tbuckley/cabot-search huggingface dataset:
Association of radiomics and outcome in esophageal cancer following neoadjuvant chemo-radiation.
Authors: India Eaford, Anupam Rishi, Geoffrey Zhang, Alexander Viera, Kujtim Latifi, Jessica M. Frakes, Jose Mario Pimiento, Jacques-Pierre Fontaine, Sarah E. Hoffe
Journal: Journal of Clinical Oncology (2018)

146 Background: Radiomic data extraction from medical images has the potential to differentiate tumor phenotypes. We investigated the potential of esophageal cancer radiomic features to differentiate clinical outcomes following neoadjuvant chemoradiation (NACRT). Methods: We retrospectively reviewed 68 biopsy-proven mid-distal esophageal/gastroesophageal junction (GEJ) cancer patients treated from 2007-2014 with NACRT followed by esophagectomy on an IRB approved study in which patients were eligible if imaging was performed at our institution. The primary tumor was segmented on baseline computed tomography (CT) and 18-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) scans with contour review by two independent radiation oncologists. A total of 126 quantitative 3-D shape and intensity-based radiomics features were extracted using in-house data algorithm software. Locoregional control (LRC), metastasis free survival (DFS), metastasis free survival (MFS) and overall survival (OS) were estimated by Kaplan-Meier analysis and multivariate Cox proportion hazard. Results: Estimated actuarial 5-year RFS, LRC, MFS, OS was 56.6% (mean: 67.8 months, 95% CI 53.7-81.8 months), 83.1% (mean: 92.8 months, 95% CI 81.4-104.2 months), 64.9% (mean: 76.4 months, 95% CI 62.2-90.7 months), 39.5% (median survival 40 months, 95% CI 24.59-55.40), respectively. Pathological complete response (pCR) was achieved in 34 (50%) patients. Tumor Regression Grade (TRG) 0-1 indicative of complete response was associated with improved LRC [p = 0.04; Hazard Ratio (HR) 4.24 (1.01-19.01)]. On univariate analysis, 16 PET-based and 14 CT-based radiomics features were found to independently predict pCR. On multivariate analysis (MVA), three PET-CT based radiomic features [sphericity (p = 0.04), compactness (p = .05) and PET_TGV (p = 0.08)] were found to closely predict pCR. When grouped by median, PET sphericity independently predicted RFS [p = 0.014; Hazard Ratio (HR) 0.31 95% Confidence Interval (CI) 0.11-0.83]. Conclusions: This study suggests pre-treatment radiomic features in esophageal cancer may be prognostic for response assessment (pCR) and overall outcome following NACRT.
Doctors make the best managers, US study concludes
Authors: Zosia Kmietowicz
Journal: BMJ (2011)

Hospitals run by doctors outperform those run by managers, a study of 300 of the best hospitals in the United States has found ( Social Science and Medicine 2011, doi:10.1016/j.socscimed.2011.06.025).

A qualified doctor was the chief executive in 51 of the top 100 cancer hospitals in the US, 34 of the best 100 hospitals for digestive disorders, and 37 of the top 100 cardiac hospitals. 

Amanda Goodall, a senior research fellow at the Institute for the Study of Labour in Bonn, Germany, looked at the 100 hospitals that performed best in 2009 in each of three specialties—cancer, digestive disorders, and …
Therapeutic effects of 2B8T2M, a novel fusion of ALT-803, an IL-15 superagonist, with 4 single-chains of anti-CD20 antibody in combination with expanded natural killer cells against rituximab sensitive and resistant Burkitt lymphoma (BL).
Authors: Yaya Chu, Nang Kham Su, Sarah Alter, Emily Jeng, Peter R. Rhode, Matthew John Barth, Dean Anthony Lee, Hing C. Wong, Mitchell S. Cairo
Journal: Journal of Clinical Oncology (2018)

