tbuckley/cabot-search huggingface dataset:
LUX-breast 3: Randomized phase II study of afatinib alone or with vinorelbine versus investigator’s choice of treatment in patients (pts) with HER2-positive breast cancer (BC) with progressive brain metastases (BM) after trastuzumab or lapatinib-based therapy.
Authors: Heikki Joensuu, Mahmoud Ould Kaci
Journal: Journal of Clinical Oncology (2012)

TPS647 Background: Approximately 1/3 of pts with HER2-positive, advanced BC will develop BM with a poor prognosis. Efficacy of systemic therapies is limited since few drugs can readily cross the blood-brain barrier. BC BM represents a high unmet medical need for which novel targeted therapies are needed. Afatinib is a small molecule, irreversible ErbB Family Blocker that has shown preclinical activity in trastuzumab-resistant cell lines and HER2-positive tumor xenografts. Its clinical efficacy has been demonstrated in pts with heavily pre-treated, HER2-positive metastatic BC, who progressed after trastuzumab therapy, with partial responses in 10% and clinical benefit in 46% of pts. In a Phase I afatinib trial a sustained PR was observed in a NSCLC pt with BM, and in a phase II trial in NSCLC, pts with or without BM achieved comparable outcome on afatinib. The purpose of this study (NCT01441596) is to investigate whether afatinib alone or in combination with vinorelbine has any effect on HER2-positive BC with BM after failure of prior trastuzumab or lapatinib. Methods: Key eligibility criteria: histologically confirmed HER2-positive BC; recurrent/progressive BM during/after prior trastuzumab or lapatinib therapy; ≥1 measurable BM (≥10 mm on T1-weighted, gadolinium-enhanced MRI); extra-CNS lesions allowed; prior surgery, whole brain radiotherapy or stereotactic radiosurgery allowed; ECOG 0–2. Eligible pts are stratified by: ECOG score 0–1 vs 2; No of BM ≤ 3 vs &gt;3; prior lapatinib therapy. Pts are randomized to (n = 40/arm): Arm A: afatinib (40 mg/d oral); Arm B: afatinib (40 mg/d oral) + vinorelbine (25 mg/m 2 / week); Arm C: investigator’s choice of medical treatment approved for metastatic BC. Primary endpoint: pt benefit at 12 weeks (i.e. absence of CNS/extra CNS disease progression as per RECIST 1.1) and no tumour-related worsening of neurological signs/symptoms or increase in steroid dosage. Secondary endpoints: PFS, OS, safety and afatinib concentration in plasma/cerebrospinal fluid in ≥12 pts. The study began in October 2011 and enrollment is ongoing.
Blocking IL-6 trans-Signaling Prevents High-Fat Diet-Induced Adipose Tissue Macrophage Recruitment but Does Not Improve Insulin Resistance
Authors: Michael J. Kraakman, Helene L. Kammoun, Tamara L. Allen, Virginie Deswaerte, Darren C. Henstridge, Emma Estevez, Vance B. Matthews, Bronwyn Neill, David A. White, Andrew J. Murphy, Lone Peijs, Christine Yang, Steve Risis, Clinton R. Bruce, Xiao-Jun Du, Alex Bobik, Robert S. Lee-Young, Bronwyn A. Kingwell, Ajithkumar Vasanthakumar, Wei Shi, Axel Kallies, Graeme I. Lancaster, Stefan Rose-John, Mark A. Febbraio
Journal: Cell Metabolism (2016)
Strengthening institutional capacity for equitable health research: lessons from Latin America and the Caribbean
Authors: Marshall K Tulloch-Reid, Nancy Gore Saravia, Rodolfo J Dennis, Andres Jaramillo, Luis Gabriel Cuervo, Susan P Walker, Luis Alejandro Salicrup
Journal: BMJ (2018)

Marshall Tulloch-Reid and colleagues argue that development of research capacity in Latin America and the Caribbean requires investment in both individuals and regional institutions
Leukaemia and myeloid malignancy among people exposed to low doses (&lt;100 mSv) of ionising radiation during childhood: a pooled analysis of nine historical cohort studies
Authors: Mark P Little, Richard Wakeford, David Borrego, Benjamin French, Lydia B Zablotska, M Jacob Adams, Rodrigue Allodji, Florent de Vathaire, Choonsik Lee, Alina V Brenner, Jeremy S Miller, David Campbell, Mark S Pearce, Michele M Doody, Erik Holmberg, Marie Lundell, Siegal Sadetzki, Martha S Linet, Amy Berrington de González
Journal: The Lancet Haematology (2018)
Weekly docetaxel in patients with metastatic breast cancer: A Bangladeshi perspective.
Authors: Ehteshamul Hoque, Shanaz Karim, Rakib Uddin Ahmed
Journal: Journal of Clinical Oncology (2012)

