tbuckley/cabot-search huggingface dataset:
Juniors demand clarity over part time pay under new contract
Authors: Abi Rimmer
Journal: BMJ (2016)

Junior doctors have called for clarity on how less than full time (LTFT) trainees will be paid under the proposed new contract amid concerns about weekend pay for these doctors.

On Friday 27 May NHS Employers published the full terms and conditions of service for NHS doctors and dentists in training in England.1 On the same day the Department of Health published an equalities statement for the proposed new contract.2

The equalities statement highlighted changes that had been made to the contract which were beneficial for LTFT and female trainees. These included accelerated learning, which it said would help trainees who had taken time out of work to catch up with their peers.

But Helen Jawahar, a second year specialty trainee in paediatrics, told …
Renal cell carcinoma (RCC) primary tumor shrinkage on vascular endothelial growth factor (VEGF)-targeted therapy (TT): A pooled analysis.
Authors: Dominick Bosse, Xun Lin, Ronit Simantov, Aly-Khan A. Lalani, Ithaar Derweesh, Steven Lee Chang, Toni K. Choueiri, Rana R. McKay
Journal: Journal of Clinical Oncology (2018)

629 Background: Cytoreductive nephrectomy (CRN) is an important treatment modality in patients (pts) with advanced RCC, however the role and timing in the context of VEGF-TT remains under investigation. The aim of this study is to determine the efficacy of VEGF-TT to induce primary tumor shrinkage in advanced RCC. Methods: We conducted a pooled analysis of 12 Pfizer-sponsored trials in pts with metastatic RCC treated with sunitinib, sorafenib, axitinib, bevacizumab, termsirolimus or interferon-α. Primary endpoint was the primary tumor objective response rate (ORR) by RECIST in pts who have not undergone prior nephrectomy. Kaplan-Meier method was used to estimate median overall survival (OS) of responders (PR or CR) v. non-responders. Cox regression adjusting for demographics, histology type, prior therapy, metastasis sites, IMDC risk factors and neutrophil-to-lymphocyte ratio was used to compare OS between pts with and without primary tumor ORR. Results: 565 (12%) out of 4736 pts included had their primary tumors intact, of which 360 (8%) received VEGF-TT. In pts with primary tumor intact, 87% had clear-cell RCC and IMDC risk group were 4% favourable, 33% intermediate, 39% poor, 24% unknown. 35% had bone metastasis and 32% had liver metastases. 65% had ECOG performance status ≥1. Compared to pts with prior nephrectomy, primary tumor intact pts were more likely to have bone or liver metastases or to be IMDC poor risk. Primary tumor ORR was 17% (95% exact CI, 14, 20) in all pts, 19% (95% exact CI, 16, 23) in first line treated pts and 23% (95% Exact CI, 19, 28) in pts treated with VEGF-TT (any line). Primary tumor ORR was 20% (95% exact CI, 15, 26) in IMDC intermediate risk pts and 9% (95% exact CI, 5 – 13) in the poor risk. No pts had PD as best response in their primary tumor at the time they stopped systemic therapy. Median OS was 33.98 months in pts with primary tumor ORR and 9.8 months in pts without ORR, adjusted HR 0.42 [95%CI, 0.28, 0.6; p &lt; 0.0001]. Conclusions: VEGF-TT resulted in primary tumor shrinkage in 23% of pts with IMDC intermediate and poor risk advanced RCC who have not undergone CRN. VEGF-TT may potentially facilitate future CRN in select pts. Trials assessing the utility of CRN are underway.
Abstract P5-22-05: Evaluation of simplified lymphatic microsurgical preventing healing approach (SLYMPHA) for the prevention of breast cancer-related clinical lymphedema after axillary lymph node dissection
Authors: T Ozmen, M Lazaro, Y Zhou, A Vinyard, E Avisar
Journal: Cancer Research (2018)

