tbuckley/cabot-search huggingface dataset:
Abstract 036: Dietary Fatty Acids and the Risk of Fatal and Non-Fatal Coronary Heart Disease in Middle-Aged or Older Men: The Kuopio Ischaemic Heart Disease Risk Factor Study
Authors: Jyrki K Virtanen, Jaakko Mursu, Tomi-Pekka Tuomainen, Sari Voutilainen
Journal: Circulation (2013)

Background: The epidemiological evidence of the role of dietary saturated fatty acids (SFA) in the etiology of coronary heart disease (CHD) is inconsistent. In general, however, replacement of SFA ...
Influence of the Site of a Hymenoptera Sting on the Severity of Anaphylaxis in Silesia, Poland
Authors: Radoslaw Gawlik, Justyna Maciejiczek, Anna Dzienniak, Izabela Kolodziej, Magdalena Marcak, Lawrence M. Dubuske, Andrzej Bozek
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 12934: Universal Versus Platelet Reactivity Assay-Driven Use of P2Y12 Inhibitors in Acute Coronary Syndrome Patients: A Cost-Effectiveness Analysis From a United Kingdom Perspective
Authors: Craig I Coleman, Brendan L Limone
Journal: Circulation (2013)

Background: On-treatment platelet reactivity assay (PRA) monitoring can accurately predict which patients will respond poorly to clopidogrel. We sought to determine the cost-effectiveness of univer...
Royal college is urged to drop infant formula sponsorship
Authors: Gareth Iacobucci
Journal: BMJ (2019)

The Royal College of Paediatrics and Child Health has been urged to drop all sponsorship by infant formula manufacturers from its upcoming Middle East and North Africa conference, after an outcry from doctors and campaigners.

The conference, being held in Cairo on 29 January, is described by the college as “a platform for academia, industry, civil society organisations, entrepreneurs and the private sector . . . to generate better child health outcomes.”1 Listed sponsors of the event include the breastmilk substitute manufacturers Abbott Nutrition, Nutricia, Danone, and Nestle.

In a letter to Russell Viner, president of the college, 12 charities and advocacy groups and 84 …
Epidermal micro-perforation potentiates the efficacy of epicutaneous vaccination
Authors: Pierre-Louis Hervé, Véronique Dhelft, Camille Plaquet, Anaïs Rousseaux, Adeline Bouzereau, Laetitia Gaulme, Sylvain Tilleul, Mélanie Ligouis, Nathalie Donne, Paul-Henri Lambert, Pham Hong-Thai, Wassana Wijagkanalan, Hugh A. Sampson, Lucie Mondoulet
Journal: Journal of Controlled Release (2019)
CRISPR/Cas9 Genome Editing to Treat Sickle Cell Disease and B-Thalassemia: Re-Creating Genetic Variants to Upregulate Fetal Hemoglobin Appear Well-Tolerated, Effective and Durable.
Authors: Michelle I. Lin, Elizabeth Paik, Bibhu Mishra, David Burkhardt, Andrew Kernytsky, Michael Pettiglio, Yi-Shan Chen, Kaleigh Tomkinson, Amanda Woo, Mauricio Cortes, Siyuan Tan, Todd D Borland, Lawrence Klein, Angela Yen, Sudipta Mahajan, Eric Chan, Brenda Eustace, Matthew Porteus, Tirtha Chakraborty, Chad Cowan, Rodger Novak, Ante Lundberg
Journal: Blood (2017)
Prognostic significance of nutritional and inflammatory markers in patients with unresectable pancreatic ductal adenocarcinoma treated with chemotherapy.
Authors: Ryosuke Kobiyama, Isaku Yoshioka, Takayuki Ando, Shinya Kajiura, Kazuto Shibuya, Shinichi Sekine, Katsuhisa Hirano, Hayato Baba, Mie Arai, Kenta Sukegawa, Toru Watanabe, Isaya Hashimoto, Shozo Hojo, Tomoyuki Okumura, Takuya Nagata, Kenta Murotani, Ichiro Yasuda, Tsutomu Fujii
Journal: Journal of Clinical Oncology (2019)

