tbuckley/cabot-search huggingface dataset:
It’s in the Field of View!
Authors: Harvey S. Hecht, Jagat Narula, Jonathon Leipsic
Journal: Circulation Research (2018)

S everal questions of great importance to the cardiovas- cular community loom large in chest CT imaging: 1.Is the imager responsible for reporting all relevant cardiovascular findings in the field of view? 2. If imaging of the requested organs (aorta and pulmonary arteries) on computed tomographic angiography is enhanced by simple techniques that enable analysis of the coronary arteries, should the acquisition standard of care be changed to permit coronary analysis and reporting?Coronary Artery Calcium Analysis on Noncontrast Chest CT Scans The Society of Cardiovascular Computed Tomography and Society of Thoracic Radiology have answered the first question in the 2016 SCCT/STR Guidelines for Coronary Artery Calcium Scoring of noncontrast noncardiac chest CT scans. 1 Because Coronary Artery Calcium Scoring analysis is always feasible and the information provides robust prediction of cardiovascular events in asymptomatic patients, the guideline states that Coronary Artery Calcium Scoring by quantitative or semiquantitative analysis should be part of every noncontract chest CT analysis and report, whether gated or nongated, even though it has not been requested by the referring physician.
Drug Interactions With Non–Vitamin K Oral Anticoagulants
Authors: Sara R. Vazquez, Arthur Allen
Journal: JAMA (2018)

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Health Education England seeks doctors’ views on moving GMC registration
Authors: Abi Rimmer
Journal: BMJ (2015)

Health Education England (HEE) will gather UK doctors’ views on the plan to move full registration with the General Medical Council from the end of the first year of foundation training to the point of graduation from medical school.

The plan was first proposed in the UK-wide Shape of Training review, led by David Greenaway,1 and was also set out in the government’s mandate for HEE.2 The BMA has previously warned against …
Cost-effectiveness of immune checkpoint inhibition in metastatic gastric and esophageal tumors.
Authors: Sassan Ostvar, Jin G. Choi, Jacqueline N. Chu, Michael Lawrence Dougan, Justin F. Gainor, Kerry Lynn Reynolds, Ryan David Nipp, Chung Yin Kong, Chin Hur
Journal: Journal of Clinical Oncology (2018)

