tbuckley/cabot-search huggingface dataset:
Persistently elevated exhaled nitric oxide fraction is associated with increased risk of exacerbation in COPD
Authors: Bernardino Alcázar-Navarrete, Oliverio Ruiz Rodríguez, Pablo Conde Baena, Pedro José Romero Palacios, Alvar Agusti
Journal: European Respiratory Journal (2018)

Preventing the occurrence of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is a major therapeutic goal. We hypothesise that persistently increased levels of exhaled nitric oxide ( F eNO ) during follow-up can identify a group of COPD patients at higher risk of AECOPD. To test this hypothesis, we measured F eNO levels (HypAir F eNO ®, Medisoft; Sorinnes, Belgium) prospectively in 226 clinically stable COPD outpatients at recruitment and during follow-up (at 6 and 12 months). Patients were stratified according to the number of visits with F eNO ≥20 ppb. F eNO was &lt;20 ppb in all three visits in 44.2% of patients, 29.6% in visit 1 and 26.1% in visit 2 or 3. These three groups suffered progressively higher AECOPD rates during follow-up (0.67, 0.91 and 1.42, respectively, p&lt;0.001). After adjusting for potential confounding variables (log-rank test), the hazard ratio for AECOPD was higher in the latter group (1.579 (95% CI 1.049–2.378), p=0.029). Likewise, time to first moderate and severe AECOPD was shorter in these patients. Finally, there was no relationship between F eNO levels and circulating eosinophils. Persistent F eNO levels ≥20 ppb in clinically stable COPD outpatients are associated with a significantly higher risk of AECOPD.
Germline Lysine-Specific Demethylase 1 (<i>LSD1/KDM1A</i>) Mutations Confer Susceptibility to Multiple Myeloma
Authors: Xiaomu Wei, M. Nieves Calvo-Vidal, Siwei Chen, Gang Wu, Maria V. Revuelta, Jian Sun, Jinghui Zhang, Michael F. Walsh, Kim E. Nichols, Vijai Joseph, Carrie Snyder, Celine M. Vachon, James D. McKay, Shu-Ping Wang, David S. Jayabalan, Lauren M. Jacobs, Dina Becirovic, Rosalie G. Waller, Mykyta Artomov, Agnes Viale, Jayeshkumar Patel, Jude Phillip, Selina Chen-Kiang, Karen Curtin, Mohamed Salama, Djordje Atanackovic, Ruben Niesvizky, Ola Landgren, Susan L. Slager, Lucy A. Godley, Jane Churpek, Judy E. Garber, Kenneth C. Anderson, Mark J. Daly, Robert G. Roeder, Charles Dumontet, Henry T. Lynch, Charles G. Mullighan, Nicola J. Camp, Kenneth Offit, Robert J. Klein, Haiyuan Yu, Leandro Cerchietti, Steven M. Lipkin
Journal: Cancer Research (2018)

Given the frequent and largely incurable occurrence of multiple myeloma, identification of germline genetic mutations that predispose cells to multiple myeloma may provide insight into disease etiology and the developmental mechanisms of its cell of origin, the plasma cell (PC). Here, we identified familial and early-onset multiple myeloma kindreds with truncating mutations in lysine-specific demethylase 1 (LSD1/KDM1A), an epigenetic transcriptional repressor that primarily demethylates histone H3 on lysine 4 and regulates hematopoietic stem cell self-renewal. In addition, we found higher rates of germline truncating and predicted deleterious missense KDM1A mutations in patients with multiple myeloma unselected for family history compared with controls. Both monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma cells have significantly lower KDM1A transcript levels compared with normal PCs. Transcriptome analysis of multiple myeloma cells from KDM1A mutation carriers shows enrichment of pathways and MYC target genes previously associated with myeloma pathogenesis. In mice, antigen challenge followed by pharmacologic inhibition of KDM1A promoted PC expansion, enhanced secondary immune response, elicited appearance of serum paraprotein, and mediated upregulation of MYC transcriptional targets. These changes are consistent with the development of MGUS. Collectively, our findings show that KDM1A is the first autosomal-dominant multiple myeloma germline predisposition gene providing new insights into its mechanistic roles as a tumor suppressor during post-germinal center B-cell differentiation.
Abstract PD6-01: Prevalence of PDL1 and tumor infiltrating lymphocytes (TILs) in primary and metastatic TNBC
Authors: Y Li, C-W Chang, D Tran, M Denker, P Hegde, L Molinero
Journal: Cancer Research (2018)