Abstract Background: Lymphedema (LE) is a serious complication of axillary lymph node dissection (ALND) with an incidence rate of 16%. Lymphatic Microsurgical Preventing Healing Approach (LYMPHA) has been proposed as an effective adjunct to ALND for the prevention of LE. This procedure however requires microsurgical techniques. The aim of this study was to assess the efficiency of Simplified-LYMPHA (SLYMPHA) in preventing LE in a prospective cohort of patients. Methods: All patients, undergoing ALND with or without SLYMPHA between January 2014 and December 2016 were included in the study. SLYMPHA is a slightly modified and simplified version of LYMPHA. It is performed by the operating surgeon performing the ALND. One or more lymphatic channels identified by reverse arm mapping are inserted using a sleeve technique into the cut end of a neighboring vein. During follow-up visits, tape-measuring limb circumference method was used to detect clinical LE. Demographic, clinical, surgical and pathologic factors were recorded. The incidence of clinical LE was compared between ALND with and without SLYMPHA. Univariate and multivariate analysis were used to assess the role of other factors in the appearance of clinical LE. Results: 406 patients were included in the study. SLYMPHA procedure was attempted in 81 patients and was completed successfully in 90% of patients. Early complication rates were similar between patients who underwent SLYMPHA and who did not (4% vs. 4.13%; p = 0.948). Median follow-up time was 15±13.73 [1-32] months. Patients, who underwent SLYMPHA, had a significantly lower rate of clinical LE both in univariate and multivariate analysis (3% vs 19%; p = 0.001; OR 0.12 [0.03-0.5]). Excising &amp;gt; 22 lymph nodes and a co-diagnosis of diabetes were also correlated with higher clinical LE rates on univariate analysis, but only excising &amp;gt; 22 lymph nodes remained to be significant on multivariate analysis. Conclusions: SLYMPHA is a safe and relatively simple method, which decreases incidence of clinical LE dramatically. It should be considered as an adjunct procedure to ALND for all patients during initial surgery. Citation Format: Ozmen T, Lazaro M, Zhou Y, Vinyard A, Avisar E. Evaluation of simplified lymphatic microsurgical preventing healing approach (SLYMPHA) for the prevention of breast cancer-related clinical lymphedema after axillary lymph node dissection [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 P5-22-05.
SYSTEMATIC REVIEW OF PREVALENT AND INCIDENT HEART FAILURE IN CARDIOVASCULAR OUTCOME TRIALS OF PATIENTS WITH TYPE 2 DIABETES
Authors: Stephen Greene, Muthiah Vaduganathan, Muhammad Khan, George Bakris, Matthew Weir, Jonathan Seltzer, Naveed Sattar, Darren McGuire, James Januzzi, Norman Stockbridge, Javed Butler
Journal: Journal of the American College of Cardiology (2018)
Houston Consensus Conference on Testing for Helicobacter pylori Infection in the United States
Authors: Hashem B. El-Serag, John Y. Kao, Fasiha Kanwal, Mark Gilger, Frank LoVecchio, Steven F. Moss, Sheila Crowe, Adam Elfant, Thomas Haas, Ronald J. Hapke, David Y. Graham
Journal: Clinical Gastroenterology and Hepatology (2018)
CT MYOCARDIAL PERFUSION IMAGING FAILS TO IMPROVE DIAGNOSTIC ACCURACY OF CT CORONARY ANGIOGRAPHY TO DETERMINE STENT PATENCY
Authors: Armin Arbab-Zadeh, Richard George, Julie Miller, John Texter, Gustavo Godoy, Mohammad Ostovaneh, Andrea Vavere, Marc Dewey, Carlos Rochitte, Hiroyuki Niinuma, Marcus Chen, Matthew Matheson, Klaus Kofoed, Melvin Clouse, Christopher Cox, Joao Lima, Jeffrey Brinker, Roger Laham
Journal: Journal of the American College of Cardiology (2018)
Gut Microbiota Signature in Heart Failure Defined From Profiling of 2 Independent Cohorts
Authors: Martin Kummen, Cristiane C.K. Mayerhofer, Beate Vestad, Kaspar Broch, Ayodeji Awoyemi, Christopher Storm-Larsen, Thor Ueland, Arne Yndestad, Johannes R. Hov, Marius Trøseid
Journal: Journal of the American College of Cardiology (2018)
A CLINICALLY USEFUL MODEL TO PREDICT 90-DAY READMISSION RISK AFTER HOSPITALIZATION FOR ACUTE MYOCARDIAL INFARCTION
Authors: Vinay Kini, Pamela Peterson, John Spertus, Kevin Kennedy, Jason Wasfy, Suzanne Arnold, Steven Bradley, Michael Ho, Jeptha Curtis, Amit Amin, Frederick A. Masoudi
Journal: Journal of the American College of Cardiology (2018)
Efficacy and Safety of First-line Avelumab Treatment in Patients With Stage IV Metastatic Merkel Cell Carcinoma
Authors: Sandra P. D’Angelo, Jeffery Russell, Céleste Lebbé, Bartosz Chmielowski, Thilo Gambichler, Jean-Jacques Grob, Felix Kiecker, Guilherme Rabinowits, Patrick Terheyden, Isabella Zwiener, Marcis Bajars, Meliessa Hennessy, Howard L. Kaufman
Journal: JAMA Oncology (2018)

