tbuckley/cabot-search huggingface dataset:
Initial dose of apatinib in Chinese patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of stomach or gastroesophageal junction in third- or later-line setting: 500 mg or 850 mg?
Authors: Wenying Deng, Shukui Qin, Jin Li, Lu Wen, Junsheng Wang, Guifang Zhang, Haijun Zhong, Jianwei Yang, Yi Ba, Yuxian Bai, Xiaoyan Lin, Mei Wang, Lin Wang, Likun Liu, Yifu He, Min Tao, Congying Xie, Feng Ye, Xiang-yuan Wu, Tongfu Jia
Journal: Journal of Clinical Oncology (2018)

35 Background: A fine balance between maintaining efficacy and reducing toxicity is necessary for drug therapies in many cancers. This study seeks to review the data from phase IV clinical trial of Ahead-G201 to help elucidate the optimal initial dose of apatinib in advanced gastric cancer. Methods: Pts data from the Ahead-G201 study at cut-off date of Jul 10, 2017 were extracted to explore the correlation of apatinib initial dose (500 mg vs 850 mg) with safety and clinical efficacy. Results: 864 of eligible pts received apatinib at an initial dose of 500 mg, and 58 pts received at 850 mg. Dose interruption occurred in 258 pts (33.1%) at 500 mg and in 27 pts (46.5%) at 850 mg. For safety, the most common adverse events (AEs) were proteinuria, hypertension and leukocyte decrease in both groups. Moreover, the incidence of all AEs and grade 3-4 AEs in pts at 500 mg was significantly lower than pts at 850 mg (Table). For efficacy, pts at 500 mg achieved an objective response rate (ORR) of 10.8% and a disease control rate (DCR) of 70.6%, at best response, which were 10.3% and 55.2% in pts at 850 mg. Pts at 500 mg got a significantly longer median progression-free survival (mPFS) and median overall survival (mOS) than pts at 850 mg (PFS, 4.6 mos vs 2.2 mos; OS, 6.8 mos vs 4.0 mos). Multivariate analysis indicated that apatinib treatment at an initial dose of 500 mg was significantly associated with longer mOS in advanced gastric cancer pts (6.8 mos vs 4.0 mos: hazard ratio, 0.5; 95%CI, 0.3 to 0.8), compared to initial dose of 850 mg. Conclusions: Compared to receiving apatinib at initial dose of 850mg, oral administration of apatinib starting from 500 mg seemed to bring more clinical benefit for patients with advanced gastric cancer, whilst with lower toxicities. Clinical trial information: NCT02426034. [Table: see text]
A TNM-LIKE STAGING SYSTEM FOR RISK STRATIFICATION IN HEART FAILURE PATIENTS
Authors: Maria Alfarano, Paolo Severino, Mariateresa Pucci, Ilaria Mancini, Ilaria Ferrari, Stefano Peroni, Simone Calcagno, Antonio Fusto, Danilo Alunni Fegatelli, Susanna Sciomer, Annarita Vestri, Massimo Mancone, Francesco Fedele
Journal: Journal of the American College of Cardiology (2018)
Training in clinical oncology⇓
Authors: Carrie Featherstone, Nicholas S Reed
Journal: BMJ (2005)

It can be emotionally draining, but it has sociable on-call commitments, structured training, and huge potential for doing research. <b>Lye Mun Tho</b>, <b>Carrie Featherstone</b>, and <b>Nicholas Reed</b> offer a guide to training in clinical oncology
INCIDENCE OF ACUTE MYOCARDIAL INFARCTION AND HURRICANE KATRINA: FOUR-FOLD INCREASE ELEVEN YEARS AFTER THE STORM
Authors: Bradley Deere, John Moscona, Sudesh Srivastav, Michael Zimmerman, Sonal Mallya, Miachael Razavi, Nickolas Scherzer, Jalal Maghfour, Stephen P. Morris, Hassan Baydoun, Anand Irimpen
Journal: Journal of the American College of Cardiology (2018)
Department of Health moves to end “open but full” GP lists
Authors: Helen Jaques
Journal: BMJ (2012)

The Department of Health has announced plans to remove incentives for general practices to have “open but full” patient lists, to make the practice list system more transparent to patients.

