tbuckley/cabot-search huggingface dataset:
Expression of endogenous retroviruses and response to immune checkpoint therapy in renal cell cancer.
Authors: Anshuman Panda, Aguirre De Cubas, Katy Beckermann, Gregory Riedlinger, Mark N. Stein, Tina M. Mayer, Janice M. Mehnert, Kimryn Rathmell, Gyan Bhanot, Shridar Ganesan
Journal: Journal of Clinical Oncology (2018)

104 Background: In certain cancers, including renal cell carcinoma (RCC), no clear correlation exists between mutation burden and response to immune checkpoint therapy. To look for other markers of immune activation, we investigated the correlation between expression of endogenous retroviruses (ERV) and evidence of immune checkpoint activation in multiple cancer types. Methods: RNA-seq data of 4,910 tumors of 21 cancers from TCGA was analyzed to identify cancers in which there was correlation between ERV expression and evidence of immune checkpoint activation as shown by increased expression of immune checkpoint genes and evidence of CD8+ T-cell infiltration. Expression of candidate ERVs was measured by quantitative RT-PCR in a set of 20 RCC specimens. Results: In the TCGA clear-cell renal cancer, ER+HER2- breast cancer, and colon cancer datasets showed correlation between expression of a subset of ERVs and markers of local immune checkpoint activation. Using hierarchical clustering, tumors could be classified into 3 groups (high/intermediate/low) based on expression of these ERVs. In all these cancer types, the high ERV expressing group showed evidence of immune activation (robust immune infiltration with high CD8 + T cell fraction) and checkpoint (PD-1, CTLA-4) pathway over-expression. Expression of gene pathways associated with histone modification was significantly correlated with overall ERV expression, suggesting underlying dysregulation of chromatin silencing. Of ERVs analyzed ERV3.2 and ERVK-2 were most consistently associated with markers of immune checkpoint activation in multiple cancer types. For validation, expression of ERVs were measured in tumor sepcimens 20 clear cell renal cancer patients treated with immune checkpoint blockade. Expression of ERV3-2 and ERVK-2, was significantly increased in patients with clinical response to immune checkpoint therapy in this cohort. Conclusions: These data suggest that expression of ERV may be associated with activation of immune checkpoint pathways in renal cell cancer and may predict response to immune checkpoint therapy. Similar associations may also exist in some other solid tumors.
IN-STENT RESTENOSIS OF DRUG-ELUTING STENTS COMPARED TO A MATCHED GROUP OF PATIENTS WITH DE NOVO CORONARY ARTERY STENOSIS
Authors: Ron Waksman, Kyle Buchanan, M. Chadi Alraies, Micaela Iantorno, Deepakraj Gajanana, Toby Rogers, Linzhi Xu, Jiaxiang Gai, Rebecca Torguson, William Suddath, Itsik Ben-Dor, Lowell Satler
Journal: Journal of the American College of Cardiology (2018)
Recognition of microbial viability via TLR8 drives TFH cell differentiation and vaccine responses
Authors: Matteo Ugolini, Jenny Gerhard, Sanne Burkert, Kristoffer Jarlov Jensen, Philipp Georg, Friederike Ebner, Sarah M. Volkers, Shruthi Thada, Kristina Dietert, Laura Bauer, Alexander Schäfer, Elisa T. Helbig, Bastian Opitz, Florian Kurth, Saubashya Sur, Nickel Dittrich, Sumanlatha Gaddam, Melanie L. Conrad, Christine S. Benn, Ulrike Blohm, Achim D. Gruber, Andreas Hutloff, Susanne Hartmann, Mark V. Boekschoten, Michael Müller, Gregers Jungersen, Ralf R. Schumann, Norbert Suttorp, Leif E. Sander
Journal: Nature Immunology (2018)
Abstract 5114: The role of microvesicles on immune function in response to cancer
Authors: Ritu Jaiswal, Deep Pokharel, Mary Bebawy
Journal: Cancer Research (2016)

