tbuckley/cabot-search huggingface dataset:
Mucosal injury of small intestine in patients with advanced gastric cancer who developed chemotherapy induced diarrhea (CID).
Authors: Miho Sakumura, Takayuki Ando, Ayumu Hosokawa, Hiroshi Mihara, Hiroaki Takagi, Hiroki Yoshita, Sohachi Nanjo, Akira Ueda, Haruka Fujinami, Shinya Kajiura, Kohei Ogawa, Toshiro Sugiyama
Journal: Journal of Clinical Oncology (2018)

28 Background: Fluoropyrimidine is a key drug for patients with advanced or recurrent gastric cancer. It causes diarrhea, a common non-hematological toxicity. The consensus guideline suggests aggressive treatment including intravenous fluids and antibiotics, is necessary for patients with severe diarrhea accompanied by fever and sepsis. However, the frequency of complicating signs and the actual degree of damage of small intestinal mucosa have not been reported. We evaluated complicating signs and mucosal injury in patients with complicated CID. Methods: Between April 2007 and December 2016, 170 patients with advanced or recurrent gastric cancer who underwent S-1 or capecitabine based chemotherapy were retrospectively analyzed. Diarrhea was evaluated with CTCAE v4.0, and complicated CID was defined as CTC grade 3 or 4 diarrhea or grade 1 or 2 diarrhea with following signs: cramping, vomiting, decreased performance status, fever, sepsis, neutropenia, frank bleeding, and dehydration. To evaluate mucosal injury of small intestine, capsule endoscopy was performed in patients with complicated CID. Results: Among 170 patients, 15 patients (8.8%) showed complicated CID during chemotherapy (S-1 based chemotherapy, n = 13/148; capecitabine based chemotherapy, n = 2/22). Among the profile of complicated signs, cramping, fever, and vomiting were frequent, and observed in 11 (73%), 7 (47%), and 5 (33%) patients, respectively. Ten patients received capsule endoscopy after improvement of CID, and 6 (60%) patients had multiple erosions or ulcerations in small intestine. Conclusions: The incidence of complicated CID caused by fluoropyrimidine based chemotherapy was less frequent in patients with advanced or recurrent gastric cancer. However, most patients showed mucosal injury of small intestine in capsule endoscopy. Therefore, these findings strongly support the guideline that recommends aggressive therapeutic approach for patients with complicated CID.
The Future Burden of Colorectal Cancer Among US Blacks and Whites
Authors: Marzieh Araghi, Miranda M Fidler, Melina Arnold, Ahmedin Jemal, Freddie Bray, Isabelle Soerjomataram
Journal: JNCI Journal of the National Cancer Institute (2017)

Although overall colorectal cancer (CRC) incidence rates in the United States are declining, rates among younger persons (age < 55 years) are increasing, particularly among US whites. We assessed how these trends will impact the future burden (up to 2040) of CRC among US blacks and whites using an age-period-cohort model. Over the last four decades (1973 to 2014), CRC incidence rates for all ages (both sexes) have dropped by 6.6% and 33.9% in US blacks and whites, respectively. Yet we predict an upward turn in CRC cancer incidence rates over the next quarter century, particularly among US whites. The age-standardized rates of CRC were 55.4 and 43.2 per 100 000 among US blacks and whites in 2014, respectively, and are projected to be 49.5 and 43.1 in 2040, respectively. Future interventions are needed to reduce the striking differences in CRC incidence between blacks and whites.
Platelets Enhance Multiple Myeloma Progression via IL-1β Upregulation
Authors: Satoshi Takagi, Shokichi Tsukamoto, Jihye Park, Kelly E. Johnson, Yawara Kawano, Michele Moschetta, Chia-Jen Liu, Yuji Mishima, Katsutoshi Kokubun, Salomon Manier, Karma Z. Salem, Daisy Huynh, Antonio Sacco, Jodi Forward, Aldo M. Roccaro, Elisabeth M. Battinelli, Irene M. Ghobrial
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Tumor cell–platelet interactions contribute to tumor progression and metastasis in solid tumors. However, the role of platelets in hematological malignancies is not clear. We investigated the association of platelet activation status with clinical stages in multiple myeloma (MM) patients and explored the role of platelets in MM progression. Experimental Design: Platelets were obtained from healthy donors and MM patients. We examined platelet activation status in MM patients by flow cytometry and transmission electron microscopy. We also observed the enriched pathways that are involved with platelet activation in RNA sequencing of platelets. MM cell lines were used to assess the effect of platelets on MM cell proliferation in vitro and their engraftment in vivo. RNA sequencing of MM cell lines was performed to explore molecular mechanisms underlying MM cell–platelet interaction and a CRISPR/Cas9 knockout approach was used for validation. Results: Platelets from MM patients were highly activated with disease progression. RNA sequencing of platelets revealed that genes involved in platelets were enriched in patients with smoldering MM (SMM) or MM. Platelets promoted MM cell proliferation in vitro and contributed to tumor engraftment in bone marrow in vivo. RNA sequencing revealed that IL-1β was upregulated in MM cell lines co-cultured with platelets, whereas IL-1β knockout in MM cell lines abrogated the effects of platelets on MM cell proliferation and engraftment in vivo. Conclusions: Platelets from MM patients were highly activated with disease progression. IL-1β is critical to platelet-mediated MM progression and might be a potential target for MM treatment. Clin Cancer Res; 24(10); 2430–9. ©2018 AACR.
Practices in poor areas are more likely to face CQC sanctions
Authors: Gareth Iacobucci
Journal: BMJ (2018)