32 Background: Patients retreated with rituximab often relapse which limit patient treatment options (Goldman/Cairo, Leukemia, 2013). Our group has successfully expanded functional and active peripheral blood NK cells (exPBNK) to target BL (Chu/Cairo, et al, Can Imm Res, 2015). 2B8T2M was generated by fusing ALT-803, an IL-15 superagonist, to four single-chains of rituximab (Liu/Wong, et al, JBC, 2016). 2B8T2M displayed tri-specific CD20 binding activity, activated NK cells to enhance antibody-dependent cellular cytotoxicity, and induced apoptosis of B-lymphoma cells (Liu/Wong, et al, JBC, 2016). Methods: ALT-803 and 2B8T2M were generously provided by Altor BioScience Corporation. NK expansion, NK receptors expression and cytotoxicity were examined as we previous described (Chu/Cairo, et al, Can Imm Res 2015). IFNg and granzyme B levels were examined by ELISA assays. Equal doses of IgG, Rituximab, ALT-803, Rituximab+ALT-803, obinutuzumab (obinu, generously provided by Christian Klein, PhD from Roche) were used for comparison. Results: 2B8T2M significantly enhanced exPBNK cytotoxicity against rituximab-sensitive Raji cells compared to the controls IgG, Rituximab, ALT-803, Rituximab+ALT-803, obinu (p &lt; 0.001, E:T = 1:1). 2B8T2M also significantly enhanced exPBNK cytotoxicity against rituximab-resistant Raji-2R cells (p &lt; 0.001, E:T = 1:1) and resistant Raji-4RH cells (p &lt; 0.001, E:T = 1:1). Furthermore, 2B8T2M significantly enhanced IFN-g and granzyme B production from exPBNK against Raji, Raji-2R and Raji-4RH compared to IgG (p &lt; 0.001), rituximab (p &lt; 0.001), ALT-803 (p &lt; 0.001), Rituximab+ALT-803 (p &lt; 0.001), and obinutuzumab (p &lt; 0.001). Conclusions: 2B8T2M compared to rituximab, ALT-803 or obinutuzumab significantly enhanced exPBNK in vitro cytotoxicity against rituximab-sensitive and –resistant BL cells. The in vivo functions of 2B8T2M with exPBNK using humanized NSG models are under investigation.
IN VIVO, IN VITRO AND IN SILICO COMPARISON OF TWO DEVICES TO MEASURE FRACTIONAL FLOW RESERVE
Authors: Stephane Carlier, Julien Saussez, Alessandro Scalia, Kamil Chodzynski, Shunji Nishio, Kathleen Thaysse, Philippe Brunner, Karim Zouaoui Boudjeltia
Journal: Journal of the American College of Cardiology (2018)
Quantification of HBV core antibodies may help predict HBV reactivation in patients with lymphoma and resolved HBV infection
Authors: Hung-Chih Yang, Hsiao-Hui Tsou, Sung-Nan Pei, Cheng-Shyong Chang, Jia-Hong Chen, Ming Yao, Shyh-Jer Lin, Johnson Lin, Quan Yuan, Ningshao Xia, Tsang-Wu Liu, Pei-Jer Chen, Ann-Lii Cheng, Chiun Hsu
Journal: Journal of Hepatology (2018)
Telephone referrals from accident and emergency
Authors: Mayank Roy, Delia Parnham-Cope
Journal: BMJ (2005)

Making telephone referrals from A&E can be a daunting process, especially for a complicated case and to specialties where it is difficult to refer. The voice on the other end of the phone might sound much more experienced and knowledgeable than you, but remember that you always have an added advantage—the patient is in front of you. Here are a few tips to help …
ERG3 and ERG11 genes are critical for the pathogenesis of Candida albicans during the oral mucosal infection
Authors: Yujie Zhou, Min Liao, Chengguang Zhu, Yao Hu, Ting Tong, Xian Peng, Mingyun Li, Mingye Feng, Lei Cheng, Biao Ren, Xuedong Zhou
Journal: International Journal of Oral Science (2018)