Merkel cell carcinoma (MCC) is an aggressive skin cancer that is associated with poor survival outcomes in patients with distant metastatic disease. Results of part A of the JAVELIN Merkel 200 trial (avelumab in patients with Merkel cell carcinoma) showed that avelumab, an anti-programmed cell death ligand 1 (PD-L1) antibody, demonstrated efficacy in second-line or later treatment of patients with metastatic MCC (mMCC).
THE DIFFERENT EFFECTS OF STATIN AND EZETIMIBE COMBINATION ON CORONARY ATHEROMA PLAQUE IN PATIENTS WITH AND WITHOUT DIABETES MELLITUS: SUB-ANALYSIS OF PRECISE-IVUS TRIAL
Authors: Koichiro Fujisue, Suguru Nagamatsu, Seigo Sugiyama, Hitoshi Sumida, Hideki Shimomura, Takuro Yamashita, Kenji Sakamoto, Koichi Nakao, Sunao Nakamura, Masaharu Ishihara, Kunihiko Matsui, Naritsugu Sakaino, Natsuki Nakamura, Nobuyasu Yamamoto, Shunichi Koide, Toshiyuki Matsumura, Kazuteru Fujimoto, Ryusuke Tsunoda, Yasuhiro Morikami, Koushi Matsuyama, Shuichi Oshima, Koichi Kaikita, Seiji Hokimoto, Hisao Ogawa, Kenichi Tsujita
Journal: Journal of the American College of Cardiology (2018)
Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma
Authors: Robert J. Motzer, Nizar M. Tannir, David F. McDermott, Osvaldo Arén Frontera, Bohuslav Melichar, Toni K. Choueiri, Elizabeth R. Plimack, Philippe Barthélémy, Camillo Porta, Saby George, Thomas Powles, Frede Donskov, Victoria Neiman, Christian K. Kollmannsberger, Pamela Salman, Howard Gurney, Robert Hawkins, Alain Ravaud, Marc-Oliver Grimm, Sergio Bracarda, Carlos H. Barrios, Yoshihiko Tomita, Daniel Castellano, Brian I. Rini, Allen C. Chen, Sabeen Mekan, M. Brent McHenry, Megan Wind-Rotolo, Justin Doan, Padmanee Sharma, Hans J. Hammers, Bernard Escudier
Journal: New England Journal of Medicine (2018)