219 Background: Recently, several nutritional and inflammatory markers have been reported to be involved in cancer progression. The aim of this study is to evaluate whether nutritional and inflammatory biomarkers such as the modified Glasgow prognostic score (mGPS), the neutrophil‐to-lymphocyte ratio (NLR), the platelet‐to-lymphocyte ratio, the systemic-immune-inflammation index (SIII), controlling nutritional status (CONUT) score, prognostic nutritional index, and the lymphocyte‐to-monocyte ratio (LMR) could predict the prognosis in patients with unresectable pancreatic ductal adenocarcinoma (UR-PDAC) who underwent chemotherapy as first-line therapy, using disease-specific survival as the primary outcome. Methods: All UR-PDAC patients were retrospectively evaluated between January 2011 and May 2017 at Toyama University Hospital. Baseline clinicopathological characteristics and pre-treatment laboratory values such as absolute neutrophil, lymphocyte and platelet counts, C-reactive protein, albumin and CA19-9 levels, were collected. Results: A total of 184 patients were diagnosed as UR-PDAC. Among them, 151 patients who underwent chemotherapy were enrolled in this study. There were significant relationships between survival and elevated mGPS, elevated NLR, elevated SIII, decreased LMR, decreased serum cholinesterase level, and low CONUT score (p &lt; 0.001, p &lt; 0.001, p = 0.001, p &lt; 0.001, p = 0.026 and p &lt; 0.001, respectively, by log-rank test). The median survival time of patients with metastatic lesions was significantly shorter than that of patients with unresectable locally advanced PDAC (9.0 vs 15.5 months, respectively; p = 0.033). There was no significant difference in survival in pre-treatment CA19-9 level and tumor location. Multivariate analysis using Cox regression model revealed that NLR and CONUT score were independent prognostic factors. Conclusions: Pre-treatment NLR and CONUT score may predict clinical outcome in patients with UR-PDAC undergoing chemotherapy as first-line therapy.
Abbreviated Magnetic Resonance Imaging (MRI) for Breast Cancer Screening: Rationale, Concept, and Transfer to Clinical Practice
Authors: Christiane K. Kuhl
Journal: Annual Review of Medicine (2019)

Given the increasing understanding of cancer as a heterogeneous group of diseases, detection methods should offer a sensitivity profile that ensures perfect sensitivity for biologically important cancers while screening out self-limiting pseudocancers. However, mammographic screening is biased toward detection of ductal carcinoma in situ and slowly growing cancers—and thus frequently fails to detect biologically aggressive cancers. This explains the persistently high rates of interval cancers and high rates of breast cancer mortality observed in spite of decades of mammographic screening. Magnetic resonance imaging (MRI), in contrast, has a sensitivity profile that matches clinical needs. Conventional MRI is not suitable for population-wide screening due to high cost, limited tolerability, and lack of availability. We introduced abbreviated MRI in 2014. Abbreviated MRI will change the way MRI is used in clinical medicine. This article describes the rationale to use MRI in general, and abbreviated MRI in particular, for breast cancer screening.
Effects of Sacubitril/Valsartan on Biomarkers of Extracellular Matrix Regulation in Patients With HFrEF
Authors: Michael R. Zile, Eileen O'Meara, Brian Claggett, Margaret F. Prescott, Scott D. Solomon, Karl Swedberg, Milton Packer, John J.V. McMurray, Victor Shi, Martin Lefkowitz, Jean Rouleau
Journal: Journal of the American College of Cardiology (2019)
Editing aberrant splice sites efficiently restores β-globin expression in β-thalassemia
Authors: Shuqian Xu, Kevin Luk, Qiuming Yao, Anne H. Shen, Jing Zeng, Yuxuan Wu, Hong-Yuan Luo, Christian Brendel, Luca Pinello, David H. K. Chui, Scot A. Wolfe, Daniel E. Bauer
Journal: Blood (2019)
What’s hot that the other lot got
Authors: Conor Walsh
Journal: Thorax (2019)

