tbuckley/cabot-search huggingface dataset:
Reconstructive trauma surgery interface fellowship
Authors: AV Giblin, TC Wright, M Henley, DPS Sandhu, D Evriviades
Journal: BMJ (2012)

Interface fellowships have been created in areas where surgical specialties overlap to offer doctors the benefits of multidisciplinary teaching and surgical practice. Unbundling specialty territoriality in this way allows the fellows to expand their understanding of surgery and improve their ability to provide the best quality care for their patients.1

The United Kingdom has 18 interface fellowships in reconstructive aesthetic surgery, 10 in hand surgery, nine in breast and oncoplastic surgery, seven in head and neck surgery, and six in cleft lip and palate surgery.2 These fellowships are open to surgical trainees from numerous specialties and have approval from the General Medical Council, the royal colleges, and postgraduate deaneries.

The reconstructive trauma surgery interface fellowship at the Queen Elizabeth Hospital, Birmingham, is a new addition to the interface fellowship family and has been running for a year. The posts were initially for three months but have now been increased to four months after feedback from fellows, with start dates in March, July, and November. 

The main aims of the fellowship are for doctors to take an active role in all aspects of major soft tissue and skeletal trauma and to work closely with all individuals and teams involved …
Impact of palbociclib plus letrozole on patient-reported health-related quality of life: results from the PALOMA-2 trial
Authors: H.S. Rugo, V. Diéras, K.A. Gelmon, R.S. Finn, D.J. Slamon, M. Martin, P. Neven, Y. Shparyk, A. Mori, D.R. Lu, H. Bhattacharyya, C.H.u.a.n.g. Bartlett, S. Iyer, S. Johnston, J. Ettl, N. Harbeck
Journal: Annals of Oncology (2018)

<h2>Abstract</h2><h3>Background</h3> Patient-reported outcomes are integral in benefit–risk assessments of new treatment regimens. The PALOMA-2 study provides the largest body of evidence for patient-reported health-related quality of life (QOL) for patients with metastatic breast cancer (MBC) receiving first-line endocrine-based therapy (palbociclib plus letrozole and letrozole alone). <h3>Patients and methods</h3> Treatment-naïve postmenopausal women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) MBC were randomized 2 : 1 to palbociclib plus letrozole (<i>n</i>=444) or placebo plus letrozole (<i>n</i>=222). Patient-reported outcomes were assessed at baseline, day 1 of cycles 2 and 3, and day 1 of every other cycle from cycle 5 using the Functional Assessment of Cancer Therapy (FACT)-Breast and EuroQOL 5 dimensions (EQ-5D) questionnaires. <h3>Results</h3> As of 26 February 2016, the median duration of follow-up was 23months. Baseline scores were comparable between the two treatment arms. No significant between-arm differences were observed in change from baseline in FACT-Breast Total, FACT-General Total, or EQ-5D scores. Significantly greater improvement in pain scores was observed in the palbociclib plus letrozole arm (−0.256 versus −0.098; <i>P</i>=0.0183). In both arms, deterioration of FACT-Breast Total score was significantly delayed in patients without progression versus those with progression and patients with partial or complete response versus those without. No significant difference was observed in FACT-Breast and EQ-5D index scores in patients with and without neutropenia. <h3>Conclusions</h3> Overall, women with MBC receiving first-line endocrine therapy have a good QOL. The addition of palbociclib to letrozole maintains health-related QOL and improves pain scores in treatment-naïve postmenopausal patients with ER+/HER2− MBC compared with letrozole alone. Significantly greater delay in deterioration of health-related QOL was observed in patients without progression versus those who progressed and in patients with an objective response versus non-responders. ClinicalTrials.gov: NCT01740427 (https://clinicaltrials.gov/ct2/show/NCT01740427)
Abstract P2-12-06: Re-excision rates in breast conserving surgery for invasive breast cancer after neoadjuvant chemotherapy with and without the use of a radiopaque tissue transfer and X-ray system
Authors: H-C Kolberg, L Akpolat-Basci, M Stephanou, S Wetzig, Y Cubuk, J Gerharz, C Liedtke
Journal: Cancer Research (2018)

