tbuckley/cabot-search huggingface dataset:
Concurrent weekly cisplatin during radiation treatment of locally advanced bladder carcinoma in elderly patients
Authors: H. Jouhadi, S. Sahraoui, A. Benider
Journal: Journal of Clinical Oncology (2008)

16109 Background: In Morocco chemoradiation is an alternative to radical cystectomy in invasive bladder cancer since 1995. The classical schedule associate definitive radiotherapy delivering 65 Gy in 7 weeks with 5FU and cisplatin (5FU: 1000 mg/m 2 day 1 to day 5 and cisplatin 100 mg/m 2 day 1) at Week 1, Week 3 and Week 7. Complete response was achieved in 70% but toxicity is high and inacceptable especially in elderly patients (Age >65 year). Aim of study: To assess efficacy and tolerance of new schedule of concurrent weekly cisplatin chemotherapy in conjunction with radiotherapy in the treatment of locally advanced bladder cancer. Methods: From March 2000 and December 2005 the Averroes oncology center enrolled 52 patients in Phase II study of weekly cisplatin (30 mg/m(2) × 6 doses) Plus radiation to a dose of 65 Gy equivalent: (24 × 2.5 gy) over 6 weeks. Inclusion criteria: was -bladder urothelial carcinoma, stage T3-T4, -age >65 year and -TUR. Results: Grade 3 vesical toxicity occurred in 27% of the patients. Twenty one patients (40%) experienced grade 2 rectal mucositis. Incidence of late complications was moderate (9%). Thirty five patients (67%) achieved complete remission at cystoscopic evaluation. After a minimal follow up of 2 years, local recurrence was seen in 6 of the 35 patients (17%). The local control rate was near 56% with a functional bladder being retained in 21 of the 29 patients (72%). Conclusions: this new schedule seems to be effective with an acceptable toxicity in elderly patients with bladder carcinoma. This approach is now being a real alternative to others schedules of chemoradiation. No significant financial relationships to disclose.
B cells in tumor draining lymph nodes act as efficient antigen presenting cells in cancer patients
Authors: A Ali Zirakzadeh, David Krantz, Malin Winerdal, Christian Lundgren, Ciputra Adijaya Hartana, Emma Ahlén Bergman, Johan Hansson, Benny Holmström, Alexander Sidiki, Janos Vasko, Markus Johansson, Per Marits, Amir Sherif, Ola Winqvist
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Overall Survival of patients with muscle invasive urothelial bladder cancer MIBC remains around 50% (5 years), albeit some improvements by combining neoadjuvant chemotherapy with radical surgery. Our previous work has demonstrated that in vitro expansions of sentinel node-acquired
The need for ethical reflection on the use of molecular microbial characterisation in outbreak management
Authors: B Rump, C Cornelis, F Woonink, M Verweij
Journal: Eurosurveillance (2013)

Current thinking on the development of molecular microbial characterisation techniques in public health focuses mainly on operational issues that need to be resolved before incorporation into daily practice can take place. Notwithstanding the importance of these operational challenges, it is also essential to formulate conditions under which such microbial characterisation methods can be used from an ethical perspective. The potential ability of molecular techniques to show relational patterns between individuals with more certainty brings a new sense of urgency to already difficult ethical issues associated with privacy, consent and a moral obligation to avoid spreading a disease. It is therefore important that professionals reflect on the ethical implications of using these techniques in outbreak management, in order to be able to formulate the conditions under which they may be applied in public health practice.
Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent and mantle cell lymphomas (MCL): Updated results from the StiL NHL1 study.
Authors: Mathias J. Rummel, Norbert Niederle, Georg Maschmeyer, Andre G. Banat, Ulrich von Gruenhagen, Christoph Losem, Dorothea Kofahl-Krause, Gerhard Heil, Manfred Welslau, Christina Balser, Ulrich Kaiser, Eckhart Weidmann, Heinz A. Duerk, Harald Ballo, Martina Stauch, Juergen Barth, Axel Hinke, Wolfram Brugger
Journal: Journal of Clinical Oncology (2012)

3 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Sunday, June 3, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.
IGF-I-dependent upregulation of ZEB1 expression drives EMT in human prostate cancer cells in vitro
Authors: Tisheeka Graham, Haiyen Zhau, Valerie Odero-Marah, Adeboye Osunkoya, Mourad Tighiouart, Tongrui Liu, Jonathan Simons, Ruth O'Regan
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

