tbuckley/cabot-search huggingface dataset:
Methylphenidate (MPH) in the management of fatigue in patients (pts) with advanced pancreatic cancer (APC): A retrospective analysis.
Authors: Wasif M. Saif, Zhenyang Jiang, Harriet Butler-Bowen, Teresa Rodriguez, Marie C Garcon, Brandie Jackson, Valerie Relias, Melissa Hennessey Smith
Journal: Journal of Clinical Oncology (2015)

e20692 Background: Fatigue is the most common symptom (90%) in pts with APC and has a detrimental effect on pt's physical, emotional, and social aspects of life. No proven treatment exists for this devastating symptom. MPH is typically prescribed for ADHD and has been tested to treat fatigue with inconsistent results in other cancers. We performed a retrospective study to assess benefit of MPH in ameliorating fatigue in pts with APC. Methods: We retrospectively reviewed records of pts with APC seen at our outpt clinics between Jun 2011 – Nov 2014. Fatigue based on a Visual Analog Fatigue Scale (VAFS) was recorded on days when pts received chemotherapy. Data on pts with APC with VAFS of ≥ 4 out of 10 was collected per NCCN recommendations. Pts were then classified as grade 1 (VAFS 1,2,3), grade 2 (VAFS 4,5,6) and grade 3 (VAFS 7,8,9,10) to correspond with Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. MPH was dosed at 5 mg daily in AM and escalated to 10mg after 2 wks according to response and side effects. Primary end point was change in CTCAE grade of fatigue at end of 4-wk period. Secondary outcomes included effect on depression, anorexia and adverse effects. Results: A total of 71 pts (median age 67-yr) were evaluable. 67% received doublet, 13% triplet, and 20% single chemotherapy. Mean baseline VAFS was 7. Baseline CTCAE grade was 2 in 55% and 3 in 45% of pts. 93% of pts tolerated and benefited at 5mg and only 7% escalated to 10mg. After 4 wks, most pts had improved fatigue: 55% improved by 1 grade, 8% by 2 grades, 23% had fatigue resolved, and 14% showed no benefit and hence discontinued. Overall, the mean VAFS after 4 wks of MPH dropped to 4. In addition, 72% of pts maintained chemotherapy intensity. 39% of pts felt less depression and 52% had improved appetite. 10% pts had to stop MPH due to side effects. Grade 3/4 adverse events included insomnia, restlessness, palpitations and anorexia. However, effect of concomitant chemotherapy cannot be ruled out. Conclusions: Our findings support benefit of a low dose MPH to treat fatigue in pts with APC. MPH also improved depression and anorexia. Pts tolerated MPH well and most pts continued it. A large randomized clinical trial is needed to confirm its usage and safety.
Proposal and validation of a modified staging system to improve the prognosis predictive performance of the 8th AJCC/UICC pTNM staging system for gastric adenocarcinoma: a multicenter study with external validation
Authors: Cheng Fang, Wei Wang, Jing‐Yu Deng, Zhe Sun, Sharvesh Raj Seeruttun, Zhen‐Ning Wang, Hui‐Mian Xu, Han Liang, Zhi‐Wei Zhou
Journal: Cancer Communications (2018)