Abstract The hyphal development of Candida albicans ( C. albicans ) has been considered as an essential virulent factor for host cell damage. However, the missing link between hyphae and virulence of C. albicans is also been discovered. Here, we identified that the null mutants of ERG3 and ERG11 , two key genes in ergosterol biosynthesis pathway, can form typical hyphae but failed to cause the oral mucosal infection in vitro and in vivo for the first time. In particular, the erg3Δ/Δ and erg11Δ/Δ strains co-cultured with epithelial cells significantly reduced the adhesion, damage, and cytokine (interleukin-1α (IL-1α)) production, whereas the invasion was not affected in vitro. Importantly, they were incapable of extensive hyphal invasion, formation of micro-abscesses, and tongue epithelium damage compared to wild type due to the decrease of the colonization and epithelial infection area in a murine oropharyngeal candidiasis model. The fluconazole (FLC), an antifungal targeted at ergosterol biosynthesis, relieved the epithelial infection of C. albicans in vitro and in vivo even under non-growth inhibitory dosage confirming the virulent contribution of ergosterol biosynthesis pathway. The erg3Δ/Δ and erg11Δ/Δ strains were cleared by macrophages similar to wild type, whereas their virulence factors including agglutinin-like sequence 1 (Als1), secreted aspartyl proteinase 6 (Sap6), and hyphal wall protein-1 (Hwp1) were significantly reduced indicated that the non-toxicity might not result from the change on immune tolerance but the defective virulence. The incapacity of erg3Δ/Δ and erg11Δ/Δ in epithelial infection highlights the contribution of ergosterol biosynthesis pathway to C. albicans pathogenesis and fluconazole can not only eliminate the fungal pathogens but also reduced their virulence even at low dosage.
Results of a phase II trial of neoadjuvant abiraterone + prednisone+ enzalutamide + leuprolide (APEL) versus enzalutamide + leuprolide (EL) for patients with high-risk localized prostate cancer (PC) undergoing radical prostatectomy (RP).
Authors: Rana R. McKay, Wanling Xie, Rosina Lis, Huihui Ye, Zhenwei Zhang, Quoc-Dien Trinh, Steven Lee Chang, Lauren Christine Harshman, Ashley Ross, Kenneth J. Pienta, Daniel W. Lin, William J Ellis, Robert B. Montgomery, Peter Chang, Andrew Wagner, Glenn Bubley, Adam S. Kibel, Mary-Ellen Taplin
Journal: Journal of Clinical Oncology (2018)

79 Background: Patients with high-risk PC have an increased risk of recurrence and mortality despite therapy. Abiraterone, a CYP17 inhibitor, and enzalutamide, a next generation anti-androgen, have demonstrated improved overall survival in metastatic PC. In this multicenter randomized phase II trial, we evaluate the impact of second generation hormone therapy on RP pathologic outcomes. Methods: Eligible patients had biopsy Gleason score ≥4+3=7, PSA &gt;20 ng/mL or cT3 disease (by prostate MRI). Lymph node were require to be &lt;20 mm. Patients were randomized 2:1 to APE:EL for 6 cycles (24 weeks) followed by RP. All RPs underwent central pathology review. The primary endpoint was the rate of pathologic complete response (pCR) or minimum residual disease (MRD, tumor ≤5 mm). Secondary endpoints include PSA response, surgical staging at RP, positive margin rate, and safety. Results: 75 patients were enrolled at four sites: DFCI/BWH (n=55), BIDMC (n=11), UW (n=5), JHU (n=4). Median age was 62 years. Most patients had NCCN high-risk disease [n=66, 88%; cT3 n=21 (28%), Gleason 8-10 n=59 (79%), PSA &gt;20 ng/mL n=17 (23%)]. All patients completed 6 cycles followed by RP. Median PSA nadir was 0.03 and 0.02 ng/mL and time to nadir was 3.7 and 4.6 months in the APEL and EL arms, respectively. The combined pCR or MRD rate was 30% (n=15/50) in the APEL arm and 16% (n=4/25) in the EL arm. The response difference was 14% (80% CI -3%-30%, p=0.263). 15 patients (14 in APEL; 1 in EL) had grade 3 adverse events (AEs). The most common grade 3 AEs were hypertension (n=7) and ALT increase (n=5). No grade 4-5 AEs occurred. Conclusions: Neoadjuvant hormone therapy plus RP in men with high-risk PC resulted in favorable pathologic responses (≤5 mm residual tumor) in 16-30% with a trend towards improved pathologic outcomes with APEL and acceptable safety profile. Follow-up is necessary to evaluate the impact of therapy on recurrence rates. Clinical trial information: NCT02268175. [Table: see text]
Safety and efficacy of everolimus (E), bevacizumab (B), and docetaxel (D) for castration resistant prostate cancer (CRPC).
Authors: Mitchell E. Gross, Tanya B. Dorff, David I. Quinn, Kristy Massopust, Patricia M Diaz, Olga O. Castellanos, David B. Agus
Journal: Journal of Clinical Oncology (2015)

