tbuckley/cabot-search huggingface dataset:
Persistence and Growth of Rat Liver Neoplastic Nodules Following Cessation of Carcinogen Exposure&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: N Hirota, G M Williams
Journal: JNCI Journal of the National Cancer Institute (1979)

Altered (hyperplastic) foci and neoplastic (hyperplastic) nodules identified by their resistance to iron accumulation were induced in the livers of F344 rats by limited feeding of N-2-fluorenylacetamide for three, four, or five cycles of 4-week intervals separated by 1 week of a basal diet. Foci were present by the end of three feeding cycles and increased in number with further carcinogen exposure. No nodules were present at the end of three or four cycles, but they appeared at later intervals after removal of the carcinogen. Nodules were present at the end of five cycles of feeding and increased in number later. Thus nodules were found to be persistent and to have the progressive growth ability in situ that is characteristic of neoplasms.
Assessing the Prognostic Value of Coronary Computed Tomography Angiography⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Stephan Achenbach
Journal: Journal of the American College of Cardiology (2008)

Computed tomography (CT) imaging of the coronary arteries is challenging. The coronary vessels are small, and they move very rapidly, so that tremendously high spatial and temporal resolution are necessary to obtain sharp images of the coronary tree. The first CT system successfully used to
Expression of activation markers in circulating basophils and the relationship to allergen-induced bronchoconstriction in subjects with mild allergic asthma
Authors: Brittany M. Salter, Graeme Nusca, Damian Tworek, John-Paul Oliveria, Steve G. Smith, Rick M. Watson, Tara Scime, Catie Obminski, Roma Sehmi, Gail M. Gauvreau
Journal: Journal of Allergy and Clinical Immunology (2015)
NICE rejects trastuzumab emtansine for use on NHS
Authors: Zosia Kmietowicz
Journal: BMJ (2015)

The advanced breast cancer treatment trastuzumab emtansine (marketed by Roche as Kadcyla) will not be available through normal funding routes on the NHS in England, final guidance from the UK National Institute for Health and Care Excellence has said.1

The drug has been licensed to treat HER2 positive metastatic breast cancer that has stopped responding to initial treatment. It is capable of extending the life of patients with advanced breast cancer by six months, but the cost of £90 000 (€130 000; $140 000) for an average course of treatment (14.5 months) gives trastuzumab a cost per quality adjusted life year (QALY) of £166 000, well above the normal threshold for drugs used at the end …
Annual mammography in women 40 to 48 y of age reduced breast cancer mortality at 10 y but not at a median 17.7 y
Authors: Melvyn Jones
Journal: Annals of Internal Medicine (2015)

Source Citation Moss SM, Wale C, Smith R, et al. Effect of mammographic screening from age 40 years on breast cancer mortality in the UK Age trial at 17 years' follow-up: a randomised controlled trial. Lancet Oncol. 2015;16:1123-32. 26206144
Pluripotent stem cells isolated from adult human lung tissue exhibit anti-fibrotic properties
Authors: Katrin Hostettler, Laura Keglowich, Thomas Geiser, Michael Tamm, Didier Lardinois, Michael Roth, Amid Gazdhar
Journal: European Respiratory Journal (2013)

