tbuckley/cabot-search huggingface dataset:
Abstract OT3-1-01: A randomized phase II study of maintenance hormone therapy with or without capecitabine after induction chemotherapy with bevacizumab plus paclitaxel in hormone receptor positive and HER2 negative metastatic breast cancer (KBCSG-TR1214)
Authors: T Yoshinami, T Nakayama, M Ikeda, M Iwamoto, Y Komoike, T Takashima, J Tsurutami, K Yoshidome, S Morita, N Masuda
Journal: Cancer Research (2013)

Abstract Background: The combination therapy of Bevacizumab (B) and Paclitaxel (P) has demonstrated to prolong progression free survival (PFS) in E2100 study. Because its PFS is very long, developing optimal therapeutic strategy of B+P, including management of toxicity is crucial. At the 1st International Consensus Conference for Advanced Breast Cancer, most experts agreed the maintenance endocrine therapy after effective induction chemotherapy. In KBCSG-TR 1214 study, we planned to examine the following clinical questions. 1. As a maintenance therapy, which is more effective either endocrine therapy alone (E) or endocrine therapy with Capecitabine (E+C)? 2. Can maintenance therapy reduce toxicity of B+P and restore patient's QOL.? 3. How effective is B+P re-challenge after failure of maintenance therapy? Methods: KBCSG-TR 1214 study is multicenter open-labeled randomized phaseII trial for HR-positive and HER2-nagative metastatic breast cancer(MBC) patients. Patients will receive B (10mg/kg q2w) in combination with P (90mg/m2 on day 1, 8, and 15 q4w) as an induction therapy. Patients without progression after 6 cycles of B+P will be randomized to E or E+C. Endocrine therapy will be chosen by their physician (treatment of physician's choice). Patients in E+C will receive endocrine therapy with Capecitabine 1657mg/m2 on day1 to 21 q4w. Stratification factors for randomization are menopausal status, presence of target lesion, number of prior endocrine therapies for MBC, with or without 1st line chemotherapy for MBC. After progression of maintenance therapy (E or E+C), B+P will be started again as a reintroduction therapy. Primary end point is PFS of maintenance therapy. Secondary end points include time to failure of strategy from randomization, efficacy of reintroduction therapy, overall survival and safety of induction therapy. Translational research is also planned. VEGF, angiopoetin-1, and apelin in plasma will be measured at four points (before induction therapy, at the beginning of the maintenance therapy and the re-induction therapy, and at the end of the trial). This study has just begun and planned 120 patients will be enrolled. (UMIN000008662). Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT3-1-01.
Reduced hepatitis B virus surface antigen-specific Th1 helper cell frequency of chronic HBV carriers is associated with a failure to produce antigen-specific antibodies in the Trimera mouse
Authors: Wulf Otto Böcher, Eithan Galun, Hadar Marcus, Nili Daudi, Dov Terkieltaub, Daniel Shouval, Hanns Friedrich Löhr, Yair Reisner
Journal: Hepatology (2000)

In chronic hepatitis B virus (HBV) infection weak antiviral immune responses are associated with viral persistence. We studied possible immune deficits underlying the lack of serum antibodies of such patients against the HBV surface antigen (HBsAg) in a novel human/mouse chimeric model. A hepatitis B surface antigen (HBs) vaccination of Balb/c mice engrafted with peripheral blood mononuclear cells (PBMC) of naturally HBV-immunized donors induced high frequencies of human HBsAg-specific B and T helper 1 (Th1) cells. These responses were associated with high serum anti-HBs antibody levels of the subclasses immunoglobulin G1 (IgG1) and IgG2 that are driven by interleukin-2 (IL-2) and interferon-γ (IFN-γ). In contrast, PBMC of chronic HBV carriers transplanted into the chimera failed to produce anti-HBs antibodies after vaccination with HBsAg and exhibited a deficit of antigen-specific Th1 cells. A possible influence of HBsAg or viremia was excluded by the lack of viral replication in such chimera. The observed T-cell defect was specific for HBsAg, as the B- and T-cell responses to tetanus toxoid (TT) were fully retained. Thus, our study shows that viral persistence in chronic HBV carriers is associated with an HBsAg-specific Th1 cell defect, which likely is responsible for the insufficient neutralizing anti-HBs-antibody response and is not reversed by HBs vaccination. Alternative approaches to induce HBs-specific Th1 cell responses might represent a future therapeutic option.
Efficacy of prolonged entecavir monotherapy in treatment-naïve chronic hepatitis B patients exhibiting a partial virologic response to entecavir
Authors: Han Na Choi, Jeong Eun Song, Hyeon Chul Lee, Hyeong Ho Jo, Chang Hyeong Lee, Byung Seok Kim
Journal: Clinical and Molecular Hepatology (2015)