e11533 Background: Docetaxel has demonstrated high antitumor activity in first and second line treatment of metastatic breast cancer. Usually it is administrated three weekly at a dose of 75mg/ m 2 . We evaluated the efficacy and toxicity of Docetaxel in metastatic breast cancer in weekly bases. This study analyzed the efficacy and toxicity of docetaxel given weekly. Methods: Thirty eight patients with metastatic breast cancer received docetaxel, 35 mg/m 2 weekly for six weeks, followed by two weeks interval. Additional cycles (three weeks' treatment, two weeks' rest) were given until disease progression or death. All patients had received prior chemotherapy. Of them 32 patients previously received anthracycline-containing regimens and 5 patients had received taxane based regimens. Results: Out of thirty eight patients thirty seven were evaluable. There was one complete response (3%), 11 patient has partial responses (30%), 17 patients with stable disease (46%) and six with disease progression (16%). Overall response rate was 78%. Median progression-free survival was 9.2 months. Three patients showed grade 3 neutropenia. 14 showed grade 3 alopecia, and various grade 1–2 non-haematological toxicities were observed. Treatment was delayed in two patients due to haemalotoxicity and stopped in one patient due to painful nail toxicity. Conclusions: Docetaxel is effective in three weekly regimens. In our study we found weekly docetaxel is as effective as the previous regimen. The efficacy of weekly docetaxel (35 mg/m 2 ) can be an effective schedule for metastatic breast cancer who has received chemotherapy previously. The toxicity in this regimen is very low and manageable.
Increased Expression of Cytoskeletal, Linkage, and Extracellular Proteins in Failing Human Myocardium
Authors: AnnetteHeling, RenéZimmermann, SawaKostin, YoshiMaeno, StefanHein, BrunoDevaux, ErwinBauer, Wolf-PeterKlövekorn, MartinSchlepper, WolfgangSchaper, JuttaSchaper
Journal: Circulation Research (2000)

Abstract—Experimental studies have shown that in hypertrophy and heart failure, accumulation of microtubules occurs that impedes sarcomere motion and contributes to decreased ventricular compliance. We tested the hypothesis that these changes are present in the failing human heart and that an entire complex of structural components, including cytoskeletal, linkage, and extracellular proteins, are involved in causing functional deterioration. In explanted human hearts failing because of dilated cardiomyopathy (ejection fraction ≤20%), expression of α- and β-tubulin, desmin, vinculin, fibronectin, and vimentin was determined by Northern and Western blot analysis and compared with normal myocardium from explants not used for transplantation. The mRNA for α- and β-tubulin was increased to 2.4-fold (P<0.01) and 1.25-fold (NS), respectively; for desmin, 1.2-fold (P<0.05); for fibronectin, 5-fold (P<0.001); and for vimentin, 1.7-fold (P<0.05). Protein levels for α-tubulin increased 2.6-fold (P<0.02); for β-tubul...
Abstract 16691: Reduced Aortic Elasticity in Children With Connective Tissue Disorders Regardless of Aortic Dilatation
Authors: Yohei Akazawa, Noriko Motoki, Akira Hachiya, Daisuke Akagawa
Journal: Circulation (2016)

Introduction:  Previous studies have demonstrated that reduced aortic elasticity in connective tissue disorders (CTDs) and the aortic stiffness could be an independent predictor of the progressive aortic dilatation. However, the evidence for aortic elasticity is less clear in children with CTDs, especially those who with non-dilated aortic root (AoR). The purpose of this study is to assess the aortic elasticity in children with CTDs who have dilated and non-dilated AoR.   Methods:  A total of 31 children (age: 12±7 years) with CTDs including Marfan syndrome, Loeys-Dietz syndrome and aneurysms-osteoarthritis syndrome and 15 healthy age- and sex-matched children were studied. Aortic elasticity indexes including aortic distensibility, aortic strain were derived from echocardiography at the AoR and ascending aorta (AA). CTDs children with dilated AoR (z score ≧2.5, n=17), non-dilated AoR (z score    Results:  Aortic distensibility and aortic strain at the AoR were decreased in both dilated and non-dilated groups compared to controls(aortic distensibility: 0.5±0.3х10 -3  vs. 1.5±0.9х10 -3  vs. 2.4±1.1х10 -3 , p   Conclusions:  Aortic elasticity is impaired in children with CTDs. Moreover, CTDs children with non-dilated AoR showed impairment of aortic elastic properties. Measuring aortic elasticity may help to identify children with CTDs at greater risk for aortic complications.
Environmental exposures and systemic hypertension are risk factors for decline in lung function
Authors: Catherine H Miele, Matthew R Grigsby, Trishul Siddharthan, Robert H Gilman, J Jaime Miranda, Antonio Bernabe-Ortiz, Robert A Wise, William Checkley
Journal: Thorax (2018)

