bluuebunny/crossref_metadata_2025_split huggingface dataset:
Craniopharyngiomas: intratumoral chemotherapy with interferon-α: a multicenter preliminary study with 60 cases
Authors: Cavalheiro Sergio , Di Rocco Concezzio , Valenzuela Sergio , Dastoli Patricia A. , Tamburrini Gianpiero , Massimi Lucca , Nicacio Jardel M. , Faquini Igor V. , Ierardi Daniela F. , Silva Nasjla S. , Pettorini Benedetta Ludovica , Toledo Silvia R. C. 
Published: April 2010

Object
The authors assessed the efficacy of intratumoral interferon-α (IFNα)–based chemotherapy in pediatric patients with cystic craniopharyngiomas.

Methods
In a prospective multicenter study of 60 pediatric patients, the authors assessed the efficacy of intratumoral INFα2A-based chemotherapy. The study was conducted between 2000 and 2009 at 3 locations: the Medical School of the Federal University of São Paulo, Catholic University of Rome, and the Neurosurgery Institute of Santiago, Chile. The assessment included clinical and radiological control examinations, side effects observed, and total dose used.

Results
Sixty cases of cystic craniopharyngioma were analyzed. The cohort consisted of 35 male and 25 female children (mean age 11 years). Clinical and radiological improvement was achieved in 76% of the cases. New endocrinological deficits were observed in 13% of the cases. In approximately 30% of the patients, the evolution included some light side effects, the most common being headache (33%) and eyelid edema (28%). The number of cycles varied from 1 to 9 (mean 5 cycles), and the total dose applied per cycle was 36,000,000 IU.

Conclusions
This has been the largest documented series of intratumoral chemotherapy using INFα for the control of cystic craniopharyngiomas. The treatment has proved efficacious; there was no mortality, and morbidity rates were low.
Craniopharyngioma and other cystic epithelial lesions of the sellar region: a review of clinical, imaging, and histopathological relationships
Authors: Zada Gabriel , Lin Ning , Ojerholm Eric , Ramkissoon Shakti , Laws Edward R. 
Published: April 2010

Object
Cystic epithelial masses of the sellar and parasellar region may be difficult to differentiate on a clinical, imaging, or even histopathological basis. The authors review the developmental relationships and differentiating features of various epithelial lesions of the sellar region.

Methods
The authors performed a review of the literature to identify previous studies describing the etiological relationships and differentiating features of various cystic sellar lesions, including craniopharyngioma (CP), Rathke cleft cyst, xanthogranuloma, and dermoid and epidermoid cysts.

Results
There is significant evidence in the literature to support a common ectodermal origin of selected sellar and suprasellar cystic lesions, which may account for the overlap of features and transitional states observed in some cases. Research obtained from animal studies and reports of transitional cystic epithelial masses or lesions crossing over from typical to more aggressive pathological subtypes have collectively provided a solid foundation for this theory. Histological features that signify transitional entities beyond simple benign Rathke cleft cysts include squamous metaplasia, stratified squamous epithelium, and ciliated or mucinous goblet cells in squamous-papillary CPs. Several studies have identified key clinical, imaging, and histopathological features that can be used in the differentiation of these lesions.

Conclusions
The pattern of embryological formation of the hypothalamic-pituitary axis plays a major role in its propensity for developing cystic epithelial lesions. Subsequent inflammatory, metaplastic, and neoplastic processes may promote further progression along the pathological continuum, ranging from benign epithelial cysts to aggressive neoplastic cystic CPs. Selected clinical, imaging, and histopathological features can be used collectively to help differentiate these lesions and assign a formal diagnosis, thus accurately guiding further treatment.
Cost-effectiveness analysis of roadmap models in chronic hepatitis B using tenofovir as the rescue therapy
Authors: Lui Yanni Yan-Ni , Tsoi Kelvin Kam-Fai , Wong Vincent Wai-Sun , Kao Jia-Horng , Hou Jin-Lin , Teo Eng-Kiong , Mohamed Rosmawati , Piratvisuth Teerha , Han Kwang-Hyub , Mihm Ulrike , Wong Grace Lai-Hung , Chan Henry Lik-Yuen 
Published: April 2010