56 Background: Immune checkpoint inhibition has shown early promising results in patients with chemotherapy-refractory metastatic or advanced tumors of the esophagus, gastroesophageal junction, and stomach. We explore the cost-effectiveness of checkpoint inhibitors as second-line treatment agents for this group of patients using a decision analytic approach. Methods: A Markov model was developed to simulate the course of a virtual cohort of patients treated by (i) nivolumab 3 mg/kg, (ii) combination of ipilimumab 3 mg/kg and nivolumab 1 mg/kg, and (iii) best supportive care (BSC). Patients in the hypothetical cohort were 55-year-olds in an advanced/metastatic stage who had received at least one prior line of chemotherapy. Patients who remained stable in treatment were monitored for adverse events until death. Rates of cancer-specific mortality, disease progression, and drug-related adverse events were estimated using results from the CheckMate 032 clinical trial. The primary endpoints were survival, measured in life-years (LY), quality adjusted life years (QALY), and incremental cost-effectiveness ratios (ICER). Cost-effectiveness of each strategy was evaluated from a US-payer perspective considering costs of drugs, treatment, and management of immune-related adverse events. Cost-effectiveness was defined with a willingness to pay threshold of $100,000/QALY. Results: Combination therapy with nivolumab and ipilimumab yielded the highest effectiveness (QALYs = 0.47, LYs = 1.09) in our base case modeling results, compared with nivolumab (QALYs = 0.43, LYs = 1.03), and BSC (QALYs = 0.19, LYs = 0.42). Nivolumab had an incremental cost of $84,555/QALY compared with BSC, while nivolumab with ipilimumab resulted in an incremental cost of $1.1M/QALY compared with nivolumab alone. The cost gap between the two was associated with the higher price of ipilimumab, and costs of managing increased toxicity. Conclusions: Our modeling analysis finds that combination therapy of ipilimumab and nivolumab is the most effective, but from a cost-effectiveness perspective, it is expensive, making nivolumab monotherapy the cost-effective option. Additional clinical data are needed to confirm our modeling results.
PROGNOSTIC VALUE OF RIGHT VENTRICULAR SYSTOLIC DYSFUNCTION IN HEART FAILURE WITH REDUCED EJECTION FRACTION
Authors: Anne-Catherine Pouleur, Marie-Bénédicte Bénats, Sylvie A. Ahn, Christophe de Meester, Mihaela Amzulescu, David Vancraeynest, Agnès Pasquet, Jean-Louis Vanoverschelde, Bernhard Gerber, Michel Rousseau
Journal: Journal of the American College of Cardiology (2018)
Evaluating Mismatch Repair Deficiency in Pancreatic Adenocarcinoma: Challenges and Recommendations
Authors: Zishuo I. Hu, Jinru Shia, Zsofia K. Stadler, Anna M. Varghese, Marinela Capanu, Erin Salo-Mullen, Maeve A. Lowery, Luis A. Diaz, Diana Mandelker, Kenneth H. Yu, Alice Zervoudakis, David P. Kelsen, Christine A. Iacobuzio-Donahue, David S. Klimstra, Leonard B. Saltz, Ibrahim H. Sahin, Eileen M. O'Reilly
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Immune checkpoint inhibition has been shown to generate profound and durable responses in mismatch repair deficient (MMR-D) solid tumors and has elicited interest in detection tools and strategies to guide therapeutic decision-making. Herein we address questions on the appropriate screening, detection methods, patient selection, and initiation of therapy for MMR-D pancreatic ductal adenocarcinoma (PDAC) and assess the utility of next-generation sequencing (NGS) in providing additional prognostic and predictive information for MMR-D PDAC. Experimental Design: Archival and prospectively acquired samples and matched normal DNA from N = 833 PDAC cases were analyzed using a hybridization capture–based, NGS assay designed to perform targeted deep sequencing of all exons and selected introns of 341 to 468 cancer-associated genes. A computational program using NGS data derived the MSI status from the tumor-normal paired genome sequencing data. Available germline testing, IHC, and microsatellite instability (MSI) PCR results were reviewed to assess and confirm MMR-D and MSI status. Results: MMR-D in PDAC is a rare event among PDAC patients (7/833), occurring at a frequency of 0.8%. Loss of MMR protein expression by IHC, high mutational load, and elevated MSIsensor scores were correlated with MMR-D PDAC. All 7 MMR-D PDAC patients in the study were found to have Lynch syndrome. Four (57%) of the MMR-D patients treated with immune checkpoint blockade had treatment benefit (1 complete response, 2 partial responses, 1 stable disease). Conclusions: An integrated approach of germline testing and somatic analyses of tumor tissues in advanced PDAC using NGS may help guide future development of immune and molecularly directed therapies in PDAC patients. Clin Cancer Res; 24(6); 1326–36. ©2018 AACR.
Doctors will no longer be removed from performers lists without full GMC investigation
Authors: Abi Rimmer
Journal: BMJ (2014)

The Department of Health for England is consulting on proposals to ensure that doctors have been fully investigated by the General Medical Council before they are removed from the performers list. The department has issued a consultation document proposing to reverse changes introduced in 2013,1 which it said were disproportionate and unfair.

The 2004 NHS (Performers List) Regulations, which cover GPs, dentists, and opticians, were amended in 2013 to reflect changes introduced by the Health and Social Care Act, including the abolition of …
Injection of Cultured Cells with a ROCK Inhibitor for Bullous Keratopathy
Authors: Shigeru Kinoshita, Noriko Koizumi, Morio Ueno, Naoki Okumura, Kojiro Imai, Hiroshi Tanaka, Yuji Yamamoto, Takahiro Nakamura, Tsutomu Inatomi, John Bush, Munetoyo Toda, Michio Hagiya, Isao Yokota, Satoshi Teramukai, Chie Sotozono, Junji Hamuro
Journal: New England Journal of Medicine (2018)

