tbuckley/cabot-search huggingface dataset:
Bivalirudin versus Heparin Monotherapy in Myocardial Infarction
Authors: David Erlinge, Elmir Omerovic, Ole Fröbert, Rikard Linder, Mikael Danielewicz, Mehmet Hamid, Eva Swahn, Loghman Henareh, Henrik Wagner, Peter Hårdhammar, Iwar Sjögren, Jason Stewart, Per Grimfjärd, Jens Jensen, Mikael Aasa, Lotta Robertsson, Pontus Lindroos, Jan Haupt, Helena Wikström, Anders Ulvenstam, Pallonji Bhiladvala, Bo Lindvall, Anders Lundin, Tim Tödt, Dan Ioanes, Truls Råmunddal, Thomas Kellerth, Leszek Zagozdzon, Matthias Götberg, Jonas Andersson, Oskar Angerås, Ollie Östlund, Bo Lagerqvist, Claes Held, Lars Wallentin, Fredrik Scherstén, Peter Eriksson, Sasha Koul, Stefan James
Journal: New England Journal of Medicine (2017)

The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial-artery access for PCI and administration of potent P2Y12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors.In this multicenter, randomized, registry-based, open-label clinical trial, we enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y12 inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors. The patients were randomly assigned to receive bivalirudin or heparin during PCI, which was performed predominantly with the use of radial-artery access. The primary end point was a composite of death from any cause, myocardial infarction, or major bleeding during 180 days of follow-up.A total of 6006 patients (3005 with STEMI and 3001 with NSTEMI) were enrolled in the trial. At 180 days, a primary end-point event had occurred in 12.3% of the patients (369 of 3004) in the bivalirudin group and in 12.8% (383 of 3002) in the heparin group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.10; P=0.54). The results were consistent between patients with STEMI and those with NSTEMI and across other major subgroups. Myocardial infarction occurred in 2.0% of the patients in the bivalirudin group and in 2.4% in the heparin group (hazard ratio, 0.84; 95% CI, 0.60 to 1.19; P=0.33), major bleeding in 8.6% and 8.6%, respectively (hazard ratio, 1.00; 95% CI, 0.84 to 1.19; P=0.98), definite stent thrombosis in 0.4% and 0.7%, respectively (hazard ratio, 0.54; 95% CI, 0.27 to 1.10; P=0.09), and death in 2.9% and 2.8%, respectively (hazard ratio, 1.05; 95% CI, 0.78 to 1.41; P=0.76).Among patients undergoing PCI for myocardial infarction, the rate of the composite of death from any cause, myocardial infarction, or major bleeding was not lower among those who received bivalirudin than among those who received heparin monotherapy. (Funded by the Swedish Heart-Lung Foundation and others; VALIDATE-SWEDEHEART ClinicalTrialsRegister.eu number, 2012-005260-10 ; ClinicalTrials.gov number, NCT02311231 .).
Multiple Intracranial Parenchymal Lesions Evolving Over a Decade
Authors: Lin Shi, Jian-Guo Zhang, Kai Zhang
Journal: JAMA Neurology (2017)

A teenage Chinese girl with intermittent limp and increasing headache was admitted to our the hospital in December 2016. A brain magnetic resonance imaging showed multiple parenchymal lesions, involving the pons, bilateral amygdala, and the left temporal pole. What is your diagnosis?
A Bridge Back to the Future: Public Health Ethics, Bioethics, and Environmental Ethics
Authors: Lisa M. Lee
Journal: The American Journal of Bioethics (2017)

Contemporary biomedical ethics and environmental ethics share a common ancestry in Aldo Leopold's and Van Rensselaer Potter's initial broad visions of a connected biosphere. Over the past five decades, the two fields have become strangers. Public health ethics, a new subfield of bioethics, emerged from the belly of contemporary biomedical ethics and has evolved over the past 25 years. It has moved from its traditional concern with the tension between individual autonomy and community health to a wider focus on social justice and solidarity. Public health has a broad focus that includes individual, community, and environmental health. Public health ethics attends to these broad commitments reflected in the increasing concern with the connectedness of health of individuals to the health of populations, to the health of animals, to the health of the environment; it is well situated to reconnect all three “fields” of ethics to promote a healthier planet.
The DETECT study concept: Individualized therapy of metastatic breast cancer.
Authors: Arkadius Polasik, Amelie Schramm, Thomas W. P. Friedl, Brigitte Kathrin Rack, Elisabeth Katharina Trapp, Peter A. Fasching, Florin-Andrei Taran, Andreas D. Hartkopf, Andreas Schneeweiss, Volkmar Mueller, Bahriye Aktas, Klaus Pantel, Franziska Meier-Stiegen, Pauline Wimberger, Wolfgang Janni, Tanja N. Fehm
Journal: Journal of Clinical Oncology (2016)