3585 

The epithelial to mesenchymal transition (EMT) is crucial for the migration and invasion of many epithelial tumors including prostate cancer. Although it is known that ZEB1 overexpression promotes EMT primarily through down-regulation of E-cadherin in a variety of cancers, the soluble ligands responsible for the activation of ZEB1 have yet to be identified. In the present study, we investigated the role of IGF-I in the regulation of ZEB1 during EMT associated with prostate tumor cell migration. We found that ZEB1 is expressed in highly aggressive prostate cancer cells and in poorly differentiated human prostate tumors. IGF-I upregulates ZEB1 expression in prostate cancer cells exhibiting an epithelial phenotype. Conversely, in prostate cancer cells displaying a mesenchymal phenotype, ARCaPM, ZEB1 inhibition reverses the suppression of E-cadherin protein and down-regulates the expression of the mesenchymal markers, N-cadherin and fibronectin. Furthermore, ZEB1 blockade decreases migratory and invasive potential in ARCaPM compared to the control. These results identify ZEB1 as a key transcriptional regulator of EMT in prostate cancer and suggest that the aberrant expression of ZEB1 in prostate cancer cells occurs in part in response to IGF-I stimulation.
Case selection bias affected results
Authors: I. Campbell
Journal: BMJ (1996)

EDITOR,—Charles R Gillis and David J Hole provide clear evidence that patients of specialist surgeons have a higher survival rate from breast cancer than those of non-specialist surgeons.1 However, they go on to conclude that this association is one of cause and effect, rather than due to differences in the cases referred to the two groups of surgeons (case selection bias). Their reason is that the difference in outcome persisted after adjustment for some prognostic factors; but statistical techniques can correct …
A Randomized Trial of Circumferential Pulmonary Vein Ablation Versus Antiarrhythmic Drug Therapy in Paroxysmal Atrial Fibrillation
Authors: Carlo Pappone, Giuseppe Augello, Simone Sala, Filippo Gugliotta, Gabriele Vicedomini, Simone Gulletta, Gabriele Paglino, Patrizio Mazzone, Nicoleta Sora, Isabelle Greiss, Andreina Santagostino, Laura LiVolsi, Nicola Pappone, Andrea Radinovic, Francesco Manguso, Vincenzo Santinelli
Journal: Journal of the American College of Cardiology (2006)
Doctor gets suspended prison sentence for not giving priority to “very sick boy”
Authors: Clare Dyer
Journal: BMJ (2015)

A paediatrician found guilty of gross negligence manslaughter after a 6 year old boy in her care died of septic shock has been sentenced to two years in prison, suspended for two years.

Hadiza Gawa-Barba, 39, was a specialist paediatric registrar at Leicester Royal Infirmary when Jack Adcock, who had Down’s syndrome, was admitted with vomiting, diarrhoea, and breathlessness in February 2011.1 She diagnosed gastroenteritis but failed to notice “seriously abnormal” blood test results showing that his kidneys were shutting down.

When Jack went into cardiac arrest Gawa-Barba stopped the …
Unusual life-threatening Rosai-Dorfman disease of the trachea: role of NF- B
Authors: L.-F. Zhou, L. Chen, Q. Zhu, C. Wang, H. Xu, X.-F. Cui, L.-F. Jiang, S.-H. He, M. Huang, K.-S. Yin
Journal: Thorax (2010)

Rosai–Dorfman disease (RDD) is a rare non-neoplastic histioproliferative disorder characterised by painless lymphadenopathy, low fever, high erythrocyte sedimentation rate, leucocytosis and hypergammaglobulinaemia. Overactivity of nuclear factor κB (NF-κB) is linked with inflammatory, cancerous and autoimmune diseases. The first case is described of an unusual life-threatening RDD of the trachea with no lymphadenopathy at risk of suffocation in a 39-year-old Chinese woman. A diagnosis of RDD was made following CT scans, thoracotomy and histological examination. Gel shift assay revealed an essential role for NF-κB overactivity in RDD. The patient remains well with no evidence of progression without treatment. Histological confirmation should be sought in all cases as the clinical manifestation of RDD is similar to asthma or lung carcinoma.
Complete Response to Erlotinib and Bevacizumab in a Patient With Biphenotypic (Hepatobiliary) Primary Liver Carcinoma
Authors: Amy Zhou, Manik Amin, Kathryn J. Fowler, Elizabeth M. Brunt, Jesse Keller, Benjamin Tan
Journal: Journal of the National Comprehensive Cancer Network (2015)