Background/Aims The optimal management of patients exhibiting a partial virologic response (PVR) to entecavir (ETV) has not been determined. The aim of this study was to determine the long-term efficacy of prolonged ETV monotherapy in treatment-naÃ¯ve chronic hepatitis B (CHB) patients exhibiting a PVR to ETV therapy. Methods This study included 364 treatment-naÃ¯ve CHB patients treated with ETV for â¥48 weeks and who received continuous ETV monotherapy for â¥96 weeks. PVR was defined as a decrease in serum hepatitis B virus (HBV) DNA of more than 2 log10 IU/mL from baseline but with detectable HBV DNA by real-time PCR assay at week 48. Results Fifty-two of the 364 patients (14.3%) showed a PVR. Among them, 41 patients received continuous ETV monotherapy for â¥96 weeks (median duration 144 weeks, range 96-312 weeks), and 40 of these patients (95%) achieved a virologic response (VR, HBV DNA <20 IU/mL) during prolonged ETV monotherapy (median duration 78 weeks, range 60-288 weeks). The cumulative probabilities of a VR at weeks 96, 144, and 192 from treatment initiation were 78.0%, 92.7%, and 95.1%, respectively. The VR rate was 97.2% (35/36) in HBeAg-positive patients and 100% (5/5) in HBeAg-negative patients. In multivariate analysis, HBeAg positivity (odds ratio [OR], 9.231; 95% confidence interval [CI], 1.03-82.91; P=0.047) and a high baseline HBV DNA level (OR, 0.170; 95% CI, 0.08-0.37; P=0.000) were independently associated with a delayed virologic response. No patient developed genotypic resistance to ETV during follow-up. Conclusions Long-term ETV monotherapy is effective for achieving a VR in treatment-naÃ¯ve CHB patients exhibiting a PVR to ETV. HBeAg positivity and high baseline HBV DNA level were independently associated with a delayed virologic response. Keywords: Chronic hepatitis B; Entecavir; Partial virologic response
P87 The Impact of Respiratory Viruses and Pulmonary Exacerbations on FEV1 Decline in Adults with Cystic Fibrosis
Authors: WG Flight, KJ Mutton, AK Webb, RJ Bright-Thomas, AM Jones
Journal: Thorax (2012)

<h3>Introduction</h3> Viral respiratory infection (VRI) is associated with an increased rate of decline in lung function in children with cystic fibrosis (CF) but the long-term clinical impact of VRI in adults is poorly described. We performed a prospective observational study to determine the effect of VRI on lung function in adults with CF. <h3>Methods</h3> 100 adults with CF were followed for 12 months. Patients were seen every two months routinely and also at onset of new respiratory symptoms. Sputum, nose- and throat-swabs were collected at each visit for virological analysis. Polymerase chain reaction assays for adenovirus, influenza A&amp;B, metapneumovirus, parainfluenza 1–3, respiratory syncytial virus and rhinovirus were performed on each sample. Spirometry was recorded at each visit. Treatment failure was defined as a failure of the FEV1 to return to ≥90% of baseline after intravenous antibiotics. Statistical analysis utilised generalized linear models and multiple linear regression as appropriate, taking into account multiple observations from participants. <h3>Results</h3> 191/626 (30.5%) study visits were positive for ≥1 virus with rhinovirus accounting for 72.5%. The incidence of VRI and pulmonary exacerbation (PEx) was 1.6 and 2.5 cases/patient-year respectively. VRI was associated with increased risk of PEx (OR 2.2; 95% CI 1.6 – 3.1; p&lt;0.001). There was no significant difference in relative fall from baseline FEV<sub>1</sub> at virus-positive compared with virus-negative visits (8.7 vs 9.4%, p=0.4). Acute fall in FEV<sub>1</sub> was lower in virus-positive PEx compared with virus-negative PEx (12.7 vs 15.6%; p=0.04). Rate of PEx, but not of VRI, was associated with a statistically significant decline in FEV<sub>1</sub> over one year, adjusted for age, sex and baseline lung function (β coefficient –1.79; 95% CI –3.4 to –0.2; p=0.02). Intravenous antibiotics were given for 122 PEx of which 90 had pre- and post-antibiotic FEV<sub>1</sub> data available. 26/90 (29%) were classified as treatment failures. There was a trend towards lower likelihood of treatment failure in virus-positive PEx (OR 0.55; 95% CI 0.1 to 2.7; p=0.46). <h3>Conclusions</h3> Incidence of PEx, but not VRI, is associated with accelerated decline in FEV1 in adults with CF. Virus-positive PEx are associated with a lower acute fall in FEV1 than virus-negative PEx.
Evolution of Left Ventricular Ejection Fraction After Acute Myocardial Infarction
Authors: Johanna Sjöblom, Josephine Muhrbeck, Nils Witt, Mahbubul Alam, Viveka Frykman-Kull
Journal: Circulation (2014)

