Miracle-dz/UniFAR-FTUs huggingface dataset:
Patterns of Recurrence and outcome according to breast cancer subtypes in lymph node-negative disease: results from international breast cancer study group trials VIII and IX.

PURPOSE To retrospectively evaluate the pattern of recurrence and outcome of node-negative breast cancer (BC) according to major subtypes. PATIENTS AND METHODS In all, 1,951 patients with node-negative, early-stage BC randomly assigned in International Breast Cancer Study Group Trials VIII and IX with centrally reviewed pathology data were included. BC subtypes were defined as triple negative (TN; n = 310), human epidermal growth factor receptor 2 (HER2) positive (n = 369), and hormone receptor positive with high (luminal B-like [LB-like]; n = 763) or low (luminal A-like [LA-like]; n = 509) proliferative activity by Ki-67 labeling index. BC-free interval (BCFI) events were invasive BC recurrence in local, contralateral breast, nodal, bone, or visceral sites. Time to first site-specific recurrence was evaluated by using cumulative incidence and competing risks regression analysis. RESULTS Median follow-up was 12.5 years. The 10-year BCFI was higher for patients with LA-like (86%) BC compared with LB-like (76%), HER2 (73%), and TN (71%; P < .001) BC. TN and HER2 cohorts had higher hazard of BCFI event in the first 4 years after diagnosis (pre-trastuzumab). LB-like cohorts had a continuously higher hazard of BCFI event over time compared with LA-like cohorts. Ten-year overall survival was higher for LA-like (89%) compared with LB-like (83%), HER2 (77%), and TN (75%; P < .001) BC. LB-like subtypes had higher rates of bone as first recurrence site than other subtypes (P = .005). Visceral recurrence as first site was lower for the LA-like subgroup, with similar incidence among the other subgroups when treated with chemotherapy (P = .003). CONCLUSION BC subtypes have different distant recurrence patterns over time. Defining different patterns of BC recurrence can improve BC care through surveillance guidelines and can guide the design of clinical studies.
Moving radioimmunotherapy forward for follicular lymphoma.

The treatment of follicular non-Hodgkin lymphoma (NHL), which is the second most common NHL in Western countries, continues to evolve. In this issue of Journal of Clinical Oncology, two important reports deal with the upfront use of radioimmunotherapy (RIT) in follicular lymphoma (FL). Both of these studies enrolled FL patients who were considered to be in need of therapy. The report by Scholz et al 1 used RIT as a single-agent without any chemotherapy, whereas the second study by Press et al 2 was a phase III randomized trial of the standard six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) versus six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with RIT as consolidation (Southwest Oncology Group [SWOG] S0016). The results of these studies have implications for current care and the design of future studies but, as is typical for FL studies, leave us with nagging unanswered questions. RIT is a unique therapeutic modality that uses an antibody carrier to target high-energy, short–path-length radionuclides to tumor sites with little effect on other solid organs. If pretherapy guidelines are followed, the only toxicity is reversible myelosuppression. The known sensitivity of FL to conventional radiation therapy and the usual widespread nature of FL make this type of NHL an attractive target for RIT. Indeed, early randomized studies of unlabeled antibody versus the radiolabeled version of essentially the same antibody in relapsed indolent NHL demonstrated the advantage of the radioimmunoconjugate (RIC) with respect to the overall response rate (ORR) and complete response (CR) rates. 3,4
Initial clinical sensitivity and acquired resistance to MET inhibition in MET-mutated papillary renal cell carcinoma.

Introduction Papillary renal cell carcinoma (RCC) is the most prevalent nonclear cell histologic subtype of renal carcinoma and constitutes approximately 10% of renal cancers, affecting 5,400 patients per year in the United States. Activating MET mutations are present in the majority of hereditary papillary RCCs and up to 13% of sporadic papillary RCCs. Here we describe a patient with MET-mutated papillary RCC that responded to MET inhibition with a small molecule kinase inhibitor, PF-04217903, for 26 months. At the time of acquired resistance to treatment, we identified a genomic duplication that encompassed the mutated kinase domain of MET.
Alcohol consumption before and after breast cancer diagnosis: associations with survival from breast cancer, cardiovascular disease, and other causes.