Abstract Background The 8th edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) pathological tumor‐node‐metastasis (pTNM) staging system may have increased accuracy in predicting prognosis of gastric cancer due to its important modifications from previous editions. However, the homogeneity in prognosis within each subgroup classified according to the 8th edition may still exist. This study aimed to compare and analyze the prognosis prediction abilities of the 8th and 7th editions of AJCC/UICC pTNM staging system for gastric cancer and propose a modified pTNM staging system with external validation. Methods In total, clinical data of 7911 patients from three high‐capacity institutions in China and 10,208 cases from the Surveillance, Epidemiology, and End Results (SEER) Program Registry were analyzed. The homogeneity, discriminatory ability, and monotonicity of the gradient assessments of the 8th and 7th editions of AJCC/UICC pTNM staging system were compared using log‐rank χ 2 , linear‐trend χ 2 , likelihood‐ratio χ 2 statistics and Akaike information criterion (AIC) calculations, on which a modified pTNM classification with external validation using the SEER database was proposed. Results Considerable stage migration, mainly for stage III, between the 8th and 7th editions was observed in both cohorts. The survival rates of subgroups of patients within stage IIIA, IIIB, or IIIC classified according to both editions were significantly different, demonstrating poor homogeneity for patient stratification. A modified pTNM staging system using data from the Chinese cohort was then formulated and demonstrated an improved homogeneity in these abovementioned subgroups. This staging system was further validated using data from the SEER cohort, and similar promising results were obtained. Compared with the 8th and 7th editions, the modified pTNM staging system displayed the highest log‐rank χ 2 , linear‐trend χ 2 , likelihood‐ratio χ 2 , and lowest AIC values, indicating its superior discriminatory ability, monotonicity, homogeneity and prognosis prediction ability in both populations. Conclusions The 8th edition of AJCC/UICC pTNM staging system is superior to the 7th edition, but still results in homogeneity in prognosis prediction. Our modified pTNM staging system demonstrated the optimal stratification and prognosis prediction ability in two large cohorts of different gastric cancer populations.
Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with metastatic oesophageal cancer: a JSMO–ESMO initiative endorsed by CSCO, KSMO, MOS, SSO and TOS
Authors: K. Muro, F. Lordick, T. Tsushima, G. Pentheroudakis, E. Baba, Z. Lu, B.C. Cho, I.M. Nor, M. Ng, L -T Chen, K. Kato, J. Li, M -H Ryu, W I Wan Zamaniah, W -P Yong, K -H Yeh, T.E. Nakajima, K. Shitara, H. Kawakami, Y. Narita, T. Yoshino, E. Van Cutsem, E. Martinelli, E.C. Smyth, D. Arnold, H. Minami, J. Tabernero, J -Y Douillard
Journal: Annals of Oncology (2018)

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of oesophageal cancer was published in 2016, and covered the management and treatment of local/locoregional disease, limited disease, locally advanced disease and the management of advanced/metastatic disease. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special guidelines meeting immediately after the JSMO Annual Meeting in 2018. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic oesophageal cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic oesophageal cancer representing the oncological societies of Japan (JSMO), China (CSCO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices and the drug availability and reimbursement situations in the individual participating Asian countries.
Brexit: Doctors must speak up about risks to patients, says BMA chair
Authors: Tom Moberly
Journal: BMJ (2018)

Doctors have a “duty” to speak up about the risks that Brexit poses to patients, the BMA has said.

Chaand Nagpaul, the association’s chair of council, said that the UK’s departure from the EU might prevent doctors giving their patients the care they need. “As doctors, we have an ingrained duty of care and we adhere to the maxim of ‘do no harm,’” he said. “We have a professional responsibility to raise concerns when we believe there will be detriment to patient care. We must as doctors speak out when necessary.”

Nagpaul was speaking at an event organised by …
Genetic predictors of response to specific drugs in primary myelofibrosis
Authors: Domenico Penna, Natasha Szuber, Terra L. Lasho, Christy M. Finke, Rangit R. Vallapureddy, Curtis A. Hanson, Rhett P. Ketterling, Animesh Pardanani, Naseema Gangat, Ayalew Tefferi
Journal: Blood Cancer Journal (2018)
Annals Consult Guys – The Art of Medicine—or Medicine in Art?
Authors: Geno J. Merli, Howard H. Weitz
Journal: Annals of Internal Medicine (2018)