5066 Safety and efficacy of Everolimus (E), bevacizumab (B), and docetaxel (D) for castration resistant prostate cancer (CRPC) Background: Based on studies suggesting co-targeting mTOR and angiogenic pathways potentiates chemotherapy, we studied combining mTOR (E, formerly RAD001) and VEGF (B) inhibition with D in CRPC. Methods: Eligible patients (pts) had progressive, metastatic, chemo-naive CRPC. D+B was given IV day 1 with E PO daily on a 21 d cycle at level 1 (D 75 mg/m2, E 2.5 mg), level 2 (D 75 mg/m2, E 5 mg), or level 3 (D 65 mg/m2, E 5 mg). B 15 mg/kg was given at all levels. B/E without D (B/E-D) was allowed after ≥ 6 cycles. Prophylactic growth factor support was allowed only after cycle 1, if required The primary endpoint was response, defined as maximal confirmed PSA decline and RECIST criteria. Results: Dose level 1 was identified as the recommended phase 2 dose (Gross et al, 2009) thus 37 of 43 patients received level 1 dosing. Median age was 65 (50-79) years, PSA 76.6 (0-1847) ng/mL, alkaline phosphatase 114 (37-768) U/L, hemoglobin 12.5 (0.0-15.7) g/dl. Metastatic sites included: bone 38 (88%), lymph nodes 19 (44%), and viscera in 8 (19%) pts. Median cycles delivered was 10 (3-21) which included B/E-D maintenance in 24 pts for 3 (1-10) cycles. Maximal PSA decline ≥ 30% and ≥ 50% was achieved in 33 (79%) and 31 (74%) of pts. RECIST responses were assessable in 25 pts with best response complete or partial in 20 (80%) of pts. Hematologic toxicities were the most common treatment related grade ≥ 3 adverse events including: febrile neutropenia 12 (28%), lymphopenia 12 (28%), leukocytes 10 (23%), neutrophils 9 (21%), and hemoglobin 2 (5%). Non-hematologic grade ≥ 3 AEs included: hypertension 8 (19%), fatigue 3 (7%), pneumonia 3 (7%), and mucositis 4 (5%). There was 1 treatment related death due to neutropenic fever and pneumonia on a pt treated at dose level 3 despite dose modifications and prophylactic growth factor support. Conclusions: The combination of E/B/D demonstrates significant clinical activity against mCRPC which must be balanced against hematologic and other toxicities. Correlative biomarker studies are ongoing to better define patient subsets which may be more likely to benefit from this therapy. Clinical trial information: NCT00574769.
NHS training and workforce planning must be reviewed, finance directors say
Authors: Matthew Limb
Journal: BMJ (2014)

The system of training and workforce planning in the NHS in England is failing and must be reviewed, NHS finance directors have said.

A survey of finance directors has shown that increased spending on agency staff is now a major factor in worsening financial performance and that urgent cuts to spending on agency staff are being sought. The Healthcare Financial Management Association surveyed its members working in trusts, clinical commissioning groups, and area teams across the country. Members said that the NHS faced a rapidly deteriorating financial outlook for this financial year and “increasingly bleak” prospects for 2015-16.