Currently if a practice wants to close its patient list and stop accepting new patients it risks losing the right to provide additional and enhanced services. As a result some practices keep their list open but stop accepting new patients, declaring their list …
Urocortin-2 improves right ventricular function and attenuates pulmonary arterial hypertension
Authors: Rui Adão, Pedro Mendes-Ferreira, Diana Santos-Ribeiro, Carolina Maia-Rocha, Luís D Pimentel, Cláudia Monteiro-Pinto, Eamon P Mulvaney, Helen M Reid, B Therese Kinsella, François Potus, Sandra Breuils-Bonnet, Miriam T Rademaker, Steeve Provencher, Sébastien Bonnet, Adelino F Leite-Moreira, Carmen Brás-Silva
Journal: Cardiovascular Research (2018)

Pulmonary arterial hypertension (PAH) is a devastating disease and treatment options are limited. Urocortin-2 (Ucn-2) has shown promising therapeutic effects in experimental and clinical left ventricular heart failure (HF). Our aim was to analyse the expression of Ucn-2 in human and experimental PAH, and to investigate the effects of human Ucn-2 (hUcn-2) administration in rats with monocrotaline (MCT)-induced pulmonary hypertension (PH).Tissue samples were collected from patients with and without PAH and from rats with MCT-induced PH. hUcn-2 (5 μg/kg, bi-daily, i.p., for 10 days) or vehicle was administered to male wistar rats subjected to MCT injection or to pulmonary artery banding (PAB) to induce right ventricular (RV) overload without PAH. Expression of Ucn-2 and its receptor was increased in the RV of patients and rats with PAH. hUcn-2 treatment reduced PAH in MCT rats, resulting in decreased morbidity, improved exercise capacity and attenuated pulmonary arterial and RV remodelling and dysfunction. Additionally, RV gene expression of hypertrophy and failure signalling pathways were attenuated. hUcn-2 treatment also attenuated PAB-induced RV hypertrophy.Ucn-2 levels are altered in human and experimental PAH. hUcn-2 treatment attenuates PAH and RV dysfunction in MCT-induced PH, has direct anti-remodelling effects on the pressure-overloaded RV, and improves pulmonary vascular function.
General medicine’s recruitment crisis: what happened to all the heroes?
Authors: John Blakey, Ivan LeJeune, Miles Levy, Dominick E Shaw, Andrew F Goddard
Journal: BMJ (2013)

Despite a growing need for high quality general care, fewer doctors are opting for a career in general medicine. <b>John Blakey and colleagues</b> look at how this situation has arisen and what might be done to tackle the problem
THE HEMODYNAMIC EFFECTS OF INTRAVENOUS MILRINONE THERAPY IN HEART FAILURE WITH REDUCED EJECTION FRACTION PATIENTS ON BETA-BLOCKERS
Authors: David Tehrani, Sara Kalantari, Jonathan Grinstein, Nitasha Sarswat, Jayant Raikhelkar, Gene Kim, Gabriel Sayer, Nir Uriel
Journal: Journal of the American College of Cardiology (2018)
Biology conference in Italy sparks criticism for including anti-vaccine speakers
Authors: Marta Paterlini
Journal: BMJ (2018)

A conference set to take place in Rome at the beginning of March to celebrate the 50th anniversary of the National Order of Biologists has sparked controversy around Italy because it will host a series of speakers associated with the anti-vaccine movement.

Many Italian scientists have distanced themselves from the “New Frontiers of Biology” conference.1 But the president of the order, Vincenzo D’Anna, who has rejected the nickname AntiVaxxer, defended the conference for questioning the safety of scientific developments.

He told The BMJ that he could not understand “all the fuss” about the conference. “Should someone have something to complain about, there will be an hour …
The Ratio of Blood T Follicular Regulatory Cells to T Follicular Helper Cells Marks Ectopic Lymphoid Structure Formation While Activated Follicular Helper T Cells Indicate Disease Activity in Primary Sjögren's Syndrome
Authors: Valter R. Fonseca, Vasco C. Romão, Ana Agua‐Doce, Mara Santos, Dolores López‐Presa, Ana Cristina Ferreira, João Eurico Fonseca, Luis Graca
Journal: Arthritis & Rheumatology (2018)