Abstract Background: Published re-excision rates after breast conserving surgery for invasive breast cancer vary between 20 and 50%. In patients after neoadjuvant chemotherapy even higher re-excision rates may result from difficulties in defining the surgical target particularly in cases with excellent treatment response. Specimen radiography is reducing re-excision rates, however, defining involved margins is often difficult using standard approaches. Devices allowing horizontal and vertical examination and an exact topographic localization of the lesion in the resected tissue could reduce re-excision rates by an intraoperative detection of involved margins. Methods: 80 patients with invasive breast cancer receiving breast conserving surgery after neoadjuvant chemotherapy and an indication for wire marking by mammography were included in this analysis. All tumors were marked with titanium clips prior to chemotherapy. In 40 patients specimen radiography was performed in a standard approach (control group), in 40 patients a tissue transfer and X-ray system based on a non-radiopaque board with radiopaque topographic markers and a stand for cranio-caudal X-rays was used (study group). A univariate analysis was carried out to evaluate the association between the use of the radiopaque tissue transfer system and the re-excision rate using a logistic regression model. Calculations were performed using the XLSTAT Biomed Software (Version 19.03, Addinsoft, NY, USA.). Results: 19/80 patients (23.75%) required re-excision because of involved margins; among those patients, 14/40 (35%) were in the control group and 5/40 (12.5%) in the study group. The association between the use of the radiopaque tissue transfer system and the lower re-excision rate was statistically significant (p=0.023). Conclusion: Our analysis provides a rationale for the use of a radiopaque tissue transfer system for specimen radiography in breast conserving surgery after neoadjuvant chemotherapy for invasive breast cancer in order to reduce re-excision rates. Based on these results we are planning a study including also patients receiving primary surgery. Citation Format: Kolberg H-C, Akpolat-Basci L, Stephanou M, Wetzig S, Cubuk Y, Gerharz J, Liedtke C. Re-excision rates in breast conserving surgery for invasive breast cancer after neoadjuvant chemotherapy with and without the use of a radiopaque tissue transfer and X-ray system [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 P2-12-06.
THE USE OF MACHINE LEARNING TO PREDICT DOXORUBICIN CARDIOTOXICITY
Authors: Henry Cheng, Qiang Zheng, Xiaofeng Zhu, Amanda M. Smith, Yiwen Qian, Rupal O’Quinn, Frank Silvestry, Yuchi Han, Marielle Scherrer-Crosbie, Victor Ferrari, Kevin Duffy, Dinesh Jagasia, Christos Davatzikos, Yong Fan, Bonnie Ky
Journal: Journal of the American College of Cardiology (2018)
Allowing different providers to compete for primary care services is good news for GPs
Authors: Mark Wills
Journal: BMJ (2006)

FOR 



Health services are for patients. Primary care delivers services to patients at early and often preventive stages. Successful primary care delivers real value to health systems through early intervention, avoiding unnecessary costs and potentially traumatic care in secondary and tertiary centres.

Primary care's strength is its ability to look at the whole person, taking account of everything going on in a patient's life that might be contributing to their illness. No other part of the health system has such breadth …
OUTCOMES OF ATHERECTOMY IN PATIENTS WITH INFRAINGUINAL ARTERIAL DISEASE
Authors: Obai Abdullah, Jad Omran, Loutfi Succari, Jihad Mustapha, Tariq Enezate, Fares Alahdab, Mazen Abu-Fadel, Fadi Saab, Rugheed Ghadban, Ahmad Halawa, Kul Aggarwal, Ashraf Al-Dadah
Journal: Journal of the American College of Cardiology (2018)
Meconium Ileus in a Neonate with Cystic Fibrosis
Authors: Kelly E Wood
Journal: New England Journal of Medicine (2018)

In a newborn infant with a prenatal diagnosis of cystic fibrosis, abdominal distention and emesis developed at 12 hours of age. A radiograph of the abdomen and a water-soluble contrast enema suggested a diagnosis of meconium ileus.
Defining the role of lymphadenectomy for pancreatic neuroendocrine tumors: An eight institution study of 695 patients from the U.S. Neuroendocrine Tumor Study Group.
Authors: Alexandra G Lopez-Aguiar, Mohammad Zaidi, Mary Dillhoff, Eliza W Beal, George A. Poultsides, Eleftherios Makris, Flavio G. Rocha, Zaheer S. Kanji, Kamran Idrees, Paula Marincola Smith, Clifford Cho, Megan Beems, Sharon M. Weber, Alexandra V. Fisher, Ryan C Fields, Bradley A. Krasnick, Kenneth Cardona, Shishir Maithel
Journal: Journal of Clinical Oncology (2018)