Corneal endothelial cell (CEC) disorders, such as Fuchs's endothelial corneal dystrophy, induce abnormal corneal hydration and result in corneal haziness and vision loss known as bullous keratopathy. We investigated whether injection of cultured human CECs supplemented with a rho-associated protein kinase (ROCK) inhibitor into the anterior chamber could increase CEC density.We performed an uncontrolled, single-group study involving 11 persons who had received a diagnosis of bullous keratopathy and had no detectable CECs. Human CECs were cultured from a donor cornea; a total of 1×106 passaged cells were supplemented with a ROCK inhibitor (final volume, 300 μl) and injected into the anterior chamber of the eye that was selected for treatment. After the procedure, patients were placed in a prone position for 3 hours. The primary outcome was restoration of corneal transparency, with a CEC density of more than 500 cells per square millimeter at the central cornea at 24 weeks after cell injection. Secondary outcomes were a corneal thickness of less than 630 μm and an improvement in best corrected visual acuity equivalent to two lines or more on a Landolt C eye chart at 24 weeks after cell injection.At 24 weeks after cell injection, we recorded a CEC density of more than 500 cells per square millimeter (range, 947 to 2833) in 11 of the 11 treated eyes (100%; 95% confidence interval [CI], 72 to 100), of which 10 had a CEC density exceeding 1000 cells per square millimeter. A corneal thickness of less than 630 μm (range, 489 to 640) was attained in 10 of the 11 treated eyes (91%; 95% CI, 59 to 100), and an improvement in best corrected visual acuity of two lines or more was recorded in 9 of the 11 treated eyes (82%; 95% CI, 48 to 98).Injection of human CECs supplemented with a ROCK inhibitor was followed by an increase in CEC density after 24 weeks in 11 persons with bullous keratopathy. (Funded by the Japan Agency for Medical Research and Development and others; UMIN number, UMIN000012534 .).
A 30-Year-Old Man With Recurrent Dyspnea and Palpitations
Authors: Paurush Ambesh, Shiv Raj, Chukwudi Obiagwu
Journal: JAMA Cardiology (2018)

A 30-year-old man presented for evaluation of palpitations and exertional dyspnea when climbing stairs, mostly at night. The electrocardiogram showed sinus rhythm and early repolarization changes. What would you do next?
Reply to Hou <i>et al</i>.: Can Magnetic Resonance Imaging Effectively Evaluate the Prognosis of Patients with Pulmonary Arterial Hypertension?
Authors: Andrew J. Swift, Jim M. Wild, David G Kiely
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

imaging parameters and clinical data could effectively predict the outcome of patients with pulmonary arterial hypertension.Dr. Swift and colleagues (1) incorporated demographic, magnetic resonance imaging, and right heart catheterization data into univariate analysis; however, some well-known potential risk factors were ignored, such as pulmonary function test, echocardiogram, and the level of brain natriuretic peptide (2).It is well known that an accurate prognostic model should incorporate risk factors as much as possible.It is quite possible that if some new variables were entered into the multivariate analysis, the prognostic model may also contain different variables.
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for nonresectable peritoneal carcinomatosis from gastric cancer.
Authors: Mohammad Alyami, Pierre Emmanuel Bonnot, Laurent Villeneuve, Naoual Bakrin, Olivier Glehen
Journal: Journal of Clinical Oncology (2018)

149 Background: PIPAC is a recent approach for intraperitoneal chemotherapy with promising results for patients with peritoneal carcinomatosis (PC). We aimed to evaluate survival and postoperative outcome of PIPAC in patients with non-resectable PC from gastric cancer. Methods: This is a retrospective analysis. Sixty-nine PIPAC were applied in 22 consecutive patients pretreated non-resectable PC from gastric cancer. All patients had undergone previous lines of systemic chemotherapy (median, two lines). Cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 were given for 30 min at 37 °C and 12 mmHg at 6-week intervals.The treatment schedule proposed alternating 2 systemic chemotherapy followed by 1 PIPAC cycles. Outcome criteria were survival, adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Results: At the time of the first PIPAC, the median PCI was 18 (1-35). Median consecutive PIPAC cycles were 4 (1-9). Survival time was 19.5 months. Major complications (CTCAE - III, IV) occurred for 6 PIPAC (8.7%) and 1 (4.5%) patients died within 30 days of the PIPAC procedure a cause related to aspiration pneumonia during the general anesthesia. Systemic chemotherapy was associated with PIPAC and could be administered after PIPAC with a median delay of 14 days (7-28). Conclusions: PIPAC with low-dose cisplatin and doxorubicin was safe and feasible in association with systemic chemotherapy. Survival data are encouraging and justify further clinical studies in this indication.
Comparative Safety of Sulfonylureas and the Risk of Sudden Cardiac Arrest and Ventricular Arrhythmia
Authors: Charles E. Leonard, Colleen M. Brensinger, Christina L. Aquilante, Warren B. Bilker, Denise M. Boudreau, Rajat Deo, James H. Flory, Joshua J. Gagne, Margaret J. Mangaali, Sean Hennessy
Journal: Diabetes Care (2018)