Background The roadmap approach is recommended to guide chronic hepatitis B treatment. We evaluated the cost- effectiveness of various treatment strategies in the global market. Methods Lamivudine and telbivudine were tested in roadmap models with switch-to tenofovir if HBV was detectable at week 24 or add-on tenofovir if resistance developed at year 1. Tenofovir and entecavir were tested as continuous monotherapy. In the reference arm, lamivudine was used with add-on tenofovir if resistance developed at year 1. The primary measure of effectiveness was undetectable HBV DNA at year 2. Cost-effectiveness was measured by incremental cost-effectiveness ratio (ICER) in US dollars against the reference arm. Results In the US and Germany, costs of the reference arms were US $14,486 and US $9,998 for hepatitis B e antigen (HBeAg)-positive and US $11,398 and US $7,531 for HBeAg-negative patients, respectively. In HBeAg-positive patients, the lamivudine roadmap was most cost-effective (ICER US $15,260 in the US and US $29,113 in Germany) with comparable effectiveness (75.1%) to other strategies. In HBeAg-negative patients, tenofovir and entecavir monotherapies were most effective (91–96%) and cost- effective (ICER US $31,297–43,387 in the US and US $53,976–59,822 in Germany). In Asia, where telbivudine cost was lower, both telbivudine and lamivudine roadmaps were cost-effective in HBeAg-positive patients. Tenofovir would be most cost-effective in HBeAg-negative patients if its cost equaled that of telbivudine in Asia. Conclusions In HBeAg-positive patients, lamivudine roadmap was most cost-effective; in Asia, telbivudine roadmap had comparable cost-effectiveness to lamivudine roadmap because of the relatively low price of telbivudine. In HBeAg-negative patients, entecavir and tenofovir monotherapies were more cost-effective than the roadmap models.
Differential effects of interferon and lamivudine on serum HBV RNA inhibition in patients with chronic hepatitis B
Authors: Huang Yi-Wen , Chayama Kazuaki , Tsuge Masataka , Takahashi Shoichi , Hatakeyama Tsuyoshi , Abe Hiromi , Hu Jui-Ting , Liu Chun-Jen , Lai Ming-Yang , Chen Ding-Shinn , Yang Sien-Sing , Kao Jia-Horng 
Published: April 2010

BackgroundLamivudine and interferon have been widely used for the treatment of patients with chronic HBV infection. Serum HBV RNA is detected during lamivudine therapy as a consequence of interrupted reverse transcription and because RNA replicative intermediates are unaffected by the drug. In this study, we aimed to determine the detectability of serum HBV RNA during sequential combination therapy of interferon and lamivudine.MethodsHBV DNA and RNA in serum samples were quantified by reverse transcription of HBV nucleic acid extract and real-time PCR. Samples were analysed every 2 weeks to 3 months from three groups of patients: 10 male patients treated with nucleoside analogue mono-therapy for 44–48 weeks (5 with lamivudine and 5 with entecavir), 6 males on sequential interferon and lamivudine combination therapy, and 3 males on lamivudine monotherapy for 20–24 weeks.ResultsHBV RNA was not detectable in any patients before treatment, but became detectable in 15 during antiviral treatment. Among the three groups, pre-treatment HBV DNA (8.1 ±2.4 versus 7.7 ±1.4 versus 5.1 ±0.3 log10copies/ml; P=0.06), treatment and follow-up durations (45.5 ±2.0 versus 49.7 ±5.6 versus 48.7 ±6.4 weeks; P=0.32) were comparable. HBV RNA was detectable at the end of treatment or follow-up in all patients with monotherapy, but in none of those with sequential combination therapy (100% versus 0%; P<0.001).ConclusionsCompared with lamivudine therapy with detectable serum HBV RNA in patients with chronic HBV infection, interferon treatment might reduce HBV DNA replication through the inhibition of HBV RNA replicative intermediates, resulting in the loss of serum HBV RNA.
The Protease Inhibitors Ritonavir and Saquinavir Influence Lipid Metabolism: A Pig Model for the Rapid Evaluation of New Drugs
Authors: Petersen Eskild , Mu Huiling , Porsgaard Trine , Bertelsen Lone S 
Published: April 2010