TPS634 Background: Circulating tumor cells (CTCs) are found in blood samples of patients with early as well as metastatic breast cancer (MBC). The prognostic and predictive value of CTCs, whose phenotype may differ from the primary tumor, has been described already. However, treatment decisions often still result from the primary tumor's phenotype without considering CTC-characteristics. The importance of CTC phenotypes for guiding therapeutic decisions will be investigated within the DETECT studies. Methods: The DETECT study concept provides a prospective, multicenter, open-label clinical trial program comprising two phase III studies (DETECT III and V) and one phase II study (DETECT IV). Women with HER2-negative MBC are tested for CTCs and their HER2-phenotype. CTC detection is performed by the FDA-approved CellSearch System (Janssen Diagnostics, Raritan, USA). Patients with HER2-positive CTCs are recruited into DETECT III and randomized to a physician's choice chemo- or endocrine therapy +/- additional HER2-targeted treatment with lapatinib. Patients with only HER2-negative CTCs are included in DETECT IV. Postmenopausal women with hormone-receptor (HR)-positive MBC are treated with everolimus and a physician's choice endocrine therapy (DETECT IVa); women with triple-negative MBC or HR-positive tumors with indication for chemotherapy receive eribulin (DETECT IVb). In DETECT V/CHEVENDO, which started in autumn 2015, women with HER2- and HR-positive MBC are randomized to a dual HER2-directed therapy with pertuzumab and trastuzumab plus either chemotherapy or endocrine therapy. CTC-presence is not obligatory in DETECT V, but translational research projects focus on CTC-enumeration and the assessment of marker expression on CTCs in order to calculate an endocrine-responsiveness-score, which will be evaluated regarding to its suitability to predict treatment success. Perspective: Changes in the dynamic of CTCs during therapy and their HER2-phenotype may influence following therapy decisions. The DETECT study program evaluates the prognostic and predictive role of CTCs as well as a CTC based therapy and enables the establishment of a more personalized therapy for patients with MBC. Clinical trial information: NCT01619111, NCT 02035813, NCT02344472.
Acute pancreatitis: recent advances through randomised trials
Authors: Sven M van Dijk, Nora D L Hallensleben, Hjalmar C van Santvoort, Paul Fockens, Harry van Goor, Marco J Bruno, Marc G Besselink
Journal: Gut (2017)

Acute pancreatitis is one of the most common GI conditions requiring acute hospitalisation and has a rising incidence. In recent years, important insights on the management of acute pancreatitis have been obtained through numerous randomised controlled trials. Based on this evidence, the treatment of acute pancreatitis has gradually developed towards a tailored, multidisciplinary effort, with distinctive roles for gastroenterologists, radiologists and surgeons. This review summarises how to diagnose, classify and manage patients with acute pancreatitis, emphasising the evidence obtained through randomised controlled trials.
Emergence of KRAS mutations and acquisition of resistance to EGFR blockade.
Authors: Takeshi Yamada, Goro Takahashi, Takuma Iwai, Kohki Takeda, Kohji Ueda, Michihiro Koizumi, Seiichi Shinji, Yasuyuki Yokoyama, Keisuke Hara, Akihisa Matsuda, Satoshi Matsumoto, Keiichiro Ohta, Uchida Eiji
Journal: Journal of Clinical Oncology (2017)