Introduction: Dysregulated wound healing of the alveolar epithelium and increased proliferation of mesenchymal cells contribute to the development of pulmonary fibrosis. Hepatocyte growth factor (HGF) improved alveolar epithelial wound repair, and HGF-transfected bone marrow derived stromal cells reduced bleomycin-induced lung fibrosis in an animal model. We studied the role of HGF-expressing stem cells in the pathogenesis of lung fibrosis.  Methods: Primary human stem cells were isolated from fibrotic lung parenchyma. The effect of stem cell-derived conditioned media (CM) on myofibroblast proliferation and on alveolar epithelial wound repair (using human A549 cells) was studied.  Results: The pluripotency of the primary human stem cells was proven by positive stainings for Oct3/4 and NANOG. CXCR4 expression indicated the cells’ bone marrow origin. Stem cell-derived CM exerted a significant anti-proliferative effect on primary human lung myofibroblasts (22% growth inhibition). Stem cells secreted HGF as demonstrated by ELISA. Compared to control medium, alveolar epithelial repair was markedly increased in the presence of stem cell-derived CM (+ 32%). This positive repair effect was abolished in the presence of neutralizing anti-HGF-antibodies.  Conclusions: Our data demonstrate that CM obtained from bone marrow-derived lung resident stem cells inhibits the proliferation of myofibroblasts and enhances alveolar epithelium wound repair. Our data indicate that the anti-fibrotic effect is mediated via HGF. We hypothesize that HGF-expressing lung resident stem cells have fibro-protective properties and might therefore be a novel therapeutic approach for patients with idiopathic pulmonary fibrosis.
Systematic review and meta regression of factors affecting midline incisional hernia rates: An analysis of 14,618 patients
Authors: D. Bosanquet, J. Ansell, T. Abdelrahman, J. Cornish, R. Harries, A. Stimpson, L. Davies, J. Glasbey, K. Frewer, N. Frewer, D. Russell, I. Russell, J. Torkington
Journal: International Journal of Surgery (2015)
Evaluation of Short-Term Changes in Serum Creatinine Level as a Meaningful End Point in Randomized Clinical Trials
Authors: Steven G. Coca, Azadeh Zabetian, Bart S. Ferket, Jing Zhou, Jeffrey M. Testani, Amit X. Garg, Chirag R. Parikh
Journal: Journal of the American Society of Nephrology (2015)

Observational studies have shown that acute change in kidney function (specifically, AKI) is a strong risk factor for poor outcomes. Thus, the outcome of acute change in serum creatinine level, regardless of underlying biology or etiology, is frequently used in clinical trials as both efficacy and safety end points. We performed a meta-analysis of clinical trials to quantify the relationship between positive or negative short–term effects of interventions on change in serum creatinine level and more meaningful clinical outcomes. After a thorough literature search, we included 14 randomized trials of interventions that altered risk for an acute increase in serum creatinine level and had reported between–group differences in CKD and/or mortality rate ≥3 months after randomization. Seven trials assessed interventions that, compared with placebo, increased risk of acute elevation in serum creatinine level (pooled relative risk, 1.52; 95% confidence interval, 1.22 to 1.89), and seven trials assessed interventions that, compared with placebo, reduced risk of acute elevation in serum creatinine level (pooled relative risk, 0.57; 95% confidence interval, 0.44 to 0.74). However, pooled risks for CKD and mortality associated with interventions did not differ from those with placebo in either group. In conclusion, several interventions that affect risk of acute, mild to moderate, often temporary elevation in serum creatinine level in placebo–controlled randomized trials showed no appreciable effect on CKD or mortality months later, raising questions about the value of using small to moderate changes in serum creatinine level as end points in clinical trials.
Fracture risk estimation may facilitate the treatment gap in osteoporosis
Authors: Willem F Lems
Journal: Annals of the Rheumatic Diseases (2015)

Osteoporosis is a systemic disease, characterised by low bone mass and a deteriorated microarchitecture, leading to an increased susceptibility to fractures.1 SCOPE, a scorecard for osteoporosis in Europe, documents that the number of osteoporotic fractures in the 27 European Union (EU) countries will rise by 35% from 3.49 million in 2010 to 4.48 million in 2025.2 The analysis was performed with the assumption that age-specific and gender-specific incidence rates of fractures will remain constant over the period of 15 years. It is possible that the incidence rate will increase even more, due to an unhealthy lifestyle (immobility) and/or vitamin D deficiency, while the incidence rate may flatten when physicians will be more capable of closing the treatment gap (the proportion of individuals with high risk of fracture with adequate treatment vs the proportion of individuals with high risk of fracture without adequate treatment). At the moment, the treatment gap for osteoporosis is substantial, and varies widely between EU countries, from 25% to 95%2; there is no evidence that the treatment gap is substantially lower in other parts of the world.