Abstract Background: Metastatic Triple Negative Breast Cancer (TNBC) is an aggressive breast cancer subtype with a high unmet medical need and limited therapeutic options. PDL1 on immune cells (IC) and TILs were associated with activity to the anti-PDL1 mAB atezolizumab in mTNBC (Schmid AACR 2017). PDL1 IC &amp;gt;=1% is the diagnostic hypothesis for TNBC atezolizumab studies. The goal of the current project was to evaluate the prevalence of PDL1 and TILs in primary and metastatic TNBC samples. Methods: FFPE tumor tissue from pathology documented TNBC tissues were centrally tested for PDL1 IHC on tumor cells (TC) and infiltrating immune cells (IC) (VENTANA SP142 assay) and quantified as percentage of tumor area. TILs were evaluated as a percentage of tumor area and PD-L1 gene (CD274) expression was quantified by Fluidigm. Results: 669 tumors were evaluable for PD-L1 by IHC and TILs. 280 samples were annotated as primary tumors and 179 as metastases with 210 denoted as unknown. PDL1 IC and TC immunostaining was correlated to PD-L1 transcript expression (r = 0.55 and r = 0.51, respectively). 84% of samples had no tumor cells expressing PDL1 and 16% had at least 1% of PDL1 in TC. 44% of the samples had no PDL1 in the immune cells, 35% expressed PDL1 IC [31% to &amp;lt;5%] and 21% PDL1 IC 35%. PDL1 distribution was similar between primary and metastases, with median of 1% and 0% for PDL1 IC and TC, respectively. Analyses of anatomical locations suggest that PDL1 IC is highest in lymph nodes (median IC = 3%), lowest in liver metastases (median IC = 0.5%) while breast tissue is intermediate (median IC = 1%). The correlation between PDL1 IC and TILs is r = 0.69. TILs were numerically higher in primary compared to metastases (10% vs 5%). Anatomical TIL distribution confirmed liver metastases as least infiltrated, while breast, lymph node and lung metastases with similarly higher values (5% vs 10%, respectively). Concordance analyses in intra-individual synchronous and asynchronous matched pairs were performed at a cutoff of PDL1 IC 31%. Concordance of matched specimens was 82% in 11 synchronous pairs and 75% in 20 asynchronous pairs. Conclusions: Prevalence of PDL1 IHC is similar between primary and metastatic TNBC samples. Although PDL1 IC and TILs are highly correlated, TILs are less prevalent in metastases compared to primary tissue. Anatomical location may influence prevalence of both PDL1 IC and TILs. Concordance of PDL1 in matched pairs is high, suggesting PDL1 IC may be a stable biomarker. Citation Format: Li Y, Chang C-W, Tran D, Denker M, Hegde P, Molinero L. Prevalence of PDL1 and tumor infiltrating lymphocytes (TILs) in primary and metastatic TNBC [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 PD6-01.
Diploma in Anaesthesia, Trauma, and Critical Care (Dip ATACC)
Authors: David Southern
Journal: BMJ (2005)

Doctors from acute specialties with an interest in multiple trauma. Also, ambulance personnel, firemen, and combat medical technicians.

Any time from senior house officer to consultant.

It teaches advanced management of multiply injured patients, both prehospital and in the resuscitation room.