3598 Background: Epidermal growth factor receptor (EGFR) blockade can effectively shrink tumors in patients with metastatic colorectal cancer (CRC). However, most patients who benefit from EGFR blockade acquire resistance. Although RAS mutation is established as a main cause of primary resistance, the mechanisms of this acquired resistance remain unclear. Here, we aimed to identify the mechanisms underlying acquired resistance to EGFR blockade by using circulating cell-free (ccf)DNA to track emerging KRAS, BRAF and S492R mutations during chemotherapy. Methods: We enrolled 33 patients with metastatic CRC and no RAS mutations in their primary tumors. Patients were treated with first-line systemic chemotherapy that included EGFR blockade. We obtained ccfDNA from each patient before they started chemotherapy, and every 2–3 months during chemotherapy until disease progression. We detected KRAS (codons 12, 13, 61, and 146), BRAF (V600E) and S492R mutations using digital polymerase chain reaction. Results: KRAS mutations were detected in the ccfDNA of 4 of the 33 patients (12%) before chemotherapy. The response rate was 88% (29/33); all four non-responders had KRAS mutations in their ccfDNA and one of the four had both KRAS and BRAF mutations before starting chemotherapy. A response was detected in all patients (29/29) with no KRAS or BRAF mutations in their ccfDNA before chemotherapy. Of the 29 initial responders, 14 (48%) acquired resistance. Emerging KRAS mutations were detected in the ccfDNA of 13 of these 14 patients (93%); eight of these patients had multiple mutations (e.g. G12D and G12V; G13D and Q61H). BRAF mutations were also detected in six patients (43%); none of the patients had solo BRAF mutations. Six patients (43%) had S492R mutations; none of the patients had solo S492R mutations. Only one patient had no KRAS, BRAF or S492R mutations. Conclusions: Emergence of KRAS, BRAF or S492R mutations that were undetectable before the start of chemotherapy may be a mechanism underlying acquisition of resistance to EGFR blockade. Notably, emerging KRAS mutations were detected in most of the patients (93%) who acquired resistance. This indicates that KRAS mutation emergence may play a major role in the acquisition of resistance to EGFR blockade.
老化:長期的な低用量Δ9‐テトラヒドロカンナビノール(THC)投与は老齢マウスの認知機能を回復させる
Authors: Bilkei‐Gorzo Andras, Albayram Onder, Michel Kerstin, Piyanova Anastasia, Racz Ildiko, Imbeault Sophie, Zimmer Andreas, Draffehn Astrid, Ulas Thomas, Schultze Joachim L, Oppenheimer Hannah, Dvir‐Ginzberg Mona, Bab Itai
Journal: Nature Medicine (2017)
Advances in the diagnosis and management of neck pain
Authors: Steven P Cohen, W Michael Hooten
Journal: BMJ (2017)

Neck pain imposes a considerable personal and socioeconomic burden-it is one of the top five chronic pain conditions in terms of prevalence and years lost to disability-yet it receives a fraction of the research funding given to low back pain. Although most acute episodes resolve spontaneously, more than a third of affected people still have low grade symptoms or recurrences more than one year later, with genetics and psychosocial factors being risk factors for persistence. Nearly half of people with chronic neck pain have mixed neuropathic-nociceptive symptoms or predominantly neuropathic symptoms. Few clinical trials are dedicated solely to neck pain. Muscle relaxants and non-steroidal anti-inflammatory drugs are effective for acute neck pain, and clinical practice is mostly guided by the results of studies performed for other chronic pain conditions. Among complementary and alternative treatments, the strongest evidence is for exercise, with weaker evidence supporting massage, acupuncture, yoga, and spinal manipulation in different contexts. For cervical radiculopathy and facet arthropathy, weak evidence supports epidural steroid injections and radiofrequency denervation, respectively. Surgery is more effective than conservative treatment in the short term but not in the long term for most of these patients, and clinical observation is a reasonable strategy before surgery.
Water Exchange to Facilitate Unsedated Colonoscopy
Authors: Zhouwen Tang, Deepak Agrawal
Journal: JAMA (2017)

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シリコンイオンとVEGFの相乗作用によるメソ多孔性マイクロキャリアによる血管新生の促進【Powered by NICT】
Authors: Dashnyam Khandmaa, Jin Guang-Zhen, Kim Joong-Hyun, Perez Roman, Jang Jun-Hyeog, Kim Hae-Won
Journal: Biomaterials (2017)
The progesterone-regulated protein TRIM22 forms nuclear and nucleolar bodies
Authors: Gayathri Sivaramakrishnan, Yang Sun, Si Kee Tan, Valerie Lin Chun Ling
Journal: Clinical Cancer Research (2007)