General practices in England’s more deprived areas are nearly three times as likely as those in affluent areas to face sanctions from the health services regulator, a BMJ investigation has found.1

Richard Vautrey, chair of the BMA’s General Practitioners Committee, said that the Care Quality Commission’s inspection regime was “too simplistic” and didn’t reflect the difficulties that practices in poorer areas faced. “Many practices in urban deprived areas have struggled with premises, funding, recruitment, and retention and yet had very challenging populations,” he said. “It’s fairly obvious that some of those practices will then fail to deliver on some of the …
Gene Therapy in Alzheimer Disease—It May Be Feasible, but Will It Be Beneficial?
Authors: Lawrence S. Honig
Journal: JAMA Neurology (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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Neurology journal
Subcutaneous Abatacept in Patients With Polyarticular‐Course Juvenile Idiopathic Arthritis
Authors: Hermine I. Brunner, Nikolay Tzaribachev, Gabriel Vega‐Cornejo, Ingrid Louw, Alberto Berman, Inmaculada Calvo Penadés, Jordi Antón, Francisco Ávila‐Zapata, Rubén Cuttica, Gerd Horneff, Ivan Foeldvari, Vladimir Keltsev, Daniel J. Kingsbury, Diego Oscar Viola, Rik Joos, Bernard Lauwerys, Maria Eliana Paz Gastañaga, Maria Elena Rama, Carine Wouters, John Bohnsack, Johannes Breedt, Michel Fischbach, Thomas Lutz, Kirsten Minden, Tatiana Miraval, Mahmood M. T. M. Ally, Nadina Rubio‐Pérez, Elisabeth Solau Gervais, Riana van Zyl, Xiaohui Li, Marleen Nys, Robert Wong, Subhashis Banerjee, Daniel J. Lovell, Alberto Martini, Nicolino Ruperto
Journal: Arthritis & Rheumatology (2018)

Objective To investigate the pharmacokinetics, effectiveness, and safety of subcutaneous ( SC ) abatacept treatment over 24 months in patients with polyarticular‐course juvenile idiopathic arthritis ( JIA ). Methods In this phase III , open‐label, international, multicenter, single‐arm study, patients with polyarticular JIA (cohort 1, ages 6–17 years and cohort 2, ages 2–5 years) in whom treatment with ≥1 disease‐modifying antirheumatic drug was unsuccessful received weight‐tiered SC abatacept weekly: 10 to &lt;25 kg (50 mg), 25 to &lt;50 kg (87.5 mg), ≥50 kg (125 mg). Patients who had met the JIA –American College of Rheumatology 30% improvement criteria (achieved a JIA ‐ ACR 30 response) at month 4 were given the option to continue SC abatacept to month 24. The primary end point was the abatacept steady‐state serum trough concentration (C minss ) in cohort 1 at month 4. Other outcome measures included JIA ‐ ACR 30, 50, 70, 90, 100, and inactive disease status, the median Juvenile Arthritis Disease Activity Score in 71 joints using the C‐reactive protein level ( JADAS ‐71– CRP ) over time, safety, and immunogenicity. Results The median abatacept C minss at month 4 (primary end point) and at month 24 was above the target therapeutic exposure (10 μg/ml) in both cohorts. The percentage of patients who had achieved JIA ‐ ACR 30, 50, 70, 90, or 100 responses or had inactive disease responses at month 4 (intent‐to‐treat population) was 83.2%, 72.8%, 52.6%, 28.3%, 14.5%, and 30.1%, respectively, in cohort 1 (n = 173) and 89.1%, 84.8%, 73.9%, 58.7%, 41.3%, and 50.0%, respectively, in cohort 2 (n = 46); the responses were maintained to month 24. The median (interquartile range) JADAS ‐71– CRP improved from baseline to month 4: cohort 1, from 21.0 (13.5, 30.3) to 4.6 (2.1, 9.4); cohort 2, from 18.1 (14.0, 23.1) to 2.1 (0.3, 4.4). Improvements were sustained to month 24, at which time 27 of 173 patients (cohort 1) and 11 of 22 patients (cohort 2) had achieved JADAS ‐71– CRP remission. No unexpected adverse events were reported; 4 of 172 patients (2.3%) in cohort 1 and 4 of 46 (8.7%) in cohort 2 developed anti‐abatacept antibodies, with no clinical effects. Conclusion Weight‐stratified SC abatacept yielded target therapeutic exposures across age and weight groups, was well tolerated, and improved polyarticular JIA symptoms over 24 months.
Wales launches campaign to attract young doctors
Authors: Ingrid Torjesen
Journal: BMJ (2012)