One month reading for the course; three months for the dissertation. Two nights on call with the emergency response team and two occasions on subsequent courses as …
VALIDATION OF OBJECTIVE SOFTWARE-BASED LESION DEMARCATION SYSTEM DURING PULMONARY VEIN ANTRUM ISOLATION
Authors: Pouria Alipour, Yaariv Khaykin, Zahra Azizi, Meysam Pirbaglou, Stacey Morris, Alona Avoulov, Sereena Nath, Nikhil Nath, Mehras Motamed, Jamie Forman, Patrick Mallany, Paul Ritvo, Alfredo Pantano, Atul Verma
Journal: Journal of the American College of Cardiology (2018)
Relationship between tumor-infiltrating lymphocytes (TIL) and absolute lymphocyte count (ALC) or lymphocyte to neutrophil ratio (LTN) in cholangiocarcinoma (CCA).
Authors: Alexander Lim, Domenico Coppola, Young Doo Chang, Daniel A. Anaya, Dae Won Kim, Richard D. Kim
Journal: Journal of Clinical Oncology (2018)

343 Background: Tumor microenvironment is potentially a powerful predictive and prognostic marker of immunotherapy. The presence of CD8 TIL has been suggested as a predictive and prognostic marker of PD-1 inhibitor therapy in several malignancies. However, evaluation of TIL is not always feasible especially during or after immunotherapy. Therefore, easily accessible markers are needed for immune monitoring. In CCA, ALC and LTN in peripheral blood have been reported as prognostic factors. We evaluate the relationship between ALC or LTN and CD8 TILs in CCA. Methods: Formalin-fixed paraffin-embedded tumor samples from 41 patients with resected and histologically verified CCA between 1990 and 2015 were identified and immunohistochemically (IHC) stained with anti-CD8. Absolute lymphocyte and neutrophil count of the patients was obtained within 1 week before surgery. The association between ALC, LTN and CD8+ TIL status was investigated using unpaired Student t test and Spearman rank correlation. Results: The median age was 64 (41-85) with 53% male. 22%, 41% and 37% were stage I, II, and III respectively. In CD8 TIL positive, the average ALC was 1764 and in CD8 TIL negative, the average ALC was 2072. There was no significant difference between the two groups (p = 0.38). No difference of LTN was observed between CD8 TIL positive and negative tumors (0.39 vs 0.38, p = 0.69). The correlation between density of CD8 TILs and ALC or LTN was evaluated. No correlation was observed between CD8 TIL density and ALC (R = 0.02, P = 0.3) or LTN (R = 0.02, P = 0.8). Conclusions: ALC or LTN in peripheral blood may not predict CD8 TIL status in patients with CCA.
The Prevalence of Extranodal Extension in Papillary Thyroid Cancer Based on the Size of the Metastatic Node: Adverse Histologic Features Are Not Limited to Larger Lymph Nodes
Authors: Meghan E. Rowe, Umut Ozbek, Rosalie A. Machado, Lauren E. Yue, Juan C. Hernandez-Prera, Alessandro Valentino, Muhammad Qazi, Margaret Brandwein-Weber, Xulei Liu, Bruce M. Wenig, Mark L. Urken
Journal: Endocrine Pathology (2018)
Early Warning Systems for Hospitalized Pediatric Patients
Authors: Neil A. Halpern
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Effect of PDL1 signaling blockade on NK cell cytolytic activity towards ovarian cancer.
Authors: Jeremiah Oyer, Sarah B. Gitto, Deborah Altomare, Robert Igarashi, Alicja Copik
Journal: Journal of Clinical Oncology (2018)