A26  Tripartite motif containing protein 22 (TRIM22) is also referred to as Stimulated Transacting Factor of 50kDa (Staf50). It was originally identified as an interferon-inducible gene in human lymphoblastoid Daudi cells. It is a member of the RING-finger family of proteins and it has been implicated in antiviral response, cell growth and differentiation. To date, literature on the localization of endogenous TRIM22 is non-existent and the function of the protein in mammary epithelial cells is unknown. In this study, we found that the TRIM22 is greatly enhanced by progesterone at both the mRNA and protein levels in breast cancer cells. EGFP-tagged TRIM22 forms nuclear bodies in a variety of cell lines, with a polyclonal antibody generated against the 498 aa protein identifying similar nuclear body structures in breast cancer cells. In the MDA-MB-231-derived ABC28 cell line that stably expresses the progesterone receptor, progesterone was able to induce endogenous TRIM22 bodies to localize extensively within nucleoli. As progesterone has previously been found to inhibit growth of T47D and ABC28 cells by G0/G1 arrest, we also investigated the cell-cycle dependent changes in the distribution of TRIM22 in synchronized HELA cells stably expressing TRIM22-EGFP. We observed more cells with nucleolar TRIM22-EGFP in populations of cells in which the majority of cells (72.2%) were in the G0/G1 phase. In addition, in MCF7 cells stably expressing TRIM22-EGFP, these bodies aggregated when serum-starved or when treated with the DNA synthesis inhibitor methotrexate while serum treatment led to dispersion of these bodies into multiple smaller foci. These results suggest that TRIM22 is a dynamic protein which is likely to have a function within nucleoli. Ongoing studies on the cell cycle dependent distribution of endogenous TRIM22 and the identification of proteins interacting with TRIM22 at each phase of the cell cycle are likely to shed light on the function(s) of TRIM22.
Hepatocellular carcinoma (HCC) outcomes in a public hospital setting: Characteristics and outcomes from the Interim LSU Public Hospital (ILH) in New Orleans.
Authors: Navjot Dhillon, Edgar Castillo D'Andreis, Brian C. Boulmay
Journal: Journal of Clinical Oncology (2015)

e17533 Background: HCC is the third leading cause of cancer mortality worldwide and its incidence rate is increasing in the United States. HCC survival rates have doubled between 1992 and 2004, as more patients are diagnosed with localized and regional HCC amenable to procedural based therapies. The under- or uninsured patients served by public hospital systems are often unable to get recommended screening and timely standard therapy which may lead to higher morbidity and mortality. Methods: 107 patients with HCC were identified treated at ILH from 1/1/2007-2/1/2013. A retrospective chart review was performed and data collected included sex, ethnicity, hepatitis C (HC) and hepatitis B (HB) infection history, HCC surveillance, treatment modalities as well as percentage of survival after a year of diagnosis. Results: The majority of patients were men: 85% (91) versus 5% (16) females. 63% were black, 25% white, the remaining 12% were either Asian or Hispanic. 75% were HC positive and 9% were HB positive, of the HC and HB positive patients, 15% were on a screening protocol. Treatment of patients included: 18% had sorafenib, 10% transarterial chemoembolization (TACE) and 7% patients had radiofrequency ablation, 9% of patients were referred for transplantation, 8% had curative intent resection. The one year OS was 29% Conclusions: The one year survival rate at ILH is lower as compared to historical standard in this under- and uninsured patient population. Screening rates for HB and HC positive patients were low, with low utilization of sorafenib, TACE and transplant, all factors contributing to poor outcomes. The majority of the patient cohort analyzed were treated in the immediate post-Hurricane Katrina setting with limited access to hepatologist, liver transplant and interventional radiologist services. We noted increased utilization of sorafenib and procedural based therapies from 2011-2013.
Selexipag for the treatment of connective tissue disease-associated pulmonary arterial hypertension
Authors: Sean Gaine, Kelly Chin, Gerry Coghlan, Richard Channick, Lilla Di Scala, Nazzareno Galiè, Hossein-Ardeschir Ghofrani, Irene M. Lang, Vallerie McLaughlin, Ralph Preiss, Lewis J. Rubin, Gérald Simonneau, Olivier Sitbon, Victor F. Tapson, Marius M. Hoeper
Journal: European Respiratory Journal (2017)