Background— Implantable cardioverter-defibrillator therapy improves survival in patients with reduced left ventricular ejection fraction (LVEF) after acute myocardial infarction (AMI). Although the risk of sudden cardiac death is highest in the first month after AMI, there is no survival benefit of early implantable cardioverter-defibrillator implantation, and the optimal time frame has yet to be established. Thus, the aim of this study was to investigate what proportion of post-AMI patients had improved LV function to such an extent that the indication for implantable cardioverter-defibrillator was no longer present. Methods and Results— Patients admitted for AMI with reduced LVEF (≤40%) were eligible for inclusion. Repeat echocardiographic examinations were performed 5 days, 1 month, and 3 months after the AMI. We prospectively included 100 patients with LVEF of 31±5.8% after AMI. At the 1-month follow-up, 55% had an LVEF &gt;35%. The main improvement in LVEF had occurred by 1 month. The mean difference in LVEF over the next 2 months was small, 1.9 percentage units. During the first 9 weeks, 10% of the patients suffered from life-threatening arrhythmias. Conclusions— Most patients have improved LVEF after AMI, and in the majority, the improvement can be confirmed after 1 month, implying that further delay of implantable cardioverter-defibrillator implantation may not be warranted. Life-threatening arrhythmias occurred in 10% of the patients, illustrating the high risk for sudden cardiac death in this population.
Estimating treatment effects for individual patients based on the results of randomised clinical trials
Authors: J. A. N. Dorresteijn, F. L. J. Visseren, P. M. Ridker, A. M. J. Wassink, N. P. Paynter, E. W. Steyerberg, Y. van der Graaf, N. R. Cook
Journal: BMJ (2011)

<b>Objectives</b> To predict treatment effects for individual patients based on data from randomised trials, taking rosuvastatin treatment in the primary prevention of cardiovascular disease as an example, and to evaluate the net benefit of making treatment decisions for individual patients based on a predicted absolute treatment effect. <b>Setting</b> As an example, data were used from the Justification for the Use of Statins in Prevention (JUPITER) trial, a randomised controlled trial evaluating the effect of rosuvastatin 20 mg daily versus placebo on the occurrence of cardiovascular events (myocardial infarction, stroke, arterial revascularisation, admission to hospital for unstable angina, or death from cardiovascular causes). <b>Population</b> 17 802 healthy men and women who had low density lipoprotein cholesterol levels of less than 3.4 mmol/L and high sensitivity C reactive protein levels of 2.0 mg/L or more. <b>Methods</b> Data from the Justification for the Use of Statins in Prevention trial were used to predict rosuvastatin treatment effect for individual patients based on existing risk scores (Framingham and Reynolds) and on a newly developed prediction model. We compared the net benefit of prediction based rosuvastatin treatment (selective treatment of patients whose predicted treatment effect exceeds a decision threshold) with the net benefit of treating either everyone or no one. <b>Results</b> The median predicted 10 year absolute risk reduction for cardiovascular events was 4.4% (interquartile range 2.6-7.0%) based on the Framingham risk score, 4.2% (2.5-7.1%) based on the Reynolds score, and 3.9% (2.5-6.1%) based on the newly developed model (optimal fit model). Prediction based treatment was associated with more net benefit than treating everyone or no one, provided that the decision threshold was between 2% and 7%, and thus that the number willing to treat (NWT) to prevent one cardiovascular event over 10 years was between 15 and 50. <b>Conclusions</b> Data from randomised trials can be used to predict treatment effect in terms of absolute risk reduction for individual patients, based on a newly developed model or, if available, existing risk scores. The value of such prediction of treatment effect for medical decision making is conditional on the NWT to prevent one outcome event. <b>Trial registration number</b> Clinicaltrials.gov NCT00239681.
Death of baby with anencephaly after mother was refused an abortion sparks controversy in India
Authors: M. Chaudhuri
Journal: BMJ (2012)

A recent case of a 22 year old pregnant woman whose baby had anencephaly and who had been denied an abortion by several doctors has sparked a debate about the upper time limit for abortion in India.

