tbuckley/cabot-search huggingface dataset:
Immunological and genomic correlates of response to anti-PD1 checkpoint therapy in mismatch proficient and deficient patients with metastasized castration resistant prostate cancer.
Authors: Minke Smits, Maarten Johannes van der Doelen, Harm Westdorp, Inge M. van Oort, Michiel Sedelaar, Antoine Van Der Heijden, Alfred Witjes, Jack A. Schalken, Jolanda De Vries, Winald R. Gerritsen, James L. Gulley, Niven Mehra
Journal: Journal of Clinical Oncology (2018)

248 Background: Response to anti-PD1/PDL1 checkpoint therapy has been witnessed in only a minority of patients with castration-resistant prostate cancer (CRPC). Microsatellite instability (MSI) is the only biomarker predictive of response; additional immune and genomic correlates are needed to improve the proportion of patients that may benefit from checkpoint immunotherapy. Methods: CRPC patients were treated with anti-PD1 checkpoint immunotherapy in two basket-studies, depending on PDL1-positivity ( &gt; 1%) or presence of MSI, and consented to prospective immune-oncology biomarker study. Genomic and immune correlates of response were studied in both MSI as microsatellite stable CRPC patients, and included PDL1 expression , whole genome sequencing on a baseline fresh metastatic biopsy, tumor microenvironment (immuno)profiling using multi-color immunohistochemistry, computational prediction of neoantigens, T-cell receptor sequencing and MHC-tetramer staining. Response was evaluated according to PCWG3 criteria and treatment was continued until radiological progression with lack of clinical benefit or toxicity. Results: At present 11 CRPC patients were included in the program and treated with nivolumab (n = 4) and pembrolizumab (n = 7). Treatment is currently ongoing in 7/11 (64%) of patients, with treatment discontinuation due to immune-related colitis (n = 2) and disease progression (n = 2). Biochemical PSA ( &gt; 50%) responses were seen in both MSI and PDL1 positive patients. Median progression-free survival has not yet been reached. Translational studies on genomic and immune correlates of response will be presented in detail. Conclusions: Encouraging responses to anti-PD1 checkpoint immunotherapy were seen in CRPC patients selected for PDL1-positivity and MSI. An integrative biomarker suite will likely be needed to predict response to anti-PD1 therapy in CRPC.
Magnetic Resonance Imaging of Cardiovascular Function and the Brain
Authors: Albert de Roos, Jeroen van der Grond, Gary Mitchell, Jos Westenberg
Journal: Circulation (2017)

The proximal aorta acts as a coupling device between heart and brain perfusion, modulating the amount of pressure and flow pulsatility transmitted into the cerebral microcirculation. Stiffening of the proximal aorta is strongly associated with age and hypertension. The detrimental effects of aortic stiffening may result in brain damage as well as heart failure. The resulting cerebral small vessel disease and heart failure may contribute to early cognitive decline and (vascular) dementia. This pathophysiological sequence of events underscores the role of cardiovascular disease as a contributory mechanism in causing cognitive decline and dementia and potentially may provide a starting point for prevention and treatment. Magnetic resonance imaging is well suited to assess the function of the proximal aorta and the left ventricle (eg, aortic arch pulse wave velocity and distensibility) as well as the various early and late manifestations of cerebral small vessel disease (eg, microbleeds and white matter hyperintensities in strategically important regions of the brain). Specialized magnetic resonance imaging techniques are explored for diagnosing preclinical changes in white matter integrity or brain microvascular pulsatility.
Association Between Pemphigus and Neurologic Diseases
Authors: Khalaf Kridin, Shira Zelber-Sagi, Doron Comaneshter, Arnon D. Cohen
Journal: JAMA Dermatology (2018)

