tbuckley/cabot-search huggingface dataset:
2017 EULAR/ACR classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups: little emphasis on autoantibodies, why?
Authors: Anand N Malaviya
Journal: Annals of the Rheumatic Diseases (2017)

The publication of the EULAR/ACR classification criteria for ‘idiopathic inflammatory myopathy’ group of disease would be considered a landmark work in this field.1 The tremendous efforts of a large number of dedicated workers in the field of myositis from around the world coming together to produce this seminal document deserve high praise. The hope is that it will aid the drug trials on homogeneous subsets of this group of diseases yielding meaningful results. However, there is some concern for ‘an outsider’, a general rheumatologist like me, for not putting more emphasis on myositis-specific antibodies (MSAs). Most of the authors of this document …
The utilization and impact of oncology supportive care clinics on patients with metastatic lung cancer.
Authors: Yan S Kim, Esther J Luo, Matthew T Chin, Shelley Leong, Sudhir S Rajan, Gabriel J Escobar
Journal: Journal of Clinical Oncology (2017)

123 Background: The American Society of Clinical Oncology has endorsed early integration of oncology with palliative care. In 2012, Kaiser Permanente Northern California (KPNC) introduced Oncology Supportive Care Clinics (OSCCs). OSCCs are outpatient palliative care clinics designed to incorporate palliative care into standard oncology practice at the time of a patient's cancer diagnosis. This study examines the utilization and impact of OSCCs on patients with metastatic lung cancer. Methods: We identified adult patients with incidental stage IV lung cancer using the KPNC cancer registry from 2012-2015 and followed them for 12 months. We ascertained OSCC utilization using KPNC’s electronic health record. We examined the patterns of OSCC referral/utilization and compared survival, in-hospital death, and treatment received in patients who used and did not use OSCC services. Results: A total of 607 patients were included and 245 (40.4%) were referred to OSCC. The median time from diagnosis to referral was 48 days and ¼ were referred within 15 days. The majority (86%) of the patients referred were seen by OSCC. Only 22 patients (9.0%) refused to be seen. We found no large patient- or facility-level differences between patients referred and not referred to OSCC. At the end of follow up, 398 (65.6%) of the patients died. Patients seen by OSCC were less likely to die (59.2% vs. 68.9%, p &lt; 0.02) at 1 year. Fewer patients who used OSCC died in the hospital compared to those who did not (26 or 12.3% vs. 67 or 16.9%); however, it did not achieve statistical significance (p = 0.13). Among patients who used OSCC, 166 (78.7%) received anti-cancer treatment, compared to 221 (55.8%) among those who did not (p &lt; 0.001). Conclusions: Despite having a robust infrastructure and integrated system in place, over half of the patients diagnosed with metastatic lung cancer did not receive a referral. Future work is needed to understand the reasons why so many patients were not referred. Furthermore, our data showed that receiving OSCC services did not adversely impact survival and the receipt of anti-cancer treatment. These findings serve to reassure patients and providers that the addition of palliative care does not harm patients or limit their treatment.
A molecular signature predictive of clinical outcome following pazopanib therapy in advanced soft tissue sarcoma
Authors: P. Huang, A. Lee, F. McCarthy, K. Thway, J. Morden, C. Messiou, F. Daley, R. Buus, C. Fisher, M. Cheang, I. Judson, R. Jones
Journal: Annals of Oncology (2017)
Randomized phase III trial to evaluate radiopharmaceuticals and zoledronic acid in the palliation of osteoblastic metastases from lung, breast, and prostate cancer: Report of RTOG 0517.
Authors: Michael J. Seider, Stephanie Shook, Corey J. Langer, Gwen Wyatt, William F. Demas, Afshin Rashtian, Cathy L Clausen, Jerry Derdel, Sean F Cleary, Christopher A. Peters, Ashok Ramalingam, James E. Clarkson, Michael B. Tomblyn, Rachel Rabinovitch, Lisa A. Kachnic, Lawrence B. Berk
Journal: Journal of Clinical Oncology (2012)