In theory, it is not too difficult to close the gap, since dual-energy X-ray absorptiometry (DXA) machines are widely available for diagnosing osteoporosis, and since effective, relatively safe and inexpensive (generic) drugs are currently available. With DXA, the bone mineral density (BMD) of the spine and hips is measured; a BMD ≥ 2.5 SD below the young female adult mean (T-score ≤−2.5) at the lumbar spine or hip is (arbitrarily) defined as osteoporosis.1 Earlier, it has been documented that the risk of osteoporotic fractures increases continuously as BMD decreases, resulting in a 1.5-fold to 3-fold increase in risk of fracture for each decrease in SD.3 In addition, risk of fracture is elevated in patients with …
Debunking the curse of the rainbow jersey: historical cohort study
Authors: Thomas Perneger
Journal: BMJ (2015)

To understand the underlying mechanism of the "curse of the rainbow jersey," the lack of wins that purportedly affects the current cycling world champion.Historical cohort study.On the road.Professional cyclists who won the World Championship Road Race or the Tour of Lombardy, 1965-2013.Number of professional wins per season in the year when the target race was won (year 0) and in the two following years (years 1 and 2; the world champion wears the rainbow jersey in year 1). The following hypotheses were tested: the "spotlight effect" (that is, people notice when a champion loses), the "marked man hypothesis" (the champion, who must wear a visible jersey, is marked closely by competitors), and "regression to the mean" (a successful season will be generally followed by a less successful one).On average, world champions registered 5.04 wins in year 0, 3.96 in year 1, and 3.47 in year 2; meanwhile, winners of the Tour of Lombardy registered 5.08, 4.22, and 3.83 wins. In a regression model that accounted for the propensity to win of each rider, the baseline year accrued more wins than did the other years (win ratio 1.49, 95% confidence interval 1.24 to 1.80), but the year in the rainbow jersey did not differ significantly from other cycling seasons.The cycling world champion is significantly less successful during the year when he wears the rainbow jersey than in the previous year, but this is best explained by regression to the mean, not by a curse.
Nutritional status in elderly cancer patients: Why is it so important?
Authors: C. Terret, D. Pérol, G. Albrand, C. Fingal, P. Roux, P. Courpron, J. Droz
Journal: Journal of Clinical Oncology (2006)

8532 Background: To assess the prevalence of malnutrition in elderly patients (pts) with cancer and to determine the effect of malnutrition on Overall Survival (OS). Methods: Cancer pts aged 65 and older underwent a multidimensional geriatric assessment at our institution. Data were collected for calorie and protein intakes, Mini Nutritional assessment (MNA Nestlé), functional status (ADL score), and comorbidity (CIRS-G). Survival time was defined as the time from geriatric assessment to date of death or last follow-up. A Cox regression model was used to estimate the hazards ratio (HR) and 95 percent confidence intervals (95%CI) of risk factors for death. Results: 133 consecutive pts (68% male, 50% hospitalized) were evaluated from 05/1999 to 08/2002. Median age was 78 years (range: 66–92). Main tumour sites were prostate (36%), breast (15%), bladder (12%) and Head and Neck (10%). Forty eight pts (36%) had metastatic disease. Only 55 pts (43%) were fully independent in ADLs (score = 6), and 15 pts were completely independent in IADLs (score = 14). Fifty one pts (43%) had mild to severe disability/morbidity status (CIRS-G severity index ≥2). Regarding nutritional status, only 34% were estimated well nourished with MNA &gt;23.5, 54% had calorie intake ≤1500 kcal/day and 38% had body weight loss &gt; 5% in the last 3 months. Survival analysis was performed with a 16-month median follow up. Median survival time was 7 months (95%CI 6–9 months). In the univariate analysis, male gender, metastatic stage, MNA, ADL score and CIRS-G severity index were significantly correlated with OS. In the multivariate analysis, male gender (HR=2.3, 95% CI: 1.3–4.1), metastasis (HR=1.6, 95% CI: 1.0–2.6), MNA&lt;23.5 (HR=3.3, 95% CI: 1.8–6.0), CIRS-G severity index ≥2 (HR=2.8, 95%CI: 1.7–4.7) and ADL score &lt;6 (HR=1.9, 95%CI: 1.1–3.3), were found to be independent prognostic factors for shorter OS. Conclusions: These data show that malnutrition has a major impact on survival independently of cancer severity. Thus, nutritional status must be systematically assessed before treatment decision-making. Benefits of nutritional interventions need to be studied in future trials. No significant financial relationships to disclose.
Rituximab-CHOP (R-CHOP) plus maintenance pegylated interferon (PegInt) for patients (pts) with follicular lymphoma (FL) and no prior anthracycline-based therapy
Authors: A. S. Marr, F. Loberiza, J. M. Vose, P. J. Bierman, J. O. Armitage, M. Gaul, S. Blumel, R. G. Bociek
Journal: Journal of Clinical Oncology (2008)