Biphenotypic (hepatobiliary) primary liver carcinomas [B(H-B)PLCs] are rare tumors with features of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). These tumors are associated with a poor overall prognosis and treatment is not well defined. Research over the past 20 years has identified aberrations in several molecular pathways, including epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) in hepatocellular and biliary tract cancers. These discoveries led to the evaluation of targeted therapies, such as tyrosine kinase inhibitors, for the treatment of HCC and ICC. We report a case of a patient with metastatic B(H-B)PLC found to have a single nucleotide variant in the EGFR gene locus R521K who achieved a complete response on imaging after treatment with the combination of an EGFR inhibitor and a VEGF inhibitor. This case prompts consideration of further genomic analysis of these rare tumors and the potential use of targeted therapies in the treatment of patients with B(H-B)PLCs.
Abstract P401: Predicting Future Coronary Heart Disease Mortality Trends In England And Wales: A Bayesian Age Period Cohort Forecast Up To 2030
Authors: Maria Guzman Castillo, Duncan Gillespie, Kirk Allen, Piotr Bandosz, Volker Schmid, Simon Capewell, Martin O'Flaherty
Journal: Circulation (2014)

Background: Although the rate of death (mortality) from Coronary Heart Disease (CHD) has halved since the 1970s, CHD remains a major cause of all-cause mortality in the UK. Furthermore, population ageing plus recent increases in obesity and diabetes may soon increase total CHD deaths. Predictions of future CHD mortality are thus potentially problematic. Here we explore future projections of CHD mortality in England &amp; Wales under two conventional but dramatically contrasting assumptions. Materials and Methods: In SCENARIO A, we used a conventional counterfactual, assuming that the last-observed CHD mortality rates (ONS) from 2011 would persist unchanged to 2030.The future number of deaths was then calculated by applying those rates onto 2012-2030 population estimates. In SCENARIO B, we assumed that the recent trend in CHD mortality rates would continue. We used a well-established hierarchical Bayesian Age Period Cohort (BAPC) model, which works under the assumption that variability in CHD mortality can be explained by a combination of age, period and cohort effects. We fitted this model to the observed CHD mortality from 1979 to 2011 and then continued the linear trends in age, period and cohort effects up to 2030. We then used the BAPC model to predict mortality rates in 2012-2030, and then applied these rates to population projections to compute future deaths. Results: In scenario A, by assuming that 2011 mortality rates would continue at that level, the number of CHD deaths would increase 61.5% (39,597 of 64,323) by 2030. In scenario B, by assuming recent trends continued, the number of deaths would decrease 56.7% (-36,500 of 64,323) by 2030. This substantial decrease would occur despite a predicted slowing of mortality decline in middle aged groups. Conclusion: The decline in CHD mortality has been reasonably continuous since 1979, and there is little reason to believe it will soon halt. The underlying assumption of a commonly used mortality counterfactual thus appears slightly dubious. By contrast, the BAPC model offers a far more plausible prediction of future trends by simultaneously considering age, period and cohort effects and projecting each into the future. Thus, despite population ageing, we estimated that the number of CHD deaths would halve again between 2011 and 2030. Even so, shifts in population risk factors might still cause CHD mortality to move away from a trajectory of decline. There is no room for complacency and the promotion of cardiovascular health remains a top policy priority.
Risk Factors Associated With Severe Hypoglycemia in Older Adults With Type 1 Diabetes
Authors: Ruth S. Weinstock, Stephanie N. DuBose, Richard M. Bergenstal, Naomi S. Chaytor, Christina Peterson, Beth A. Olson, Medha N. Munshi, Alysa J.S. Perrin, Kellee M. Miller, Roy W. Beck, David R. Liljenquist, Grazia Aleppo, John B. Buse, Davida Kruger, Anuj Bhargava, Robin S. Goland, Rachel C. Edelen, Richard E. Pratley, Anne L. Peters, Henry Rodriguez, Andrew J. Ahmann, John-Paul Lock, Satish K. Garg, Michael R. Rickels, Irl B. Hirsch
Journal: Diabetes Care (2015)