Objective To investigate whether the balance of blood follicular helper T (Tfh) cells and T follicular regulatory (Tfr) cells can provide information about ectopic lymphoid neogenesis and disease activity in primary Sjögren's syndrome ( SS ). Methods We prospectively recruited 56 patients clinically suspected of having SS . Sixteen of these patients subsequently fulfilled the American–European Consensus Group criteria for SS and were compared to 16 patients with non‐ SS sicca syndrome. Paired blood and minor salivary gland ( MSG ) biopsy samples were analyzed to study Tfr cells and subsets of Tfh cells in both compartments. Results Patients with primary SS had normal Tfh cell counts in peripheral blood; however, activated programmed death 1–positive ( PD ‐1+) inducible costimulator–positive ( ICOS +) Tfh cells in peripheral blood were strongly associated with disease activity assessed by the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (r = 0.8547, P = 0.0008). Conversely, the blood Tfr cell:Tfh cell ratio indicated ectopic lymphoid structure formation in MSG s, being strongly associated with B cell, CD 4+ T cell, and PD ‐1+ ICOS + T cell infiltration in MSG s, and was especially increased in patients with focal sialadenitis. Further analysis showed that the blood Tfr cell:Tfh cell ratio allowed discrimination between SS patients and healthy donors with excellent accuracy and was a strong predictor of SS diagnosis (odds ratio [ OR ] 12.96, P = 0.028) and the presence of focal sialadenitis ( OR 10, P = 0.022) in patients investigated for sicca symptoms, thus highlighting the potential clinical value of this marker. Conclusion The blood Tfr cell:Tfh cell ratio and PD ‐1+ ICOS + Tfh cells constitute potential novel biomarkers for different features of primary SS . While the blood Tfr cell:Tfh cell ratio is associated with ectopic lymphoid neogenesis, activated Tfh cells indicate disease activity.
Smart Hospital Discharges to Address a Neglected Epidemic in Sepsis in Low- and Middle-Income Countries
Authors: Matthew O. Wiens, Niranjan Kissoon, Jerome Kabakyenga
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
CAROTID INTIMA-MEDIA THICKNESS VERSUS CORONARY ARTERY CALCIUM SCORE IN PREDICTING INCIDENT CORONARY HEART DISEASE AND STROKE AMONG AFRICAN AMERICANS: THE JACKSON HEART STUDY
Authors: Valery Effoe, Alain Bertoni, Fengxia Yan, Nchang Taka, Obiora Egbuche, Titilope Olanipekun, Demilade Adedinsewo, Ervin Fox, Herman Taylor
Journal: Journal of the American College of Cardiology (2018)
P011 Expanded T-cell clones are present in the synovium before the onset of clinical rheumatoid arthritis
Authors: G Balzaretti, P Klarenbeek, M Doorenspleet, M de Hair, B van Schaik, R Esveldt, M van de Sande, D Gerlag, A van Kampen, F Baas, PP Tak, N de Vries
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> T-cells are thought to be key players in the initiation and progression of rheumatoid arthritis (RA). Earlier we showed that already at the seropositive <i>at-risk</i> stage uninflamed synovial tissue contains T-cell infiltrates.<sup>1</sup> In another study we showed that inflamed synovium harbours expanded T-cell clones.<sup>2</sup> <h3>Objectives</h3> Following up on these observations, we longitudinally investigated whether the expanded T-cell clones found in the inflamed synovial tissue at onset of RA are already present in the <i>at-risk</i> stage. <h3>Methods</h3> Next-Generation Sequencing of the TCRβ repertoire was performed on 20 randomly selected individuals with elevated IgM-RF and/or ACPA levels. Ten individuals did not develop RA during at least 3 years of follow-up, and 10 individuals did. Peripheral blood and synovial tissue samples were analysed during the <i>at-risk</i> phase and, for individuals that developed RA, again after RA onset. T-cell clones were identified by their unique TCRβ sequence.<sup>3</sup> For each sample 3,570 TCRβ sequences were analysed. <h3>Results</h3> During the <i>at-risk</i> phase the TCRβ repertoire in the synovium is characterised by expanded clones. This is observed both in <i>at-risk</i> individuals that did and did not develop RA. Interestingly, a higher impact of expanded clones inversely correlated with a longer disease-free follow-up time (p=0.02). During progression to RA, the <i>at-risk</i> TCRβ repertoire is largely maintained in the tissue. Further characterisation of the synovial CDR3 sequences showed no significant differences between clones that were maintained in the tissue during progression to clinical disease and clones that were uniquely present in the <i>at-risk</i> phase or at RA onset. <h3>Conclusions</h3> Expanded T-cell clones are present in the synovial tissue in the <i>at-risk</i> phase regardless of future development of RA, and are maintained after onset of clinical disease. The resemblance in TCRβ repertoires indicates that the process leading to disease – at least at the T-cell level – constitutes a smooth development. Elucidating the role of these synovial T cells (resident memory, regulatory or autoreactive) might help understanding the earliest pathogenic events in RA. <h3>References</h3> . de Hair MJ, et al. Arthritis Rheum2014. . Klarenbeek PL, et al. Ann Rheum Dis2012. . Klarenbeek PL, et al. Immunol Lett2010. <h3>Acknowledgements</h3> MED, NdV, DMG and PPT received support from BTCURE, a research project from the Innovative Medicines Initiative Joint Undertaking (grant no 115142–2), NdV from the Dutch Arthritis Foundation, and from ZonMw, the Netherlands Organisation for Health Research and Development, in the program 2Treat (Grant 436001001). <h3>Disclosure of interest</h3> None declared
Wide Expression and Significance of Alternative Immune Checkpoint Molecules, B7x and HHLA2, in PD-L1–Negative Human Lung Cancers
Authors: Haiying Cheng, Alain Borczuk, Murali Janakiram, Xiaoxin Ren, Juan Lin, Amer Assal, Balazs Halmos, Roman Perez-Soler, Xingxing Zang
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Immunotherapy targeting the PD-1/PD-L1 pathway has changed the treatment landscape of non–small cell lung carcinoma (NSCLC). We demonstrated that HHLA2, a newly identified immune inhibitory molecule, was widely expressed in NSCLC. We now compared the expression and function of PD-L1 with alternative immune checkpoints, B7x and HHLA2. Experimental Design: Expression was examined in tissue microarrays consisting of 392 resected NSCLC tumors. Effects of PD-L1, B7x, and HHLA2 on human T-cell proliferation and cytokine production were investigated. Results: PD-L1 expression was identified in 25% and 31% of tumors in the discovery and validation cohorts and was associated with higher stage and lymph node involvement. The multivariate analysis showed that stage, TIL status, and lymph node involvement were independently associated with PD-L1 expression. B7x was expressed in 69% and 68%, whereas HHLA2 was positive in 61% and 64% of tumors in the two sets. The coexpression of PD-L1 with B7x or HHLA2 was infrequent, 6% and 3%. The majority (78%) of PD-L1–negative cases expressed B7x, HHLA2, or both. The triple-positive group had more TIL infiltration than the triple-negative group. B7x-Ig and HHLA2-Ig inhibited TCR-mediated proliferation of CD4 and CD8 T cells more robustly than PD-L1-Ig. All three significantly suppressed cytokine productions by T cells. Conclusions: The majority of PD-L1–negative lung cancers express alternative immune checkpoints. The roles of the B7x and HHLA2 pathway in mediating immune evasion in PD-L1–negative tumors deserve to be explored to provide the rationale for an effective immunotherapy strategy in these tumors. Clin Cancer Res; 24(8); 1954–64. ©2018 AACR.
A Distinct Oncogenerative Multinucleated Cancer Cell Serves as a Source of Stemness and Tumor Heterogeneity
Authors: David Díaz-Carballo, Sahitya Saka, Jacqueline Klein, Tobias Rennkamp, Ali H. Acikelli, Sascha Malak, Holger Jastrow, Gunther Wennemuth, Clemens Tempfer, Inge Schmitz, Andrea Tannapfel, Dirk Strumberg
Journal: Cancer Research (2018)