8605 Background: The use of interferon alfa in pts with FL has been associated with improved disease-free survival and in some cases overall survival in a number of randomized trials. Methods: A phase I/II trial of CHOP-rituximab followed by maintenance PegInt in pts with FL and no prior anthracycline-based therapy. Treatment consisted of R-CHOP (rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 2 mg and prednisone 100 mg orally daily x 5 days) repeated at 21 day intervals for 6–8 cycles to a maximum response. Pts achieving at least a PR were assigned PegInt subcutaneously weekly for a planned 52 weeks individually dosed to maintain ≤ grade 2 toxicity profile. Results: Twenty seven pts were enrolled; four withdrew prior to receiving any therapy and one prior to receiving the first dose of PegInt. Twenty two pts were evaluable per protocol specifications. The median age of pts was 56 years (range 20–73). Nineteen patients had received no prior therapy; two patients had received one prior chemotherapy, and one patient had received prior radiation therapy. All patients who received at least one dose of PegInt were included in the analysis. Eighteen pts received 6 cycles of R-CHOP, and four pts received 8 cycles. The overall response rate to R-CHOP was 95% (complete response 15/22 or 68%; partial response 6/22 or 27% ). Fourteen pts (63%) completed 52 weeks of PegInt with the remainder stopping between 1 and 40 weeks because of toxicity. The median dose of PegInt tolerated by patients was 2.0 mcg/kg/wk. The most common toxicities (approximately 50% of patients each) from PegInt were fatigue, headache, anemia, neutropenia, and thrombocytopenia. Ten pts experienced grade 3 neutropenia at some point during therapy and the majority of toxicities otherwise were grade 1 or 2. With a median duration of follow-up for surviving pts of 34 months the 3 year probabilities of progression free and overall survival are 70% and 94% respectively. Conclusions: PegInt is feasible to administer in a maintenance fashion after R-CHOP in pts with FL. Pt willingness to accept grade 1–2 toxicities limited the number of pts who completed one year of therapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Schering-Plough
An annual rhythm in the battering of women
Authors: R P Michael, D Zumpe
Journal: American Journal of Psychiatry (1986)

Over 27,000 reports about women abused by their live-in male partners were provided by 23 shelter organizations in five locations in the United States. Cosinor analyses revealed statistically significant annual rhythms in the frequencies of abuse, with maxima in the summer. The rhythms were closely related to annual changes in ambient temperature in these locations, and the time of the maxima was similar to those previously reported for assaults and rapes. The findings support the hypothesis that violence by men toward women increases in summer independently of any major seasonal changes in the opportunity for contact between perpetrator and victim.
Shingles is linked to increased risk of cardiovascular events
Authors: Jacqui Wise
Journal: BMJ (2015)

A patient’s risk of stroke and myocardial infarction may increase in the six months after herpes zoster infection (shingles), research published in PLOS Medicine has shown.1

The self controlled case series analysis looked at 42 954 US Medicare beneficiaries aged 65 or older who had had a herpes zoster diagnosis and an ischaemic stroke, as …
A Single Lung Metastasis of Endometrioid Adenocarcinoma Synchronous with a Primary Bronchioloalveolar Carcinoma in the Same Lobe
Authors: Alberto Cavazza, Amalia Carpi, Massimiliano Paci, Annessi Valerio, Guglielmo Ferrari, Salvatore De Franco, Giorgio Sgarbi
Journal: Journal of Thoracic Oncology (2006)
Bendamustine Plus Rituximab (B-R) Versus CHOP Plus Rituximab (CHOP-R) As First-Line Treatment in Patients with Indolent and Mantle Cell Lymphomas (MCL) – 7 Year Updated Results from the StiL NHL1 Study
Authors: Mathias J. Rummel, Georg Maschmeyer, Arnold Ganser, Andrea Heider, Ulrich von Grünhagen, Christoph Losem, Gerhard Heil, Manfred Welslau, Christina Balser, Ulrich Kaiser, Eckhart Weidmann, Heinz Dürk, Hans Peter Böck, Martina Beate Stauch, Jürgen Barth, Wolfgang Blau, Alexander Burchardt, Frank Kauff, Axel Hinke, Wolfram Brugger
Journal: Blood (2014)
Higher body mass index is associated with plantar fasciopathy/‘plantar fasciitis’: systematic review and meta-analysis of various clinical and imaging risk factors
Authors: K D B van Leeuwen, J Rogers, T Winzenberg, M van Middelkoop
Journal: British Journal of Sports Medicine (2015)