Background Chronic lung disease is a leading contributor to the global disease burden; however, beyond tobacco smoke, we do not fully understand what risk factors contribute to lung function decline in low-income and middle-income countries. Methods We collected sociodemographic and clinical data in a randomly selected, age-stratified, sex-stratified and site-stratified population-based sample of 3048 adults aged ≥35 years from four resource-poor settings in Peru. We assessed baseline and annual pre-bronchodilator and post-bronchodilator lung function over 3 years. We used linear mixed-effects models to assess biological, socioeconomic and environmental risk factors associated with accelerated lung function decline. Results Mean±SD enrolment age was 55.4±12.5 years, 49.2% were male and mean follow-up time was 2.36 (SD 0.61) years. Mean annual pre-bronchodilator FEV 1 decline was 30.3 mL/year (95% CI 28.6 to 32.0) and pre-bronchodilator FVC decline was 32.2 mL/year (30.0 to 34.4). Using multivariable linear mixed-effects regression, we found that urban living, high-altitude dwelling and having hypertension accounted for 25.9% (95% CI 15.7% to 36.1%), 21.3% (11.1% to 31.5%) and 15.7% (3.7% to 26.9%) of the overall mean annual decline in pre-bronchodilator FEV 1 /height 2 , respectively. Corresponding estimates for pre-bronchodilator FVC/height 2 were 42.1% (95% CI% 29.8% to 54.4%), 36.0% (23.7% to 48.2%) and 15.8% (2.6% to 28.9%) of the overall mean annual decline, respectively. Conclusion Urbanisation, living at high altitude and hypertension were associated with accelerated lung function decline in a population with low daily smoking prevalence.
Randomized phase II trial of CapOX plus bevacizumab versus CapIRI plus bevacizumab as first-line treatment in Japanese patients with metastatic colorectal cancer (CCOG-1201).
Authors: Masahiro Sasahara, Goro Nakayama, Kiyoshi Ishigure, Hiroyuki Yokoyama, Keisuke Uehara, Akiharu Ishiyama, Takanori Matsui, Hiroshi Nakayama, Daisuke Kobayashi, Shinichi Umeda, Yuki Sunagawa, Kenta Murotani, Yuichi Ando, Yasuhiro Kodera
Journal: Journal of Clinical Oncology (2018)

781 Background: The aim of this randomized, multicenter, non-comparative phase II trial was to investigate the efficacy and safety of capecitabine/oxaliplatin (CapOX) plus bevacizumab (BEV) and capecitabine/irinotecan (CapIRI) plus BEV as a first-line treatment in Japanese patients with metastatic colorectal cancer (mCRC). Methods: Patients with untreated mCRC were randomly assigned to the following treatment arms; CapOX/BEV arm (bevacizumab 7.5mg/kg and oxaliplatin 130 mg/m 2 on day 1, and oral capecitabine 1000 mg/m 2 bid on day 1-14, every 3 weeks) and CapIRI/BEV arm (bevacizumab 7.5mg/kg and irinotecan 200 mg/m 2 on day 1, and capecitabine 800 mg/m 2 bid on day 1-14, every 3 weeks). The primary endpoint was overall response rate (ORR), and secondary end points included progression-free survival (PFS), overall survival (OS), and safety. Results: A total of 107 patients were enrolled. The intent-to-treat population comprised 52 patients in CapOX/BEV arm and 51 patients in CapIRI/BEV arm. The ORR was 58% in CapOX/BEV arm and 57% in CapIRI/BEV arm ( p= 0.545). The median tumor shrinkage rate (DpR) was 36.0% (range, -24.0 to 100%) and 36.7% (range, -26.0 to 100%), respectively (p = 0.399). Median PFS was 12.4 months (95% confidence interval [CI], 10.6–14.3 months) in CapOX/BEV arm and 11.5 months (95% CI, 9.6–13.4 months) in CapIRI/BEV arm (hazard ratio [HR], 1.145; 95% CI, 0.760–1.725; p= 0.517). The median OS was 26.6 months (95% CI, 21.5–31.8 months) and 28.7 months (95% CI, 19.6–37.9), respectively (HR, 1.206; 95% CI, 0.0.733–1.907; p= 0.461). The frequency of hematological and non-hematological adverse events (≥grade3) were 10% and 27% in CapOX/BEV arm, and 16% and 27% in CapIRI/BEV arm, respectively. Conclusions: Both regimens, CapOX plus BEV and CapIRI plus BEV, could be equally feasible first-line treatment for Japanese patients with mCRC. Clinical trial information: UMIN_000007545.
Long-Term Results of Catheter Ablation in Paroxysmal Atrial Fibrillation
Authors: FeifanOuyang, RolandTilz, JulianChun, BorisSchmidt, ErikWissner, ThomasZerm, KarsNeven, BulentKöktürk, MelanieKonstantinidou, AndreasMetzner, AlexanderFuernkranz, Karl-HeinzKuck
Journal: Circulation (2010)