Usha Jethwa approached clinics for an abortion after she learnt in July this year that she was carrying a malformed fetus but she was turned away from all of them because she was 26 weeks pregnant at the time the defect was discovered. The baby was born in October and died within hours.

In India abortion is legal but is permitted only in certain circumstances. The Medical Termination of Pregnancy or MTP Act (1971), amended in 2003, allows a …
Nuclear DNA origin of mitochondrial complex I deficiency in fatal infantile lactic acidosis evidenced by transnuclear complementation of cultured fibroblasts
Authors: Vincent Procaccio, Bénédicte Mousson, Réjane Beugnot, Hervé Duborjal, François Feillet, Guy Putet, Isabelle Pignot-Paintrand, Anne Lombès, René De Coo, Hubert Smeets, Joël Lunardi, Jean-Paul Issartel
Journal: Journal of Clinical Investigation (1999)

We have studied complex I (NADH-ubiquinone reductase) defects of the mitochondrial respiratory chain in 2 infants who died in the neonatal period from 2 different neurological forms of severe neonatal lactic acidosis. Specific and marked decrease in complex I activity was documented in muscle, liver, and cultured skin fibroblasts. Biochemical characterization and study of the genetic origin of this defect were performed using cultured fibroblasts. Immunodetection of 6 nuclear DNA–encoded (20, 23, 24, 30, 49, and 51 kDa) and 1 mitochondrial DNA–encoded (ND1) complex I subunits in fibroblast mitochondria revealed 2 distinct patterns. In 1 patient, complex I contained reduced amounts of the 24- and 51-kDa subunits and normal amounts of all the other investigated subunits. In the second patient, amounts of all the investigated subunits were severely decreased. The data suggest partial or extensive impairment of complex I assembly in both patients. Cell fusion experiments between 143B206 ρ° cells, fully depleted of mitochondrial DNA, and fibroblasts from both patients led to phenotypic complementation of the complex I defects in mitochondria of the resulting cybrid cells. These results indicate that the complex I defects in the 2 reported cases are due to nuclear gene mutations.
Association between industry affiliation and position on cardiovascular risk with rosiglitazone: cross sectional systematic review
Authors: A. T Wang, C. P McCoy, M. H. Murad, V. M Montori
Journal: BMJ (2010)

Objective To explore a possible link between authors’ financial conflicts of interest and their position on the association of rosiglitazone with increased risk of myocardial infarction in patients with diabetes. Data sources On 10 April 2009, we searched Web of Science and Scopus for articles citing and commenting on either of two index publications that contributed key data to the controversy (a meta-analysis of small trials and a subsequent large trial). Data selection Articles had to comment on rosiglitazone and the risk of myocardial infarction. Guidelines, meta-analyses, reviews, clinical trials, letters, commentaries, and editorials were included. Data extraction For each article, we sought information about the authors’ financial conflicts of interest in the report itself and elsewhere (that is, in all publications within two years of the original publication and online). Two reviewers blinded to the authors’ financial relationships independently classified each article as presenting a favourable (that is, rosiglitazone does not increase the risk of myocardial infarction), neutral, or unfavourable view on the risk of myocardial infarction with rosiglitazone and on recommendations on the use of the drug. Results Of the 202 included articles, 108 (53%) had a conflict of interest statement. Ninety authors (45%) had financial conflicts of interest. Authors who had a favourable view of the risk of myocardial infarction with rosiglitazone were more likely to have financial conflicts of interest with manufacturers of antihyperglycaemic agents in general, and with rosiglitazone manufacturers in particular, than authors who had an unfavourable view (rate ratio 3.38, 95% CI 2.26 to 5.06 and 4.29, 2.63 to 7.02, respectively). There was likewise a strong association between favourable recommendations on the use of rosiglitazone and financial conflicts of interest (3.36, 1.94 to 5.83). These links persisted when articles rather than authors were used as the unit of analysis (4.69, 2.84 to 7.72), when the analysis was restricted to opinion articles (6.29, 2.15 to 18.38) or to articles in which the rosiglitazone controversy was the main focus (6.50, 2.56 to 16.53), and both in articles published before and after the Food and Drug Administration issued a safety warning for rosiglitazone (3.43, 0.99 to 11.82 and 4.95, 2.87 to 8.53, respectively). Conclusions Disclosure rates for financial conflicts of interest were unexpectedly low, and there was a clear and strong link between the orientation of authors’ expressed views on the rosiglitazone controversy and their financial conflicts of interest with pharmaceutical companies. Although these findings do not necessarily indicate a causal link between the position taken on the cardiac risk of rosiglitazone in patients with diabetes and the authors’ financial conflicts of interest, they underscore the need for further changes in disclosure procedures in order for the scientific record to be trusted.
Distinct mechanisms of epithelial adhesion for Candida albicans and Candida tropicalis. Identification of the participating ligands and development of inhibitory peptides.
Authors: C M Bendel, M K Hostetter
Journal: Journal of Clinical Investigation (1993)