Background Studies of the effects of antiretroviral drugs on lipid metabolism are limited by the availability of suitable models. We have thus developed an animal model utilising Göttingen mini-pigs. The normal lipid metabolism of mini-pigs closely reflects that of humans and they are expected to have similar reactions to antiretroviral drugs. Methods The pigs were treated orally with high doses of the protease inhibitors ritonavir and saquinavir for 4 weeks. The model allows repeated concomitant biopsies from liver, muscle, adipose tissue and plasma samples. Results The study showed a general decrease in poly-unsaturated fatty acids; changes in both saturated and monounsaturated fatty acids were also apparent after antiretroviral treatment. The changes were observed after 4 weeks of treatment. At 4 weeks post-treatment, the levels of all fatty acids were lower compared with pre-treatment levels, suggesting a prolonged effect of the antiretroviral drug treatment lasting beyond the 4 week post-treatment observation period. Conclusions The Göttingen mini-pig model is a promising animal model for rapid screening of the metabolic effects induced by antiretroviral drugs.
Long-term adefovir dipivoxil monotherapy for up to 5 years in lamivudine-resistant chronic hepatitis B
Authors: Lee Jung Min , Park Jun Yong , Kim Do Young , Nguyen Tin , Hong Sun Pyo , Kim Soo Ok , Chon Chae Yoon , Han Kwang-Hyub , Ahn Sang Hoon 
Published: April 2010

Background Large clinical studies assessing long-term adefovir dipivoxil salvage monotherapy in patients with lamivudine-resistant chronic hepatitis B (CHB) are lacking, particularly in patients positive for hepatitis B e antigen (HBeAg). We assessed the efficacy and resistance profile of adefovir dipivoxil monotherapy for up to 5 years in a large cohort of Korean patients with lamivudine-resistant CHB. Methods A total of 320 patients (81.3% HBeAg-positive; 100% genotype C) with confirmed genotypic lamivudine-resistant CHB were switched to adefovir dipivoxil 10 mg once daily. Liver function tests and HBV DNA were monitored every 3 months. Genotypic resistance to adefovir dipivoxil was performed in patients with detectable HBV DNA. Results The overall cumulative virological response rate at 5 years of adefovir dipivoxil therapy was 48.8%. The virological response rate was significantly higher in HBeAg-negative patients (62.0% versus 45.9%; P=0.010). Most cases of virological response (131/134, 97.8%) occurred within the first 36 months of therapy. The 5-year cumulative probability of genotypic resistance and virological breakthrough was 65.6% and 61.8%, respectively. Predictive factors for a virological response included baseline HBeAg seronegativity, HBV DNA≤8 log10 copies/ml and achievement of an on-treatment initial virological response. Conclusions Adefovir dipivoxil salvage monotherapy for lamivudine-resistant CHB resulted in a modest cumulative virological response rate at 5 years, which was associated with progressive antiviral resistance. Consequently, adefovir monotherapy is not preferable as a first-line strategy for lamivudine resistance where combination lamivudine plus adefovir dipivoxil therapy is available.
Positive and Negative drug Selection Pressures on the N348I Connection Domain Mutation: New Insights from in vivo Data
Authors:   UK Collaborative Group on HIV Drug Resistance,   UK Collaborative HIV Cohort Study, Price Huw , Asboe David , Pozniak Anton , Gazzard Brian , Fearnhill Esther , Pillay Deenan , Dunn David 
Published: April 2010