The association between pemphigus and neurologic diseases was not evaluated systematically in the past. In a recent uncontrolled cross-sectional study, Parkinson disease was found to be significantly associated with pemphigus; in the same study, epilepsy had a nonsignificant association with pemphigus. Several case reports have suggested that pemphigus coexists with multiple sclerosis and dementia.To estimate the association between pemphigus and 4 neurologic conditions (dementia, epilepsy, Parkinson disease, and multiple sclerosis), using one of the largest cohorts of patients with pemphigus.A retrospective population-based cross-sectional study was performed between January 1, 2004, and December 31, 2014, using the database of Clalit Health Services, the largest public health care organization in Israel, in the setting of general community clinics, primary care and referral centers, and ambulatory and hospitalized care. A total of 1985 patients with a new diagnosis of pemphigus and 9874 controls were included in the study.The proportion of dementia, epilepsy, Parkinson disease, and multiple sclerosis was compared between patients diagnosed with pemphigus and age-, sex-, and ethnicity-matched control participants. Logistic regression was used to calculate odds ratios (ORs) for dementia, epilepsy, Parkinson disease, and multiple sclerosis. The association was examined after a sensitivity analysis that included only patients treated with long-term, pemphigus-specific medications (corticosteroids, immunosuppressants, or rituximab) and after adjustment for several confounding factors.When comparing the 1985 cases (1188 women and 797 men; mean [SD] age, 72.1 [18.5] years) with the 9874 controls (5912 women and 3962 men; mean [SD] age, 72.1 [18.5] years), dementia was seen in 622 cases (31.3%) vs 1856 controls (18.8%), with an OR of 1.97 (95% CI, 1.77-2.20). Epilepsy was present in 74 cases (3.7%) vs 210 controls (2.1%), with an OR of 1.78 (95% CI, 1.36-2.33). Parkinson disease was seen in 175 cases (8.8%) vs 437 controls (4.4%), with an OR of 2.09 (95% CI, 1.74-2.51). Multiple sclerosis was present in 2 cases (0.1%) vs 6 controls (0.01%), with an OR of 1.65 (95% CI, 0.34-8.22). Study findings were robust to sensitivity analysis that included patients receiving pemphigus-specific treatments. Estimates were not altered significantly after controlling for comorbidities and overuse of health care.An association was observed between pemphigus and specific neurologic diseases, including dementia, Parkinson disease, and epilepsy. Physicians treating patients with pemphigus should be aware of this possible association. Patients with pemphigus should be carefully assessed for comorbid neurologic disorders and receive appropriate treatment.
Additional response to the correspondence: ‘Switching from the bio-originators to biosimilar: is it premature to recommend this procedure?’ by Cantini and Bennuci
Authors: Marc Scherlinger, Thierry Schaeverbeke
Journal: Annals of the Rheumatic Diseases (2018)

We read with great interest Cantini and Benucci’s response to our letter.1 However, we would like to add some points to the debate.

To date and to our knowledge, every single clinical trial investigating efficacy and safety of biosimilars in rheumatology using a double-blinded design has failed to report any clinical difference with the original biologic. The double-blinded controlled trial NOR-SWITCH as well as open-label extension studies such as PLANETRA investigating efficacy and safety of the switch from original to biosimilar infliximab also failed to report any difference.2 3 These studies unequivocally condone the grade 1b recommendation 6 regarding the efficacy and safety of the switch published …
COMPARATIVE EFFICACY AND SAFETY OF RIVAROXABAN-BASED DUAL-PATHWAY ANTITHROMBOTIC THERAPY VERSUS DUAL ANTIPLATELET THERAPY: A POOLED ANALYSIS OF CONTEMPORARY RANDOMIZED CONTROLLED TRIALS
Authors: Adeel Jamil, Umer Jamil, Michela Faggioni, Jolanta Marszalek, Sara Mehrsefat, Seyedmahdi Pahlavani, Usama Talib, Zahra Karimi, Miroslav Radulovic, Gerald Chi, James J. Peters
Journal: Journal of the American College of Cardiology (2018)
TREATMENT BIAS AND OUTCOMES OF PATIENTS WITH HUMAN IMMUNODEFICIENCY VIRUS INFECTION ADMITTED FOR ACUTE MYOCARDIAL INFARCTION
Authors: Gbolahan Ogunbayo, Le Dung Ha, Qamar Ahmad, Naoki Misumida, Ayman Elbadawi, Odunayo Olorunfemi, Suartcha Prueksaritanond, Patricia Santos, Adrian Messerli
Journal: Journal of the American College of Cardiology (2018)
False-Positive Results in 18F-Fluorocholine PET/CT for a Thymoma in Workup of a Hereditary Primary Hyperparathyroidism
Authors: Léopoldine Bricaire, Capucine Richard, Mathieu Gauthé, Béatrix Cochand-Priollet, Sébastien Gaujoux
Journal: Clinical Nuclear Medicine (2018)