OBJECTIVE To examine the association between individual antidiabetic sulfonylureas and outpatient-originating sudden cardiac arrest and ventricular arrhythmia (SCA/VA). RESEARCH DESIGN AND METHODS We conducted a retrospective cohort study using 1999–2010 U.S. Medicaid claims from five large states. Exposures were determined by incident use of glyburide, glimepiride, or glipizide. Glipizide served as the reference exposure, as its effects are believed to be highly pancreas specific. Outcomes were ascertained by a validated ICD-9–based algorithm indicative of SCA/VA (positive predictive value ∼85%). Potential confounding was addressed by adjustment for multinomial high-dimensional propensity scores included as continuous variables in a Cox proportional hazards model. RESULTS Of sulfonylurea users under study (N = 519,272), 60.3% were female and 34.9% non-Hispanic Caucasian, and the median age was 58.0 years. In 176,889 person-years of sulfonylurea exposure, we identified 632 SCA/VA events (50.5% were immediately fatal) for a crude incidence rate of 3.6 per 1,000 person-years. Compared with glipizide, propensity score-adjusted hazard ratios for SCA/VA were 0.82 (95% CI 0.69–0.98) for glyburide and 1.10 (0.89–1.36) for glimepiride. Numerous secondary analyses showed a very similar effect estimate for glyburide; yet, not all CIs excluded the null. CONCLUSIONS Glyburide may be associated with a lower risk of SCA/VA than glipizide, consistent with a very small clinical trial suggesting that glyburide may reduce ventricular tachycardia and isolated ventricular premature complexes. This potential benefit must be contextualized by considering putative effects of different sulfonylureas on other cardiovascular end points, cerebrovascular end points, all-cause death, and hypoglycemia.
Effects of a 6-month moderate-intensity exercise program on metabolic parameters and bone mineral density in men on androgen deprivation therapy for prostate cancer.
Authors: Shabbir M.H. Alibhai, Sara Durbano, Meagan O'Neill, Daniel Santa Mina, Paul Ritvo, Catherine Sabiston, Murray Dale Krahn, George A. Tomlinson, Andrew Matthew, Padraig Richard Warde, Narhari Timilshina, Roanne Segal, S. Nicole Culos-Reed
Journal: Journal of Clinical Oncology (2018)

237 Background: Androgen deprivation therapy (ADT) is commonly used to treat prostate cancer (PC) but is associated with significant side effects including metabolic abnormalities and bone loss. Although multiple trials have demonstrated that exercise is associated with improvements in multiple side effects of ADT, its effects on metabolic and skeletal outcomes is unclear. We conducted a phase II randomized controlled trial (RCT) comparing three different exercise delivery models. The present analysis examined prespecified endpoints of change in metabolic parameters and bone mineral density. Methods: Men with stage TxNxMx PC starting or continuing ADT for at least 6 months were enrolled and randomized equally to personal training (n = 18), supervised group training (n = 14), or home-based training (n = 16). Participants in all intervention arms underwent moderate to vigorous physical activity with a target of 150 minutes per week for 6 months. Fasting blood work and dual x-ray absorptiometry (DXA) were done at baseline and 6 months (blood work) and 12 months (DXA). Paired t-tests and ANCOVA were used to analyze findings. Results: 48 participants (mean age 69.9 years) were enrolled. The primary analysis demonstrated no significant difference between arms on most quality of life and fitness outcomes so groups were combined for the present analysis. Exercise was not associated with statistically significant changes in hemoglobin, total cholesterol, low density lipoprotein, high density lipoprotein, triglycerides, or fasting blood glucose (p = 0.075 to 0.87). Similarly, exercise was not associated with changes in bone mineral density at lumbar spine, total hip, or femoral neck sites on DXA (p = 0.44 to 0.71). Mean weight change was +0.8 kg. There was no difference between exercise arms on any outcome. Conclusions: Although our study is limited by a small sample size, our results suggest that 6 months of moderate intensity exercise is not associated with improvements in either metabolic or skeletal outcomes in men on ADT. More intensive behavioural interventions and/or pharmacological interventions will be required to reverse the deleterious effects of ADT. Clinical trial information: NCT02046837.
Gene expression profile of genes-related canceration, invasion, or conversion for metastasis in patients with poorly differentiated adenocarcinoma treated by gastric ESD.
Authors: Natsuko Kawanishi, Mizutomo Azuma, Atsuko Takeuchi, Sakiko Yamane, Akinori Watanabe, Takuya Wada, Kenji Ishido, Takafumi Yano, Chikatoshi Katada, Satoshi Tanabe, Tsutomu Yoshida, Wasaburo Koizumi
Journal: Journal of Clinical Oncology (2018)