TPS9150 Background: Skeletal related events (SREs) diminish quality of life (QOL) as well as overall survival (OS) in patients with bone metastases, a common event in breast, lung and prostate cancer. SREs can be reduced or delayed by the use of bisphosphonates. It is postulated that the radiopharmaceuticals, Strontium-89 (Sr89) and Samarium-153 (Sm153), when added to a bisphosphonate can decrease the incidence of SREs. Methods: RTOG 0517 randomized patients with breast, lung and prostate cancer and blastic bone metastases to either Zoledronic acid (ZA) alone or ZA plus a single standard dose of either Sr89 or Sm153. No limitations were placed on additional therapy such as chemotherapy or hormonal treatment. The projected median time to SRE [pathological bone fracture, spinal cord compression, surgery to bone, or radiation to bone] for the ZA arm was 10.4 months requiring 257 SRE events to detect a 33% relative reduction for the radiopharmaceutical arm in the time to development of an SRE with 90% power. Other study objectives included quality of life, pain control, OS and toxicity. Results: 261 patients (median age 68; 62% male; 55% prostate, 35% breast, 10% lung) were accrued from July 2006 through February 2011 (4.6 patients/month). Due to a lower than expected rate of SREs in the control (ZA) arm, the study was closed early and therefore did not reach the targeted accrual. 28 (17.4%) patients in the ZA arm and 27 (16.8%) in the radiopharmaceutical arm experienced an SRE. Median time to development of an SRE in the ZA and radiopharmaceutical arms was 11.60 and 16.74 months, respectively (p=.47). Median OS in the ZA arm and radiopharmaceutical arm was 15.95 and 11.18 months, respectively (p=0.12). Cox proportional hazards regression model showed that baseline characteristics, including gender, race, ethnicity, primary disease site or number of bone metastases, had no significant impact on OS. There was no difference in QOL parameters or toxicities between the two arms. Conclusion: Patients receiving ZA only experienced a much lower SRE rate than was hypothesized. The addition of Sr89 or Sm153 did not result in a difference in SREs, OS, or QOL
Toxicity of sequential immune therapy and radiation for cervical and thoracic spine metastases.
Authors: W. Tristram Arscott, Abigail Doucette, Pallavi Kumar, John Peter Plastaras, Amit Maity, Joshua Adam Jones
Journal: Journal of Clinical Oncology (2017)

130 Background: Palliative radiation is an effective treatment modality for spinal metastases. Expanding use of immune therapy in metastatic cancer raises concern that side effects from treatment may be exaggerated, particularly to sensitive organs such as the esophagus. This retrospective review evaluates the toxicity of combined radiation and immune therapy in patients with cervical or thoracic spine metastases. Methods: Patients receiving radiation for cervical or thoracic spine metastases from 2012-2017 were selected based on (1) concurrent use of immune therapy and radiation (within 7 days) OR radiation within 30 days following immune therapy, (2) 3D conformal or simpler treatment technique, and (3) minimum 30 days follow up from end of treatment. Patient demographics, radiation treatment parameters, immune therapy agent(s), and maximum toxicity were extracted from the medical record. Isoeffective dose was calculated using the EQD2 model, assuming α/β of 3. Statistical analyses included t tests. Results: Twenty-two patients were identified. Pembrolizumab was most commonly combined with radiation (8 patients), followed by nivolumab (7), ipilimumab (3), and atezoliumab (2). Two patients received both nivolumab and ipilimumab. Three patients (14%) had grade 3 toxicity requiring hospitalization (vomiting, esophagitis), 8 patients (36%) had grade 2 toxicity (esophagitis, dysphagia), 3 patients (14%) had grade 1 toxicity (hoarseness, dysphagia), 8 patients (36%) had no toxicity. Two patients (67%) with grade 3 toxicity received concurrent nivolumab and ipilimumab. Median dose was 3600 cGy (EQD2) in 10 fractions. There was a trend to greater toxicity with increased number of vertebral levels treated (mean 3.4, 4.6, 5.625 and 6.3 for toxicity grade 0, 1, 2 and 3, respectively; p= 0.053). Dose, fractionation, and immune therapy agent were not found to be significant contributors. Conclusions: In this small cohort, combined immune therapy and radiation for palliation of cervical or thoracic spine metastases suggests increased toxicity when greater number of vertebral bodies are irradiated or when combined immune therapy agents are utilized. Further investigation with a larger cohort is warranted.
Efficacy and side effect profile of olanzapine versus haloperidol for symptoms of delirium in hospitalized patients with advanced cancer: A multicenter, investigator-blinded, randomized, controlled trial (RCT).
Authors: Maurice Van Der Vorst, Elisabeth C.W. Neefjes, Manon S.A. Boddaert, Bertha A.T.T. Verdegaal, Aart Beeker, Saskia C.C. Teunissen, Aartjan TF Beekman, Janneke A. Wilschut, Johannes Berkhof, Henk M.W. Verheul
Journal: Journal of Clinical Oncology (2017)