Severe hypoglycemia is common in older adults with long-standing type 1 diabetes, but little is known about factors associated with its occurrence.A case-control study was conducted at 18 diabetes centers in the T1D Exchange Clinic Network. Participants were ≥60 years old with type 1 diabetes for ≥20 years. Case subjects (n = 101) had at least one severe hypoglycemic event in the prior 12 months. Control subjects (n = 100), frequency-matched to case subjects by age, had no severe hypoglycemia in the prior 3 years. Data were analyzed for cognitive and functional abilities, social support, depression, hypoglycemia unawareness, various aspects of diabetes management, C-peptide level, glycated hemoglobin level, and blinded continuous glucose monitoring (CGM) metrics.Glycated hemoglobin (mean 7.8% vs. 7.7%) and CGM-measured mean glucose (175 vs. 175 mg/dL) were similar between case and control subjects. More case than control subjects had hypoglycemia unawareness: only 11% of case subjects compared with 43% of control subjects reported always having symptoms associated with low blood glucose levels (P < 0.001). Case subjects had greater glucose variability than control subjects (P = 0.008) and experienced CGM glucose levels <60 mg/dL for ≥20 min on 46% of days compared with 33% of days in control subjects (P = 0.10). On certain cognitive tests, case subjects scored worse than control subjects.In older adults with long-standing type 1 diabetes, greater hypoglycemia unawareness and glucose variability are associated with an increased risk of severe hypoglycemia. A study to assess interventions to prevent severe hypoglycemia in high-risk individuals is needed.
Effect of Hemodynamics on Stroke Risk in Symptomatic Atherosclerotic Vertebrobasilar Occlusive Disease
Authors: Sepideh Amin-Hanjani, Dilip K. Pandey, Linda Rose-Finnell, Xinjian Du, DeJuran Richardson, Keith R. Thulborn, Mitchell S. V. Elkind, Gregory J. Zipfel, David S. Liebeskind, Frank L. Silver, Scott E. Kasner, Victor A. Aletich, Louis R. Caplan, Colin P. Derdeyn, Philip B. Gorelick, Fady T. Charbel
Journal: JAMA Neurology (2015)

Atherosclerotic vertebrobasilar (VB) occlusive disease is a significant etiology of posterior circulation stroke, with regional hypoperfusion as an important potential contributor to stroke risk.To test the hypothesis that, among patients with symptomatic VB stenosis or occlusion, those with distal blood flow compromise as measured by large-vessel quantitative magnetic resonance angiography (QMRA) are at higher risk of subsequent posterior circulation stroke.A prospective, blinded, longitudinal cohort study was conducted at 5 academic hospital-based centers in the United States and Canada; 82 patients from inpatient and outpatient settings were enrolled. Participants with recent VB transient ischemic attack or stroke and 50% or more atherosclerotic stenosis or occlusion in vertebral and/or basilar arteries underwent large-vessel flow measurement in the VB territory using QMRA. Physicians performing follow-up assessments were blinded to QMRA flow status. Follow-up included monthly telephone calls for 12 months and biannual clinical visits (for a minimum of 12 months, and up to 24 months or the final visit). Enrollment took place from July 1, 2008, to July 31, 2013, with study completion on June 30, 2014; data analysis was performed from October 1, 2014, to April 10, 2015.Standard medical management of stroke risk factors.The primary outcome was VB-territory stroke.Of the 82 enrolled patients, 72 remained eligible after central review of their angiograms. Sixty-nine of 72 patients completed the minimum 12-month follow-up; median follow-up was 23 (interquartile range, 14-25) months. Distal flow status was low in 18 of the 72 participants (25%) included in the analysis and was significantly associated with risk for a subsequent VB stroke (P = .04), with 12- and 24-month event-free survival rates of 78% and 70%, respectively, in the low-flow group vs 96% and 87%, respectively, in the normal-flow group. The hazard ratio, adjusted for age and stroke risk factors, in the low distal flow status group was 11.55 (95% CI, 1.88-71.00; P = .008). Medical risk factor management at 6-month intervals was similar between patients with low and normal distal flow. Distal flow status remained significantly associated with risk even when controlling for the degree of stenosis and location.Distal flow status determined using a noninvasive and practical imaging tool is robustly associated with risk for subsequent stroke in patients with symptomatic atherosclerotic VB occlusive disease. Identification of high-risk patients has important implications for future investigation of more aggressive interventional or medical therapies.
Desperately Seeking a Randomized Clinical Trial of Resynchronization Therapy for Patients With Heart Failure and Atrial Fibrillation⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Jonathan S. Steinberg
Journal: Journal of the American College of Cardiology (2006)
Characteristics of reoffending accommodation sites in Europe with clusters of Legionnaires’ disease, 2003–2007
Authors: K D Ricketts, R Yadav, M C Rota, C A Joseph, None on behalf of the European Working G
Journal: Eurosurveillance (2010)

