorst, Peter; del Cañizo, Consuelo; Guerci-Bresler, Agnès; Nilsson, Lars; Lübbert, Michael; Quesnel, Bruno; Ganser, Arnold; Bowen, David; Schlegelberger, Brigitte; Göhring, Gudrun; Fu, Tommy; Benettaib, Bouchra; Hellström-Lindberg, Eva; Fenaux, Pierre

    2014-01-01

    Objective A subset analysis of the randomised, phase 3, MDS-004 study to evaluate outcomes in patients with International Prognostic Scoring System (IPSS)-defined Low-/Intermediate (Int)-1-risk myelodysplastic syndromes (MDS) with isolated del(5q). Methods Patients received lenalidomide 10 mg/d (days 1–21; n = 47) or 5 mg/d (days 1–28; n = 43) on 28-d cycles or placebo (n = 45). From the placebo and lenalidomide 5 mg groups, 84% and 58% of patients, respectively, crossed over to lenalidomide 5 or 10 mg at 16 wk, respectively. Results Rates of red blood cell-transfusion independence (RBC-TI) ≥182 d were higher in the lenalidomide 10 mg (57.4%; P < 0.0001) and 5 mg (37.2%; P = 0.0001) groups vs. placebo (2.2%). Cytogenetic response rates (major + minor responses) were 56.8% (P < 0.0001), 23.1% (P = 0.0299) and 0%, respectively. Two-year cumulative risk of acute myeloid leukaemia progression was 12.6%, 17.4% and 16.7% in the lenalidomide 10 mg, 5 mg, and placebo groups, respectively. In a 6-month landmark analysis, overall survival was longer in lenalidomide-treated patients with RBC-TI ≥182 d vs. non-responders (P = 0.0072). The most common grade 3–4 adverse event was myelosuppression. Conclusions These data support the clinical benefits and acceptable safety profile of lenalidomide in transfusion-dependent patients with IPSS-defined Low-/Int-1-risk MDS with isolated del(5q). PMID:24813620

  2. [Patient advice].

    PubMed

    Lucio-Villegas Menéndez, M Eulalia; González, Laura López; Gutiérrez Pérez, M Isabel; Lluch, Natalia Aresté; Morató Agustí, M Luisa; Cachafeiro, Santiago Pérez

    2014-05-01

    In wound care, knowing what to do is as important as knowing what not to do. The first step is to evaluate the severity of the lesion and to know whether it is necessary to attend a health center or not. If the wound is simple, the recommended course of action is cleansing with serum or water after washing one's hands, followed by wound disinfection with the most appropriate antiseptic. Antiseptics not should be used for wound cleansing (physiological serum or tap water should be used) or for wound healing with granulation tissue. Equally, antiseptics should not be used in the ear or near the eyes; if there is accidental application, the eye should be washed in abundant water. Povidone iodine should not be used in pregnant women, nor should iodine preparations be used in neonates, in patients with thyroid alterations or in those allergic to iodine. Currently, merbromine/mercurochrome is not used because of its mercury content. Before an antiseptic is applied, all inorganic residues (foreign bodies) and dead tissue should be removed; detritus, slough, purulent exudate, scabs… This will aid healing and the action of antiseptics, since they become inactive in the presence of organic material.

  3. Evaluating Tumor Response of Non-Small Cell Lung Cancer Patients With {sup 18}F-Fludeoxyglucose Positron Emission Tomography: Potential for Treatment Individualization

    SciTech Connect

    Toma-Dasu, Iuliana; Uhrdin, Johan; Lazzeroni, Marta; Carvalho, Sara; Elmpt, Wouter van; Lambin, Philippe; Dasu, Alexandru

    2015-02-01

    Objective: To assess early tumor responsiveness and the corresponding effective radiosensitivity for individual patients with non-small cell lung cancer (NSCLC) based on 2 successive {sup 18}F-fludeoxyglucose positron emission tomography (FDG-PET) scans. Methods and Materials: Twenty-six NSCLC patients treated in Maastricht were included in the study. Fifteen patients underwent sequential chemoradiation therapy, and 11 patients received concomitant chemoradiation therapy. All patients were imaged with FDG before the start and during the second week of radiation therapy. The sequential images were analyzed in relation to the dose delivered until the second image. An operational quantity, effective radiosensitivity, α{sub eff}, was determined at the voxel level. Correlations were sought between the average α{sub eff} or the fraction of negative α{sub eff} values and the overall survival at 2 years. Separate analyses were performed for the primary gross target volume (GTV), the lymph node GTV, and the clinical target volumes (CTVs). Results: Patients receiving sequential treatment could be divided into responders and nonresponders, using a threshold for the average α{sub eff} of 0.003 Gy{sup −1} in the primary GTV, with a sensitivity of 75% and a specificity of 100% (P<.0001). Choosing the fraction of negative α{sub eff} as a criterion, the threshold 0.3 also had a sensitivity of 75% and a specificity of 100% (P<.0001). Good prognostic potential was maintained for patients receiving concurrent chemotherapy. For lymph node GTV, the correlation had low statistical significance. A cross-validation analysis confirmed the potential of the method. Conclusions: Evaluation of the early response in NSCLC patients showed that it is feasible to determine a threshold value for effective radiosensitivity corresponding to good response. It also showed that a threshold value for the fraction of negative α{sub eff} could also be correlated with poor response. The proposed

  4. Utility of [18F] Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) in the Initial Staging and Response Assessment of Locally Advanced Breast Cancer Patients Receiving Neoadjuvant Chemotherapy.

    PubMed

    Hulikal, Narendra; Gajjala, Sivanath Reddy; Kalawat, Teck Chand; Kottu, Radhika; Amancharla Yadagiri, Lakshmi

    2015-12-01

    In India up to 50 % of breast cancer patients still present as locally advanced breast cancer (LABC). The conventional methods of metastatic work up include physical examination, bone scan, chest & abdominal imaging, and biochemical tests. It is likely that the conventional staging underestimates the extent of initial spread and there is a need for more sophisticated staging procedure. The PET/CT can detect extra-axillary and occult distant metastases and also aid in predicting response to chemotherapy at an early point in time. To evaluate the utility of FDG PET/CT in initial staging and response assessment of patients with LABC receiving NACT. A prospective study of all biopsy confirmed female patients diagnosed with LABC