231 Background: Delirium is highly prevalent in patients with advanced cancer. Patients experiencing delirium may require pharmacological treatment to reduce distressing symptoms. Atypical antipsychotics, like olanzapine, are potentially safer and more effective than haloperidol, but no phase III RCTs are reported in patients with advanced cancer. Methods: Hospitalized patients with advanced cancer diagnosed with delirium ( DSM-IV-TR criteria) were randomly assigned centrally (1:1) to olanzapine or haloperidol. Dosages were up-titrated. Primary endpoint was delirium resolution rate (DRR), defined as Delirium Rating Scale-Revised-98 (DRS-R-98) total severity score &lt; 15.25 points and ≥ 4.5 points reduction. Secondary endpoints: time to recovery, grade ≥ 3 side effects (Common Terminology Criteria for Adverse Events version 3.0), and distress (Delirium Experience Questionnaire). The study was powered to increase DRR with 25% for olanzapine compared to haloperidol. Results: Between January 2010 and June 2016, 100 of the anticipated 200 patients were enrolled in the study from 6 sites in the Netherlands and randomly assigned to olanzapine (n = 50) or haloperidol (n = 50). Baseline characteristics were well balanced. Interim analysis showed a difference in DRR of -12.2% (95% confidence interval (CI) = -32.0%- 7.4%); 45% for olanzapine (95% CI 31.0-58.8) vs 57% for haloperidol (95% CI 43.3-71.0), P = 0.22).Time to recovery was 4.5 days in the olanzapine arm vs 2.8 days in the haloperidol arm (P = 0.20). There was no difference in grade ≥ 3 side effects between both arms (OR 0.44, 95% CI 0.14-1.40; P = 0.16). Mean level of distress in patients was 2.1 (SD 1.4) for olanzapine vs 2.3 (SD 1.4) for haloperidol (P = 0.80). Formal interim futility analysis indicated a conditional power of 0.086, implying a very low likelihood (8.6%) of reaching the expected DRR superiority rate of 25% for olanzapine. Therefore, the study was prematurely terminated. Conclusions: No difference in efficacy and side effect profile was observed between haloperidol or olanzapine treatment for delirium in patients with advanced cancer. Clinical trial information: NCT01539733.
An official European Respiratory Society statement: pulmonary haemodynamics during exercise
Authors: Gabor Kovacs, Philippe Herve, Joan Albert Barbera, Ari Chaouat, Denis Chemla, Robin Condliffe, Gilles Garcia, Ekkehard Grünig, Luke Howard, Marc Humbert, Edmund Lau, Pierantonio Laveneziana, Gregory D. Lewis, Robert Naeije, Andrew Peacock, Stephan Rosenkranz, Rajeev Saggar, Silvia Ulrich, Dario Vizza, Anton Vonk Noordegraaf, Horst Olschewski
Journal: European Respiratory Journal (2017)