Background—Paroxysmal atrial fibrillation (AF) naturally progresses toward chronic AF at an estimated rate of 15% to 30% over a 1- to 3-year period. Pulmonary vein (PV) isolation is increasingly performed for the treatment of drug-refractory paroxysmal AF. The long-term data on clinical outcome after circumferential PV isolation are limited. Methods and Results—From 2003 to late 2004, 161 patients (121 men; age, 59.8±9.7 years) with symptomatic paroxysmal AF and normal left ventricular function underwent circumferential PV isolation guided by 3-dimensional mapping and double Lasso technique. Right-sided and left-sided continuous circular lesions encircling the ipsilateral PVs were placed with irrigated radiofrequency energy. The procedure end point was the absence of all PV spikes for at least 30 minutes after PV isolation verified by 2 Lasso catheters placed within the ipsilateral PVs. Sinus rhythm was present in 75 patients (46.6%) after the initial procedure during a median follow-up period of 4.8 year...
Image Gallery: Flush in carcinoid syndrome
Authors: A. Marchetti, A. Nosbaum
Journal: British Journal of Dermatology (2018)

Funding sources: none. Conflicts of interest: none to declare. dear editor, A 72‐year‐old man was referred for diarrhoea and a well‐limited migratory macular erythema. This occurred over the upper part of the body and induced a burning sensation, lasting 4 h and relapsing after meals. The pictures were taken 2 h apart during one episode (a, b). Investigations found liver and peritoneal metastases, related to a well‐differentiated neuroendocrine gastric tumour. Somatostatin analogues induced complete clinical relief. Flush features in carcinoid syndrome are dependent on the anatomical location of the neuroendocrine tumour; gastric carcinoid tumours cause a pruritic reddish‐brown flush over the entire body and last for minutes to hours.1,2
Improved Outcome of Elderly Patients (≥75 Years of Age) With Acute Myocardial Infarction From 1981-1983 to 1992-1994 in Israel
Authors: ShmuelGottlieb, UriGoldbourt, ValentinaBoyko, GabrielBarbash, LoriMandelzweig, HenriettaReicher-Reiss, ShlomoStern, SolomonBehar
Journal: Circulation (1997)

Background The number of elderly patients experiencing acute myocardial infarction (AMI) is growing rapidly, and their hospital mortality rate remains high, although mortality after AMI declined in the 1990s with the introduction of new therapeutic modalities. Methods and Results We compared the management, in-hospital complications, and 30-day and 1-year mortality rates in two cohorts of elderly (≥75 years of age) AMI patients in the coronary care units in Israel before and after the reperfusion era. The first cohort of 789 consecutive patients was from the Secondary Prevention Reinfarction Israel Nifedipine Trial registry in 1981-1983; the second 366 patients came from two prospective nationwide surveys in 1992 and 1994. Reperfusion therapies were not used in 1981-1983 but were used in 1992-1994. The 30-day mortality rate declined from 38% in 1981-1983 to 27% in 1992-1994 (odds ratio, 0.49; 95% confidence interval [CI], 0.34 to 0.71), and the cumulative 1-year mortality rate declined from 52% to 38% (ha...
The genomic impact of historical hybridization with massive mitochondrial DNA introgression
Authors: Fernando A. Seixas, Pierre Boursot, José Melo-Ferreira
Journal: Genome biology (2018)