Background There is conflicting evidence on specific reverse transcriptase inhibitors to which the N348I mutation in the connection domain of HIV type-1 reverse transcriptase confers resistance. Here, we examined associations between the emergence of N348I and anti-retroviral history in a large clinical database. Methods We analysed 5,353 resistance tests (that were sequenced beyond codon 348) among 2,266 antiretroviral-experienced patients. Associations between N348I and individual antiretroviral drug exposure were estimated using a matched case-control approach. Cases were defined as the first resistance test where N348I was detected; for each case, the 10 closest (in calendar time) N348N tests were selected as controls. Odds ratios (ORs) adjusted for effects of all other drugs were estimated by conditional logistic regression. Results N348I was detected in 198 (8.7%) cases. Drugs that were statistically significantly positively associated with N348I were efavirenz (OR 1.55, 95% confidence interval [CI] 1.08–2.23; P=0.017) and nevirapine (OR 2.06, 95% CI 1.49–2.85; P<0.001). Tenofovir disoproxil fumarate (TDF) was significantly negatively associated (OR 0.27, 95% CI 0.15–0.48; P<0.001) with N348I. Similar findings were observed when the analysis was repeated to include only those tests within 2 years of the resistance test. Effects for zidovudine and stavudine were evident only in an additional analysis, which considered exposure to both drugs jointly within 2 years prior to the resistance test: exposure to zidovudine alone (OR 4.61, 95% CI 1.83–11.61; P<0.001) and exposure to stavudine alone (OR 3.39, 95% CI 1.32–8.71; P=0.011). Conclusions This is the first clinical evidence to suggest that efavirenz might select for N348I in addition to nevirapine, that stavudine might select for N348I in addition to zidovudine and that TDF might protect against the mutation.
Predicting the magnitude of short-term CD4+ T-cell recovery in HIV-infected patients during first-line highly active antiretroviral therapy
Authors: Castagna Antonella , Galli Laura , Torti Carlo , Monforte Antonella D'Arminio , Mussini Cristina , Antinori Andrea , Cozzi-Lepri Alessandro , Ladisa Nicoletta , De Luca Andrea , Seminari Elena , Gianotti Nicola , Lazzarin Adriano 
Published: April 2010

Background The extent of short-term CD4+ T-cell recovery in patients tolerating first-line highly active antiretroviral therapy (HAART) and attaining undetectable HIV RNA levels is inadequately defined. Methods We retrospectively analysed patients in four Italian cohorts who started HAART between January 1996 and September 2006. All patients had known HCV coinfection status, did not modify the regimen for 6 months and had <50 HIV RNA copies/ml at the end of the sixth month. Results The analysis involved 1,488 patients (1,096 males, 73.7%) with a median age of 43 years (interquartile range [IQR] 39–49); 435 (29.2%) were positive for HCV, 71 (4.8%) were positive for hepatitis B surface antigen (HBsAg) and 76 (5.1%) had experienced a previous AIDS-defining event. At baseline, patient CD4+ T-cell counts were 226 cells/μl (IQR 99–332), CD4+ T-cell percentages were 14.7% (IQR 8.7–21.2) and HIV RNA levels were 4.91 log10 copies/ml (IQR 4.38–5.34). Overall, 24-week CD4+ T-cell recovery was 144 cells/μl (IQR 70–240). At multivariable analysis, T-cell recovery was positively related to the use of a boosted protease inhibitor ( P<0.0001) or thymidine analogues ( P<0.0001), baseline HIV RNA levels ( P<0.0001), the baseline percentage of CD4+ T-cells ( P<0.0001) and the absence of HCV coinfection ( P=0.006). Age, gender, baseline CD4+/CD8+ T-cell ratio and a history of AIDS-defining events had no independent effect on CD4+ T-cell recovery. Conclusions Among HIV-infected patients tolerating first-line HAART and with undetectable HIV RNA after 6 months, CD4+ T-cell recovery is significantly greater in those without HCV coinfection, with a high baseline viral load, a high baseline percentage of CD4+ T-cells and in those treated with a boosted protease inhibitor.
Intravenous immunoglobulin therapy for patients with idiopathic cardiomyopathy and endomyocardial biopsy-proven high PVB19 viral load
Authors: Dennert Robert , Velthuis Sebastiaan , Schalla Simon , Eurlings Luc , van Suylen Robert-Jan , van Paassen Pieter , Tervaert Jan William Cohen , Wolffs Petra , Goossens Valère J , Bruggeman Catrien , Waltenberger Johannes , Crijns Harry J , Heymans Stephane 
Published: April 2010