There is growing recognition of the clinical importance of pulmonary haemodynamics during exercise, but several questions remain to be elucidated. The goal of this statement is to assess the scientific evidence in this field in order to provide a basis for future recommendations.Right heart catheterisation is the gold standard method to assess pulmonary haemodynamics at rest and during exercise. Exercise echocardiography and cardiopulmonary exercise testing represent non-invasive tools with evolving clinical applications. The term "exercise pulmonary hypertension" may be the most adequate to describe an abnormal pulmonary haemodynamic response characterised by an excessive pulmonary arterial pressure (PAP) increase in relation to flow during exercise. Exercise pulmonary hypertension may be defined as the presence of resting mean PAP <25 mmHg and mean PAP >30 mmHg during exercise with total pulmonary resistance >3 Wood units. Exercise pulmonary hypertension represents the haemodynamic appearance of early pulmonary vascular disease, left heart disease, lung disease or a combination of these conditions. Exercise pulmonary hypertension is associated with the presence of a modest elevation of resting mean PAP and requires clinical follow-up, particularly if risk factors for pulmonary hypertension are present. There is a lack of robust clinical evidence on targeted medical therapy for exercise pulmonary hypertension.
Abstract P287: The Association Between Usual Fast Food Intake Over 25 Years and Non-alcoholic Fatty Liver Disease: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Andrew O Odegaard, David R Jacobs, Lyn M Steffen, Mark A Pereira
Journal: Circulation (2016)

Introduction: Nonalcoholic Fatty Liver Disease (NAFLD) is a common obesity related complication that is strongly associated with cardiometabolic morbidity. Despite being a major cardiometabolic risk factor, there is minimal understanding of the relationship between modifiable factors such as diet with NAFLD. Therefore, we examined the association between usual fast food intake habits over 25 years beginning in young adulthood and the odds of having NAFLD during middle age. Hypothesis: A higher average frequency of visits to fast food restaurants over 25 years is positively associated with NAFLD. Methods: We analyzed data from the CARDIA study and included participants with at least 2 assessments of fast food restaurant visit frequency (assessed exam year 0, 7, 10, 15, 20, 25) over 25 years and Computed Tomography (CT) quantification of liver fat at the year 25 exam (age 43-55 years). NAFLD was defined as liver attenuation ≤ 40 Hounsfield units after the exclusion of other causes of liver fat (e.g. heavy alcohol use). Logistic regression models were used to test the association between the average fast food restaurant visit frequency and NAFLD. This analysis includes 2,682 participants. Results: The prevalence of NAFLD at year 25 was 9.8% (264/2682). There was a strong positive association between higher fast food restaurant visit frequency over 25 years and the odds of NAFLD independent of sugar and artificially sweetened beverages, overall diet, and relative lifestyle factors (Table). This association was still positive after adjustment for BMI at year 25. Results were consistent by sex, race, and BMI. Conclusions: These results underscore how a higher usual frequency of fast food intake from early adulthood through middle age is positively associated with NAFLD during middle age, and driven by but not dependent on higher levels of relative weight.
2017 ACC/HRS Lifelong Learning Statement for Clinical Cardiac Electrophysiology Specialists
Authors: Cynthia M. Tracy, George H. Crossley, T. Jared Bunch, Grant V. Chow, Amy Leiserowitz, Julia H. Indik, Fred Kusumoto, Lisa A. Mendes, Thomas M. Munger, Srinivas Murali, Kristen K. Patton, Andrea M. Russo, Melvin Scheinman, John A. Schoenhard, Jeffrey R. Winterfield
Journal: Journal of the American College of Cardiology (2017)
P2.07-044 Thyroid Disfunction in Advanced NSCLC Patients Treated with Nivolumab out of Clinical Trial: A Real-World Data Analysis
Authors: R. Palmero, J.C. Ruffinelli, E. Alanya, J.A. Marin, M. Ferrer, M. Jove, C. Mesia, M. Arellano, I. Brao, F. Cardenal, I. Peiro, E. Nadal
Journal: Journal of Thoracic Oncology (2017)
Reply to Eleftheriadis and to Sharma et al.
Authors: Vivek Kumbhari, Mouen Khashab
Journal: Endoscopy (2017)