A campaign has been launched in Wales to attract more young doctors to the country. Currently 201 vacancies for doctors are being advertised in Wales.

A shortage of doctors has already caused problems in some areas, including the Abertawe Bro Morgannwg University Health Board, which runs hospitals in Swansea, Bridgend, Neath, and Port Talbot, and …
WEB-BASED COGNITIVE BEHAVIOR THERAPY FOR DEPRESSION AND ANXIETY AMONG PATIENTS WITH A RECENT MYOCARDIAL INFARCTION: THE U-CARE HEART RANDOMIZED TRIAL
Authors: Fredrika Norlund, Emma Wallin, Erik Olsson, John Wallert, Gunilla Burell, Claes Held
Journal: Journal of the American College of Cardiology (2018)
Potential lymphangiogenesis therapies: Learning from current antiangiogenesis therapies—A review
Authors: Michael Yamakawa, Susan J. Doh, Samuel M. Santosa, Mario Montana, Ellen C. Qin, Hyunjoon Kong, Kyu‐Yeon Han, Charles Yu, Mark I. Rosenblatt, Andrius Kazlauskas, Jin‐Hong Chang, Dimitri T. Azar
Journal: Medicinal Research Reviews (2018)

Abstract In recent years, lymphangiogenesis, the process of lymphatic vessel formation from existing lymph vessels, has been demonstrated to have a significant role in diverse pathologies, including cancer metastasis, organ graft rejection, and lymphedema. Our understanding of the mechanisms of lymphangiogenesis has advanced on the heels of studies demonstrating vascular endothelial growth factor C as a central pro‐lymphangiogenic regulator and others identifying multiple lymphatic endothelial biomarkers. Despite these breakthroughs and a growing appreciation of the signaling events that govern the lymphangiogenic process, there are no FDA‐approved drugs that target lymphangiogenesis. In this review, we reflect on the lessons available from the development of antiangiogenic therapies (26 FDA‐approved drugs to date), review current lymphangiogenesis research including nanotechnology in therapeutic drug delivery and imaging, and discuss molecules in the lymphangiogenic pathway that are promising therapeutic targets.
Loss of RSPO3 as a potential mechanism of greater invasiveness in prostate cancer.
Authors: Aruz Mesci, Xiaoyong Huang, David Shin, Christianne Hoey, Jessica Ray, Stanley K. Liu
Journal: Journal of Clinical Oncology (2018)

333 Background: While prostate cancer can often manifest as an indolent disease, locally-advanced or metastatic disease can cause significant morbidity or mortality. Better understanding of molecular mechanisms leading to more aggressive presentations can lead to identification of prognostic or predictive biomarkers, as well as to possible therapeutic targets. Methods: We describe the generation of prostate cancer cell lines that have been selected through a course of hypofractionated radiotherapy. We show that R-spondin 3, a protein implicated previously as a marker of aggressive disease in colorectal and non-small cell lung cancer, is downregulated in these cell lines compared to parental cells. Then, we test the functional consequences of R-spondin 3 downregulation by siRNA-mediated interference using in vitro assays of radiation resistance, proliferation, and invasiveness . Experiments investigating any change in metastatic propensity following R-spondin 3 downregulation are forthcoming. We further investigate signaling pathways that may be implicated in the mechanism of R-spondin 3 action. Lastly, we use the Oncomine Platform to look for any changes in R-spondin 3 levels between normal prostate tissue and prostate adenocarcinoma. Results: Although siRNA-mediated loss of R-spondin 3 does not confer radiation resistance in vitro, it does result in increased invasiveness in Matrigel assays. Paradoxically, R-spondin 3 downregulation results in decreased proliferation. Interference with R-spondin 3 also results in decreased β-catenin, ERK, and Akt signaling, but increased JNK signaling. In support of our in vitro results, R-spondin 3 expression is lower in human prostate adenocarcinoma compared to normal prostate in several gene expression datasets. Conclusions: Our preliminary data suggest that R-spondin 3 loss may lead to increased disease aggression via altered cell signaling. R-spondin 3 downregulation may represent a potential biomarker to identify patients at greater risk of developing locally advanced or metastatic disease, or a potential mechanism to target in future therapeutic efforts.
Abstract P1-13-14: Triple positive breast cancer ; a distictive subtype and consideration of systemic therapeutic approach
Authors: JS Kim, YS Kim, SH You
Journal: Cancer Research (2018)