We present the case of a severe familial primary hyperparathyroidism related to a germline deletion in the HRPT2 (CDC73) gene. Morphological explorations revealed 2 potential hyperfunctioning parathyroid glands: a left cervical lesion on the neck ultrasound, and an ectopic mediastinal lesion on the parathyroid scintigraphy using Tc-methoxyisobutylisonitrile and on F-fluorocholine PET/CT. Surgery removal and histopathological examination determined that the mediastinal mass corresponded to a thymoma and the cervical lesion to a parathyroid adenoma. Those interesting images illustrate that a thymoma can produce false-positive results both on Tc-methoxyisobutylisonitrile scintigraphy and F-fluorocholine PET/CT.
Representing the profession
Authors: Tom Moberly
Journal: BMJ (2016)

Medicine still has some way to go to improve entry to the profession for people from a wide variety of different backgrounds and to expand career opportunities it offers to all doctors.

This week Theodore Pezas focuses on the issue of diversity among surgeons http://careers.bmj.com/careers/advice/Are\_surgeons\_still\_all\_privileged\_white\_men%3F. He says that, although efforts have been made to increase diversity …
Complications With Insulin Pump Therapy vs Insulin Injection Therapy
Authors: Viral N. Shah
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
Long‐term outcomes and predictive scores for hepatocellular carcinoma and hepatitis B surface antigen seroclearance after hepatitis B e‐antigen seroclearance
Authors: James Fung, Ka‐Shing Cheung, Danny Ka‐Ho Wong, Lung‐Yi Mak, Wai‐Pan To, Wai‐Kay Seto, Ching‐Lung Lai, Man‐Fung Yuen
Journal: Hepatology (2018)

The significance of hepatitis B e‐antigen (HBeAg) seroclearance (ESC) in the long term is not well defined. The current study aimed to determine the clinical outcomes, the factors and predictive scores for hepatocellular carcinoma (HCC), and hepatitis B surface antigen (HBsAg) seroclearance of a large cohort of patients undergoing ESC. Patients with documented ESC were followed up 3‐ to 6‐monthly. Baseline characteristics and longitudinal laboratory results were recorded. Predictive scores for HCC (HCC‐ESC) and HBsAg seroclearance (HBsAg‐ESC) were derived from multivariate Cox regression models. A total of 723 patients underwent ESC with a median ESC age and follow‐up of 36.0 and 18.3 years, respectively. Only 3.5% and 3.0% had persistently normal alanine aminotransferase (ALT) and HBV DNA &lt;2logs IU/mL, respectively, after ESC. For patients with 100%, 100%‐90%, 90%‐50%, 50%‐10%, 10%‐0%, and 0% normal ALT after HBeAg seroclearance, the rate of HCC was 4.3%, 2.2%, 3.6%, 3.9%, 17.3%, and 37.2% at 20 years after ESC, respectively ( P &lt; 0.001). At 20 years after ESC, the cumulative incidence of HCC and HBsAg seroclearance was 7.9% and 13.5%, respectively, with an overall survival of 91.5%. ESC age, male sex, cirrhosis, hypoalbuminemia, viral load, and ALT were significant factors for HCC, whereas ESC age, male sex, viral load, and antiviral therapy were significant factors for HBsAg seroclearance. The area under receiver operating characteristics for HCC‐ESC and HBsAg‐ESC scores to predict HCC and HBsAg seroclearance at 20 years after ESC was 0.92 and 0.74, respectively. Conclusion : Male sex, older age at ESC, ALT, and higher level of HBV DNA were associated with higher rates of HCC after ESC. HCC‐ESC and HBsAg‐ESC predictive scores can determine the likelihood of developing HCC and achieving HBsAg seroclearance. (H epatology 2018)
How do I obtain a position as an English speaking general practitioner in the Costa Blanca area of Spain?
Authors: James Sherifi
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>
Role model: Ian Nesbitt
Authors: Anne Gulland
Journal: BMJ (2018)

Anne Gulland speaks to Ian Nesbitt, a consultant in anaesthesia and critical care at Freeman Hospital, Newcastle Upon Tyne

When the World Trade Center was destroyed on 11 September 2001 Ian Nesbitt knew life was about to change. As an army reservist, Nesbitt was about to go on a military training exercise to Oman. When he arrived in the Gulf state, the Americans were using the British army camp as a base to bomb Afghanistan.