Abstract Cell to cell communication is vital for the co-ordination of physiological process and the regulation of an organism's phenotype. More recently communication via extracellular membrane vesicles has gained recognition. We first described a novel mechanism for the spread and dominance of multidrug resistance (MDR) and enhanced metastatic capacity in cancer via submicron microparticles (MPs). MPs are plasma membrane vesicles released spontaneously from various cell types, carrying bioactive material and are implicated in different physiological and pathophysiological processes. Through this communication apparatus, cancer cells can acquire and secure a survival advantage by various mechanisms. This study aims to examine a role of MPs in altering immune cell function in cancer. The effects of MPs isolated from human breast cancer cells were examined on antigen presenting cells (APC) in vitro. MP-mediated effects on cell phenotype and functionality was assessed by cytokine profiling and migration assay. We observed a cancer cell induced change in immune cell phenotype and functionality which have the potential to support a reduced global immune response in cancer. The elucidation of this pathway provides novel therapeutic strategies which can be exploited for the treatment of cancer. Citation Format: Ritu Jaiswal, Deep Pokharel, Mary Bebawy. The role of microvesicles on immune function in response to cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5114.
Baby with brain damage dies after parents run out of legal options
Authors: Clare Dyer
Journal: BMJ (2018)

A profoundly brain damaged baby at the centre of a legal battle over the withdrawal of life support has died after his parents exhausted all possible legal avenues in a bid to keep him alive.

Doctors at Kings College Hospital in London took 12 month old Isaiah Haastrup off the ventilator at 1 pm on 7 March and he died shortly before 8 pm that evening. The day before, a last ditch …
HDAC4 regulates vascular inflammation via activation of autophagy
Authors: Di Yang, ChenXi Xiao, Fen Long, ZhengHua Su, WanWan Jia, Ming Qin, MengWei Huang, WeiJun Wu, Rinkiko Suguro, XinHua Liu, YiZhun Zhu
Journal: Cardiovascular Research (2018)

Angiotensin II (Ang II) causes vascular inflammation, leading to vascular endothelial cell dysfunction, and is associated with the development of cardiovascular diseases. Therefore, interventions in inflammation may contribute to the reduction of cardiovascular diseases. Here, we aim to demonstrate that HDAC4, one of class IIa family histone de-acetylases (HDACs) members, promotes autophagy-dependent vascular inflammation.By loss-of-function approaches, our study provides the first evidence that HDAC4 mediates Ang II-induced vascular inflammation in vitro and in vivo. In response to the Ang II, HDAC4 expression is up-regulated rapidly, with increased autophagic flux and inflammatory mediators in vascular endothelial cells (VECs). In turn, HDAC4 deficiency suppresses activation of autophagy, leading to reduced inflammation in Ang II-induced VECs. Consistently, using autophagy inhibitor or silencing LC3-II also alleviates vascular inflammation. Furthermore, HDAC4 regulates autophagy via facilitating transcription factor forkhead box O3a (FoxO3a) de-acetylation, thereby to increase its transcriptional activity. Loss of HDAC4 in VECs results in inhibition of FoxO3a de-acetylation to block its transcriptional activity, leading to downregulation of the downstream FoxO3a target, and hence reduces autophagy and vascular inflammation. FoxO3a silencing using siRNA approach significantly inhibits activation of autophagy. Finally, knockdown of HDAC4 in Ang II-infused mouse models ameliorates vascular inflammation, suggesting that inhibitor of HDAC4 may be potential therapeutics for vascular diseases associated with inflammation.These results suggest that HDAC4-mediated FoxO3a acetylation regulates Ang II-induced autophagy activation, which in turn plays an essential role in causing vascular inflammation.
NHS could save £75m by using electronic rostering and monitoring of staffing
Authors: Caroline White
Journal: BMJ (2014)

The NHS could save £71m and improve patient safety by comprehensively adopting electronic systems for rostering and monitoring staffing levels, a report has suggested.1

The report by the Policy Analysis Centre and the London School of Economics says that many health service trusts have so far adopted only partial electronic rostering systems.1 Such systems have been limited to certain staff groups and have not incorporated additional systems to monitor time keeping and attendance.