Abstract Introduction: Triple positive breast cancer is one of intrinsic subtype in breast cancer that is defined namely, ER/PR/Her2 positive tumors. It has multiple strategies for systemic therapy according to the characteristics of hormonal and anti-HER2 responsiveness. Each targeted therapy plays cross-talks between HER-2 and estrogen receptor signaling pathway resulting in endocrine resistance and anti Her2 resistance. Methods: We compared the triple positive subtype to the other breast cancer intrinsic subtypes to distinguish the uniqueness in their position among other breast cancer subtypes using retrospective analysis of two different cohorts; Korea Breast Cancer Society (KBCS) Breast cancer registry data (N=31266, Jan. 2006 – Dec. 2010) and database from St. Mary`s hospital Breast cancer registry (N=2216, Apr. 2009 – Mar. 2016). Results: Median follow up duration of 76 months in KBCS cohort (2006-2010) showed the overall survival graph of triple positive breast cancer located in the middle in between Luminal A intrinsic subtype and HER2 enriched subtype(P&amp;lt;.001). Also HER2 directed trastuzumab therapy did not improve the overall survival in triple positive breast cancer patients (P=.899) in contrast to the improved overall survival using trastuzumab therapy in HER2 enriched subtype (P=.018). Like the preceding results, CMC breast cancer data showed the similar results in recurrence free survival (P&amp;lt;.001). and no recurrence free survival improvement using trastuzumab therapy in triple positive breast cancer patient during the median follow up of 33 months (P=0.800). Conclusion: 1) Anti-HER2 therapy seems less beneficial in Triple positive breast cancer subtype regardless of breast cancer stage. 2) Triple positive breast cancer may require different therapeutic approaches 3) Other targeted agents (mTOR inhibitor, CDK4/6 inhibitor, PIK3CA inhibitor) can be a substitute option for the Trastuzumab therapy in triple positive breast cancer. Citation Format: Kim JS, Kim YS, You SH. Triple positive breast cancer ; a distictive subtype and consideration of systemic therapeutic approach [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-13-14.
CQC outlines full details of registration compliance
Authors: Helen Jaques
Journal: BMJ (2013)

The Care Quality Commission (CQC) has outlined the final details of everything general practitioners (GPs) have to do to ensure that they comply with its standards of care and inspections.

Legislation requires that all general practices and other providers of primary medical services in England have to be registered with the CQC from April 2013. All providers must comply with the CQC’s 16 essential standards of quality and safety. These standards fall under five categories: treating people with respect, providing care that meets …
Consultants must take on new role outside hospitals, says King’s Fund
Authors: Abi Rimmer
Journal: BMJ (2014)

A new role must be developed for consultants outside hospitals, the King’s Fund has said in a new report.

The think tank looked at six examples of consultants delivering care outside hospitals, including consultant led community rheumatology clinics and consultant participation in a community geriatrician service. The report said that specialist knowledge was currently “concentrated in the hospital” and that where consultants did take on new roles they became educators of primary and community care and champions for service redesign.1

“Our case studies …
SNX10 mediates alcohol-induced liver injury and steatosis by regulating the activation of chaperone-mediated autophagy
Authors: Yan You, Wan-Zhen Li, Sulin Zhang, Bin Hu, Yue-Xuan Li, Hai-Dong Li, Huan-Huan Tang, Qian-Wen Li, Yun-Yun Guan, Li-Xin Liu, Wei-Lian Bao, Xiaoyan Shen
Journal: Journal of Hepatology (2018)
Junior doctors are an “untapped resource” in quality improvement
Authors: Helen Jaques
Journal: BMJ (2012)

Most junior doctors have ideas on how to improve their workplace, but only one in 10 have had their suggestions implemented, indicating that trainees are an “untapped resource” when it comes to quality improvement, a new study concludes ( BMJ Quality & Safety doi:10.1136/bmjqs-2011-000611).