Between 2003 and 2007, 21% (n=100/477) of accommodation sites linked to clusters of two or more cases of Legionnaires’ disease that were investigated by the European Surveillance Scheme for Travel-Associated Legionnaires’ Disease (EWGLINET) went on to be associated with at least one further case, despite reporting that satisfactory control measures had been implemented at the time the cluster was first detected. This paper examines these sites (termed reoffenders) in order to determine whether they share any characteristics that may have contributed to the reoffence. All investigations conducted at cluster sites between 2003 and 2007 were included in the analysis, giving a total of 615 investigations conducted at 477 sites. Every country that investigated more than three cluster sites had to deal with at least one reoffence, and one site reoffended five times. The cases involved in the cluster that stayed elsewhere during their incubation periods could be used to help assess the probability of exposure, and therefore the risk, posed by particular cluster sites. A more extensive investigation and control regime may be needed in some instances to better control the risk of Legionnaires’ disease at an accommodation site.
Minimally invasive approach for adrenal lesions: Systematic review of laparoscopic versus retroperitoneoscopic adrenalectomy and assessment of risk factors for complications
Authors: G. Conzo, E. Tartaglia, C. Gambardella, D. Esposito, V. Sciascia, C. Mauriello, A. Nunziata, G. Siciliano, G. Izzo, F. Cavallo, G. Thomas, M. Musella, L. Santini
Journal: International Journal of Surgery (2015)
INT230-6 shows strong synergy with anti-PD-1 and can induce high complete response rates with T cell memory response in a colon cancer mouse model
Authors: Anja C Bloom, Lewis H Bender, Masaki Terabe, Jay A Berzofsky, Ian B Walters
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Intratumorally (IT) administered INT230-6 (a combination of cisplatin, vinblastine and an amphiphilic cell penetration excipient) induces complete responses (CR) in large established tumors, durable protection against re-inoculation, and the ability to shrink and/or resolve non-
Broadly neutralizing human monoclonal JC polyomavirus VP1–specific antibodies as candidate therapeutics for progressive multifocal leukoencephalopathy
Authors: Ivan Jelcic, Benoit Combaluzier, Ilijas Jelcic, Wolfgang Faigle, Luzia Senn, Brenda J. Reinhart, Luisa Ströh, Roger M. Nitsch, Thilo Stehle, Mireia Sospedra, Jan Grimm, Roland Martin
Journal: Science Translational Medicine (2015)

Human monoclonal antibodies broadly neutralize multiple PML-causing JC polyomavirus variants.
Regulation of Hepcidin by Erythropoiesis: The Story So Far
Authors: Sant-Rayn Pasricha, Kirsty McHugh, Hal Drakesmith
Journal: Annual Review of Nutrition (2016)

Hepcidin is the master regulator of systemic iron homeostasis, facilitating iron balance by controlling intestinal iron absorption and recycling. Hepcidin levels are suppressed when erythropoiesis is stimulated, for example following acute blood loss, appropriately enhancing cellular iron export to the plasma to support production of new red blood cells. However, persistent increased and ineffective erythropoiesis, for example in thalassemia, results in sustained elevations in iron absorption, which cause iron overload with associated organ toxicities. The ligands, receptors, and canonical pathways by which iron loading and inflammation upregulate hepcidin expression have been largely established. However, although several mechanisms have been proposed, the means by which erythropoiesis causes hepcidin suppression have been unclear. The erythroid-derived hormone erythroferrone appears to be a convincing candidate for the link between increased erythropoiesis and hepcidin suppression. If confirmed to be clinically and physiologically relevant in humans, potentiation or inhibition of erythroferrone activity could be a crucial pharmaceutical strategy.
Effect of Vitamin D Supplementation on Aortic Stiffness and Arterial Hemodynamics in People With Osteoarthritis and Vitamin D Deficiency
Authors: Panagiota Veloudi, C. Leigh Blizzard, Changhai H. Ding, Flavia M. Cicuttini, Xingzhong Jin, Anita E. Wluka, Tania Winzenberg, Graeme Jones, James E. Sharman
Journal: Journal of the American College of Cardiology (2015)
Echocardiographic Dyssynchrony and Health Status Outcomes From Cardiac Resynchronization Therapy
Authors: Paul S. Chan, Taiyeb Khumri, Eugene S. Chung, Stefano Ghio, Kimberly J. Reid, Bart Gerritse, Brahmajee K. Nallamothu, John A. Spertus
Journal: JACC. Cardiovascular imaging (2010)