<h3></h3> A 50 year old Afro-Caribbean gentleman with a background of Ro52 and MDA5 antibody positive anti- synthetase syndrome on prednisolone and mycophenolate mofetil presented with a tight band like pain around his thorax and abdominal pain. Examination identified severe dysaesthesia with a T6 spinal level, as well as lower limb and truncal weakness. MRI showed an expansile T2 hyperintense lesion from C7 to T8 with patchy enhancement in keeping with a NMOSD. He had no optic nerve involvement, confirmed by OCT. The weakness and dysaesthesia responded rapidly to high dose methylprednisolone however he developed constipation, recurrent neuropathic pain and tonic spasms. Serum AQP4 antibodies were present. At presentation serum CK was also raised. Up to 25% of patients with NMOSD have co-existing autoimmunity. However, there are very few reports of anti-synthetase syndrome and NMOSD. Ro-antibodies are well documented in studies on Sjögren's disease and transverse myelitis. Patients with autoimmune connective tissue diseases who develop neurological symptoms should be investigated for neurological autoantibodies too as they are at risk of multiple autoimmune disorders. Furthermore, neurologists should be observant to other systems when presented with a patient with NMOSD as they may have other diseases which are currently asymptomatic or minimally symptomatic.
Telomere Length Is Associated with Epigenetic Programming in CLL and Is a Superior Predictor of Clinical Outcome with the Ability to Bifurcate Patients with the Same CLL-IPI Score
Authors: Kevin Norris, Christopher C. Oakes, Brian Giacopelli, Tait D. Shanafelt, Neil E. Kay, Kari G. Chaffee, Christopher Fegan, Duncan M Baird, Chris Pepper
Journal: Blood (2018)
YH25448, an Irreversible EGFR-TKI with Potent Intracranial Activity in EGFR Mutant Non–Small Cell Lung Cancer
Authors: Jiyeon Yun, Min Hee Hong, Seok-Young Kim, Chae-Won Park, Soyoung Kim, Mi Ran Yun, Han Na Kang, Kyoung-Ho Pyo, Sung Sook Lee, Jong Sung Koh, Ho-Juhn Song, Dong Kyun Kim, Young-Sung Lee, Se-Woong Oh, Soongyu Choi, Hye Ryun Kim, Byoung Chul Cho
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Given that osimertinib is the only approved third-generation EGFR-TKI against EGFR activating and resistant T790M mutated non–small cell lung cancer (NSCLC), additional mutant-selective inhibitors with a higher efficacy, especially for brain metastases, with favorable toxicity profile are still needed. In this study, we investigated the antitumor efficacy of YH25448, an oral, mutant-selective, irreversible third-generation EGFR-TKI in preclinical models. Experimental Design: Antitumor activity of YH25448 was investigated in vitro using mutant EGFR-expressing Ba/F3 cells and various lung cancer cell lines. In vivo antitumor efficacy, ability to penetrate the blood–brain barrier (BBB), and skin toxicity of YH25448 were examined and compared with those of osimertinib using cell lines and PDX model. Results: Compared with osimertinib, YH25448 showed a higher selectivity and potency in kinase assay and mutant EGFR-expressing Ba/F3 cells. In various cell line models harboring EGFR activating and T790M mutation, YH25448 effectively inhibited EGFR downstream signaling pathways, leading to cellular apoptosis. When compared in vivo at equimolar concentrations, YH25448 produced significantly better tumor regression than osimertinib. Importantly, YH25448 induced profound tumor regression in brain metastasis model with excellent brain/plasma and tumor/brain area under the concentration–time curve value. YH25448 rarely suppressed the levels of p-EGFR in hair follicles, leading to less keratosis than osimertinib in animal model. The potent systemic and intracranial activity of YH25448 has been shown in an ongoing phase I/II clinical trial for advanced EGFR T790M mutated NSCLC (NCT03046992). Conclusions: Our findings suggest that YH25448 is a promising third-generation EGFR inhibitor, which may be more effective and better tolerated than the currently approved osimertinib.
CA19-9 decrease and overall survival according to platelet level in patients with metastatic pancreatic cancer.
Authors: Yang Chen, Guanghai Dai
Journal: Journal of Clinical Oncology (2019)