See also: Should we focus on the fight against achalasia or equivocal results of reflux after peroral endoscopic myotomy?Endoscopy 2017; 49(12): 1282-1282DOI: 10.1055/s-0043-119639 See also: Gastroesophageal reflux after peroral endoscopic myotomyEndoscopy 2017; 49(12): 1283-1283DOI: 10.1055/s-0043-121145
Epidémie de Escherichia coli O157 en Suède
Authors: T Ziese, Y Anderson, B de Jong, S Löfdahl, M Ramberg
Journal: Eurosurveillance (1996)

Les infections a Escherichia coli O157 se manifestent par des diarrhees benignes, des colites hemorragiques severes et par le syndrome hemolytique uremique (SHU). Entre 2% et 21% des cas observes developpent un SHU avec un taux de letalite de 3 a 7% (1). E. coli O157 peut etre isole dans les feces. Le diagnostic du SHU est clinique et peut etre confirme par l'isolement de l'organisme ou l'identification des anticorps anti-lipopolysaccharidiques de E. coli dans le sang. Plusieurs epidemies de E. coli O157 sont survenues en Grande Bretagne, au Canada et aux Etats Unis au cours des dernieres annees.
Multi-platform ’Omics Analysis of Human Ebola Virus Disease Pathogenesis
Authors: Amie J. Eisfeld, Peter J. Halfmann, Jason P. Wendler, Jennifer E. Kyle, Kristin E. Burnum-Johnson, Zuleyma Peralta, Tadashi Maemura, Kevin B. Walters, Tokiko Watanabe, Satoshi Fukuyama, Makoto Yamashita, Jon M. Jacobs, Young-Mo Kim, Cameron P. Casey, Kelly G. Stratton, Bobbie-Jo M. Webb-Robertson, Marina A. Gritsenko, Matthew E. Monroe, Karl K. Weitz, Anil K. Shukla, Mingyuan Tian, Gabriele Neumann, Jennifer L. Reed, Harm van Bakel, Thomas O. Metz, Richard D. Smith, Katrina M. Waters, Alhaji N'jai, Foday Sahr, Yoshihiro Kawaoka
Journal: Cell Host & Microbe (2017)
Actin cytoskeleton remodeling drives epithelial‐mesenchymal transition for hepatoma invasion and metastasis in mice
Authors: Jei‐Ming Peng, Rabindranath Bera, Chih‐Yung Chiou, Ming‐Chin Yu, Tse‐Chin Chen, Chia‐Wei Chen, Tsung‐Rui Wang, Wan‐Ling Chiang, Shin‐Pei Chai, Yongkun Wei, Huamin Wang, Mien‐Chie Hung, Sen‐Yung Hsieh
Journal: Hepatology (2017)

