tbuckley/cabot-search huggingface dataset:
Relationship between mismatch repair status and long-term survival in patients with resected periampullary adenocarcinoma.
Authors: Margareta Heby, Sebastian Lundgren, Jacob Elebro, Bjorn Nodin, Jakob Eberhard, Karin Jirstrom
Journal: Journal of Clinical Oncology (2018)

289 Background: Periampullary adenocarcinomas, including pancreatic cancer, are a heterogenous group of tumors with poor prognosis. Emerging evidence indicates that tumor morphology, i.e. intestinal type (I-type) or pancreatobiliary type (PB-type), is a more relevant prognostic factor than anatomical tumor origin. The extent and clinical significance of deficient mismatch repair (dMMR) in periampullary adenocarcinoma is relatively unexplored. In this study, we examined the associations of MMR status with survival in patients with resected periampullary adenocarcinoma, with particular reference to tumor morphology and adjuvant treatment response. Methods: MMR status was assessed by immunohistochemistry on tissue microarrays with primary tumors from a retrospective consecutive cohort of 172 patients with periampullary adenocarcinoma treated with pancreaticoduodenectomy during 2001-2011 in Malmö and Lund University Hospitals, Sweden. Cox proportional hazards models were applied to calculate hazard ratios (HR) and 95% confidence intervals (CI) for death. Results: After a mean follow-up of 46.5 months (range 1.9-185.1), 35 patients (20.3%) were alive, 24 with I-type and 11 with PB-type tumors. Adjuvant chemotherapy was given in 77 (44.8%) cases, 18/63 (28.6%) I-type tumors and 59/109 (54.1%) PB-type tumors. MMR status could be evaluated in 170 cases, in which dMMR was denoted in 22 (12.9%) cases, 13/61(21.3%) in I-type and 9/109 (8.3%) in PB-type tumors. dMMR was associated with a significantly prolonged overall survival in the entire cohort (HR = 0.32, 95% CI 0.17-0.61), and in I-type tumors (HR = 0.27, 95% CI 0.09-0.79), however not independent of conventional prognostic factors. In PB-type tumors, dMMR was only prognostic in non-adjuvant treated cases (HR = 0.26, 95% CI 0.08-0.85), and there was a significant negative interaction between dMMR and adjuvant treatment (p interaction = 0.008). Conclusions: dMMR signifies a prolonged survival in patients with periampullary adenocarcinoma, but may be a negative predictor of response to adjuvant chemotherapy in PB-type tumors. This finding may be highly relevant for clinical decision making and warrants further study.
Can ultrasound of the major salivary glands assess histopathological changes induced by treatment with rituximab in primary Sjögren’s syndrome?
Authors: Esther Mossel, Konstantina Delli, Suzanne Arends, Erlin A Haacke, Bert van der Vegt, Jolien F van Nimwegen, Alja J Stel, Fred K L Spijkervet, Arjan Vissink, Frans G M Kroese, Hendrika Bootsma
Journal: Annals of the Rheumatic Diseases (2018)

In conclusion, rituximab treatment leads to significant improvements in histopathological characteristics of salivary gland biopsies.This improvement was not reflected by a similar improvement in the amount of hypoechogenic areas identified with ultrasound by Fisher et al, 1 but this could be due to several reasons, that is, ultrasound is not sensitive enough to detect the histopathological differences or does not reflect the changes seen in the biopsies and the TRACTISS study was a negative study, perhaps due to the chosen inclusion criteria.In order to make a statement about whether or not ultrasound is the right tool to measure treatment effect, the sensitivity to change should be determined in positive clinical trials.At this point, the baseline histopathological characteristics of the parotid gland should be used to predict the effect of rituximab therapy and to help us to determine a personalised treatment approach.
Treatment adherence, healthcare resource utilization, and costs in patients with gastrointestinal neuroendocrine tumors (GI NETs).
Authors: Beilei Cai, Michael Broder, Eunice Chang, Jessie Tingjian Yan, Al Bowen Benson
Journal: Journal of Clinical Oncology (2018)