203 Background: Several studies have linked a decrease of carbohydrate antigen (CA) 19-9 to lengthened survival in pancreatic cancer. Experimental evidence supported that CA19-9 may be involved in platelet/tumor cell interactions. The object of this study was to correlate a decline in CA19-9 with survival according to platelet level in metastatic pancreatic cancer. Methods: A retrospective analysis of patients with histologically diagnosed metastatic pancreatic cancer was performed. CA19-9 serum concentration and platelet level was measured at baseline and every 6 weeks. Results: Total 174 metastatic pancreatic cancer patients with baseline and week-6 CA19-9 measurements were analyzed. Median follow-up from initial chemotherapy was 29.2 months, and median survival from initial chemotherapy was 6.7 months. Multivariate analyses confirmed an early decrease in CA19-9 concentrations of 25% after two cycles of chemotherapy were associated with a favorable survival compared with patients who did not have a decrease of 25% (HR = 0.56 [95% CI: 0.40-0.78]). The association of CA19-9 decrease with overall survival differed by platelet level ( P interaction &lt; 0.001). Multivariable adjusted hazard rations for decrease in CA19-9 of 25% were 0.30 (0.18-0.49) in patients with low platelet level (PLT &lt; 190 × 10 9 /L) and 0.85 (0.53-1.35) in patients with high platelet level (PLT ≥ 190×10 9 /L). Conclusions: In patients with MPC, 25% decrease at week-6 could be an early marker for prognosis. The association of CA19-9 decrease with pancreatic cancer survival is stronger in patients with platelet low tumors than platelet high tumors. Our findings suggest a differential prognostic effect of CA19-9 according to platelet level.
Impact of an inter-professional clinic on pancreatic cancer outcomes: The Princess Margaret Cancer Centre (PM) experience.
Authors: Hamzeh Albaba, Anna Dodd, Rebecca M. Prince, Kyaw Lwin Aung, David W. Hedley, Steven Gallinger, John Kim, James D. Brierley, Shari Moura, Stephanie Moignard, Adriana Fraser, Shawn Hutchinson, Osvaldo Espin-Garcia, Carolanne Moulton, Alice Chia-chi Wei, Paul David Greig, Ian M McGilvray, Neesha C. Dhani, Elena Elimova, Jennifer J. Knox
Journal: Journal of Clinical Oncology (2019)

444 Background: Patients with pancreatic ductal adenocarcinoma (PDAC) have limited treatment options. Management of complex symptoms and psychosocial implications requires an interprofessional approach as prognosis is often measured in months. A multidisciplinary approach has been associated with improvement in clinical outcomes including survival. We aimed to evaluate the impact of an inter-professional approach for PDAC patients at the Wallace McCain Centre for Pancreatic Cancer (WMCPC) at PM on their management and clinical outcomes. Methods: We undertook retrospective review of all patients with PDAC seen at PM two years before (July ‘12 – June ‘14) and two years after (July ‘14 – June ‘16) establishment of the WMCPC. Standard therapies (surgical approach, chemotherapy, radiation therapy) were the same during both time periods. Comparison of overall survival (OS), stage at diagnosis, surgical outcomes, waiting times, and proportion seen by social worker, dietician and clinical nurse specialist (CNS) was explored with descriptive statistic and survival analysis. Results: A total of 993 patients were reviewed; 482 patients pre- and 511 patients post-WMCPC. Age (median 67 yrs), sex (54% men) and stage III/IV (52%) were similar in both groups. There was a trend to improved OS in the post-WMCPC group (9.6 vs. 10.9 m; p = 0.055); multivariable analysis found a significant improvement in OS after adjustment for performance status and stage (p = 0.023; HR 0.84, 95% CI 0.72-0.98). Rate of R0 versus R1/R2 resection for curative surgery (n = 264, 28%) was similar in both groups. Time from referral to first clinic visit significantly decreased from 13.4 to 8.8 days in the post-WMCPC group (p &lt; 0.001) as did time from first clinic appointment to diagnostic biopsy (25.9 vs. 16.9 days, p = 0.022). Patients in the post-WMCPC were more frequently seen by a social worker, dietician or CNS (8% vs. 38%, 9% vs. 35% and 31% vs. 50% respectively, p &lt; 0.001). Conclusions: Establishment of an interprofessional clinic for the treatment of PDAC patients at PM has streamlined diagnosis, aided symptom management and improved overall survival. This has implications for planning care delivery models and proves the value of this intervention.
Cerebellar-Prefrontal Network Connectivity and Negative Symptoms in Schizophrenia
Authors: Roscoe O. Brady, Irene Gonsalvez, Ivy Lee, Dost Öngür, Larry J. Seidman, Jeremy D. Schmahmann, Shaun M. Eack, Matcheri S. Keshavan, Alvaro Pascual-Leone, Mark A. Halko
Journal: American Journal of Psychiatry (2019)