212 Background: Preoperative factors that reliably predict lymph node (LN) metastases in pancreatic neuroendocrine tumors (PanNETs) are unclear. The number of LNs needed to accurately stage PanNETs has not been defined. Methods: Patients who underwent curative-intent resection of primary non-functional PanNETs at 8 institutions from 2000-2016 were analyzed. Tumors with poor differentiation and Ki-67 &gt; 20% were excluded. Preoperative factors associated with LN metastases were identified. A procedure specific target for LN retrieval to accurately stage patients was determined. Results: Of 2182 pts with GI NETs, 695 underwent resection of PanNETs. 33% of tumors were proximal (head/uncinate), and 67% were distal (neck/body/tail). 26% of pts (n = 158) had LN+ disease, which was associated with worse 5-yr recurrence-free survival (RFS) (60% vs 86%; p &lt; 0.001). Increasing number of +LNs was not associated with worse RFS. Preoperative factors associated with +LNs included tumor size ≥2 cm (OR 6.6; p &lt; 0.001), proximal location (OR 2.5; p &lt; 0.001), moderate vs well differentiation (OR 2.1; p = 0.006), and Ki-67≥3% (OR 3.1; p &lt; 0.001). LN metastases were also present in tumors without these risk factors: &lt; 2cm (9%), distal location (19%), well differentiated (23%), and Ki-67 &lt; 3% (16%). Median LN retrieval was 13 for pancreatoduodenectomy (PD), but only 9 for distal pancreatectomy (DP). Given that PD routinely includes a complete regional lymphadenectomy, a minimum number of LNs to accurately stage pts was not identified. For DP, however, removal of &lt; 7 LNs failed to discriminate 5-yr RFS between LN (+) and (-) pts ( &lt; 7 LNs: 72% vs 83%, p = 0.198; ≥7 LNs: 67% vs 86%, p = 0.002). Conclusions: Tumor size ≥2 cm, proximal location, moderate differentiation, and Ki-67≥3% are preoperative factors that predict LN positivity in resected non-functional PanNETs. Given the 9-23% incidence of LN metastases in patients without such risk factors, routine regional lymphadenectomy should be considered. Pancreatoduodenectomy inherently includes sufficient LN retrieval, while distal pancreatectomy should aim to remove ≥7 LNs for accurate staging.
How do I register with the UK college to take the MRCPath exam in India?
Authors: Carl Gray
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>
Development of cryptotanshinone-loaded pellets for angina chronotherapy: In vitro / in vivo prediction and evaluation
Authors: Zhenghua Li, Shuangshuang Zhang, Hongxiang Yan, Jianping Liu
Journal: Asian Journal of Pharmaceutical Sciences (2018)

The clinical manifestations of variant angina is unevenly distributed during the 24 h, thus the in vivo performance of drugs should be tailored according to the angina circadian rhythm. Cryptotanshinone (CTN) is one of the representative bioactive lipid-soluble components of Danshen which has been commonly used for cardiovascular diseases such as angina pectoris. The aim of this study was to develop a novel CTN sustained-released pellets (CTN-SRPs) to precisely synchronize the CTN plasma concentrations with predicted occurrence of angina pectoris for angina chronotherapy. A deconvolution-based method was applied to develop and optimize the CTN-SRPs. The plasma concentration-time curve of CTN immediate-released formulation after oral administration in rats was used as the weight function. The predicted plasma concentration-time curve of CTN-SRPs simulated according to the incidence of variant angina during 24 h was used as the response function. Then the desired drug release profile of CTN-SRPs was calculated based on deconvolution using weight function and response function, and subsequently used for guiding the formulation optimization. CTN-SRPs were prepared with the combinations of PVP, poloxamer 127 and EC as matrix using fluidized bed technology. An orthogonal design was employed to obtain the optimal formulation with its release profile similar with the desired one. Pharmacokinetic studies validated that the actual plasma concentration-time curve of these optimized CTN-SRPs was similar with the predicted one. In addition, the percent errors (%PE) of CTN plasma concentrations in 8–12 h were less than 10%. In conclusion, this deconvolution-based method could be applied to adjust the in vivo performance of drugs for angina chronotherapy.
MORTALITY FOLLOWING INITIATION OR DISCONTINUATION OF GUIDELINE DIRECTED MEDICAL THERAPIES IN HOSPITALIZED HEART FAILURE PATIENTS IN THE ATHEROSCLEROSIS RISK IN COMMUNITIES STUDY
Authors: Richard Tran, Ahmed Aldemerdash, Patricia Chang, Carla Sueta, Brystana Kaufman, Josephine Asafu-Adjei, Orly Vardeny, Eliza Daubert, Anna Kucharska-Newton, Sally Stearns, Jo Rodgers
Journal: Journal of the American College of Cardiology (2016)
Mesoporous silica nanoparticles for drug and gene delivery
Authors: Yixian Zhou, Guilan Quan, Qiaoli Wu, Xiaoxu Zhang, Boyi Niu, Biyuan Wu, Ying Huang, Xin Pan, Chuanbin Wu
Journal: Acta Pharmaceutica Sinica B (2018)