The yeast Candida albicans is the leading cause of disseminated fungal infection in neonates, immunocompromised hosts, diabetics, and postoperative patients; Candida tropicalis is the second most frequent isolate. Because the integrin analogue in C. albicans shares antigenic, structural, and functional homologies with the beta 2-integrin subunits alpha M and alpha X, we investigated the role of integrin analogues in epithelial adhesion of C. albicans and C. tropicalis. On flow cytometry with the monoclonal antibody (mAb) OKM1, surface fluorescence was highest for C. albicans and significantly reduced for C. tropicalis (P < 0.001). However, adhesion to the human epithelial cell line HeLa S3 did not differ for these two candidal species: specific adhesion was highest for C. albicans at 44.0 +/- 1.8%, and only slightly lower for C. tropicalis at 38.8 +/- 3.6% (P = NS). The disparity between expression of the integrin analogue and epithelial adhesion suggested distinct mechanisms for this process in C. albicans versus C. tropicalis. Preincubation of C. albicans with anti-alpha M mAbs, with purified iC3b (the RGD ligand for the integrin analogue), or with 9-15-mer RGD peptides from iC3b all inhibited epithelial adhesion significantly (P < 0.001-0.04). Purified fibronectin or fibronectin-RGD peptides failed to block C. albicans adhesion. In contrast, epithelial adhesion of C. tropicalis was significantly inhibited by purified fibronectin and its RGD peptides (P < or = 0.021), but not by iC3b nor the iC3b-RGD peptides. Both iC3b and fibronectin were identified on the surface of epithelial cells after growth in serum-free medium. A polyclonal antibody to C3 inhibited C. albicans adhesion while a control antibody to fibronectin was ineffective; the converse was true for C. tropicalis. These results indicate that the pathogenic yeasts C. albicans and C. tropicalis recognize distinct RGD ligands present at the surface of the epithelial cell and that these interactions can be differentially inhibited by defined RGD peptides containing appropriate flanking sequences.
Diethylstilbestrol Therapy Gynecomastia
Authors: David A. Hendrickson
Journal: JAMA (1970)

<h3>To the Editor:—</h3> Gynecomastia may complicate prolonged hormonal therapy for adenocarcinoma of the prostate. Formation of acinar tissue with secretory activity may also arise in the breast of a man, but examples have only rarely been cited. This unusual complication occurred in a patient developing marked breast enlargement concurrent with prolonged diethylstilbestrol (stilbestrol) therapy. <h3>Report of a Case.—</h3> A 62-year-old Negro was hospitalized at Hennepin County General Hospital in February 1969 for lumbosacral back pain attributed to metastatic prostatic carcinoma. Transurethral prostatectomy 13 years previously had revealed adenocarcinoma of the prostate. Following bilateral orchiectomy the patient received 5 mg of diethylstilbestrol daily continuously until December 1968 when bone survey confirmed osteoblastic lesions secondary to metastatic carcinoma throughout the vertebral column, clavicles, calvarium, and long bones of the extremities. Diethylstilbestrol administration was then increased to 15 mg three times daily for ten days and then tapered to 5 mg three times