The interpretability of results in psychiatric neuroimaging is significantly limited by an overreliance on correlational relationships. Purely correlational studies cannot alone determine whether behavior-imaging relationships are causal to illness, functionally compensatory processes, or purely epiphenomena. Negative symptoms (e.g., anhedonia, amotivation, and expressive deficits) are refractory to current medications and are among the foremost causes of disability in schizophrenia. The authors used a two-step approach in identifying and then empirically testing a brain network model of schizophrenia symptoms.In the first cohort (N=44), a data-driven resting-state functional connectivity analysis was used to identify a network with connectivity that corresponds to negative symptom severity. In the second cohort (N=11), this network connectivity was modulated with 5 days of twice-daily transcranial magnetic stimulation (TMS) to the cerebellar midline.A breakdown of connectivity in a specific dorsolateral prefrontal cortex-to-cerebellum network directly corresponded to negative symptom severity. Restoration of network connectivity with TMS corresponded to amelioration of negative symptoms, showing a statistically significant strong relationship of negative symptom change in response to functional connectivity change.These results demonstrate that a connectivity breakdown between the cerebellum and the right dorsolateral prefrontal cortex is associated with negative symptom severity and that correction of this breakdown ameliorates negative symptom severity, supporting a novel network hypothesis for medication-refractory negative symptoms and suggesting that network manipulation may establish causal relationships between network markers and clinical phenomena.
The impact of muscle mass loss after esophagectomy for esophageal cancer on prognosis.
Authors: Yota Shimoda, Takashi Ogata, Shinsuke Nagasawa, Yuta Kumazu, Tsutomu Hayashi, Takanobu Yamada, Takashi Oshima
Journal: Journal of Clinical Oncology (2019)