The report’s authors said that development of a “paperless NHS” had largely focused on the collection of clinical data. They argued that this was due to a lack of leadership and an unwillingness to embrace digital workforce solutions. However, staff represent the largest chunk of running costs in …
Prehospital Blood Product Transfusion and Combat Injury Survival
Authors: Jean-Stéphane David, Pierre-François Wey, Sébastien Peyrefitte
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Moving point of registration is like using “sledgehammer to crack a nut,” HEE report says
Authors: Abi Rimmer
Journal: BMJ (2015)

The plan to move full registration with the General Medical Council from the end of the first year of foundation training to the point of graduation from medical school has been likened to using a “sledgehammer to crack a nut.”1

A report published by Health Education England (HEE) summarises the output of several meetings it held with various stakeholders, including the Academy of Medical Royal Colleges and the BMA. At the meetings the stakeholders considered how the plan to move the point of registration could affect oversubscription in the foundation programme and four year long postgraduate …
Doctors will not be criminally liable for failing to raise concerns about poor care
Authors: Clare Dyer
Journal: BMJ (2013)

Doctors should be open and honest with patients when things go wrong but will not face criminal sanctions if they fail to raise concerns about poor care, the government has said in its response to the inquiry into events at Mid Staffordshire NHS Foundation Trust. 

Robert Francis QC, who chaired the inquiry, recommended that it should be made a criminal offence for any doctor, nurse, or director of a healthcare organisation to provide intentionally misleading information to a patient or nearest relative, to obstruct another person in performing the duty of candour, or to make a dishonest statement to a commissioner of services or a regulator.

Jeremy Hunt, health secretary for England, said …
Ketogenic therapy:the experience of adult brain tumour patients supported by Matthews Friends
Authors: Susan Wood, Catherine Zabilowicz, Val Aldridge, Katie Sheen, Emma Williams, Matthew Williams
Journal: Neuro-Oncology (2018)

There is increasing interest in ketogenic diet (KD) as an adjuvant to standard care (surgery, chemo-radiation, dexamethasone and anticonvulsant medication) for brain tumour and associated symptom management, within the brain tumour community. Published clinical trial data is extremely limited and there are no NHS clinical services to support KD therapy in this patient group. Since 2011, Matthews Friends has provided charitably funded* specialist dietetic support to over 50 adults from across the UK and Ireland, requesting help to explore KD therapy as a component of their brain tumour management. These self-selected cases vary considerably in terms of age, tumour type, stage of treatment and degree of quality of life impairment. However recurring themes have emerged from these cases, in relation to the practical, physical and emotional experience of implementing KD as therapy. A questionnaire was devised and sent to twenty-three patients on KD therapy. Fourteen (60%) were returned. Results of this survey will be presented in relation to: The experience of starting ketogenic therapy; the ease of adaption to the diet change, the impact of the monitoring process and the effect of the lifestyle change on families. How this has been supported by their clinical team and during hospital admissions. The physical effects of the therapy in relation to weight, gastrointestinal function, seizures, headaches, vision, speech, fatigue and coordination. The effects on thoughts, feelings and their ability to function day to day. All fourteen patients were able to implement and sustain KD for between 8months-4 years, reporting varying aspects of personal benefit from this. * Astro Brain Tumour Fund and Matthew’s Friends Charities
Potential risk factors of pneumonitis associated with consolidation pembrolizumab after chemoradiation in unresectable NSCLC patients.
Authors: Shahid Sattar Ahmed, Greg Andrew Durm, John Donatelli, Huan Yao, Yongmei Liu, Colleen DesRosiers, Ziyue Liu, Feng Ming Kong, Nasser H. Hanna
Journal: Journal of Clinical Oncology (2018)