13 Background: The PD-1/PDL-1 axis is an immuno-oncology target for abrogating immune suppression. Anti-PD1 targeted mAb therapy has had success in several indications by alleviating suppression of cytolytic T cells. In addition to T cells, NK cells hold promise for adoptive applications for oncology. We developed a nanoparticle based stimulation method for producing large quantities (&gt; 1,000 fold expansion within two weeks) of highly activated NK cells with high anti-tumor cytotoxicity and enhanced cytokine delivery. These NK cells (PM21-NK) release high amounts of IFNγ in response to tumors that stimulates the expression of PDL1 on tumor, which in turn enhances Treg development. Methods: The ability of PM21-NK cells to induce expression of PDL-1 on tumors was tested in vitro and in vivo. Furthermore, the in vivo efficacy of combination treatment of PM21-NK cells and anti-PDL1 was tested in NSG mice models for ovarian cancer. Results: The IFNγ production by PM21-NK cells increased from 1.4% to 9.9% (p &lt; 0.001) upon exposure to SKOV-3 cells. SKOV-3 cells normally do not express PDL1 but PDL1 expression increased with 48 hours exposure to 20 ng/mL IFNγ (0.7% vs 65.1%). In and in vivo experiment, NSG mice intraperitoneally implanted with 1 x 10 6 SKOV-3 cells were treated with 10 7 T-cell depleted PM21-NK cells i.p. on days 8 and 13 and 25,000 U IL2 i.p. thrice weekly. Upon euthanization 21 days after tumor seeding, tumors in PM21-NK treated mice had increased PDL1+ tumors vs the untreated group (29.7% vs 14.5%, n = 6, p &lt; 0.0001). Despite T-cell depletion, T-cells made up ~22% of hCD45+ events in perfused tumors, 83% of which were Tregs. In a follow-up survival experiment, combination treatment of anti-PDL1 and NK cells were tested in SKOV-3 implanted NSG mice (as above). Groups of mice were given 10 7 T-cell depleted PM-NK or vehicle i.p. days 4 and 7 and 25,000 U IL2 3x’s weekly and groups were given 10 mg/kg anti-PDL1 (Atezolizumab) or vehicle ctrl. on day 4 and later 5 mg/kg twice weekly. Untreated and Atezo alone survival were 24 and 23.5 days, respectively. Median survival for PM-NK + Atezo was 48 days compared to 40.5 for PM-NK alone (p = 0.042; n = 8). Conclusions: These data support the use of anti-PDL1 in NK cell therapy regardless of initial tumor PDL1 status.
Patient care is being damaged by rising bureaucracy, GPs warn
Authors: Matthew Limb
Journal: BMJ (2013)

The care of patients is being damaged by spiralling bureaucracy, GPs in England have warned.

Chaand Nagpaul, who chairs the BMA’s General Practitioners Committee, said that more box ticking and administration meant GPs were spending less time caring for patients. A BMA survey of GPs, published on 20 September, showed that recent changes to the GP contract had created “additional and unnecessary” workload, he said.

The BMA surveyed 3629 GPs, just over 10% …
ANEMIA AND MORTALITY IN PATIENTS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT (TAVR): A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Napatt Kanjanahattakij, Pattara Rattanawong, Parasuram Krishnamoorthy, Natee Sirinvaravong, Pakawat Chongsathidkiet, Kamolyut Lapumnuaypol, Christian Witzke, Vincent Figueredo
Journal: Journal of the American College of Cardiology (2018)
Modeling the human bone marrow niche in mice: From host bone marrow engraftment to bioengineering approaches
Authors: Ander Abarrategi, Syed A. Mian, Diana Passaro, Kevin Rouault-Pierre, William Grey, Dominique Bonnet
Journal: The Journal of Experimental Medicine (2018)

Xenotransplantation of patient-derived samples in mouse models has been instrumental in depicting the role of hematopoietic stem and progenitor cells in the establishment as well as progression of hematological malignancies. The foundations for this field of research have been based on the development of immunodeficient mouse models, which provide normal and malignant human hematopoietic cells with a supportive microenvironment. Immunosuppressed and genetically modified mice expressing human growth factors were key milestones in patient-derived xenograft (PDX) models, highlighting the importance of developing humanized microenvironments. The latest major improvement has been the use of human bone marrow (BM) niche–forming cells to generate human–mouse chimeric BM tissues in PDXs, which can shed light on the interactions between human stroma and hematopoietic cells. Here, we summarize the methods used for human hematopoietic cell xenotransplantation and their milestones and review the latest approaches in generating humanized BM tissues in mice to study human normal and malignant hematopoiesis.
Remodelled diploma of the Royal College of Obstetricians and Gynaecologists
Authors: Lilantha Wedisinghe
Journal: BMJ (2009)

The diploma of the Royal College of Obstetricians and Gynaecologists (DRCOG) is designed for general practitioners in the United Kingdom. It is particularly useful for GPs with a special interest in women’s health care. Although the DRCOG is not a mandatory qualification, it is valuable when seeking a good GP post.