337 Background: This study aimed to assess treatment adherence, healthcare resource utilization and costs in patients with GI NETs who initiated pharmacologic treatments. Methods: In 2 US commercial claims databases, patients ≥18 years with ≥1 inpatient or ≥2 outpatient claims for GI NETs were identified. The first claim for pharmacologic treatments (e.g. somatostatin analogues [SSAs], cytotoxic chemotherapy [CC], targeted therapy) following diagnosis and between 7/1/2009 and 12/31/2013 was defined as the index date. A 6-month clean period before index date and a 6-month pre- and a ≥1-year post-index enrollment were required. Proportion of days covered (PDC) was calculated during the follow up period. Outcomes were reported separately for patients with 1 and 2 years of post-index enrollment. Descriptive statistics including means, standard deviations, and frequencies and percentages for continuous and categorical data, respectively, were reported. Results: Of 1,322 patients with 1-year of follow-up, 847 initiated SSAs, 397 CC, 35 targeted therapies, 2 interferon, and 41 various combinations. Due to sample sizes, remaining results focus only on SSAs and CC. Mean PDC (SD) was 0.669 (0.331) for SSAs and 0.466 (0.236) for CC; SSA users had 20.5 (13.5) office visits and 0.59 (1.03) hospitalizations, CC users had 30.5 (19.8) and 0.89 (1.45) office visits and hospitalizations respectively; total annual cost for SSA-treated patients during the 1 st year was $99,691 (82,423) and $134,912 (116,078) for CC. Among 685 patients with 2 years of follow-up, the annual mean costs in the second year were $8,071 and $58,944 lower than the first year for SSAs and CC, respectively. Conclusions: In this descriptive non-comparative study, we reported the resource utilization and costs associated with different treatment therapies. Overall, costs were higher in the first year than in the second year. This 2-database study offers new information on the magnitude and trends in the cost of pharmacologically treated GI NETs. Additional research with a larger sample size would be needed to better understand real-world utilization and costs for GI NET patients treated with different pharmacological therapies.
ST-ELEVATION MYOCARDIAL INFARCTION-DERIVED CORONARY MICROVASCULAR OBSTRUCTION IS NOT THROMBUS DEPENDENT: RESULTS IN A PORCINE CORONARY MODEL
Authors: Giovanni Pellegrini, Nikola Cesarovic, Mareika Gastl, Jon Hoem, Martin Rothman, Oliver Bludau, Blathnaid Feldman, Sho Torii, Renu Virmani, Robert Schwartz
Journal: Journal of the American College of Cardiology (2018)
Progressive blurred vision in a 44 year old woman
Authors: Aled R Daniels, Becky Hunt, Mario Teo, Kathreena M Kurian
Journal: BMJ (2018)

A 44 year old woman presented to her optometrist with a 10 week history of progressive blurred vision. She had no headaches or nausea. Funduscopy showed bilateral papilloedema. Subsequent magnetic resonance imaging (MRI) of the brain (fig 1, 2, 3) revealed a large frontal durally based lesion involving the superior sagittal sinus, causing mass effect and vasogenic oedema.



Fig 1 
Sagittal T1 volume post gadolinium 1 mm reconstruction showing a large, avidly enhancing, left frontal convexity extra axial mass with a broad dural base and bony hyperostosis. There is mass effect with sulcal effacement and compression of left frontal lobe and distortion of the anterior body and genu of the corpus callosum





Fig 2 
Axial T1 volume post gadolinium 1 mm reconstruction





Fig 3 
Coronal T1 volume post gadolinium 1 mm reconstruction





### 1. What are the causes of bilateral papilloedema?

#### Short answer

Papilloedema is the term given to optic disc swelling caused by raised intracranial pressure. Causes include intracranial lesions, cerebral oedema, increased production of cerebrospinal fluid, decreased absorption of cerebrospinal fluid, obstruction of venous outflow, or idiopathic intracranial hypertension.

#### Discussion

Papilloedema occurs because of raised intracranial pressure being transmitted through the optic nerve sheath to the optic disc. The raised pressure disrupts axoplasmic flow within the nerve, resulting in accumulation of fluid and protein within an oedematous-appearing optic disc.1

Early changes on funduscopy include the loss of spontaneous venous pulsations, progressing to elevation of the optic disc, obliteration of the cup, and …
Recruitment into anaesthesia could be increased by improving working environment
Authors: Matthew Limb
Journal: BMJ (2016)

More supportive working and learning environments for anaesthesia trainees would help tackle problems of low recruitment and high attrition in the specialty, researchers have said.