78 Background: We encounter some cases of early gastric cancer treated by endoscopic submucosal dissection (ESD) that are out of the indication criteria after pathologic diagnosis. These cases require additional treatments because of a risk of lymph node metastasis in Japanese Classification. So further prediction factors associated with lymph node metastasis is expected. We are focusing on poorly differentiated adenocarcinomas in early gastric cancer that we treated by ESD and used these tissues to characterize their gene expression profiles related to canceration, invasion or conversion for metastasis. Methods: We examined two cases of intramucosal carcinoma and three of submucosal infiltrating carcinoma histologically diagnosed as poorly differentiated adenocarcinoma after ESD. Those samples are separated five adjacent normal tissues (N), five tumor tissues in mucosal layer (M) and three tumor tissues in submucosal layer (SM) in total 13 lesions. Formalin-fixed, paraffin-embedded tissues were dissected by the laser-captured microdissection technique and were analyzed for targeted 158 gene expressions using a quantitative real-time polymerase chain reaction (PCR) using commercial PCR plate (profile PCR array of genes related to cancer stem cells and epithelial mesenchymal transition). Results: Among genes that elevated in the cancer tissues (M or SM) against the normal tissues, five gene expressions (DKK1, TIMP1, THY1, FN1, COL1A2) were tended to much higher in the submucosal layer compared to the mucosal layer (N &lt; M &lt; SM). When we compared tumor gene expressions in depth of M, three gene expressions (FZD7, ZEB 2, CD 44) are higher in the tumors with submucosal invasion compared to within mucosal layer. Conclusions: Poorly differentiated adenocarcinoma of stomach had high expression level in cancer-related genes even if it was intramucosal tumor. Some of these genes tended to increase as its depth of invasion and the presence of invasion of the SM. It suggested that the biopsy specimen could be a prediction factor of invasion from the surface of gastric cancer, but additional specimens and analysis are necessary to prove these findings.
New contract may adversely affect trainees’ finances, says RCGP
Authors: Abi Rimmer
Journal: BMJ (2015)

Maureen Baker, chair of the Royal College of General Practitioners, has said that she was “very concerned” about GP trainees being financially disadvantaged by the new junior doctor contract.

Speaking at the college’s annual conference in Glasgow on Thursday 1 October, Baker said, “I have been very concerned about the possibility of GP trainees being financially disadvantaged as part of the ongoing discussions about the junior doctors’ contract.”

Her comments, which received a round of applause from the audience, referred to a recommendation made by the Review Body on Doctors’ and Dentists’ …
GMC to be more proactive in regulation
Authors: Caroline White
Journal: BMJ (2012)

The UK General Medical Council has signalled that it will be more proactive in regulating doctors than it has been to date.

At a meeting of the House of Commons health select committee earlier this month, which was convened to scrutinise the regulator’s progress over the past year, the GMC’s chief executive, Niall Dickson, told MPs that the GMC planned to examine certain problem before formal concerns arose.

Speaking about concerns that doctors had …
Application of <i>in vivo</i> reflectance confocal microscopy and <i>ex vivo</i> fluorescence confocal microscopy in the most common subtypes of basal cell carcinoma and correlation with histopathology
Authors: A. Villarreal-Martinez, A. Bennàssar, S. Gonzalez, J. Malvehy, S. Puig
Journal: British Journal of Dermatology (2018)
I'm starting a GP vocational training scheme in August. I opted for a flexible training post when I applied, but now I want to go for full time training. How do I go about it?
Authors: Bill Irish
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>