The effects of anticancer treatments on cell heterogeneity and their proliferative potential play an important role in tumor persistence and metastasis. However, little is known about de-polyploidization, cell fate, and physiologic stemness of the resulting cell populations. Here, we describe a distinctive cell type termed "pregnant" P1 cells found within chemotherapy-refractory ovarian tumors, which generate and gestate daughter generation Gn cells intracytoplasmically. Release of Gn cells occurred by ejection through crevices in the P1 cell membrane by body contractions or using a funiculus-like structure. These events characterized a not yet described mechanism of cell segregation. Maternal P1 cells were principally capable of surviving parturition events and continued to breed and nurture Gn progenies. In addition, P1 cells were competent to horizontally transmit offspring Gn cells into other specific proximal cells, injecting them to receptor R1 cells via cell-cell tunneling. This process represents a new mechanism used by tumor cells to invade surrounding tissues and ensure life cycles. In contrast to the pregnant P1 cells with low expression of stem cell markers despite their physiologic stemness, the first offspring generations of daughter G1 cells expressed high levels of ovarian cancer stem cell markers. Furthermore, both P1 and Gn cells overexpressed multiple human endogenous retroviral envelope proteins. Moreover, programmed death-ligand 1 and the immunosuppressive domain of the retroviral envelope proteins were also overexpressed in P1 cells, suggesting effective protection against the host immune system. Together, our data suggest that P1 oncogenerative cancer cells exhibit a not yet described cell biological mechanism of persistence and transmission of malignant cells in patients with advanced cancers.Significance: P1 oncogenerative cell entities express low levels of CSC markers, which are characteristic of their histological origin. Cancer Res; 78(9); 2318-31. ©2018 AACR.
CART Targeting of Solid Tumors: More Pieces to the Puzzle
Authors: Michael Kalos
Journal: Clinical Cancer Research (2018)