PURPOSE Alcohol intake is associated with increased risk of breast cancer. In contrast, the relation between alcohol consumption and breast cancer survival is less clear. PATIENTS AND METHODS We assessed pre- and postdiagnostic alcohol intake in a cohort of 22,890 women with incident invasive breast cancer who were residents of Wisconsin, Massachusetts, or New Hampshire and diagnosed from 198 to 200 at ages 20 to 79 years. All women reported on prediagnostic intake; a subsample of 4,881 reported on postdiagnostic intake. RESULTS During a median follow-up of 11.3 years from diagnosis, 7,780 deaths occurred, including 3,484 resulting from breast cancer. Hazard ratios (HR) and 95% CIs were estimated. Based on a quadratic analysis, moderate alcohol consumption before diagnosis was modestly associated with disease-specific survival (compared with nondrinkers, HR = 0.93 [95% CI, 0.85 to 1.02], 0.85 [95% CI, 0.75 to 0.95], 0.88 [95% CI, 0.75 to 1.02], and 0.89 [95% CI, 0.77 to 1.04] for two or more, three to six, seven to nine, and ≥ 10 drinks/wk, respectively). Alcohol consumption after diagnosis was not associated with disease-specific survival (compared with nondrinkers, HR = 0.88 [95% CI, 0.61 to 1.27], 0.80 [95% CI, 0.49 to 1.32], 1.01 [95% CI, 0.55 to 1.87], and 0.83 [95% CI, 0.45 to 1.54] for two or more, three to six, seven to nine, and ≥ 10 drinks/wk, respectively). Results did not vary by beverage type. Women consuming moderate levels of alcohol, either before or after diagnosis, experienced better cardiovascular and overall survival than nondrinkers. CONCLUSION Overall alcohol consumption before diagnosis was not associated with disease-specific survival, but we found a suggestion favoring moderate consumption. There was no evidence for an association with postdiagnosis alcohol intake and breast cancer survival. This study, however, does provide support for a benefit of limited alcohol intake for cardiovascular and overall survival in women with breast cancer.
Leukotriene receptor antagonist therapy and Churg–Strauss syndrome: culprit or innocent bystander?

Randomised controlled trials can provide strong evidence of the efficacy (or lack) of new drug treatments as well as the occurrence of common side effects.1 However, clinical safety issues can arise after new medications receive regulatory approval, particularly in relation to rare serious adverse events.2 Investigation of rare adverse events is often fraught with difficulty, leading to uncertainty, particularly when there is conflicting evidence from research utilising different methodologies. One recent example is the observed association between leukotriene receptor antagonist (LTRA) therapy, used in the treatment of asthma, and Churg–Strauss syndrome (CSS), a vasculitis of uncertain aetiology (also known as allergic granulomatous angiitis). CSS is certainly both rare and serious, with a background incidence of 3 per million per year in the general population, and a 1 year mortality rate of 7%. 3–5 Soon after the introduction of LTRAs (zafirlukast, pranlukast and montelukast), numerous case reports and case series were published of patients who developed CSS after starting this therapy.6–13 The temporal relationship between the introduction of LTRA therapy and the development of CSS suggested a possible causal relationship. An underlying mechanism was proposed whereby LTRA therapy may lead to an imbalance in leukotriene receptor stimulation, resulting in unopposed activity of LTB4, a potent chemoattractant for eosinophils as well as neutrophils, which could potentially lead to eosinophilic tissue infiltration and the initiation of systemic vasculitis.14 15 A feature of a number of the case reports was that the introduction of the LTRA allowed significant oral steroid reduction, suggesting that this therapy may have unmasked previously existing CSS that had been suppressed by the steroids prescribed for asthma. Another observation was that some cases had severe or unstable asthma at the time LTRA therapy was introduced, which arguably may have represented …
Population-based molecular screening for Lynch syndrome: implications for personalized medicine.