Background Parvovirus B19 (PVB19) persistence in the heart has been associated with progressive cardiac dysfunction and evolution to dilated cardiomyopathy. In the present study, we investigated whether immunomodulation with intravenous immunoglobulin (IVIg) in addition to conventional heart failure therapy is safe and achieves virus reduction. Such therapy might improve cardiac function in patients with chronic dilated cardiomyopathy (DCM) and a significant PVB19 viral load in the heart. Methods PVB19 viral load was studied in 25 post-mortem cardiac samples of patients with a normal heart. Then, 17 consecutive patients (mean age 53 ±3 years) with DCM and symptomatic heart failure for >1 year with a PVB19 viral load in endomyocardial biopsies of >250 copies/μg DNA were treated with a high dose of IVIg (2 g/kg). Results The post-mortem cardiac samples revealed a PVB19 presence in 80% with a mean load of 131 ±40 copies/μg DNA. In the treated patients, IVIg resulted in a significant decrease of PVB19 viral load from 1,420 ±216 to 619 ±200 copies/μg DNA ( P=0.004) and significantly improved the ejection fraction from 33 ±3% 6 months before treatment and 34 ±3% at baseline to 41 ±3% 6 months ( P=0.001) after IVIg therapy. The New York Heart Association classification significantly improved from 2.5 ±0.1 at baseline to 2.1 ±0.1 at follow-up ( P=0.004). No therapy-related complications were noted. Conclusion The present pilot study demonstrates that IVIg significantly reduces viral load and improves cardiac function in patients with DCM related to increased PVB19 viral load in the heart.
The effect of tenofovir disoproxil fumarate on whole-body insulin sensitivity, lipids and adipokines in healthy volunteers
Authors: Randell Paul A , Jackson Akil G , Zhong Lijie , Yale Kitty , Moyle Graeme J 
Published: April 2010

Background Certain antiretrovirals are known to affect lipid and glucose homeostasis. The aim of this study was to assess the effect on insulin sensitivity (determined by peripheral glucose uptake using a hyperinsulinaemic euglycaemic clamp) of tenofovir disoproxil fumarate (TDF) administration compared with placebo for 2 weeks in HIV-1-seronegative healthy male volunteers. Changes in lipids, adiponectin, leptin, plasminogen activator inhibitor 1 (PAI-1) and the adhesion molecules E-selectin and P-selectin were also assessed. Methods This was a single-centre, randomized, double-blinded, placebo-controlled study that used a two-sequence, two-period cross-over design. A total of 19 HIV-negative males were recruited to the study and randomized 1:1 to receive either 2 weeks of TDF (300 mg once daily) followed by 2 weeks of placebo or placebo initially followed by tenofovir. Clamps were performed at baseline, after 2 weeks and after 4 weeks. Results All three clamps were completed by 16 participants. During the euglycaemic clamp, there were no significant changes in insulin sensitivity after 2 weeks of TDF administration compared with placebo or baseline. There was a significant reduction in the mean total cholesterol (9.4%) and low-density lipoprotein (LDL; 8.1%) cholesterol following 2 weeks of TDF compared with placebo. Levels of adiponectin, leptin, PAI-1, P-selectin and E-selectin were not significantly altered. Conclusions TDF use for 2 weeks does not affect insulin sensitivity, as assessed by the hyperinsulinaemic euglycaemic clamp in HIV-negative male volunteers. TDF use resulted in modest, but statistically significant, reductions in total and LDL cholesterol.
Treatment simplification to once daily darunavir/ ritonavir guided by the darunavir inhibitory quotient in heavily pretreated HIV-infected patients
Authors: Moltó José , Valle Marta , Santos José Ramón , Mothe Beatriz , Miranda Cristina , Cedeño Samandhy , Negredo Eugenia , Yritia Mercedes , Videla Sebastián , Barbanoj Manuel José , Clotet Bonaventura 
Published: April 2010

