tbuckley/cabot-search huggingface dataset:
The caregiver voice: Insights into caring for the young adult colorectal cancer patient.
Authors: Martha Raymond, Margaret-Ann Simonetta
Journal: Journal of Clinical Oncology (2018)

148 Background: According to data from the National Cancer Institute’s Surveillance, Epidemiology &amp; End Results (SEER) Program, since 1994 statistics show a 50% increase in young onset colorectal cancer incidence in the 20-49 age group. Researchers estimate that by 2030, more than 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in young adults under 50 years of age. Based on these alarming statistics and understanding the vital role caregivers play throughout the cancer continuum, our study explores the emotional and psychosocial implications for caregivers of young adult colorectal cancer survivors. Methods: From September 2015 – September 2017, our professional facilitator with over 25 years of cancer advocacy work hosted nationwide caregiver focus groups. Primary goals included reaching caregivers in rural, urban and community oncology settings to gain perspective from diverse populations. During the study period, we spoke with caregivers in 32 states via traditional focus group settings and online via Skype format. Results: 576 caregivers (37% male, 63% female) participated in our national focus groups. When asked to describe in one word their current feelings, the top ten responses were: Stressed, Anxious, Alone, Exhausted, Angry, Needed, Guilty, Burned-Out, Overwhelmed, Frustrated. 55% of the young caregivers reported they were experiencing self-health decline ( Can’t sleep, can’t focus – feel sad all the time). 73% reported they felt lost and totally helpless ( No control over situation or outcome). 89% reported depression ( We hurt because we can’t take their pain away). 76% reported they felt ill-equipped to help their loved one leading to stress and anxiety ( Desperate for whatever might help). Conclusions: New and expanded caregiver support services are needed. Emotional and psychosocial support are essential to the well-being of our caregivers as they provide vital support to patients in need throughout the cancer care continuum. We will continue the conversation with caregivers as we create programs and expand support services.
Cancer Lipid Metabolism Confers Antiangiogenic Drug Resistance
Authors: Hideki Iwamoto, Mitsuhiko Abe, Yunlong Yang, Dongmei Cui, Takahiro Seki, Masaki Nakamura, Kayoko Hosaka, Sharon Lim, Jieyu Wu, Xingkang He, Xiaoting Sun, Yongtian Lu, Qingjun Zhou, Weiyun Shi, Takuji Torimura, Guohui Nie, Qi Li, Yihai Cao
Journal: Cell Metabolism (2018)
Scrap the Cap: Elective care is being affected, says workforce leader
Authors: Gareth Iacobucci
Journal: BMJ (2018)

NHS Employers has lent its support to The BMJ ’s campaign to end visa restrictions that are preventing doctors and other healthcare staff from outside the European Economic Area taking up posts in the NHS.

In an interview with The BMJ , Danny Mortimer, chief executive of NHS Employers, the voice of employers across the NHS, warned that the restrictions were exacerbating staff shortages, pushing up spending on locum doctors, and making it hard for trusts to maintain services.

“The fairly consistent thing we are being told [by trusts] is that it’s generating more use of agency and locum staff,” he …
Correction: A human bone marrow mesodermal-derived cell population with hemogenic potential
Authors: Saloomeh Mokhtari, Evan Colletti, Weihong Yin, Chad Sanada, Zanetta Lamar, Paul J. Simmons, Steven Walker, Colin Bishop, Anthony Atala, Esmail D. Zanjani, Christopher D. Porada, Graça Almeida-Porada
Journal: Leukemia (2018)
Граф Карл Сонгайло — патриарх земской медицины на Екатеринославщине
Authors: M.P. Chaban, Z.I. Shevtsova, V.V. Gaponov
Journal: GASTROENTEROLOGY (2018)

Освещена история создания земской медицины в Верхнеднепровском уезде Екатеринославской губернии. Показана профессиональная деятельность земского врача графа Карла Сонгайло (1840–?). Его 25-летняя служба в Саксаганской земской больнице снискала уважение и благодарность земского собрания и пациентов. Отображена аптекарская деятельность братьев Карла Сонгайло — Феликса и Даниила.
Antibody affinity and valency impact brain uptake of transferrin receptor-targeted gold nanoparticles
Authors: Kasper Bendix Johnsen, Martin Bak, Paul Joseph Kempen, Fredrik Melander, Annette Burkhart, Maj Schneider Thomsen, Morten Schallburg Nielsen, Torben Moos, Thomas Lars Andresen
Journal: Theranostics (2018)