Researchers from Aberdeen University looked at the factors influencing the trainees’ decisions about their careers. They also found concerns about the impact of service demands on training quality.

The researchers said that, although many acute hospital specialties were experiencing low recruitment and high attrition of trainees, there had been little research exploring why anaesthesia may or may not be an attractive medical career option in …
Myocardial Stiffness Evaluation Using Noninvasive Shear Wave Imaging in Healthy and Hypertrophic Cardiomyopathic Adults
Authors: Olivier Villemain, Mafalda Correia, Elie Mousseaux, Jérome Baranger, Samuel Zarka, Ilya Podetti, Gilles Soulat, Thibaud Damy, Albert Hagège, Mickael Tanter, Mathieu Pernot, Emmanuel Messas
Journal: JACC. Cardiovascular imaging (2018)

The goal of our study was to investigate the potential of myocardial shear wave imaging (SWI) to quantify the diastolic myocardial stiffness (MS) (kPa) noninvasively in adult healthy volunteers (HVs) and its physiological variation with age, and in hypertrophic cardiomyopathy (HCM) populations with heart failure and preserved ejection function (HFpEF).
I want to work for a year in Australia to widen my breadth of medical experience before I choose which specialty to apply for. If I defer my application, will I be able to apply and be interviewed for specialty training posts without returning to the UK?
Authors: Sarah Burnett
Journal: BMJ (2007)

Have a career related problem that needs answering? Can9t find the 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>
Patient Data Ownership—Reply
Authors: Katherine A. Mikk, Harry A. Sleeper, Eric Topol
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
Efficacy of immune-checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC) patients harboring activating molecular alterations.
Authors: Laurent Mhanna, Julie Milia, Amellie Lusque, Sebastien Couraud, Celine Mascaux, Remi Veillon, Martin Frueh, Denis Moro-Sibilot, Mickaël Lattuca-Truc, Pascale Tomasini, Fabrice Barlesi, Alexander E. Drilon, Oliver Gautschi, Julien Mazieres
Journal: Journal of Clinical Oncology (2018)

172 Background: Two revolutions recently occur in the treatment of advanced NSCLC: the development of targeted therapies and of ICI). Both strategies have been shown to outperform chemotherapy. Patients with molecular alterations are usually considered as poor candidate for immunotherapy. Here, we aimed to analyze the efficacy of immunotherapy in NSCLC patients with oncogenic addiction. Methods: We conducted a retrospective multicentric study, on patients treated with ICI and carrying an activating molecular abnormality: EGFR, ALK, KRAS, ROS1, HER2, BRAF, MET and RET. We have collected anonymized data, which were evaluated for clinical characteristics and outcome (progression free survival duration of ICI treatment and overall survival since initiation of ICI). Results: 209 patients were registered from 7 centers in France and Switzerland. 198 patients had adenocarcinoma (95.2%), 6 large cell carcinoma (2.9%), 161 were former or current smokers (81.3%), 99 were female (47.4%), median age at diagnosis was 59 yrs. (range 30-79). 33 patients had EGFR mutations (15.8%), 132 KRAS mutation (63.2%), 6 ALK rearrangement (2.9 %), 2 ROS1 rearrangement (1 %), 5 HER2 mutation (2.4 %), 12 BRAF mutations (5.7 %), 7 MET alteration (3.3 %), 3 RET rearrangements (1.4 %), and 9 had concomitant multiple molecular alterations (4.3%). After validated treatment 200 patients were treated with PD1 inhibitors (nivolumab, 97.5% and pembrolizumab, 2.5%), 4 with anti CTLA4 (tremelimumab), 5 with anti PDL1 (4 atezolizumab). The median PFS was 2.8 m. [95%CI 2.3;3.5] for the whole population 2.1 for EGFR [1.7;2.8], 3.5 for KRAS [2.5;4.9], 2.7 for BRAF [1.5;NR] and not estimable for other alterations. Median exposure to ICI was 1.89 m. [0;18.5]. The median overall survival for the whole population was 13.0 m. [9.4; 15.6], for EGFR 13.3 m. [4.7; NR], KRAS 11.3 m. [8.2; 16], BRAF 10.7 m. [1.5; NR] and not yet estimable for the other alterations. Conclusions: PFS (2.8 m.) and OS (13 m.) are very similar from the ones observed in pretreated unselected NSCLC patients. ICI is associated with better PFS in patients with KRAS mutation than in EGFR mutated patients. Analysis of outcome in other molecular subgroups is ongoing.
Reading about the difficulties in getting a post as a senior house officer, I was wondering if research experience and publications in my chosen field (haematology) would help me to obtain a post?
Authors: Adrian Newland
Journal: BMJ (2004)