PURPOSE Molecular screening techniques are available to identify hereditary Lynch syndrome in people with newly diagnosed colorectal cancer (CRC). We aimed to determine whether decisions of patients or clinicians reduced detection of Lynch syndrome. PATIENTS AND METHODS A prospective cohort of 245 consecutive individuals with mismatch repair-deficient CRC recruited from a population-based molecular screening program of all incident patient cases of CRC in a health care region of 1.2 million inhabitants. All incident CRCs were analyzed for mismatch repair protein loss, supported by BRAF mutation and microsatellite instability testing. Advice regarding referral for germline testing was provided to treating surgeons. RESULTS The mean age of patients was 72.5 ± standard deviation of 12 years; 64% were women; 65% had BRAF-mutant cancers. Consent for germline testing was received from 194 patients (79%): 120 with low and 74 with high likelihood of Lynch syndrome based on tumor molecular profile. Of patients who consented, 143 provided samples for germline analysis, with 12 of 143 showing a mutation (8.4%; 95% CI, 4.4% to 14.2%). Among the 102 patients who chose not to provide a sample or did not consent, an estimated 5.3 of 102 had germline mutations (5.2%; 95% CI, 2.0% to 17.5%). CONCLUSION A universal screening strategy for Lynch syndrome is potentially effective because the overall estimate of germline mutations was 17.3 of 245 patient cases (7.1%; 95% CI, 2.8% to 18.2%). However, the true value of screening is likely to be greatly limited by the decisions and circumstances of patients in taking up germline testing.
Serum glucose and triglyceride lowering activity of some novel glitazones against dexamethasone-induced hyperlipidemia and insulin resistance

Objectives: To study the serum glucose and triglyceride lowering activity of some novel glitazones against dexamethasone-induced hyperlipidemia and insulin resistance in rats. Materials and Methods: Serum glucose and triglyceride lowering activity of the test compounds and a standard, rosiglitazone, was tested at a dose of 10 mg/kg p.o. against dexamethasone-induced hyperlipidemia and insulin resistance in Sprague-Dawley (SD) rats. On day 11 of treatment, blood was collected for the estimation of serum glucose and triglyceride levels. Results: All the 14 compounds and rosiglitazone significantly ( P Conclusion: The present study indicates that some of the newer glitazones show significant glucose and triglyceride lowering activity. In comparison to rosiglitazone, these glitazones show comparable serum glucose lowering and better triglyceride lowering activity.
The vasodilating effects of insulin and lactate are increased in precapillary arterioles in the porcine retina ex vivo

Disturbances in the diameter regulation of the larger retinal vessels are involved in the pathophysiology of a number of vision threatening retinal diseases, but the role of the smaller vessels has received less attention. Therefore, an experimental model was developed for studying diameter changes in retinal vessels at all branching levels secondary to pharmacological interventions ex vivo.
Public availability of results of trials assessing cancer drugs in the United States.

PURPOSE To evaluate to what extent results of completed trials of cancer drugs conducted in the United States are publicly available at ClinicalTrials.gov, as required by the Food and Drug Administration Amendments Act (FDAAA), or are published in journals. METHODS We searched ClinicalTrials.gov for cancer trials governed by the FDAAA: phase II to IV trials assessing drugs in the United States with a primary completion date between December 26, 2007, and May 31, 2010. For each trial, we also searched PubMed to identify the publication of results. We assessed the cumulative percentages of posted or published results over time by using the Kaplan-Meier method. RESULTS We identified 646 trials, including 209 randomized controlled trials (RCTs). At 12 months after completion of the trials, the cumulative percentages of trials with results posted at ClinicalTrials.gov, published in journals, and available either at ClinicalTrials.gov or in journals were 9% (95% CI, 7% to 11%), 12% (95% CI, 10% to 15%), and 20% (95% CI, 17% to 23%), respectively, and for RCTs, the percentages were 12% (95% CI, 8% to 16%), 5% (95% CI, 2% to 8%), and 17% (95% CI, 12% to 22%), respectively. At 36 months, these percentages were 31% (95% CI, 28% to 35%), 35% (95% CI, 31% to 39%), and 55% (95% CI, 51% to 59%), respectively, and for RCTs, they were 38% (95% CI, 31% to 45%), 32% (95% CI, 25% to 39%), and 56% (95% CI, 48% to 62%), respectively. Public availability of phase III trials was 15% (95% CI, 7% to 23%) at 12 months, 39% (95% CI, 27% to 49%) at 24 months, and 64% (95% CI, 50% to 73%) at 36 months. CONCLUSION Despite the FDAAA, results for nearly half the trials of cancer drugs in the United States were not publicly available 3 years after completion of the trials.
Quantification of visual function assessment using remote eye tracking in children: validity and applicability