Yes, there are two papers, which are 90 minutes each with a 15 minute break between them. The DRCOG exam is run twice a year, in April and October. It measures a candidate’s ability to apply knowledge and clinical …
I am a failed aspiring haematologist (six times failed part 2 MRCP on short cases). I have a second degree in maths, physics, and computer science and a little commercial experience as an embedded systems software engineer. I am currently working as a locum. Any ideas on possible career pathways?
Authors: Mohammad Al-Ubaydli
Journal: BMJ (2004)

<i>Got 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 (www.bmjcareers.com/advicezone) 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.</i>
Evaluation of treatment results in multifocal primary cutaneous anaplastic large cell lymphoma: report of the Dutch Cutaneous Lymphoma Group
Authors: R.C. Melchers, R. Willemze, M.W. Bekkenk, E.R.M. de Haas, B. Horvath, M.M. van Rossum, C.J.G. Sanders, J.C.J.M. Veraart, M.H. Vermeer, K.D. Quint
Journal: British Journal of Dermatology (2018)

There is no consensus on the treatment of multifocal primary cutaneous anaplastic large cell lymphoma (C-ALCL). Radiotherapy (RT) and methotrexate (MTX) are the current treatment options, but their efficacy is unknown. Recently, targeted therapies showed promising results in C-ALCL, and may therefore be an attractive first choice of treatment.To assess the efficacy of conventional treatment strategies for patients with multifocal C-ALCL, and to define which patients may require novel targeted therapies.In this multicentre study, treatment was evaluated in patients initially presenting (n = 24) or relapsing with multifocal C-ALCL (n = 17; 23 relapses). Distinction was made between patients with five or less lesions (n = 36) and more than five lesions (n = 11).Treatments most commonly used were RT (n = 21), systemic chemotherapy (n = 9) and low-dose MTX (n = 7) with complete response rates of 100%, 78% and 43%, respectively, and an overall response rate of 100%, 100% and 57%, respectively. Four patients showed complete spontaneous regression. In total, 16 of 24 patients (67%) first presenting with multifocal C-ALCL relapsed, including all five patients initially treated with CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone). Compared with patients presenting with two to five skin lesions, patients presenting with more than five lesions had a higher chance of developing extracutaneous relapse (56% vs. 20%) and more often died of lymphoma (44% vs. 7%).Patients with five or less lesions should be treated with low-dose RT (2 × 4 Gy). Maintenance low-dose MTX (20 mg weekly) is a suitable option in patients with more than five lesions. Targeted therapies may be considered in rare patients who are refractory to MTX or patients developing extracutaneous disease.
Although I have not yet decided on a career specialty, I am very interested in medical education. Are there any resources detailing distance courses that I could potentially enrol in at this early stage?
Authors: Paul O'Neill
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>
Trainee shortages are making workforce planning “almost impossible,” RCP says
Authors: Tom Moberly
Journal: BMJ (2014)

Shortages of trainees in acute medicine and geriatric medicine, as well as excess numbers in other specialties, are making workforce planning “almost impossible,” the Royal College of Physicians has warned.

The college has published a report of its latest census of consultant physicians in the United Kingdom. It found that more posts were advertised in acute medicine and geriatric medicine than …
THROMBIN-INDUCED CLOT STRENGTH AND PLATELET REACTIVITY FOR PREDICTION OF MAJOR CARDIOVASCULAR EVENTS FOLLOWING PERCUTANEOUS CORONARY INTERVENTION
Authors: Jong-Hwa Ahn, Jae Seok Bae, Jeong Yoon Jang, Min Gyu Kang, Kyehwan Kim, Hyun Woong Park, Jin-Sin Koh, Yongwhi Park, Seok-Jae Hwang, Choong Hwan Kwak, Jin-Yong Hwang, Young-Hoon Jeong
Journal: Journal of the American College of Cardiology (2018)
RE: Magnitude of Clinical Benefit of Cancer Drugs Approved by the US Food and Drug Administration
Authors: Nathan I Cherny, Urani Dafni, Jan Bogaerts, Nicola J Latino, George Pentheroudakis, Jean-Yves Douillard, Josep Tabernero, Christoph Zielinski, Martine J Piccart, Elisabeth G E de Vries
Journal: JNCI Journal of the National Cancer Institute (2018)