Rationale: The ability to treat invalidating neurological diseases is impeded by the presence of the blood-brain barrier (BBB), which inhibits the transport of most blood-borne substances into the brain parenchyma. Targeting the transferrin receptor (TfR) on the surface of brain capillaries has been a popular strategy to give a preferential accumulation of drugs or nanomedicines, but several aspects of this targeting strategy remain elusive. Here we report that TfR-targeted gold nanoparticles (AuNPs) can accumulate in brain capillaries and further transport across the BBB to enter the brain parenchyma. Methods: We characterized our targeting strategy both in vitro using primary models of the BBB and in vivo using quantitative measurements of gold accumulation by inductively-coupled plasma-mass spectrometry together with morphological assessments using light microscopy after silver enhancement and transmission electron microscopy with energy-dispersive X-ray spectroscopy. Results: We find that the uptake capacity is significantly modulated by the affinity and valency of the AuNP-conjugated antibodies. Specifically, antibodies with high and low affinities mediate a low and intermediate uptake of AuNPs into the brain, respectively, whereas a monovalent (bi-specific) antibody improves the uptake capacity remarkably. Conclusion: Our findings indicate that monovalent ligands may be beneficial for obtaining transcytosis of TfR-targeted nanomedicines across the BBB, which is relevant for future design of nanomedicines for brain drug delivery.
Accuracy of Endoscopic Ultrasound Imaging in Distinguishing Celiac Ganglia From Celiac Lymph Nodes
Authors: Thomas Malikowski, Heidi D. Lehrke, Michael R. Henry, Ferga C. Gleeson, Mark D. Topazian, William S. Harmsen, Naoki Takahashi, Dai Inoue, Naveen Gara, Barham K. Abu Dayyeh, Suresh T. Chari, Prasad G. Iyer, Elizabeth Rajan, Kenneth K. Wang, Michael J. Levy
Journal: Clinical Gastroenterology and Hepatology (2018)
Tumor-originated exosomal lncUEGC1 as a circulating biomarker for early-stage gastric cancer
Authors: Ling-Yun Lin, Li Yang, Qiang Zeng, Lin Wang, Mao-Li Chen, Ze-Hang Zhao, Guo-Dong Ye, Qi-Cong Luo, Pei-Yu Lv, Qi-Wei Guo, Bo-An Li, Jian-Chun Cai, Wang-Yu Cai
Journal: Molecular Cancer (2018)

Conventional tumor markers for non-invasive diagnosis of gastric cancer (GC) exhibit insufficient sensitivity and specificity to facilitate detection of early gastric cancer (EGC). We aimed to identify EGC-specific exosomal lncRNA biomarkers that are highly sensitive and stable for the non-invasive diagnosis of EGC. Hence, in the present study, exosomes from the plasma of five healthy individuals and ten stage I GC patients and from culture media of four human primary stomach epithelial cells and four gastric cancer cells (GCCs) were isolated. Exosomal RNA profiling was performed using RNA sequencing to identify EGC-specific exosomal lncRNAs. A total of 79 and 285 exosomal RNAs were expressed at significantly higher levels in stage I GC patients and GCCs, respectively, than that in normal controls. Through combinational analysis of the RNA sequencing results, we found two EGC-specific exosomal lncRNAs, lncUEGC1 and lncUEGC2, which were further confirmed to be remarkably up-regulated in exosomes derived from EGC patients and GCCs. Furthermore, stability testing demonstrates that almost all the plasma lncUEGC1 was encapsulated within exosomes and thus protected from RNase degradation. The diagnostic accuracy of exosomal lncUEGC1 was evaluated, and lncUEGC1 exhibited AUC values of 0.8760 and 0.8406 in discriminating EGC patients from healthy individuals and those with premalignant chronic atrophic gastritis, respectively, which was higher than the diagnostic accuracy of carcinoembryonic antigen. Consequently, exosomal lncUEGC1 may be promising in the development of highly sensitive, stable, and non-invasive biomarkers for EGC diagnosis.
The transfer of public health to local authorities suggests alternatives are possible
Authors: Eugene Milne
Journal: BMJ (2018)

This spring marked five years since responsibility for public health was transferred from the NHS to local authorities in England. An Association of Directors of Public Health survey found 67% of respondents agreed that the move had weakened the relationship between public health and the NHS.