167 Background: We have previously shown that consolidation pembrolizumab after chemoradiation is safe in a 93 patient-clinical trial of unresectable stage III NSCLC patients (Durm, ASCO 2016). However 15 patients (16%) developed grade ≥2 pneumonitis. There is limited data on risk factors for developing pneumonitis in this population. We conducted a retrospective review of these patients to identify potential clinical, biologic, radiographic and radiation treatment related risk factors for developing pneumonitis. Methods: We evaluated ECOG PS, age, gender, smoking status, stage, histology, chemo regimen, consolidation chemotherapy, TILs, PDL-1 status, PFTs, PET SUVs, grade of pre-existing ILD, COPD and Radiation dosimetry plans. Logistic regression and fisher’s-exact test were used for the odds ratio and p-values. Results: See Table. [1] [1] Age, histology, stage, chemo, PFTs, SUVs and PDL1 were not significant [2] n = sample size p = pneumonitis [3] Moderate/severe COPD was not seen in any patients with pneumonitis despite 94% of participants being smokers. Conclusions: This preliminary report highlights the utility of a multi-disciplinary approach to develop risk-stratification models for pneumonitis in an at-risk patient population. However larger prospective studies are needed to validate their meaningful use in the clinical setting.[Table: see text]
M54 course: coloproctology for basic surgical trainees
Authors: Salman Heydari Khajehpour, Leah Matthews
Journal: BMJ (2012)

The M54 course is organised by the Association of Coloproctology of Great Britain and Ireland. The course (named after the nearby motorway) runs at New Cross Hospital in Wolverhampton and takes place over two consecutive days.

The course is aimed at junior surgical trainees with an interest in colorectal surgery who want to improve their understanding of the pathophysiology and management principles of anorectal disease.

As trainees in general surgery we became interested in colorectal pathology and the surgical management of those diseases. Furthermore, knowledge of anorectal and colonic pathophysiology is essential in the emergency and elective work of any surgical trainee. Better understanding of the management of these patients would help us take charge of our own learning and become better …
Clinical characteristics and outcomes of metastatic or recurrent gastric cancer with high progranulin expression in patients who had received palliative chemotherapy.
Authors: Dong-Hoe Koo, Ingu Do, Tae-Kyung Yoo, Sukjoong Oh, Yun-Gyoo Lee, Kyungeun Kim, Jin Hee Sohn, Jung Ho Park, Chong Il Sohn, Byung Ho Son, Ginette Serrero, Chang Hak Yoo
Journal: Journal of Clinical Oncology (2018)

83 Background: Progranulin (PGRN), characterized as an autocrine growth and survival factor, is known to stimulate the tumorigenesis and proliferation of several cancer cell types. However, little is known about the prognostic role of PGRN in metastatic or recurrent gastric cancers (MRGCs). Methods: A retrospective analysis was performed on patients with MRGCs who had received palliative chemotherapy between January 2010 and March 2014. PGRN expression in tumor cells by immunohistochemical staining was calculated as the product of proportion (0 = none; 1 ≤ 25%; 26% ≤ 2 ≤ 50%; 3 &gt; 50%) and intensity score (0, no staining; 1, weak; 2, moderate; 3, strong), and categorized as high expression (Score ≥ 4) or low expression ( &lt; 4). Results: A total of 101 patients were analyzed with the median age of 57 years (range, 24–79) at first-line chemotherapy, and 66 patients (65%) were male. Twenty-three patients (23%) had high PGRN expression tumors, and they were almost younger patients (≤ 65 years, 96%). In terms of metastatic sites, the patients with high PGRN tumors had more liver metastasis (30% vs. 17%), and the patients with low PGRN had more bone metastasis (10% vs. 4%). There were no significant differences in the proportion of patients with a response to chemotherapy (32% vs 38%) between patients with high or low PGRN tumors. The median follow-up duration of surviving patients was 54.8 months (range 34.5-81.4 months). Overall, 90 patients (89%) died, and a median overall survival (OS) and progression free survival (PFS) were 13.1 months (95% CI, 9.5–16.8 months) and 5.6 months (95% CI, 4.7-6.5), respectively. The PFS and OS were not statistically different between patients with high PGRN tumors and those that were low PGRN (median PFS 5.2 vs 5.9 and OS 14.9 vs 13.0 months, P = 0.471 and 0.927, respectively). In addition, multivariate analysis showed that PGRN expression was not a prognostic factor in both PFS and OS after adjusting for possible confounding factors including sex, age, performance, histopathology and number of metastasis. Conclusions: There was no relationship between PGRN expression and response to chemotherapy or prognosis in patients with MRGCs.
BMA to start discussions on junior doctor contract
Authors: Helen Jaques
Journal: BMJ (2013)

The BMA’s Junior Doctors Committee has agreed to begin initial talks with NHS Employers to set out the broad terms for renegotiating the junior doctor contract.