Ian Nesbitt. Credit: Lorne Campbell/Guzelian

“There was a feeling that we could have got on a plane to go to Afghanistan at any time,” he says.

His next tour of duty was to Kosovo on what was essentially a peacekeeping mission. It brought with it, however, a new level of responsibility. “Someone got shot in the head in Pristina and we had quite a discussion about the flight and transfer. That wouldn’t have happened on an exercise,” he …
Abstract P6-09-02: Associations between hereditary cancer panel predisposition genes and breast cancer histological subtypes
Authors: J Lilyquist, H Laduca, C Hu, J Na, EC Polley, SN Hart, T Pesaran, B Tippin-Davis, DE Goldgar, JS Dolinsky, FJ Couch
Journal: Cancer Research (2018)

Abstract Background: Clinical panel testing has become routine practice for patients that are diagnosed with breast cancer at a young age and/or have a personal or family history of cancer. Associations with known breast cancer genes and breast cancer subtypes have been previously identified, such as BRCA1 associations with estrogen receptor negative (ER-) and triple negative (ER-/PR-/HER2-) breast cancers. However, the cancer predisposition genes associated with each of the four clinical subtypes of breast cancer have not been fully defined. We evaluated 24,901 Caucasian female breast cancer cases receiving clinical panel testing for 23 cancer predisposition genes and assessed associations between mutations in each gene and breast cancer subtypes. Methods: Germline hereditary cancer multigene panel testing results for cancer predisposition genes were obtained for 24,901 Caucasian female breast cancer cases evaluated by a clinical testing laboratory. Information on tumor histology, personal and family history of cancer, age at diagnosis, and previous genetic testing was provided by clinical care providers of patients receiving clinical cancer genetic testing. Breast cancer cases were classified into clinical breast cancer subtypes based on estrogen/progesterone hormone receptor status (HR) and HER2 status: Luminal A (HR+/HER2-), Luminal B (HR+/HER2-), HER2 subtype (HR-/HER2+), and Triple Negative (HR-/HER2-). The frequency of pathogenic or likely pathogenic mutations observed in each subtype was compared against the Exome Aggregation Consortium (ExAC) non-TCGA non-Finnish European population to estimate risks. Results: ATM was associated with moderate risks (odds ratio (OR)&amp;gt;2.0) of Luminal A, Luminal B, and HER2 subtypes of breast cancer, but was not associated with the Triple Negative subtype. PALB2 was associated with moderate risk for Luminal B subtype, but high risk (OR&amp;gt;5.0) for Luminal A, HER2, and triple negative subtypes. TP53 was associated with high risks for Luminal B and HER2 tumors. NBN, MRE11A, and RAD50 were not associated with any subtype of breast cancer. Conclusions: Identifying associations between inherited mutations (odds ratio (OR)&amp;gt;2.0) and breast cancer subtypes can inform clinical risk management, treatment options, and therapeutic development efforts. Citation Format: Lilyquist J, Laduca H, Hu C, Na J, Polley EC, Hart SN, Pesaran T, Tippin-Davis B, Goldgar DE, Dolinsky JS, Couch FJ. Associations between hereditary cancer panel predisposition genes and breast cancer histological subtypes [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 P6-09-02.
I'm thinking of going to Australia after F1. What do you think?
Authors: Shelley Heard
Journal: BMJ (2006)

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>
A GBM invasive region expression profile identified through a multi-region sampling approach
Authors: James Wood, Stuart Smith, Anbarasu Lourdusamy, Marcos Castellanos, Sean May, Richard Grundy, Ruman Rahman
Journal: Neuro-Oncology (2018)