A recognised feature of the transfer, however, has been improved quality of commissioning. That many services are now delivered more cost effectively shows that reduced funding is not necessarily a service cut. For example, my own council (Newcastle upon Tyne) spends around half as much on stop smoking services as at transfer, but had an increased rate of supported quitters in 2016-17.

Perversely, the centrally imposed, counterintuitive, and ultimately counterproductive cuts to the public health grant have a been a driving force behind improved commissioning. Tighter specification of process and outcomes and more disciplined procurement have buffered us—but there is a …
OWE-003 Cold snare polypectomy is safe yet under-utilised: an analysis of 281,194 UK trainee polypectomies
Authors: Daniel Wheatley, David Tate, John Anderson, Paul Dunckley
Journal: Endoscopy (2018)

<h3>Introduction</h3> Multiple techniques exist for the management of colorectal polyps. Recent ESGE guidelines<sup>1</sup> have defined an evidence based guide to the optimal technique for removing different sizes of polyps. Previously this decision often depended on an individual operator's experience and training. We sought to examine current polypectomy practice amongst United Kingdom endoscopy trainees with to these guidelines. <h3>Methods</h3> The ESGE polypectomy guideline<sup>1</sup> suggests polyps&lt;10 mm should be removed using cold snare polypectomy (CSP) or cold biopsy forceps (CBF) [≤3 mm only], 10–19 mm using endoscopic mucosal resection (EMR) or hot snare polypectomy (HSP) and ≥20 mm using EMR. The JETS database is a prospectively collected record of trainee colonoscopic procedures in the United Kingdom and its use during training is mandatory for accreditation. Data is entered by trainees on their own endoscopic procedures. Adverse events were classified as delayed bleeding or delayed perforation. We retrospectively analysed procedures entered into the JETS database from Jan 2008 to December 2017 for polypectomy technique and compared this to the 2017 ESGE guideline. <h3>Results</h3> 2 91 778 polypectomies were performed in 1 76 569 trainee-performed procedures by 3395 trainees over the study period. 10 584 polypectomies were missing data. 2 81 194 polypectomies were analysed. Of 2 50 783 polyps&lt;10 mm in size removed, 29.5% were performed using CBF, 27.9% by CSP, 25.1% by HSP, 9.5% by HBF, and 8.0% by EMR. Of 26 605 polyps 10–19 mm in size, 55.3% were removed by HSP, 31.0% by EMR and 3.5% by CSP. 8.4% of lesions were biopsied and not removed. Of 3806 polyps≥20 mm in size, 39.4% were removed by EMR, 36.3% by HSP, 1.1% were removed by CSP and 21.9% of these lesions were biopsied and not removed. Overall, adherence to the ESGE guidance was observed in 1 54 948 polypectomies (55.1%). Nurse endoscopists were more adherent (61.7%), versus physicians (57.9%) versus surgeons (44.3%), p&lt;0.001. Of 219 (0.1%) adverse events reported amongst all polypectomies, 50.8% were amongst HSP, 19.2% EMR, 16.9% CSP and 12.7% after HBF p&lt;0.001. Of 20 delayed perforations (event rate 0.01%), 55% were due to EMR, 30% to HSP and 15% to HBF. No perforations resulted from CSP. <h3>Conclusions</h3> Cold snare polypectomy is under-utilised for diminutive polypectomy, despite its proven safety and efficacy; its use amongst trainees should be promoted in line with ESGE guidance. Trainees are likely to follow the example of their trainers and, as such, this study likely provides an insight into current polypectomy practice in the wider UK endoscopic community. Trainees in the United Kingdom predominantly remove diminutive polyps with extremely low rates of adverse events. <h3>Reference</h3> . Ferlitsch M, et al. Colorectal polypectomy and endoscopic mucosal resection (EMR): Endoscopy. 2017 Mar 1;49(3):270–97.
Cancer patient (pt) attitudes and preferences towards smoking status assessment.
Authors: Lawson Eng, Sophia Liu, Qihuang Zhang, Delaram Farzanfar, Robin Milne, Sabrina Yeung, M Catherine Brown, Doris Howell, Wei Xu, David Paul Goldstein, Jennifer M. Jones, Peter Selby, William K. Evans, Meredith Elana Giuliani, Geoffrey Liu
Journal: Journal of Clinical Oncology (2018)