Background We explored a treatment simplification strategy to darunavir/ritonavir 900/100 mg once daily guided by the darunavir virtual inhibitory quotient (vIQ) in patients receiving salvage therapy with darunavir/ ritonavir 600/100 mg twice daily. Methods Open-label, randomized pilot study in HIV-infected patients on darunavir/ritonavir 600/100 mg twice daily (viral load <50 copies/ml; darunavir vIQ >2). Thirty patients were randomized to darunavir/ritonavir 900/100 mg once daily (once-daily group, n=15) or 600/100 mg twice daily (twice-daily group, n=15). Viral load, blood chemistry, and darunavir and ritonavir trough plasma concentrations (Ctrough) were determined up to 48 weeks. If the darunavir vIQ fell to <1.5, the dosage was switched to 600/100 mg twice daily. The primary end point was the percentage of 48-week treatment failure. Results Patients had taken a mean 11.6 (sd ±3.9) antiretro-viral regimens before darunavir/ritonavir administration. The proportion of patients without 48-week treatment failure was 86.7% in both groups. The median (interquartile range [IQR]) darunavir Ctrough decreased from 3.09 mg/l (IQR 2.43–3.93) at baseline to 1.60 mg/l (IQR 1.25–2.04) at week 48 ( P=0.001) in the once-daily group. Three once-daily group patients switched to darunavir/ritonavir 600/100 mg twice daily. Fewer patients had triglyceride levels >200 mg/ dl at week 48 in the once-daily group (20.0%) than in the twice-daily group (20.0% versus 57.1%; P=0.046). Conclusions Treatment simplification to darunavir/ ritonavir 900/100 mg once daily guided by the darunavir vIQ in treatment-experienced HIV-infected patients receiving darunavir/ritonavir 600/100 mg twice-daily seems to be safe enough to be tested in adequately powered clinical trials.
Estimating Indirect Costs in Primary Sjögren’s Syndrome
Authors: BOWMAN SIMON J. , ST. PIERRE YVAN , SUTCLIFFE NURHAN , ISENBERG DAVID A. , GOLDBLATT FIONA , PRICE ELIZABETH , HAMBURGER JOHN , RICHARDS ANDREA , RAUZ SAAEHA , REGAN MARIAN , RIGBY SHIRLEY , JONES ADRIAN , MULHERIN DIARMUID , CLARKE ANN E. 
Published: April 2010

Objective.To estimate the indirect costs associated with primary Sjögren’s syndrome (pSS) compared with rheumatoid arthritis (RA) and community controls.Methods.Data were obtained from 84 women patients with pSS as part of a study to develop a systemic activity measure, from 87 consecutive women patients with RA attending a hospital clinic, and from 96 women community controls on a general practice list. A modified economic component of the Stanford Health Assessment Questionnaire was used to assess lost productivity.Results.Using a conservative model, the estimated total annual indirect costs (95% CI) were £7677 (£5560, £9794) for pSS, £10,444 (£8206, £12,681) for RA, and £892 (£307, £1478) for controls. Using a model that maximizes the estimates, the equivalent figures were £13,502 (£9542, £17,463), £17,070 (£13,112, £21,028), and £3382 (£2187, £4578), respectively. These were all significantly greater at p < 0.001 for patient groups than for the control group.Conclusion.pSS is associated with significantly increased indirect costs equivalent to 69%–83% of that for patients with RA. This needs to be taken into account when evaluating the overall economic consequences of pSS.