Maximal surgical resection for the malignant brain tumour Glioblastoma (GBM) inevitably leaves residual disease that disseminates predominantly along white matter tracts in the invasive unresectable region. Multi-region sampling has revealed phylogenetic relationships amongst GBM subclones, highlighting the utility of this method for the study of these heterogeneous tumours. Here, we report on an invasive region expression profile obtained through a multi-region sampling approach. Multi-region sampling during maximal surgical resection was performed on five adult GBM patients based on MRI scans and 5-aminolevulinic acid administration for fluorescent identification of the invasive region. RNA was extracted from each region of the GBM patient and hybridized with Affymetrix GeneChip Human Gene 2.0 ST arrays. Distinct expression profiles were observed for regions within a patient, indicating intra-tumor heterogeneity of GBM. The comparison of invasive region with other tumor regions using linear models for microarray data revealed 44 differentially expressed genes (adjusted P-value < 0.05). Remarkably, all 44 genes showed elevated expression in the invasive region and were enriched with biological processes such as myelination (KLK6, MAL, and MBP), cell adhesion (CNTNAP4, CTNNA3, EDIL3, HAPLN2, MAG, and MOG), and lipid metabolic process (APOD, LRP2, and PLCL1). In addition, the GBM invasive region was characterized by the expression of several genes associated with a GBM neural subtype. Isolating and characterising tumour cells infiltrating normal brain within the invasive region remains a bottleneck to the development of therapies tailored to GBM. Gene expression analysis of the invasive region revealed the overexpression of cancer-related genes with possible involvement in invasion along white matter tracts. Although several overexpressed genes likely represent the normal white matter brain component obtained during maximal surgical removal, the identification of cancer-related genes provides proof-of-principle for -omics approaches utilising invasive region tumour tissue to identify biomarkers and targets for therapeutic evaluation.
Diploma/MSc in trauma surgery, University of Wales, Swansea
Authors: Toni Ardolino, Ewan Wilson
Journal: BMJ (2008)

Those wanting to pursue a career in trauma and orthopaedics, burns and plastics, or maxillofacial surgery. It is aimed at trainees in specialty training year 3.

October 2006, after obtaining membership of the Royal College of Surgeons and the certificate of completion of basic surgical training.

The course covers unique areas of medicine and surgery, which made it appealing. The brochure made it sound fun. There is no formal training programme for trauma surgery in the United Kingdom, and the master of science (MSc) therefore offers a good basis for expansion of knowledge and future training in that area. I wanted to learn more about the principles of trauma surgery and to improve my management of trauma patients. Modernising Medical Careers, Hospital at Night, and the European Working Time Directive have shortened and fragmented surgical training, decreasing opportunities to manage trauma patients’ care from admission to discharge. The MSc provides a good way to further one’s skills and stay competitive. It also offers a structured format to participate in research.

The course is divided into …
One in five GP prescriptions for antibiotics is inappropriate
Authors: Zosia Kmietowicz
Journal: BMJ (2018)

At least 20% of all antibiotic prescriptions in primary care in England are inappropriate, research from Public Health England (PHE) shows.1

This rate needs to fall to 10% if the target set by the UK government in 2016 to halve inappropriate prescribing by 2020 is to be achieved.

Paul Cosford, medical director of PHE, said that all general practices needed to look at how they can reduce their …
The scale of the problem of obstructive lung disease in Africa becomes clearer, but where are the solutions?
Authors: Rupert Jones
Journal: European Respiratory Journal (2018)

If you breathe in toxic air, lung damage will result. In much of sub-Saharan Africa as well as Asia, massive exposures to a range of toxic air from household air pollution, ambient air pollution and occupational exposures occur with consequent rising morbidity and mortality. The headline statistics are extraordinary: globally, in 2015, 2.8 people million died from household air pollution and 4.2 million people from ambient air pollution [1]. Chronic obstructive pulmonary disease (COPD) is now the third leading cause of death, with 3.2 million deaths worldwide and the same number dying from lower respiratory tract infections [2]. The prevalence of COPD is rising inexorably in Africa [3] but do we really understand the roots of rising tide of COPD and its relationship to air pollution? COPD is a common and important disease in rural Tanzania, and may relate to biomass smoke exposure <http://ow.ly/MCv030hKe86>
Government commits £1m to help NHS explore benefits of “John Lewis model”
Authors: Matthew Limb
Journal: BMJ (2014)

The government has announced a £1m fund to help around 10 organisations explore how public service “mutual” models could be expanded in the NHS acute sector.

The move by the Cabinet Office and the Department of Health follows publication by the think tank the King’s Fund of its review of staff engagement and empowerment in the NHS.1

The King’s Fund said that evidence was emerging that mutual models, such as the one used by the John Lewis Partnership, delivered …