177 Background: Continued smoking after a cancer diagnosis is associated with poorer outcomes. Understanding pt attitudes towards smoking status assessment will help with integrating smoking cessation programs into survivorship care. Methods: Cancer pts were surveyed on their smoking history, assessment rates and attitudes/preferences towards smoking status assessment. Multivariate logistic regression models assessed for factors associated with screening preferences. Results: Among 501 pts, 115 smoked at diagnosis, 60% quit after; 53% had a tobacco related (lung/head and neck) cancer (TRC); 40% reported that their smoking status was assessed only on their first clinic visit, while 12% were assessed at all visits. Most felt smoking status should be assessed at the first visit (95%), while half (58%) felt it should be assessed each visit. Most felt comfortable with being assessed (96%), felt it was important for clinicians to be aware of tobacco use (98%) and that smoking cessation discussions should occur at the first visit (87%). Most preferred being assessed by their oncologist (88%); less preferred being asked by another healthcare provider (44%), on paper (29%) or e-surveys (32%). Compared to ex/never smokers, current smokers were assessed more often at most/every visit (36% vs 20%) and were less comfortable being assessed (88% vs 98%). Among current smokers, lung cancer pts were more agreeable being assessed each visit compared to head/neck (aOR 2.48 95% CI [0.9-6.5] P = 0.06) and non TRCs (aOR 2.63 [1.0-6.8] P = 0.05). Among all, pts who are older (aOR 1.03 [1.0-1.1]), curative (aOR 1.92 [1.1-3.2]) and smoked less (aOR 0.98 per pkyr [0.97-0.99]) were more agreeable to routine assessment. Most pts also felt oncologists should screen for second hand smoke exposure (92%), felt its assessment was important (93%) and should help others who smoke to quit (68%). Many felt that tobacco cessation programs for both pts (75%) and others who around them who smoke (65%) should be routine cancer care. Conclusions: Most cancer pts felt that assessment of smoking status was important, were comfortable being assessed and preferred direct assessment by their oncologist. Routine screening of those currently smoking is recommended to help with cessation.
Neoadjuvant oxaliplatin and capecitabine combined with bevacizumab plus radiotherapy for locally advanced rectal cancer: results of a single‐institute phase II study
Authors: Xin Yu, Qiao‐xuan Wang, Wei‐wei Xiao, Hui Chang, Zhi‐fan Zeng, Zhen‐hai Lu, Xiao‐jun Wu, Gong Chen, Zhi‐zhong Pan, De‐sen Wan, Pei‐rong Ding, Yuan‐hong Gao
Journal: Cancer Communications (2018)

Abstract Background Neoadjuvant chemoradiotherapy followed by surgery is recommended as the standard of care for locally advanced rectal cancer, reducing local recurrence but not distant metastasis. Intensified systemic therapy is warranted to reduce the risk of distant metastasis. The present study aimed to evaluate the safety and efficacy of neoadjuvant oxaliplatin and capecitabine (XELOX) combined with bevacizumab plus radiotherapy for locally advanced rectal cancer. Methods Patients with stages II to III rectal cancer received one cycle of induction chemotherapy and concurrent chemoradiotherapy with XELOX plus bevacizumab. Surgery was performed 6–8 weeks after completion of radiotherapy, and postoperative chemotherapy with three cycles of XELOX and two cycles of capecitabine were given. The primary endpoints were pathologic complete response (pCR) rate and safety, and the secondary endpoints were 3‐year overall survival and progression‐free survival. Results Forty‐five patients were enrolled between February 2013 and April 2015. All completed the neoadjuvant therapy. Seven patients (15.6%) refused subsequent surgical therapy for personal reasons, and the other 38 patients received radical resection, with a sphincter preservation rate of 84.2% and a pCR rate of 39.5%. Toxicity was acceptable, with grades 3–4 hematological toxicity and diarrhea observed in six and two patients, respectively. Incidence of anastomotic leak that required surgical intervention was 13.3%. After a median follow‐up period of 37 months, five patients developed disease progression and two died of cancer. The 3‐year overall survival rate and 3‐year progression‐free survival rate were 95.3% and 88.6%, respectively. Conclusions The addition of bevacizumab to neoadjuvant chemoradiotherapy resulted in a satisfying pCR rate and 3‐year survival, but also may increase the risk of anastomotic leak, thus this regimen is not suitable to be considered for regular recommendation for locally advanced rectal cancer. Trial registration Clinicaltrials.gov identifierNCT01818973
Autoreactive T effector memory differentiation mirrors β cell function in type 1 diabetes
Authors: Lorraine Yeo, Alyssa Woodwyk, Sanjana Sood, Anna Lorenc, Martin Eichmann, Irma Pujol-Autonell, Rosella Melchiotti, Ania Skowera, Efthymios Fidanis, Garry M. Dolton, Katie Tungatt, Andrew K. Sewell, Susanne Heck, Alka Saxena, Craig A. Beam, Mark Peakman
Journal: Journal of Clinical Investigation (2018)