<h3>Abstract</h3> RNA splicing plays significant roles in fundamental biological activities. However, our knowledge about the roles of alternative splicing and underlying mechanisms during spermatogenesis is limited. Here, we report that Serine/arginine-rich splicing factor 2 (SRSF2), also known as SC35, plays critical roles in alternative splicing and male reproduction. Male germ cell-specific deletion of <i>Srsf2</i> by <i>Stra8-Cre</i> caused complete infertility and defective spermatogenesis. Further analyses revealed that deletion of <i>Srsf2</i> disrupted differentiation and meiosis initiation of spermatogonia. Mechanistically, by combining RNA-seq data with LACE-seq data, we showed that SRSF2 regulatory networks play critical roles in several major events including reproductive development, spermatogenesis, meiotic cell cycle, synapse organization, DNA recombination, chromosome segregation, and male sex differentiation. Furthermore, SRSF2 affected expression and alternative splicing of <i>Stra8, Stag3</i> and <i>Atr</i> encoding critical factors for spermatogenesis in a direct manner. Taken together, our results demonstrate that SRSF2 has important functions in spermatogenesis and male fertility by regulating alternative splicing.
Roles of PAD4 and NETosis in Experimental Atherosclerosis and Arterial Injury
Authors: Grégory Franck, Thomas L. Mawson, Eduardo J. Folco, Roberto Molinaro, Victoria Ruvkun, Daniel Engelbertsen, Xin Liu, Yevgenia Tesmenitsky, Eugenia Shvartz, Galina K. Sukhova, Jean-Baptiste Michel, Antonino Nicoletti, Andrew Lichtman, Denisa Wagner, Kevin J. Croce, Peter Libby
Journal: Circulation Research (2018)

Neutrophils likely contribute to the thrombotic complications of human atheromata. In particular, neutrophil extracellular traps (NETs) could exacerbate local inflammation and amplify and propagate arterial intimal injury and thrombosis. PAD4 (peptidyl arginine deiminase 4) participates in NET formation, but an understanding of this enzyme's role in atherothrombosis remains scant.This study tested the hypothesis that PAD4 and NETs influence experimental atherogenesis and in processes implicated in superficial erosion, a form of plaque complication we previously associated with NETs.Bone marrow chimeric Ldlr deficient mice reconstituted with either wild-type or PAD4-deficient cells underwent studies that assessed atheroma formation or procedures designed to probe mechanisms related to superficial erosion. PAD4 deficiency neither retarded fatty streak formation nor reduced plaque size or inflammation in bone marrow chimeric mice that consumed an atherogenic diet. In contrast, either a PAD4 deficiency in bone marrow-derived cells or administration of DNaseI to disrupt NETs decreased the extent of arterial intimal injury in mice with arterial lesions tailored to recapitulate characteristics of human atheroma complicated by erosion.These results indicate that PAD4 from bone marrow-derived cells and NETs do not influence chronic experimental atherogenesis, but participate causally in acute thrombotic complications of intimal lesions that recapitulate features of superficial erosion.
Disentangling Health Care Billing
Authors: Vivian S. Lee, Bonnie B. Blanchfield
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
A phase I study of veliparib (Vel) in combination with oxaliplatin (Ox) and capecitabine (Cap) in advanced solid tumors.
Authors: Anita Ahmed Turk, Dustin A. Deming, Sam Joseph Lubner, Daniel Mulkerin, Noelle K. LoConte, Amye Tevaarwerk, Kari Braun Wisinski, Jens C. Eickhoff, Glenn Liu
Journal: Journal of Clinical Oncology (2018)