Nivolumab plus ipilimumab produced objective responses in patients with advanced renal-cell carcinoma in a pilot study. This phase 3 trial compared nivolumab plus ipilimumab with sunitinib for previously untreated clear-cell advanced renal-cell carcinoma.
Revised cytogenetic risk stratification in primary myelofibrosis: analysis based on 1002 informative patients
Authors: Ayalew Tefferi, Maura Nicolosi, Mythri Mudireddy, Terra L. Lasho, Naseema Gangat, Kebede H. Begna, Curtis A. Hanson, Rhett P. Ketterling, Animesh Pardanani
Journal: Leukemia (2018)

Current cytogenetic risk stratification in primary myelofibrosis (PMF) is two-tiered: ‘favorable’ and ‘unfavorable’. Recent studies have suggested prognostic heterogeneity within the unfavorable risk category. In 1002 consecutive patients, we performed stepwise analysis of impact on survival from individual and prognostically ordered cytogenetic abnormalities, leading to a revised three-tiered risk model: ‘very high risk (VHR)’—single/multiple abnormalities of −7, i(17q), inv(3)/3q21, 12p−/12p11.2, 11q−/11q23, or other autosomal trisomies not including + 8/ + 9 (e.g., +21, +19); ‘favorable’—normal karyotype or sole abnormalities of 13q−, +9, 20q−, chromosome 1 translocation/duplication or sex chromosome abnormality including -Y; ‘unfavorable’—all other abnormalities. Median survivals for VHR (n = 75), unfavorable (n = 190) and favorable (n = 737) risk categories were 1.2 (HR 3.8, 95% CI 2.9–4.9), 2.9 (HR 1.7, 95% CI 1.4–2.0) and 4.4 years and survival impact was independent of clinically derived prognostic systems, driver and ASXL1/SRSF2 mutations. The revised model was also effective in predicting leukemic transformation: HRs (95% CI) were 4.4 (2.0–9.4) for VHR and 2.0 (1.2–3.4) for unfavorable. The impact of driver mutations on survival was confined to favorable and that of ASXL1/SRSF2 mutations to favorable/unfavorable cytogenetic risk categories. The current study clarifies the prognostic hierarchy of genetic risk factors in PMF and provides a more refined three-tiered cytogenetic risk model.
Stretch-induced compliance: a novel adaptive biological mechanism following acute cardiac load
Authors: André M Leite-Moreira, João Almeida-Coelho, João S Neves, Ana L Pires, João Ferreira-Martins, Ricardo Castro-Ferreira, Ricardo Ladeiras-Lopes, Glória Conceição, Daniela Miranda-Silva, Patrícia Rodrigues, Nazha Hamdani, Melissa Herwig, Inês Falcão-Pires, Walter J Paulus, Wolfgang A Linke, André P Lourenço, Adelino F Leite-Moreira
Journal: Cardiovascular Research (2018)

The heart is constantly challenged with acute bouts of stretching or overload. Systolic adaptations to these challenges are known but adaptations in diastolic stiffness remain unknown. We evaluated adaptations in myocardial stiffness due to acute stretching and characterized the underlying mechanisms.Left ventricles (LVs) of intact rat hearts, rabbit papillary muscles and myocardial strips from cardiac surgery patients were stretched. After stretching, there was a sustained >40% decrease in end-diastolic pressure (EDP) or passive tension (PT) for 15 min in all species and experimental preparations. Stretching by volume loading in volunteers and cardiac surgery patients resulted in E/E' and EDP decreases, respectively, after sustained stretching. Stretched samples had increased myocardial cGMP levels, increased phosphorylated vasodilator-stimulated phosphoprotein phosphorylation, as well as, increased titin phosphorylation, which was reduced by prior protein kinase G (PKG) inhibition (PKGi). Skinned cardiomyocytes from stretched and non-stretched myocardia were studied. Skinned cardiomyocytes from stretched hearts showed decreased PT, which was abrogated by protein phosphatase incubation; whereas those from non-stretched hearts decreased PT after PKG incubation. Pharmacological studies assessed the role of nitric oxide (NO) and natriuretic peptides (NPs). PT decay after stretching was significantly reduced by combined NP antagonism, NO synthase inhibition and NO scavenging, or by PKGi. Response to stretching was remarkably reduced in a rat model of LV hypertrophy, which also failed to increase titin phosphorylation.We describe and translate to human physiology a novel adaptive mechanism, partly mediated by titin phosphorylation through cGMP-PKG signalling, whereby myocardial compliance increases in response to acute stretching. This mechanism may not function in the hypertrophic heart.
Getting what you want
Authors: Gayathri Rabindra
Journal: BMJ (2007)