Paul Briddock, the association’s policy director, welcomed the announcement earlier this week in the chancellor’s autumn statement that the NHS would receive an extra £2bn next year. But …
Noninvasive, Quantitative Assessment of Liver Fat by MRI‐PDFF as an Endpoint in NASH Trials
Authors: Cyrielle Caussy, Scott B. Reeder, Claude B. Sirlin, Rohit Loomba
Journal: Hepatology (2018)

Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease worldwide, and the progressive form of this condition, nonalcoholic steatohepatitis (NASH), has become one of the leading indications for liver transplantation. Despite intensive investigations, there are currently no United States Food and Drug Administration–approved therapies for treating NASH. A major barrier for drug development in NASH is that treatment response assessment continues to require liver biopsy, which is invasive and interpreted subjectively. Therefore, there is a major unmet need for developing noninvasive, objective, and quantitative biomarkers for diagnosis and assessment of treatment response. Emerging data support the use of magnetic resonance imaging–derived proton density fat fraction (MRI‐PDFF) as a noninvasive, quantitative, and accurate measure of liver fat content to assess treatment response in early‐phase NASH trials. In this review, we discuss the role and utility, including potential sample size reduction, of MRI‐PDFF as a quantitative and noninvasive imaging‐based biomarker in early‐phase NASH trials. Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease worldwide. ( 1 ) NAFLD can be broadly classified into two categories: nonalcoholic fatty liver, which has a minimal risk of progression to cirrhosis, and nonalcoholic steatohepatitis (NASH), the more progressive form of NAFLD, which has a significantly increased risk of progression to cirrhosis. ( 4 ) Over the past two decades, NASH‐related cirrhosis has become the second leading indication for liver transplantation in the United States. ( 5 ) For these reasons, pharmacological therapy for NASH is needed urgently. Despite intensive investigations, there are currently no therapies for treating NASH that have been approved by the United States Food and Drug Administration. ( 6 )
THE OBESITY PARADOX IN WOMEN WITH PULMONARY HYPERTENSION USING RIGHT VENTRICULAR ECHOCARDIOGRAPHIC STRAIN IMAGING
Authors: Hiten R. Patel, Upamanyu Rampal, Suchit Bhutani, Priyank Shah, Rahul Vasudev, Hartaj Virk, Fayez Shamoon, Mahesh Bikkina, Irvin Goldfarb
Journal: Journal of the American College of Cardiology (2018)
Questions of research misconduct follow Trump’s pick for CDC director
Authors: Owen Dyer
Journal: BMJ (2018)

The virologist Robert Redfield, the Trump administration’s choice to take over the Centers for Disease Control and Prevention, has drawn widespread praise for his clinical work in the areas of HIV and AIDS, hepatitis, and addiction but also criticism for draconian and stigmatising policies that he proposed in the early days of the AIDS epidemic in the US.

Redfield is also dogged by persistent allegations of research misconduct from his time as an army doctor.

Redfield, 66, currently heads clinical care and research at the University of Maryland’s Institute of Human Virology, which he founded with the AIDS pioneer Robert Gallo. He also plays a leading role in clinical programs of PEPFAR (the …
Mathilde Krim: doyenne of AIDS research funding in the US
Authors: Bob Roehr
Journal: BMJ (2018)

Credit: Annie Leibovitz

In the beginning, there was Mathilde Krim. Amid the darkness, despair, and scientific ignorance of AIDS, when rumour, panic, and victimisation flourished, she was a beacon of reason, compassion, and action. She was able to unite the communities of science, finance, Hollywood celebrity, and the stigmatised gay community that bore the brunt of the epidemic in its early days. Her principal vehicle was the American Foundation for AIDS Research (amfAR).

Krim’s early life was the stuff of a Hollywood screenplay. Born Mathilde Galland in Como, Italy, to Swiss and Austrian parents in 1926, she grew up primarily in Geneva, isolated from the worst of the second world war. But she did see Jewish refugees and heard the distain for their requests for asylum, and later she was shocked by newsreel footage of the liberation of extermination camps.