The extent to which selection determines interspecific patterns of genetic exchange enlightens the role of adaptation in evolution and speciation. Often reported extensive interspecific introgression could be selection-driven, but also result from demographic processes, especially in cases of invasive species replacements, which can promote introgression at their invasion front. Because invasion and selective sweeps similarly mold variation, population genetics evidence for selection can only be gathered in an explicit demographic framework. The Iberian hare, Lepus granatensis, displays in its northern range extensive mitochondrial DNA introgression from L. timidus, an arctic/boreal species that it replaced locally after the last glacial maximum. We use whole-genome sequencing to infer geographic and genomic patterns of nuclear introgression and fit a neutral model of species replacement with hybridization, allowing us to evaluate how selection influenced introgression genome-wide, including for mtDNA.Although the average nuclear and mtDNA introgression patterns contrast strongly, they fit a single demographic model of post-glacial invasive replacement of timidus by granatensis. Outliers of elevated introgression include several genes related to immunity, spermatogenesis, and mitochondrial metabolism. Introgression is reduced on the X chromosome and in low recombining regions.General nuclear and mtDNA patterns of introgression can be explained by purely demographic processes. Hybrid incompatibilities and interplay between selection and recombination locally modulate levels of nuclear introgression. Selection promoted introgression of some genes involved in conflicts, either interspecific (parasites) or possibly cytonuclear. In the latter case, nuclear introgression could mitigate the potential negative effects of alien mtDNA on mitochondrial metabolism and male-specific traits.
Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study
Authors: Jeffrey J Bazarian, Peter Biberthaler, Robert D Welch, Lawrence M Lewis, Pal Barzo, Viktoria Bogner-Flatz, P Gunnar Brolinson, Andras Büki, James Y Chen, Robert H Christenson, Dallas Hack, J Stephen Huff, Sandeep Johar, J Dedrick Jordan, Bernd A Leidel, Tobias Lindner, Elizabeth Ludington, David O Okonkwo, Joseph Ornato, W Frank Peacock, Kara Schmidt, Joseph A Tyndall, Arastoo Vossough, Andy S Jagoda
Journal: The Lancet Neurology (2018)
On Gender and Reproductive Decision-Making in Uterine Transplantation
Authors: Hilary Mabel, Ruth M. Farrell, Andreas G. Tzakis
Journal: The American Journal of Bioethics (2018)

In this issue of the American Journal of Bioethics, Bruno and Arora’s Target Article (2018) and the Open Peer Commentaries thereto contribute to the ongoing discourse regarding ethical issues in ut...
Incidence, Risk Factors, and Clinical Sequelae of Angiographic Peri-Stent Contrast Staining After Sirolimus-Eluting Stent Implantation
Authors: MasaoImai, KazushigeKadota, TsuyoshiGoto, SatokiFujii, HiroyukiYamamoto, YasushiFuku, ShingoHosogi, AkitoshiHirono, HiroyukiTanaka, TakeshiTada, TakeshiMorimoto, HirokiShiomi, KenKozuma, KatsumiInoue, NobuakiSuzuki, TakeshiKimura, KazuakiMitsudo
Journal: Circulation (2011)

Background—We have noted abnormal angiographic findings—at the sites of drug-eluting stent implantation, suggesting contrast staining outside the stent struts—that do not fulfill the classic definition of coronary artery aneurysm. We propose a new term, peri-stent contrast staining (PSS), for these abnormal angiographic findings and assess their incidence, risk factors, and clinical sequelae. Methods and Results—Peri-stent contrast staining was defined as contrast staining outside the stent contour extending to ≥20% of the stent diameter. The study population consisted of 3081 lesions (1998 patients) that were treated exclusively with sirolimus-eluting stents and were evaluated by follow-up angiography within 12 months after sirolimus-eluting stent implantation in a single center. Late acquired PSS was observed in 58 lesions (1.9%) in 49 patients (2.5%). Independent risk factors of PSS included chronic total occlusion, whereas negative risk factors for PSS were left circumflex coronary artery lesion and i...
Jury awards $4.7bn damages against Johnson &amp; Johnson in talcum cancer case
Authors: Owen Dyer
Journal: BMJ (2018)

A jury in St Louis, Missouri, has ordered Johnson and Johnson to pay $550m (£415m; €471m) in compensatory damages and $4.14bn in punitive damages to women who alleged that use of the company’s talcum powder caused them to develop ovarian cancer.

The lawsuit was brought by 22 women from across the US, six of whom have since died. More than 9000 former US talcum customers have lodged suits against the company. Most claim damages for ovarian cancer, but some allege that using the product led them to develop mesothelioma.

The award is by far the biggest yet against Johnson and Johnson in litigation relating to talcum powder and the first case in which plaintiffs alleged that asbestos in talcum powder caused their disease.

“We hope this verdict will get the attention of the J&J board and that it will lead …