314 Background: Poly(ADP-ribose) polymerases (PARP) are activated by DNA strand breaks and important for DNA repair in response to platinum-based chemotherapy. PARP inhibition with Vel might enhance anti-tumor effects of Cap with Ox. This phase I study (NCI 8604) examines the tolerability, safety and preliminary efficacy of the combination of Vel with Cap and Ox. Methods: This is a phase I dose escalation protocol testing escalating doses of Vel with Cap and Ox every 28 days (Table 1). Pts were treated in cohorts of 3-6 pts until cycle 1 DLTs were defined. Key eligibility criteria included age ≥ 18 with histologically confirmed malignancy meeting at least one of the following: documented BRCA1/2 mutation and a BRCA related malignancy; a 20% probability of harboring a BRCA mutation; metastatic colorectal cancer; mucinous ovarian cancer; other GI malignancy in which Ox has demonstrated activity. Results: 17 pts (median age 52 [range 19-71]; 14 female, 3 male) were treated at 4 dose levels (DL) (Table 1). Pts had cholangiocarcinoma (6), breast (4), ovarian (4), neuroendocrine (1), pancreas (1), and colon (1) cancers. 7 pts (4 breast, 3 ovarian) are BRCA1+. Dose escalation was initiated at DL1. One DLT (mucositis) occurred at this dose level. At DL2, two DLTs (mucositis with neutropenic fever and thrombocytopenia) were noted. The protocol was amended for escalation to begin at DL1A. At DL2A, a grade 2 DLT of fatigue requiring dose delay occurred in one pt. Pts were on study for median 10 weeks (range 1 – 88). 24% of pts remained on study ≥ 6 months. Of the 14 pts with measurable disease, 5 had PR (2 ovarian, 2 breast, 1 colon) and 4 had SD (3 cholangiocarcinoma, 1 pancreas). Common AEs include nausea/vomiting (94%), diarrhea (47%), mucositis (41%), anemia (35%), neutropenia (24%), and thrombocytopenia (18%). Conclusions: Vel in combination with Cap and Ox is safe and well tolerated in pts with advanced solid malignancies. The recommended phase II dose is DL2A Vel 40mg BID (D 1-7, 15-21), Cap 1000mg/m 2 BID (D 1-7, 15-21), and Ox 85mg/m 2 (D 1 and 15). Clinical trial information: NCT01233505. [Table: see text]
Abstract 18132: Extracellular Vesicles Secreted From Mesenchymal Stem Cells Promote Mature Cardiomyocyte Proliferation
Authors: Bin Yu, Min Gong, Yuping Duan, Yi-gang Wang, Muhammad Ashraf, Meifeng Xu
Journal: Circulation (2016)

It is well known that the heart cannot regenerate adequately after injury due to limited regenerative capacity of myocardium. Previous studies indicated that the paracrine factors released from ste...
Is there funding available for medical students who are experiencing financial difficulty?
Authors: Paul O'Neill
Journal: BMJ (2006)

<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.
US opioid overdoses rise by 30% in one year
Authors: Owen Dyer
Journal: BMJ (2018)

An increased government focus on the US opioid crisis has not yet slowed the epidemic’s growth, according to new data from the Centers for Disease Control (CDC).

Emergency department visits for suspected opioid overdoses rose by 30% from July 2016 to September 2017, this month’s Vital Signs bulletin from the CDC reported.1

The rise was driven by a continued climb in overdoses from street drugs, which now outnumber those from prescription opioids. Fentanyl accounts for a growing share of the black market, having surpassed both heroin and prescription opioids as the …
Mutant IL-7Rα and mutant NRas are sufficient to induce murine T cell acute lymphoblastic leukemia
Authors: Sarah D. Cramer, Julie A. Hixon, Caroline Andrews, Ross J. Porter, Gisele O. L. Rodrigues, Xiaolin Wu, Tim Back, Kelli Czarra, Helen Michael, Maggie Cam, Jack Chen, Dominic Esposito, Emilee Senkevitch, Vijay Negi, Peter D. Aplan, Wenqing Li, Scott K. Durum
Journal: Leukemia (2018)
Adiponectin as a Biomarker at Different Stages of Ischaemic Heart Disease: From Obesity to Ischaemic Heart Failure
Authors: A S Antonopoulos, C Antoniades, D Tousoulis, A Miliou, C Bakogiannis, K Marinou, M Demosthenous, C Psarros, K M Channon, C Stefanadis
Journal: Circulation (2009)