Measurements of visual and oculomotor functions are essential for providing tailored support to visually impaired children. In young or intellectually disabled children these measurements can be difficult or even impossible to perform. Recordings of orienting gaze in response to specific visual information, made with eye tracking, may offer a solution. The aim of this study was to observe and quantify eye tracking (ET)‐based gaze responses to provide information about visual and oculomotor functioning, and to compare this information with standard visual function assessments (VFA).
British Thoracic Society Pleural Disease Guidelines - 2010 update

Pleural disease remains common, affecting over 3000 people per million population each year. It therefore presents a significant contribution to the workload of respiratory physicians. These guidelines attempt to summarise the available evidence to aid the healthcare professional in delivering good quality patient care. Since the last BTS pleural disease guidelines were published in 20031 a large number of good quality primary research papers have been published and the guidelines need to reflect this new data. In addition, there was a need to develop new sections on local anaesthetic (LA) thoracoscopy and thoracic ultrasound to reflect changes in clinical practice. The guideline is divided into the following sections: 1. Investigation of a unilateral pleural effusion in adults 2. Management of spontaneous pneumothorax 3. Management of a malignant pleural effusion 4. Management of pleural infection in adults 5. Local anaesthetic thoracoscopy 6. Chest drain insertion and thoracic ultrasound A working party was established with representation from a range of professionals with an interest in pleural disease together with a lay representative. The guidelines are based upon the best available evidence. The methodology followed the criteria as set out by the AGREE collaboration in the document, The AGREE instrument, available on-line at: http://www.agreecollaboration. org/instrument/ The scope and purpose of the guideline had been agreed and defined in consultation with all potential stakeholders representing the medical and nursing professions, patient groups, health management and industry. Guideline members identified and formulated a set of key clinical questions in PICO(T) (Population, Intervention, Comparison, Outcome and Time) format to inform the search strategies for the literature search.The BTS commissioned a bespoke literature search using the search strategies shown in detail on the BTS website (http://www.brit-thoracic.org.uk). Searches were limited to English and adult literature. 19,425 potential papers were identified by the search. 17393 abstracts were rejected through the criteria …
Carotid Artery Stenosis Correlation with Hyperhomocysteinemia in Stroke Patient Group: a Prospective Study

Carotid Artery Stenosis Correlation with Hyperhomocysteinemia in Stroke Patient Group: a Prospective Study Introduction. Stroke is the second most common cause of death worldwide and one of the major causes of long-term disability. Carotid artery stenosis is an independent risk factor for ischemic stroke and related forms of atherosclerotic vascular disease. Aim of the Study was to examine plasma homocysteine (tHcy) levels in the stroke patient's group with significant carotid artery stenosis, to determine hyperhomocysteinemia correlation with degree of carotid artery stenosis. Materials and methods. This study was prospective and all patients (n=102) included in the study were hospitalized in Pauls Stradins Clinical University hospital in Clinic of Neurology with diagnosis of acute ischemic stroke. In the group of significant carotidal stenosis we included 48 patients with various degree of stenosis ranging from 50% to total occlusion. Evaluations of stenosis of extracranial carotid arteries were done by duplex ultrasonography method. The blood of these patients was tested for homocysteine level by ELISA (IMMULITE 2000). Results. Study did not demonstrated statistically significant difference between levels of tHcy in all groups. Mean homocysteine level was not significantly higher in the symptomatic carotid stenosis patient's group. Also there were no significant differences between levels of homocysteine in patient group with different degree of stenosis. Conclusions. We found no meaningful association between a high tHcy level and extent of carotid stenosis.
Evolution of clinical trial design in early drug development: systematic review of expansion cohort use in single-agent phase I cancer trials.