107 Background: Several reports revealed that preoperative presence of sarcopenia was related with poor prognosis for esophageal cancer. However, the influence of muscle mass loss during perioperative period on prognosis is unknown. The alternation of muscle mass during perioperative period is attractive topic as surgeon have chance to intervene for maintaining muscle mass in perioperative care. The aim of this study was to assess the influence of loss of muscle after esophagectomy to discharge on prognosis. Methods: This study retrospectively analyzed 150 consecutive patients with esophageal and gastroesophageal junction cancer, who underwent the open right thoraco−abdominal approach esophagectomy, pathologically diagnosed as squamous cell carcinoma or adenocarcinoma, between September 2011 and June 2015. Patients who had pathologically diagnosed as T4 or stageⅣ according to the UICC 7th edition TNM classification were excluded. This study investigated the influence of muscle mass loss after esophagectomy to discharge on prognosis. Body composition was analyzed using the Tanita MC−190EM bioelectrical impedance analyzer, evaluated within 1 week before surgery and at discharge. The primary end−point is over−all survival after esophagectomy. Results: The median % muscle mass loss was 4.38% (range −3.3 to +18.8). Patients were divided into two groups based on the % muscle mass loss by cut−off 4.38 (group A: less % muscle mass loss, group B: more % muscle mass loss). N stage (0/1/2/3) was 39/28/6/2 in group A, and 26/23/19/7 in group B. The rate of 2/3 was significantly higher in group B. Postoperative complication rate was 31% (23/75) in group A, and 48% (36/75) in group B. The complication rate was significantly higher in group B. The 3−years survival rate was 89.2% in group A, and 70.9% in group B. Group B was significantly worse for over−all survival than group A (p = 0.033). Multivariate Cox regression analysis showed that the patients who had % muscle mass loss over 4.38 (p = 0.045; HR 2.008; HR 95% CI 1.014−3.977), T2/3 (p = 0.001; HR 3.649; HR 95% CI 1.660−8.019) associated with worse over−all survival. Conclusions: Our study found correlation between loss of muscle after esophagectomy to discharge and worse outcomes.
Effect of Laparoscopic Distal Gastrectomy vs Open Distal Gastrectomy on Long-term Survival Among Patients With Stage I Gastric Cancer
Authors: Hyung-Ho Kim, Sang-Uk Han, Min-Chan Kim, Wook Kim, Hyuk-Joon Lee, Seung Wan Ryu, Gyu Seok Cho, Chan Young Kim, Han-Kwang Yang, Do Joong Park, Kyo Young Song, Sang-Il Lee, Seong Yeob Ryu, Joo-Ho Lee, Woo Jin Hyung
Journal: JAMA Oncology (2019)

<h3>Importance</h3> Laparoscopic distal gastrectomy is gaining popularity over open distal gastrectomy for gastric cancer because of better early postoperative outcomes. However, to our knowledge, no studies have proved whether laparoscopic distal gastrectomy is oncologically equivalent to open distal gastrectomy. <h3>Objective</h3> To examine whether the long-term survival among patients with stage I gastric cancer undergoing laparoscopic distal gastrectomy is noninferior to that among patients undergoing open distal gastrectomy. <h3>Design</h3> The Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS) group, which includes 15 surgeons from 13 institutes, conducted a phase 3, multicenter, open-label, noninferiority, prospective randomized clinical trial (KLASS-01) of patients with histologically proven, preoperative clinical stage I gastric adenocarcinoma from January 5, 2006, to August 23, 2010. Survival and recurrence status of the patients was determined in December 2016. <h3>Interventions</h3> Patients were randomly assigned (1:1) to laparoscopic distal gastrectomy (n = 705) or open distal gastrectomy (n = 711). Of these patients, 85 received a surgical approach opposite the one to which they were randomized (63 randomized to the open surgery group and 22 to the laparoscopic group). <h3>Main Outcomes and Measures</h3> Difference in 5-year overall survival between the laparoscopic and open distal gastrectomy groups. The noninferiority margin was prespecified as −5% (corresponding hazard ratio of 1.54), with an assumed survival of 90% after 5 years in the open surgery group. <h3>Results</h3> Among the 1416 patients (mean [SD] age, 57.3 [11.1] years; 940 [66.4%] male) included in the study, the 5-year overall survival rates were 94.2% in the laparoscopic group and 93.3% in the open surgery group (log-rank<i>P</i> = .64). Intention-to-treat analysis confirmed the noninferiority of the laparoscopic approach compared with the open approach (difference, 0.9 percentage points; 1-sided 97.5% CI, −1.6 to infinity). The 5-year cancer-specific survival rates were similar between the 2 groups (97.1% in the laparoscopic group and 97.2% in the open surgery group, log-rank<i>P</i> = .91; difference, −0.03 percentage points; 1-sided 97.5% CI, −1.8 to infinity). Per-protocol analysis results were consistent with the intention-to-treat results for overall and cancer-specific survival rates. <h3>Conclusions and Relevance</h3> The KLASS-01 trial revealed similar overall and cancer-specific survival rates between patients receiving laparoscopic and open distal gastrectomy. Laparoscopic distal gastrectomy is an oncologically safe alternative to open surgery for stage I gastric cancer. <h3>Trial Registration</h3> ClinicalTrials.gov identifier:NCT00452751