Last year the government announced its intention to renegotiate the contract after a “scoping report” by NHS Employers branded the current terms and conditions as “not fit for purpose.”1

It highlighted working …
REDUCED BASELINE EJECTION FRACTION IS ASSOCIATED WITH INCREASED CARDIOVASCULAR MORTALITY AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT: RESULTS FROM THE PARTNER II TRIALS
Authors: Ariel Furer, Shmuel Chen, Bjorn Redfors, Sammy Elmariah, Philippe Pibarot, Howard Herrmann, Rebecca T. Hahn, Susheel K. Kodali, Vinod H. Thourani, William Fearon, Jonathan Passeri, S. Chris Malaisrie, Thomas McAndrew, Philippe Genereux, Ori Ben-Yehuda, Martin B. Leon, Daniel Burkhoff
Journal: Journal of the American College of Cardiology (2018)
Multi-institutional report on toxicities from combined radiation and nivolumab.
Authors: Sean Medard Parker, Maliha Zainib, Malcolm Mattes, Neha Amin
Journal: Journal of Clinical Oncology (2018)

39 Background: Indications for Nivolumab (NIVO), a checkpoint inhibitor immunotherapy drug, in treating a variety of metastatic malignancies has markedly increased. Radiation therapy (RT) is also commonly used in this patient population, however, there are limited data on the safety profile of combined RT-NIVO. We reviewed our experience to assess the acute toxicity profile of concurrent RT-NIVO. Methods: All consecutive patients who received NIVO from 1/2015 to 5/2017 at 4 centers across 2 institutions were retrospectively reviewed. Those patients who completed a course of RT from 1 day prior to initial NIVO infusion through 1 month after last NIVO infusion were considered to have received concurrent therapy and included in the subsequent analysis. Descriptive statistics are reported for patient/tumor/treatment characteristics and observed acute toxicities within 3 months of RT completion. Results: Among 261 patients who received NIVO, 46 (17.6%) received concurrent RT to 67 different sites. The median f/u was 3.3 (.1-19.8) months and 11/46 (24%) were still alive at last analysis. The most common histology, RT prescription, and treatment site included non-small cell lung cancer (23/46, 50%), 30 Gy in 10 fractions (16/67, 24%), and central thorax/abdomen (26/67, 39%), respectively. 79% (53/67) of irradiated sites were treated with 3D-conformal technique and palliative dose-fractionation. Grade 3, 4, and 5 toxicities were experienced by 11, 1, and 2 patients, respectively. However all grade 4 and 5 toxicities were outside of the irradiated area and attributed to the NIVO alone, and only 4/11 (36%) of the grade 3 toxicities were attributed to the RT-NIVO. The irradiated site in these cases included the brain [2/10 (20%)] and central thorax/abdomen [2/19 (10.5%)], including one unexpected grade 3 pancreatitis following stereotactic body RT to the left adrenal gland. Conclusions: Concurrent RT-NIVO is generally well tolerated, though with potentially increased rates of severe toxicity when irradiating the lung, abdomen, or brain. Pending more definitive data, we recommend counseling patients on the potentially increased rates of side effects from combined immunotherapy and radiotherapy to these locations.
Department of Health must stop sharing patient details with immigration enforcers, says BMA
Authors: Abi Rimmer
Journal: BMJ (2017)

The BMA will call on the UK Department of Health to stop sharing patient details with the Home Office for immigration enforcement.

Delegates at the BMA’s annual representative meeting in Bournemouth on 28 June voted in favour of a motion opposing the practice of sharing patients’ administrative details, including their address, with the Home Office.

The motion said, “This meeting notes and deplores the recently signed memorandum of understanding between the UK Department of Health, NHS Digital and the Home Office, which agrees to the transfer of patient administrative details . . . without the consent of the patient and the knowledge of the GP.”

It said that this agreement was a …