High invasiveness is a hallmark of human hepatocellular carcinoma (HCC). Large tumors predict invasion and metastasis. Epithelial-mesenchymal transition (EMT) is crucial for cancer invasion and metastasis. However, the mechanisms whereby large tumors tend to undergo EMT remain unclear. We conducted a subgenome-wide screen and identified KLHL23 as an HCC invasion suppressor by inhibiting EMT. KLHL23 binds to actin and suppresses actin polymerization. KLHL23 silencing induced filopodium and lamellipodium formation. Moreover, EMT was suppressed by KLHL23 through its action on actin dynamics. Traditionally, actin cytoskeleton remodeling is downstream of EMT reprogramming. It is therefore intriguing to ask why and how KLHL23 inversely regulates EMT. Activation of actin cytoskeleton remodeling by either KLHL23 silencing or treatment with actin cytoskeleton modulators augmented cellular hypoxic responses in a cell-density-dependent manner, resulting in hypoxia-inducible factor (HIF) and Notch signals and subsequent EMT. Environmental hypoxia did not induce EMT unless actin cytoskeleton remodeling was simultaneously activated and only when cells were at high density. The resulting EMT was reversed by either adenosine 5'-triphosphate supplementation or actin polymerization inhibitors. Down-regulation of KLHL23 was associated with invasion, metastasis, and poor prognosis of HCC and pancreatic cancer. Correlations of tumor size with EMT and inverse association of expression of KLHL23 with HIF/Notch signals were further validated in patient-derived xenograft HCCs in mice.Simultaneously activation of actin cytoskeleton remodeling by intrinsic (such as KLHL23 down-regulation) or microenvironment cues is crucial for cell-density-dependent and hypoxia-mediated EMT, providing a mechanistic link between large tumor size and invasion/metastasis. Our findings provide a means of developing the prevention and treatment strategies for tumor invasion and metastasis. (Hepatology 2018;67:2226-2243).
Abstract 15033: Effects of Different Dosage Hoe-642 on Neuronal Mitochondrial Function After Cardiac Arrest
Authors: Lanying Wei, Xintong Liu, Pengjiao Zhang, Wenshuai Zhao, Xifan Wang, Fei Han
Journal: Circulation (2017)

Introduction: Our previous study indicated that HOE-642, 1mg/kg, used when initiating resuscitation enhanced ΔΨm, decreased the production of ROS, and protected neuronal mitochondrial function afte...
Phase 3 efficacy results of a single dose of NEPA, a fixed combination of netupitant and palonosetron, versus a 3-day regimen of aprepitant/granisetron (APR/GRAN) for prevention of chemotherapy-induced nausea and vomiting (CINV) in Chinese patients
Authors: L. Zhang, S. Lu, A. Dechaphunkul, S. Chessari, C. Lanzarotti, K. Jordan, M. Aapro
Journal: Annals of Oncology (2017)
Faecal transplant given in oral capsule reduces recurrent<i>C difficile</i>, shows study
Authors: Susan Mayor
Journal: BMJ (2017)

Faecal microbiota transplantation delivered orally in a capsule prevents recurrent Clostridium difficile infection in at-risk adults as effectively as transplantation of donor stool material by colonoscopy, a randomised trial has found.1

Infection with C difficile is the leading cause of healthcare associated infectious diarrhoea and recurrent infection is common. Between 10% and 30% of patients have a recurrence and this risk increases to 60% after the third episode.

Faecal microbiota transplantation, which involves giving faecal matter from a healthy donor, …
Macrophages—common culprit in obesity and asthma
Authors: N. Sharma, M. Akkoyunlu, R. L. Rabin
Journal: Allergy (2017)

Macrophages are essential innate immune cells that also regulate local metabolism. Endogenous or exogenous stimuli may polarize macrophages toward phenotypes that serve distinct innate immunological metabolic functions. IFN-γ or lipopolysaccharide (LPS) polarizes macrophages toward the M1, or "classically activated" phenotype that participates in defense against intracellular pathogens. IL-4, IL-13, or chitin polarizes macrophages toward the M2, or "alternatively activated" phenotype, which defends against multicellular nematodes and fungi. As macrophages polarize in local environments, M1 and M2 macrophages may coexist in different organs and may differentially affect asthma and obesity, two comorbid diseases where polarized macrophages contribute to their pathogenesis. While M1 macrophages are considered beneficial in asthma and contribute to the pathology of obesity, M2 macrophages contribute to the pathology of asthma, but limit metabolic syndrome associated with obesity. Here, we discuss the roles for M1 and M2 macrophages in asthma and obesity, and propose a model by which M1-mediated inflammation in adipose tissue enhances M2-mediated inflammation in the asthmatic lung.