PURPOSE To evaluate the use and objectives of expansion cohorts in phase I cancer trials and to explore trial characteristics associated with their use. METHODS We performed a systematic review of MEDLINE and EMBASE, limiting studies to single-agent phase I trials recruiting adults and published after 2006. Eligibility assessment and data extraction were performed by two reviewers. Data were assessed descriptively, and associations were tested by univariable and multivariable logistic regression. RESULTS We identified 611 unique phase I cancer trials, of which 149 (24%) included an expansion cohort. The trials were significantly more likely to use an expansion cohort if they were published more recently, were multicenter, or evaluated a noncytotoxic agent. Objectives of the expansion cohort were reported in 74% of trials. In these trials, safety (80%), efficacy (45%), pharmacokinetics (28%), pharmacodynamics (23%), and patient enrichment (14%) were cited as objectives. Among expansion cohorts with safety objectives, the recommended phase II dose was modified in 13% and new toxicities were described in 54% of trials. Among trials aimed at assessing efficacy, only 11% demonstrated antitumor activity assessed by response criteria that was not previously observed during dose escalation. CONCLUSION The utilization of expansion cohorts has increased with time. Safety and efficacy are common objectives, but 26% fail to report explicit aims. Expansion cohorts may provide useful supplementary data for phase I trials, particularly with regard to toxicity and definition of recommended dose for phase II studies.
Patterns of cognitive dissonance-reducing beliefs among smokers: a longitudinal analysis from the International Tobacco Control (ITC) Four Country Survey

Objective The purpose of this paper is to assess whether smokers adjust their beliefs in a pattern that is consistent with Cognitive Dissonance Theory. This is accomplished by examining the longitudinal pattern of belief change among smokers as their smoking behaviours change. Methods A telephone survey was conducted of nationally representative samples of adult smokers from Canada, the USA, the UK and Australia from the International Tobacco Control Four Country Survey. Smokers were followed across three waves (October 2002 to December 2004), during which they were asked to report on their smoking-related beliefs and their quitting behaviour. Findings Smokers with no history of quitting across the three waves exhibited the highest levels of rationalisations for smoking. When smokers quit smoking, they reported having fewer rationalisations for smoking compared with when they had previously been smoking. However, among those who attempted to quit but then relapsed, there was once again a renewed tendency to rationalise their smoking. This rebound in the use of rationalisations was higher for functional beliefs than for risk-minimising beliefs, as predicted by social psychological theory. Conclusions Smokers are motivated to rationalise their behaviour through the endorsement of more positive beliefs about smoking, and these beliefs change systematically with changes in smoking status. More work is needed to determine if this cognitive dissonance-reducing function has an inhibiting effect on any subsequent intentions to quit.
Adjuvant ganglioside GM2-KLH/QS-21 vaccination versus observation after resection of primary tumor > 1.5 mm in patients with stage II melanoma: results of the EORTC 18961 randomized phase III trial.

PURPOSE The GM2 ganglioside is an antigen expressed in the majority of melanomas. The GM2-KLH/QS-21 vaccine induces high immunoglobulin M (IgM) and IgG antibody responses. The EORTC 18961 trial compared the efficacy of GM2-KLH/QS-21 vaccination versus observation. PATIENTS AND METHODS A total of 1,314 patients with a primary tumor > 1.50 mm in thickness (T3-4N0M0; American Joint Committee on Cancer stage II) were randomly assigned to GM2-KLH/QS-21 vaccination (n = 657) or observation (n = 657). Treatment consisted of subcutaneous injections once per week from week 1 to 4, then every 3 months for the first 2 years and every 6 months during the third year. Primary end point was relapse-free survival (RFS). Secondary end points were distant metastasis-free survival (DMFS) and overall survival (OS). Analyses were by intent to treat. RESULTS After a median follow-up of 1.8 years, the trial was stopped at the second interim analysis for futility regarding RFS (hazard ratio [HR], 1.00; P = .99) and detrimental outcome regarding OS (HR, 1.66; P = .02). After a median follow-up of 4.2 years, we had recorded 400 relapses, nine deaths without relapse, a total of 236 deaths. At 4 years, the vaccination arm showed a decreased RFS rate of 1.2% (HR, 1.03; 95% CI, 0.84 to 1.25) and OS rate of 2.1% (HR, 1.16; 95% CI, 0.90 to 1.51). Toxicity was acceptable, with 4.6% of patients ending study participation because of toxicity. CONCLUSION GM2-KLH/QS-21 vaccination does not improve outcome for patients with stage II melanoma.