Abstract Chimeric antigen receptor–modified T (CART)-cell–based targeting of solid tumors remains a considerable and worthwhile challenge in the field of immunotherapy. The role of chemotherapy to target stroma and enhance chimeric antigen receptor (CAR) cell antitumor function, expansion, and persistence is still unresolved. Clin Cancer Res; 24(6); 1246–7. ©2018 AACR. See related article by Guo et al., p. 1277
Would you explain what the level 3 or level 2/3 ICU is? What is the difference between ICU and HDU?
Authors: Peter Shirley
Journal: BMJ (2005)

<b>www.bmjcareers.com/advicezone</b> Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.
Identification of <i>Pik3ca</i> Mutation as a Genetic Driver of Prostate Cancer That Cooperates with <i>Pten</i> Loss to Accelerate Progression and Castration-Resistant Growth
Authors: Helen B. Pearson, Jason Li, Valerie S. Meniel, Christina M. Fennell, Paul Waring, Karen G. Montgomery, Richard J. Rebello, Arthi A. Macpherson, Sarah Koushyar, Luc Furic, Carleen Cullinane, Richard W. Clarkson, Matthew J. Smalley, Kaylene J. Simpson, Toby J. Phesse, Peter R. Shepherd, Patrick O. Humbert, Owen J. Sansom, Wayne A. Phillips
Journal: Cancer Discovery (2018)

Abstract Genetic alterations that potentiate PI3K signaling are frequent in prostate cancer, yet how different genetic drivers of the PI3K cascade contribute to prostate cancer is unclear. Here, we report PIK3CA mutation/amplification correlates with poor survival of patients with prostate cancer. To interrogate the requirement of different PI3K genetic drivers in prostate cancer, we employed a genetic approach to mutate Pik3ca in mouse prostate epithelium. We show Pik3caH1047R mutation causes p110α-dependent invasive prostate carcinoma in vivo. Furthermore, we report that PIK3CA mutation and PTEN loss coexist in patients with prostate cancer and can cooperate in vivo to accelerate disease progression via AKT–mTORC1/2 hyperactivation. Contrasting single mutants that slowly acquire castration-resistant prostate cancer (CRPC), concomitant Pik3ca mutation and Pten loss caused de novo CRPC. Thus, Pik3ca mutation and Pten deletion are not functionally redundant. Our findings indicate that PIK3CA mutation is an attractive prognostic indicator for prostate cancer that may cooperate with PTEN loss to facilitate CRPC in patients. Significance: We show PIK3CA mutation correlates with poor prostate cancer prognosis and causes prostate cancer in mice. Moreover, PIK3CA mutation and PTEN loss coexist in prostate cancer and can cooperate in vivo to accelerate tumorigenesis and facilitate CRPC. Delineating this synergistic relationship may present new therapeutic/prognostic approaches to overcome castration/PI3K–AKT–mTORC1/2 inhibitor resistance. Cancer Discov; 8(6); 764–79. ©2018 AACR. See related commentary by Triscott and Rubin, p. 682. This article is highlighted in the In This Issue feature, p. 663
I have a chronic back problem that causes me pain when I work long hours, especially if the work entails a lot of walking along corridors or up and down stairs. Could you please advise me on a suitable medical career. (I am a preregistration house officer.)
Authors: Carl Gray
Journal: BMJ (2005)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site. <b>www.bmjcareers.com/advicezone</b>
Trump and health department diverge on how to deal with opioid crisis
Authors: Owen Dyer
Journal: BMJ (2018)

A week of debate and policy announcements on America’s opioid crisis seems to have intensified federal efforts to tackle the public health emergency that has become the country’s leading cause of death before the age of 50.

However, a White House summit on 1 March highlighted differences of approach within the administration. Alex Azar, the new health secretary, joined Food and Drug Administration (FDA) commissioner Scott Gottlieb in calling for greatly expanded access to opioid based addiction treatments like methadone, but President Donald Trump suggested that executing drug dealers would alleviate the crisis.

“Some countries have a very tough penalty, the ultimate penalty, and they have much less of a drug problem than …