Web Exclusives20 November 2018Annals Consult Guys – The Art of Medicine—or Medicine in Art?FREEGeno J. Merli, MD and Howard H. Weitz, MDGeno J. Merli, MDThomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Search for more papers by this author and Howard H. Weitz, MDThomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W18-0026 SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Annals Consult Guys brings a new perspective to the art and science of medicine with lively discussion and analysis of real-world cases and situations. They address medically relevant topics—whether they be poignant, thought-provoking, or just plain entertaining.For more videos from and information on Annals Consult Guys, visit go.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment Mark Stokes MDNorthwell Health26 November 2018 Mona Lisa First, I wouldn't be so quick to dismiss the low iron; does look she has conjunctival pallor. Second, if the average live expectancy at that time was in the 40s, and she died in her 60s, an extra 20 years is generous with an LDL in the 190s given risk of CV disease, and the lack of facilities in the Vinci area to do PTCA. Author, Article, and Disclosure InformationAffiliations: Thomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Disclosures: Geno J. Merli, MD, reports the following: Research grants/contracts: Bristol-Myers Squibb, Bayer. Howard H. Weitz, MD, reports that he has no financial relationships or interests to disclose.Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Proctor & Gamble, Pfizer, and Johnson & Johnson. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 20 November 2018Volume 169, Issue 10Page: CG1KeywordsDiagnostic techniquesDisclosureResearch grantsResearch reporting guidelines ePublished: 20 November 2018 Issue Published: 20 November 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.Loading ...
ADTH-09 Capsule endoscopy has better diagnostic yield than gastroscopy in recurrent iron deficiency anaemia
Authors: Hey-long Ching, Melissa F Hale, Reena Sidhu, John M Hebden, Matthew Kurien, Jennifer A Campbell, Stefania Chetcuti Zammit, Ailish Healy, Victoria Thurston
Journal: Endoscopy (2018)

<h3>Introduction</h3> Repeat upper gastrointestinal (GI) examination and small bowel capsule endoscopy should be considered in iron deficiency anaemia (IDA) when recurrent/refractory. Magnetically assisted capsule endoscopy (MACE) using a handheld magnet to steer the MiroCam Navi (Intromedic Ltd., Korea) capsule around the stomach followed by passive small bowel transit might satisfy both requirements as a single procedure. <h3>Methods</h3> MACE was performed in patients with recurrent/refractory IDA who were due gastroscopy (OGD). Total (upper GI and small bowel) and upper GI diagnostic yields and patient tolerance of the two modalities were compared. Assuming a diagnostic yield of 25% and 55% for OGD and small bowel capsule endoscopy (SBCE) respectively in recurrent/refractory IDA, 41 patients were needed to achieve 80% power and 5% two-sided significance. McNemar's test was used to measure differences in paired proportions. To allow for withdrawal, 50 patients were recruited. MACE mucosal visualisation was also assessed. <h3>Results</h3> OGD was performed within 2 days (IQR=13) of MACE in 49 patients (one failed to attend for OGD; median age 64 years (IQR=13), 39% male). Combined upper and mid-gut examination using MACE and passive SBCE yielded pathology in more patients than OGD alone (32 vs 6 (CI, 0.37 to 0.69); p&lt;0.0001). Comparing only upper GI examination (proximal to D2), MACE identified more total lesions than OGD (88 vs 52, p&lt;0.0001). If only lesions recognised as sources of IDA are included (oesophagitis, altered/fresh blood, angioectasia, ulcers and villous atrophy), a difference remains (20 vs 10; p=0.04). Small bowel (distal to D2) pathology was present in 24 (49%) patients (angioectasia (n=15), erosions (n=6), polyp (n=1), active bleeding (n=1), small bowel varices (n=1) and diverticulae (n=1)), considered to cause IDA in 11 (22%) patients who had no upper GI cause. Median scores (worst-best=0–10) for pain (0 vs 2), discomfort (0 vs 3) and distress (0 vs 4) were significantly lower for MACE than OGD respectively (p=0.0001 for all). Visualisation of gastric regions differed significantly (χ<sup>2</sup>=209.5, p&lt;0.05, Kruskal-Wallis H test). Better rank visualisation scores of ≥350 were seen for the greater and lesser curve, anterior and posterior body, antrum, pylorus and D2 while lower for the oesophagus (222), GOJ (103), cardia (267), fundus (189) and D1 (198). <h3>Conclusions</h3> Combined upper GI and small bowel examination with the MiroCam Navi yields more pathology than OGD alone in patients with recurrent/refractory IDA. MACE also has better diagnostic yield than OGD in the upper GI tract and was better tolerated.
Comparing CMR Mapping Methods and Myocardial Patterns Toward Heart Failure Outcomes in Nonischemic Dilated Cardiomyopathy
Authors: Tomas Vita, Christoph Gräni, Siddique A. Abbasi, Tomas G. Neilan, Ethan Rowin, Kyoichi Kaneko, Otavio Coelho-Filho, Eri Watanabe, Francois-Pierre Mongeon, Hoshang Farhad, Carlos Henrique Rassi, Yuna L. Choi, Kathleen Cheng, Michael M. Givertz, Ron Blankstein, Michael Steigner, Ayaz Aghayev, Michael Jerosch-Herold, Raymond Y. Kwong
Journal: JACC. Cardiovascular imaging (2018)
Recent clinical trends in Toll‐like receptor targeting therapeutics
Authors: Muhammad Ayaz Anwar, Masaud Shah, Jason Kim, Sangdun Choi
Journal: Medicinal Research Reviews (2018)