Patients with connective tissue disease-associated pulmonary arterial hypertension (PAH-CTD) have a poor prognosis compared with other aetiologies. The underlying CTD can influence treatment response and outcomes. We characterised the GRIPHON study PAH-CTD subgroup and evaluated response to selexipag. Of 334 patients with PAH-CTD, PAH was associated with systemic sclerosis (PAH-SSc) in 170, systemic lupus erythematosus (PAH-SLE) in 82 and mixed CTD/CTD-other in 82. For the primary composite endpoint of morbidity/mortality, hazard ratios (HR) and 95% CI were calculated using Cox proportional hazard models. Compared with the overall GRIPHON population, the CTD subgroup was slightly older with a greater proportion of females and shorter time since diagnosis. Patients with PAH-SSc appeared to be more impaired at baseline, with a more progressive disease course. The converse was observed for PAH-SLE. Selexipag reduced the risk of composite morbidity/mortality events in patients with PAH-CTD by 41% (HR 0.59; 95% CI 0.41–0.85). Treatment effect was consistent irrespective of baseline PAH therapy or CTD subtype (interaction p=0.87 and 0.89, respectively). Adverse events were predominately prostacyclin-related and known for selexipag treatment. GRIPHON has allowed the comprehensive characterisation of patients with PAH-CTD. Selexipag delayed progression of PAH and was well-tolerated among PAH-CTD patients, including those with PAH-SSc and PAH-SLE.
浅大腿動脈のアテローム硬化性病変に対する血管内治療後の臨床転帰の予測因子としてのリポ蛋白質(a)濃度
Authors: Nakagama Shun, Hishikari Keiichi, Kimura Shigeki, Nakamura Shun, Misawa Toru, Hayasaka Kazuto, Mizusawa Masafumi, Yamakami Yosuke, Sagawa Yuichirou, Kojima Keisuke, Yamao Kazuya, Nakashima Emiko, Nakajima Jun, Tanaka Yasuaki, Ohkubo Kenji, Takagi Katsumasa, Kuwahara Taishi, Hikita Hiroyuki, Takahashi Atsushi, Isobe Mitsuaki
Journal: Circulation (2016)
Abstract 11953: Predictors of In-Hospital Mortality Among Left Ventricular Assist Device Recipients in the United States: A National Inpatient Sample Perspective
Authors: Ahmed M Mahmoud, Ali Abbas, Peter Draganov, Juan Aranda, Mustafa Ahmed
Journal: Circulation (2015)

Background: A remarkable increase in the rate of left ventricular assist devices (LVAD) placement has occurred in recent years. Despite increased utilization, there is a continued need to define the changing incidence of in-hospital mortality and their predictors. Methods: From 2009 to 2011, National Inpatient Sample database was utilized to include all adult patients with admission diagnosis codes of congestive heart failure and procedure codes for left ventricular assist device (37.66). Patients who underwent LVAD and IABP or OHT placement were excluded from the analysis. Information about demographics, insurance, year of admission, and hospital characteristics, comorbidities and acute in hospital complications were abstracted. Using in-hospital death as our outcome, variables that achieved statistical significance (p &lt;0.05) using Chi square testing were included in a multivariable regression analysis. Results: A total of 4,869 patients had LVAD placement with a mean age was 56 (49-65) years. 57% of the patients were Caucasian and near half of the patients (46%) were on Medicare insurance. Ninety eight percent of the LVAD placement was performed in teaching hospitals. The overall mortality rate was 12.4%, with reduced mortality in 2010 and 2011 as compared to 2009. The presence of acute kidney injury (AKI) requiring hemodialysis (HD) was associated with the highest risk of in-hospital death [OR 21, CI 95% 14.4-30.8, p&lt;0.001]. Other predictors of mortality included age, insurance status, end stage renal disease (ESRD), intubation and mechanical ventilation, pulmonary embolism, disseminated intravascular coagulopathy (DIC), severe liver disease and gastro-intestinal bleeding (GIB). Table 1 Conclusion: In this nationwide analysis, overall in-hospital mortality occurred in 12% of the patients following LVAD placement. The presence of older age, low socio-economic status, AKI, ESRD, GIB and DIC are associated with worse outcome following LVAD placement.