In type 1 diabetes, cytotoxic CD8+ T cells with specificity for β cell autoantigens are found in the pancreatic islets, where they are implicated in the destruction of insulin-secreting β cells. In contrast, the disease relevance of β cell–reactive CD8+ T cells that are detectable in the circulation, and their relationship to β cell function, are not known. Here, we tracked multiple, circulating β cell–reactive CD8+ T cell subsets and measured β cell function longitudinally for 2 years, starting immediately after diagnosis of type 1 diabetes. We found that change in β cell–specific effector memory CD8+ T cells expressing CD57 was positively correlated with C-peptide change in subjects below 12 years of age. Autoreactive CD57+ effector memory CD8+ T cells bore the signature of enhanced effector function (higher expression of granzyme B, killer-specific protein of 37 kDa, and CD16, and reduced expression of CD28) compared with their CD57– counterparts, and network association modeling indicated that the dynamics of β cell–reactive CD57+ effector memory CD8+ T cell subsets were strongly linked. Thus, coordinated changes in circulating β cell–specific CD8+ T cells within the CD57+ effector memory subset calibrate to functional insulin reserve in type 1 diabetes, providing a tool for immune monitoring and a mechanism-based target for immunotherapy.
The rate of novel actionable mutations in standard of care NGS panel testing in gastrointestinal malignancies.
Authors: Amir Mehrvarz Sarshekeh, Jonathan Loree, Allan Andresson Lima Pereira, Kanwal Pratap Singh Raghav, Michael Lam, Shailesh M Advani, Jennifer S Davis, A. Dasari, Van Karlyle Morris, David Menter, Cathy Eng, Kenna Rael Shaw, Russell Broaddus, Mark Routbort, Rajyalakshmi Luthra, Dipen M. Maru, Michael J. Overman, Funda Meric-Bernstam, Scott Kopetz
Journal: Journal of Clinical Oncology (2018)

640 Background: In advanced gastrointestinal (GI) malignancies, genetic profiling is often performed with the goal of facilitating enrollment of patients into clinical trials. While multigene genetic profiling has become the standard of care in many practices, the data on success rate of identifying actionable genomic alterations remain limited. In this study, we aimed to characterize the rate of actionable mutations using larger ( &gt; 150 genes) and smaller ( &lt; 150 genes) panels across different GI malignancies. Methods: We reviewed all reports of formalin-fixed paraffin-embedded clinical specimens sent for next-generation sequencing (NGS-using assays of at least 45 genes) for patients with advanced GI malignancies between 2012-2017 at MD Anderson Cancer Center. Actionable mutations were defined as those matching or informing the use of targeted therapies available in clinical trials, or FDA-approved. These were determined by a precision oncology support team (pct.mdanderson.org), using available literature and functional genomic screens. Novel actionable mutations were defined as those not used in current testing guidelines for GI malignancies. Results: Out of 11968 detected mutations, 3832(32.0%) were deemed to be actionable mutations and the remainder were either in non-actionable genes, deemed benign, or variants of unknown significance. Therefore, 1987 (65.1%) of assays had actionable mutations. When limited to novel actionable mutations, the rate fell to 21.5% (659/3052). Compared to CRC, other GI malignancies were 1.65 times more likely to have a novel actionable mutation (95% CI 1.35-2.00, p&lt; .001). The use of larger and smaller panels did not differ in detecting novel actionable mutations, but larger panels resulted in a 3.5-fold higher number of mutations not deemed clinically actionable. Conclusions: Despite incorporation of NGS in oncology practice for GI malignancies, the success rate of detecting novel actionable mutations beyond those in the current guidelines remains low. Using assays with larger gene numbers does not seem to improve this detection rate. Future studies are required to evaluate the success rate of clinical interventions when actionable alterations are present.