Toll-like receptors (TLRs) are germline-encoded receptors that are central to innate and adaptive immune responses. Owing to their vital role in inflammation, TLRs are rational targets in clinics; thus, many ligands and biologics have been reported to overcome the progression of various inflammatory and malignant conditions and support the immune system. For each TLR, at least one, and often many, drug formulations are being evaluated. Ligands reported as stand-alone drugs may also be reported based on their use in combinatorial therapeutics as adjuvants. Despite their profound efficacy in TLR-modulation in preclinical studies, multiple drugs have been terminated at different stages of clinical trials. Here, TLR modulating drugs that have been evaluated in clinical trials are discussed, along with their mode of action, suggestive failure reasons, and ways to improve the clinical outcomes. This review presents recent advances in TLR-targeting drugs and provides directions for more successful immune system manipulation.
Restricted visiting reduces nosocomial viral respiratory tract infections in high-risk neonates
Authors: Lisa Szatkowski, Rebecca McClaughry, Martin Clarkson, Don Sharkey
Journal: European Respiratory Journal (2018)

<b>Restricting visitors on the neonatal intensive care unit to parents only during a worldwide pandemic resulted in a 39% reduction in nosocomial viral respiratory tract infections in neonatal patients. These findings need validating in a prospective trial.</b>http://ow.ly/i8t430n2c2v
Factors Associated With Persistent Opioid Use Among Injured Workers’ Compensation Claimants
Authors: Nathan N. O’Hara, Andrew N. Pollak, Christopher J. Welsh, Lyndsay M. O’Hara, Alyson K. Kwok, Alexandra Herman, Gerard P. Slobogean
Journal: JAMA Network Open (2018)

<h3>Importance</h3> There is a paucity of data on persistent opioid use and factors associated with persistent opioid use among workers' compensation claimants. <h3>Objective</h3> To determine the proportion of injured workers who filled an opioid prescription beyond 90 days from injury and the factors associated with persistent opioid use among workers' compensation claimants. <h3>Design, Setting, Participants</h3> This retrospective cohort study collected workers' compensation claims data from January 1, 2008, to December 31, 2016, from the Chesapeake Employers' Insurance Company in Maryland. All workers' compensation claimants injured during the study years and with at least 1 filled opioid prescription were eligible for inclusion. For patients who had unique injury claims in multiple years of the study, only the first claimed injury was included in our analysis. Patients who died as a result of the claimed injury were excluded. The analysis was performed between October 2017 and August 2018. <h3>Main Outcomes and Measures</h3> The primary outcome was persistent opioid use, defined as an opioid prescription fulfillment beyond 90 days from the date of injury. Multivariable regression was used to determine prognostic factors of persistent opioid use. <h3>Results</h3> Of the 9596 study participants (mean [SD] age, 43 [12.3] years; 6218 [65.1%] male), 2741 (28.6%) filled an opioid prescription more than 90 days from their date of injury. Participants aged 60 years or older (odds ratio [OR], 1.92; 95% CI, 1.56-2.36), crush injuries (OR, 1.55; 95% CI, 1.28-1.89), strain and sprain injuries (OR, 1.54; 95% CI, 1.36-1.75), annual income more than $60 000 (OR, 1.31; 95% CI, 1.07-1.61), and concomitant diagnoses for chronic joint pain (OR, 1.98; 95% CI, 1.79-2.20) were significantly associated with persistent opioid use. Compared with workers with claims designated as permanent partial disability, workers with medical-only claims were significantly less likely to have persistent opioid use at 90 days postinjury (OR, 0.17; 95% CI, 0.15-0.20). <h3>Conclusions and Relevance</h3> A high proportion of persistent opioid use was observed in this workers' compensation cohort. Interventions to lower persistent opioid use in this population should target patients with the characteristics identified in this study.
Antiproliferative effect of memantine on human prostate, breast and colon cancer cell lines
Authors: S. Nicole Driggins, E. Lewis Myles, Todd Gary
Journal: Cancer Research (2004)