<h3>Abstract</h3> Cell movement propels embryonic tissues to acquire shapes required for mature function. The movements are driven both by acto-myosin signaling and by cells interacting with the extracellular matrix (ECM). Unknown is whether cell-cell interactions within a tissue are also required, and the molecular mechanisms by which such communication might occur. Here, we use the developing visual system of zebrafish as a model to understand the role cell-cell communication plays in tissue morphogenesis in the embryonic nervous system. We identify that cell-cell-mediated contact between two distinct cell populations, progenitors of the neural retina and retinal pigment epithelium (RPE), facilitates epithelial flow to produce the mature cupped retina. We identify for the first time the need in eye morphogenesis for distinct populations of progenitors to interact, and suggest a novel role for a member of a key developmental signaling family, the transmembrane Semaphorin6d, as mediating communication between distinct cell types to control tissue morphogenesis.
ASSESSMENT OF RISK FACTORS FOR THE PROGRESSION OF CORONARY ARTERY CALCIFICATION IN ASYMPTOMATIC SUBJECTS: RESULTS FROM THE KOREA INITIATIVES ON CORONARY ARTERY CALCIFICATION (KOICA) REGISTRY
Authors: Ji Hyun Lee, Kisang Yoo, David Sung, Donghee Han, Hyeonju Jung, Hyo Eun Park, Su-Yeon Choi, Eun Ju Chun, Jidong Sung, Sung Hak Park, Hae-Won Han, Ji Min Sung, Hyuk-Jae Chang
Journal: Journal of the American College of Cardiology (2018)
ATRIAL FIBRILLATION PREDICTS LONG-TERM OUTCOMES AFTER PERCUTANEOUS CORONARY INTERVENTION IN PATIENTS WITH CORONARY ARTERY DISEASE
Authors: Yasuhiro Matsuda, Takayuki Ishihara, Osamu Iida, Mitsutoshi Asai, Masaharu Masuda, Shin Okamoto, Kiyonori Nanto, Takashi Kanda, Takuya Tsujimura, Shota Okuno, Takuya Ohashi, Hiroyuki Kawai, Aki Tsuji, Yosuke Hata, Hiroyuki Uematsu, Yuki Sato, Toshiaki Mano
Journal: Journal of the American College of Cardiology (2018)
I am currently a GP working in Malaysia and recently got a degree in business administration (MBA). What opportunities are there for me in the non-medical sector?
Authors: Rodger Charlton
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>
Comparison of Surgical and Medical Therapy for Type 2 Diabetes in Severely Obese Adolescents
Authors: Thomas H. Inge, Lori M. Laffel, Todd M. Jenkins, Marsha D. Marcus, Natasha I. Leibel, Mary L. Brandt, Morey Haymond, Elaine M. Urbina, Lawrence M. Dolan, Philip S. Zeitler
Journal: JAMA Pediatrics (2018)