The survey of nearly 1500 junior doctors in the South Central strategic health authority also found that many trainees feel …
REVASCULARIZATION OF A CHRONIC TOTAL OCCLUSION BY PERCUTANEOUS CORONARY INTERVENTION IS ASSOCIATED WITH A SIGNIFICANT REDUCTION IN MORTALITY: INSIGHTS FROM A 4,327 PATIENT META-ANALYSIS
Authors: Andrea Comella, Francis Ha, Michael Michail, Nitesh Nerlekar, James Cameron, James Saponitis, Adam Brown
Journal: Journal of the American College of Cardiology (2018)
Doctors are invited to help improve NHS staff culture
Authors: Tom Moberly
Journal: BMJ (2014)

Doctors and other clinicians will be asked about their experience of working in the NHS, as part of a series of listening events aimed at improving the service’s treatment of its staff.

The first event will be held in London in September, and further events are planned for later this year and early 2015, in London and around the country. The initiative is supported by the Royal College of General Practitioners, the Royal College of Nursing, the Royal College of Psychiatrists, and the Royal Society for Public Health, as well as the Institute of Group Analysis and the Institute of Healthcare Management.

Each event will involve a guest speaker reflecting on the issues facing the NHS workforce, as well as discussions led by group analysts. A team of managers and clinicians will …
Direct Oral Anticoagulants in Addition to Antiplatelet Therapy for Secondary Prevention After Acute Coronary Syndromes
Authors: Mauro Chiarito, Davide Cao, Francesco Cannata, Cosmo Godino, Corrado Lodigiani, Giuseppe Ferrante, Renato D. Lopes, John H. Alexander, Bernhard Reimers, Gianluigi Condorelli, Giulio G. Stefanini
Journal: JAMA Cardiology (2018)

<h3>Importance</h3> Patients with acute coronary syndrome (ACS) remain at high risk for experiencing recurrent ischemic events. Direct oral anticoagulants (DOAC) have been proposed for secondary prevention after ACS. <h3>Objective</h3> To evaluate the safety and efficacy of DOAC in addition to antiplatelet therapy (APT) after ACS, focusing on treatment effects stratified by baseline clinical presentation (non–ST-segment elevation ACS [NSTE-ACS] vs ST-segment elevation myocardial infarction [STEMI]). <h3>Data Sources</h3> PubMed, Embase, BioMedCentral, Google Scholar, and the Cochrane Central Register of Controlled Trials were searched from inception to March 1, 2017. <h3>Study Selection</h3> Randomized clinical trials on DOAC after ACS were evaluated for inclusion. Overall, 473 studies were screened, 19 clinical trials were assessed as potentially eligible, and 6 were included in the meta-analysis. <h3>Data Extraction and Synthesis</h3> Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used to abstract data and assess quality and validity. The risk of bias tool, version 2.0 (Cochrane) was used for risk of bias assessment. Data were pooled using random-effects models. <h3>Main Outcomes and Measures</h3> The prespecified primary efficacy end point was the composite of cardiovascular death, myocardial infarction, and stroke. The prespecified primary safety end point was major bleeding. <h3>Results</h3> Six trials that included 29 667 patients were identified (14 580 patients [49.1%] with STEMI and 15 036 [50.7%] with NSTE-ACS). The primary efficacy end point risk was significantly lower in patients who were treated with DOAC as compared with APT alone (odds ratio [OR], 0.85; 95% CI, 0.77-0.93;<i>P</i> &lt; .001). This benefit was pronounced in patients with STEMI (OR, 0.76; 95% CI, 0.66-0.88;<i>P</i> &lt; .001), while no significant treatment effect was observed in patients with NSTE-ACS (OR, 0.92; 95% CI, 0.78-1.09;<i>P</i> = .36;<i>P </i>for interaction = .09). With respect to safety, DOACs were associated with a higher risk of major bleeding as compared with APT alone (OR, 3.17; 95% CI, 2.27-4.42;<i>P</i> &lt; .001), with consistent results in patients with STEMI (OR, 3.45; 95% CI, 1.95-6.09;<i>P</i> &lt; .001) and NSTE-ACS (OR, 2.19; 95% CI, 1.38-3.48;<i>P</i> &lt; .001;<i>P </i>for interaction = .23). <h3>Conclusions and Relevance</h3> To our knowledge, these findings are the first evidence to support differential treatment effects of DOAC in addition to APT according to ACS baseline clinical presentation. In patients with NSTE-ACS, the risk-benefit profile of DOAC appears unfavorable. Conversely, DOAC in addition to APT might represent an attractive option for patients with STEMI.