4380  Echinacea is a medicinal plant that consists of nine different species. One particular species, Echinacea purpurea, has been studied for its effect on erythroleukemic mouse models. The results of the studies have indicated that E. purpurea could possibly be essential in future treatments for anti-tumor therapy. Our studies have tested the effect of Echinacea purpurea on mammalian breast cancer cells and have indicated that an extract of the plant decreases the growth rate of the breast cancer cells and causes necrosis. Our recent studies have indicated that E. pallida, another species of Echinacea, has an effect on the mammalian breast cancer cells as well. A standard in vitro anti-carcinogenic protocol was used to determine if an extract of E. pallida exemplified an anti-carcinogenic effect on mammalian breast cancer cells. Three hundred thousand breast cancer cells, cell line BT-549, were placed in each well of a six-well plate that contained RMPI-1640 media with ten percent fetal bovine serum. The cells were then incubated in 0.5% carbon dioxide after they were treated with a control or with a certain dosage of the extract. Viable cells were then stained and counted on a hemocytometer. The data indicated that E. pallida decreases the growth rate of the breast cancer cells as the dosage amount of the extract increases. However, E. pallida does not decrease the growth rate of the mammalian cancer cells significantly as compared to E. purpurea. Further research could indicate that E. purpurea and E. pallida are effective alternative treatments for breast cancer. The treatments could possibly enable women who have been diagnosed with breast cancer to overcome the disease.
Abstract 20522: Nonagenarians Have Significantly Higher In-Hospital Morbidity and Mortality Following Percutaneous Coronary Intervention When Compared to Non-Nonagenarians
Authors: Shawn X Li, Hannah I Chaudry, Bruce W Andrus, Theodore B Curran, Shelia M Conley, Nicholas I Buss, James T DeVries
Journal: Circulation (2016)

Introduction: The number of very elderly patients undergoing percutaneous coronary intervention (PCI) is increasing, despite little data on in-hospital outcomes of nonagenarians after PCI. Whether age alone is an independent risk factor for complications remains uncertain, and the risk of intervention in this subset of patients in not known. Hypothesis: Despite nonagenarians having fewer cardiovascular comorbidities, they have increased in-hospital mortality after PCI. Methods: The Dartmouth Dynamic Registry was queried for all PCI’s between the years 2000 and 2015. Patients were subdivided into two groups based on their age (>89 and   90 years old and 182 nonagenarians underwent PCI. Nonagenarians had a lower incidence of smoking, hyperlipidemia, diabetes, but a higher incidence of chronic kidney disease (see Table 1). Nonagenarian...
Abstract 14091: Endothelial p53 Regulates Vascular Function Under Hyperglycemic and Hypoxic Conditions
Authors: Ayako nagasawa, Ippei Shimizu, Yohko Yoshida, Masanori Tsuchida, Tohru Minamino
Journal: Circulation (2017)

It is well known that p53 protects against genomic instability induced upon cellular stresses, thereby p53 is described as a guardian of genome. Accumulating evidence has shown that p53 promotes pathologies in age-associated diseases by inducing cellular senescence. We report that endothelial p53 is critically involved in the pathologies of vascular dysfunction under hyperglycemia and ischemic conditions. We found that endothelial expression of p53 was markedly up-regulated in a streptozotocin-induced type I diabetic murine model, and acetylcholine-induced vasodilatation was significantly impaired. Endothelial cell specific p53 deficiency markedly improved endothelial impairment upon hyperglycemic stress. Furthermore, p53 reduced the phosphorylation of eNOS (p-eNOS) mediated by up-regulating PTEN. In same way, p53 was markedly activated in ischemic vessels, and endothelial p53 deficiency enhanced ischemia-induced angiogenesis. To further investigate the role of endothelial p53, we used a gain-of-function ...