She converted to Judaism while a student at the University of Geneva, where she gained a PhD in biology at a time when few women did. She started smuggling guns to the Irgun, a Jewish paramilitary group fighting to create an independent Israel. Galland married David Danon in 1948, and the couple moved to Israel in 1953, but they divorced not …
Intratumoral administration of the alpha-Gal glycolipid AGI-134 to induce tumor regression in a mouse model of melanoma.
Authors: Stephen M. Shaw, Kim Wigglesworth, Jenny Middleton, Abi Vainstein Haras, Ella Sorani, Rinat Tabakman, Irit Carmi Levy, Sascha A. Kristian
Journal: Journal of Clinical Oncology (2018)

68 Background: AGI-134 is a fully synthetic alpha-Gal glycolipid for intratumoral (i.t.) treatment of solid tumors to induce a patient-specific anti-tumor immune response. AGI-134 recruits pre-existing anti-Gal antibodies to the injected lesion, leading to complement activation and enhanced tumor antigen processing. Using the B16.F10 murine melanoma model, we have previously demonstrated that AGI-134 evokes a robust abscopal anti-tumor effect, with treatment of a primary lesion protecting mice from the growth of distant lesions. In the current study, we investigated the response of injected tumors to AGI-134 administration. Methods: Tumors were induced by s.c. injection of B16.F10 or ovalbumin expressing B16 (B16.OVA) cells into the flank of α1,3galactosyltransferase knock out mice. After reaching a treatable size, the tumors were injected twice, 24 hrs apart, with PBS or 1-1.25 mg AGI-134, and tumor growth monitored for up to 32 days. In addition, to measure the activation of complement after treatment with AGI-134, tumors were processed 2 hours after treatment and the i.t. concentration of complement fragment C5a determined by ELISA. Results: Almost 50% of AGI-134-treated B16.F10 tumors fully regressed vs. 24% in the PBS controls. Moreover, AGI-134 treatment had a significant survival benefit, with 23% of AGI-134-treated mice dying or requiring euthanisia due to tumor mass by Day 27 post treatment vs. 43% in the PBS groups (p &lt; 0.05, Mantel-Cox test). In the B16.OVA model, 67% of the AGI-134 treated tumors fully regressed vs. 0% in PBS-treated mice in two independent assays. Comparison of C5a levels in B16.F10 tumors 2 hrs after AGI-134 or PBS treatment demonstrated that AGI-134 induced significant complement activation within injected tumors. Conclusions: Having previously shown that AGI-134 induces an abscopal effect that protects mice from the development of secondary tumors, we now show that AGI-134 also induces regression of injected tumors: AGI-134-treatment induces the activation of complement within the tumor and leads to complete regression of the tumor in significantly more AGI-134-treated mice than PBS-treated. Clinical trials with AGI-134 are planned for 2018.
18F-FDG PET/CT for Molecular Imaging of Hepatoblastoma in Beckwith-Wiedemann Syndrome
Authors: Thorsten Derlin, Dagmar Hartung, Katja Hueper
Journal: Clinical Nuclear Medicine (2018)

Beckwith-Wiedemann syndrome (BWS) is a rare congenital overgrowth disorder variably characterized by macrosomia, macroglossia, congenital hypoglycemia, and hemihyperplasia. The BWS predisposes affected individuals to embryonal tumors during childhood. The BWS is caused by abnormal gene regulation in a particular region of chromosome 11. We present the case of a 1-year-old boy with BWS who underwent an F-FDG PET/CT scan for restaging of hepatoblastoma. On the F-FDG PET scan, increased tracer accumulation was observed in hepatoblastoma lesions. In addition, marked hemihyperplasia was noted. This case highlights the usefulness of F-FDG PET/CT for restaging of hepatoblastoma in BWS.
How can I apply for clinical attachments in the United Kingdom to prepare for the PLAB test part 2?
Authors: Jo Constable
Journal: BMJ (2005)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site. <b>www.bmjcareers.com/advicezone</b>
Healthcare organisations back employee engagement initiative
Authors: Caroline White
Journal: BMJ (2012)

Healthcare organisations have joined a government backed push to improve the engagement of employees in the United Kingdom to increase productivity and create a working environment that favours innovation.

Fully engaged employees help drive measurable improvement in performance, creativity, and innovation, concludes a report that was issued to coincide with the first major push of the “engage for success” initiative.

The initiative, which was set up by the prime minister last year, …