Because of the substantial increase in the occurrence of type 2 diabetes in the pediatric population and the medical complications of this condition, therapies are urgently needed that will achieve better glycemic control than standard medical management.To compare glycemic control in cohorts of severely obese adolescents with type 2 diabetes undergoing medical and surgical interventions.A secondary analysis of data collected by the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) and Treatment Options of Type 2 Diabetes in Adolescents and Youth (TODAY) consortia was performed. Teen-LABS enrolled 242 adolescents (≤19 years of age) from March 1, 2007, through December 31, 2011. TODAY randomized 699 participants (aged 10-17 years) from July 24, 2004, through February 25, 2009. Data analysis was performed from July 6, 2015, to June 24, 2017. Anthropometric, clinical, and laboratory data from adolescents with severe obesity and type 2 diabetes who underwent treatment with metabolic or bariatric surgery in the Teen-LABS study or medical therapy in the TODAY study were compared.Teen-LABS participants underwent a primary bariatric surgical procedure; TODAY participants were randomized to receive metformin therapy alone or in combination with rosiglitazone or an intensive lifestyle intervention; insulin therapy was given in cases of progression of disease.Glycemic control, body mass index, prevalence of elevated blood pressure, dyslipidemia, abnormal kidney function, and clinical adverse events were measured.Data from 30 participants from Teen-LABS (mean [SD] age at baseline, 16.9 [1.3] years; 21 [70%] female; 18 [66%] white) and 63 from TODAY (mean [SD] age at baseline, 15.3 [1.3] years; 28 [44%] female; 45 [71%] white) were analyzed. During 2 years, mean hemoglobin A1c concentration decreased from 6.8% (95% CI, 6.4%-7.3%) to 5.5% (95% CI, 4.7% -6.3%) in Teen-LABS and increased from 6.4% (95% CI, 6.1%-6.7%) to 7.8% (95% CI, 7.2%-8.3%) in TODAY. Compared with baseline, the body mass index decreased by 29% (95% CI, 24%-34%) in Teen-LABS and increased by 3.7% (95% CI, 0.8%-6.7%) in TODAY. Twenty-three percent of Teen-LABS participants required a subsequent operation during the 2-year follow-up.Compared with medical therapy, surgical treatment of severely obese adolescents with type 2 diabetes was associated with better glycemic control, reduced weight, and improvement of other comorbidities. These data support the need for a well-designed, prospective controlled study to define the role of surgery for adolescents with type 2 diabetes, including health and surgical outcomes.
Von Willebrand factor for the liver: Friend or foe?
Authors: Qing Pang, Huichun Liu, Hao Jin, Lei Zhou, Zhongran Man
Journal: Hepatology (2018)

Potential conflict of interest: Nothing to report. Author names in bold designate shared co‐first authorship. In the recent publication, Starlinger et al.1 demonstrated that von Willebrand factor (vWF) was involved in platelet‐mediated liver regeneration (LR) following partial hepatectomy. In recent years, increasing evidence indicates that vWF plays critical roles in various hepatic pathophysiological processes. These findings make vWF both friend and foe for the liver. Many studies have reported the promotion of vWF in the progression of virus hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). In patients with chronic hepatitis, plasma level of vWF‐Ag is significantly higher compared to the healthy population and vWF‐Ag level is increasing with stage of fibrosis. Furthermore, a higher level of vWF‐Ag can independently predict ascites, variceal bleeding, and mortality in patients with cirrhosis.2 Moreover, Liu et al.3 highlighted that vWF was positively correlated with the tumor grade and tumor node metastasis stage in HCC. In addition, vWF promoted the invasion and migration of HCC cells in vitro.3 Despite its adverse role in HCC progress, there is growing evidence from experimental and clinical studies indicating that VWF can prevent tumor dissemination.4 The protective role of VWF against metastasis is mainly attributed to its antiangiogenic potential and proapoptotic properties.4 In addition, vWF may also play a protective role in acute liver injury (ALI). Sun et al.5 recently established the animal model of ALI in mice by the intraperitoneal injection of carbon tetrachloride. They found that vWF deficiency was associated with more severe liver injury.5 Furthermore, vWF deficiency was shown to facilitate the activation of the mitogen‐activated protein kinase signaling pathway in injured liver tissues. In conclusion, vWF can produce both protective and detrimental effects in the pathophysiological process of the liver. On the one hand, it may promote LR, relieve ALI, and inhabit metastasis. On the other hand, it is involved in the disease progression of liver cirrhosis and HCC. Therefore, further work should be encouraged so that vWF‐modulating drugs can find a place in the liver diseases.