What (risk) factors are associated with plantar fasciopathy (PF)?Systematic review with meta-analyses.Patients with PF.All factors described in prospective, case-control or cross-sectional observational studies.51 included studies (1 prospective, 46 case-control and 4 cross-sectional studies) evaluated a total of 104 variables. Pooling was possible for 12 variables. Higher body mass index (BMI) (BMI>27, OR 3.7 (95% CI 2.93 to 5.62)) in patients with PF was the only significant clinical association, and its effect was the strongest in the non-athletic subgroup. In people with PF compared to controls, pooled imaging data demonstrated a significantly thicker, hypoechogenic plantar fascia with increased vascular signal and perifascial fluid collection. In addition, people with PF were more likely to have a thicker loaded and unloaded heel fat pat, and bone findings, including a subcalcaneal spur and increased Tc-99 uptake. No significant difference was found in the extension of the first metatarsophalangeal joint.We found a consistent clinical association between higher BMI and plantar fasciopathy. This association may differ between athletic and non-athletic subgroups. While consistent evidence supports a range of bone and soft tissue abnormalities, there is lack of evidence for the dogma of clinical and mechanical measures of foot and ankle function. Clinicians can use this information in shared decision-making.
Ipilimumab safety profile: Summary of findings from completed trials in advanced melanoma.
Authors: R. A. Ibrahim, D. M. Berman, V. DePril, R. W. Humphrey, T. Chen, M. Messina, K. M. Chin, H. Y. Liu, M. Bielefield, A. Hoos
Journal: Journal of Clinical Oncology (2011)

8583 Background: Ipilimumab, an anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) antibody, has shown overall survival benefit in a phase III trial of patients with pretreated advanced melanoma (Hodi FS. NEJM 2010;363:711). Ipilimumab potentiates T cells by blocking the inhibitory function of CTLA-4; adverse events (AEs) associated with ipilimumab likely reflect this mechanism of action and are primarily inflammation-related. To further describe the safety profile of ipilimumab, a program wide review of observations from melanoma clinical trials was undertaken. Methods: A retrospective review was performed of safety data from 14 completed phase I-III trials of ipilimumab in patients with advanced melanoma. Safety data were pooled from 1498 patients treated with ipilimumab at various doses, alone and in combination with various agents, and AEs in the following categories were analyzed: all AEs; drug-related AEs; inflammation-related AEs, all serious AEs (SAEs); and drug-related SAEs. Results: Gastrointestinal (mostly diarrhea and/or colitis) and dermatologic (mostly rash, pruritus) inflammation-related AEs were the most common, with toxicities less frequently involving the liver and endocrine glands; neurological manifestations were rare. Inflammation-related AEs affecting other organ systems in <1% of patients included uveitis, pneumonitis, pancreatitis, autoimmune nephritis, myasthenia gravis, and others. Most inflammation-related AEs occurred during induction (initial 4 doses given once every 3 weeks). Conclusions: Of 1,498 patients studied, inflammation-related AEs occurred in 64.2% and resulted in death in <1% of patients. Although inflammation-related AEs associated with ipilimumab can be life threatening, these were generally mild and managed using product specific treatment guidelines that emphasize vigilance and appropriate use of immunosuppressive therapy and may require long-term hormone replacement. On-study AEs, n (%). Grade All AEs Drug-related AEs Inflammation-related AEs All SAEs Drug-related SAEs Any 1,452 (96.9) 1,271 (84.8) 962 (64.2) 597 (39.9) 319 (21.3) 3-4 689 (46.0) 379 (25.3) 266 (17.8) 470 (31.4) 241 (16.1) 5 50 (3.3) 13 (0.9) 9 (0.6) 49 (3.3) 13 (0.9)