Mesoporous silica nanoparticles (MSNs) are attracting increasing interest for potential biomedical applications. With tailored mesoporous structure, huge surface area and pore volume, selective surface functionality, as well as morphology control, MSNs exhibit high loading capacity for therapeutic agents and controlled release properties if modified with stimuli-responsive groups, polymers or proteins. In this review article, the applications of MSNs in pharmaceutics to improve drug bioavailability, reduce drug toxicity, and deliver with cellular targetability are summarized. Particularly, the exciting progress in the development of MSNs-based effective delivery systems for poorly soluble drugs, anticancer agents, and therapeutic genes are highlighted.
P065 Insulin-like growth factor 1 receptor regulates the phenotype and function of CD21+ B cells
Authors: M Erlandsson, C Wasen, G Gravina, MI Bokarewa
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Ligand to the inducible T cell costimulator (ICOSL) on B cells is essential for the ICOS-dependent follicular recruitment of activated T cells. In patients with Rheumatoid arthritis (RA) the IGF1-IGF1R axis is altered. Inhibition of IGF1R alleviated arthritis by reducing IL-6-dependent formation of Th17 cells. Here we study the role of IGF1R on CD21 +cells in experimental arthritis. <h3>Methods</h3> Female Balb/c mice were immunised with methylated BSA or with CII. Consequences of the IGF-1R inhibition for arthritis were studied in mBSA and CII-immunised mice treated with NT157 compound promoting degradation of insulin receptor substrates (mBSA) or using shRNA producing construct (mBSA +CII). At termination three sub-populations of CD21 +cells were analysed: follicular dendritic cells (FDc, CD21 +CD19-CXCR5-); marginal zone B cells (MZBc, CD21 +CD19+CXCR5-); follicular B cells (FBc, CD21 +CD19+CXCR5+). Supernatants of LPS-stimulated splenocytes and serum were analysed for production of antigen specific and autoantibodies. <h3>Results</h3> In spleen of mBSA-immunised mice, ICOSL expression on CD21 +cells correlated to IGF1R (r=0.70). Inhibition of IGF1R induced a 20% reduction in ICOSL expression in all CD21 +subsets followed by an increase in MZBc (p=0.003), while FDc and FBc were unchanged. ICOSL +MZBc were mostly IgMhi, while ICOSL +FBc were mostly IgDhi. Inhibition of IGF1R had no effect on the expression of ICOS +on CD4 T cells and the subset of CXCR5 +follicular T cells. Reduction of the ICOSL +CD21+B cells, reduced production of mBSA-specific IgM and increased production of autoreactive RF-IgM levels. <h3>Conclusions</h3> The study shows that IGF1R controls expression of ICOSL on CD21 +cells. ICOSL on MZBc is required to balance between antigen-specific response and autoantibody production. <h3>Disclosure of interest</h3> None declared
Trend Analysis on Reoperation After Lumpectomy for Breast Cancer—Reply
Authors: Monica Morrow, Paul Abrahamse, Steven J. Katz
Journal: JAMA Oncology (2018)

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<i>Lots of job advertisements stipulate “Must have a driving licence.” I do not drive for medical reasons, so does that mean I am automatically excluded from applying for these jobs?</i>
Authors: Joyce Carter
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>
New Scottish GP contract increases risk for remote and rural communities
Authors: Cathy Welch
Journal: BMJ (2018)

General practitioners in Scotland have voted to accept the 2018 contract,1 which says that “generalism, by definition, is a form of care that is person not disease centred.”2 But the fundamental approach remains unchanged from every contract in the history of medicine—designed from the urban based top, with a system centred focus on planning. Resourcing remains defined by the system’s imagined capacity rather than the real …
CORONARY ATRIAL BRANCH OCCLUSION DURING PRIMARY PERCUTANEOUS CORONARY INTERVENTION IN ST-ELEVATION MYOCARDIAL INFARCTION AND ASSOCIATION WITH ATRIAL ARRHYTHMIAS AT ONE-YEAR FOLLOW-UP
Authors: Jose Manuel Montero, Rachid Abou, Laurien Goedemans, Martin Schalij, Nina Ajmone Marsan, Jeroen J. Bax, Victoria Delgado
Journal: Journal of the American College of Cardiology (2018)
Specialty skills in plastic surgery
Authors: Jeremy Rodrigues
Journal: BMJ (2008)

Plastic surgery is a varied and stimulating specialty, but unfortunately exposure to plastics as either an undergraduate or a foundation doctor is sometimes limited. As a result, young trainees may not have had the opportunity to develop relevant skills and explore the specialty.

This is a two day course covering a broad range of skills important in plastic surgery. Its title was recently changed from “Core skills in plastic surgery,” though the course structure has not been altered.

The Royal College of Surgeons of England rates the course as suitable for specialty trainee 1 or specialty trainee 2 level. Attendees on my course …
A validated assay for gamma-H2AX as a pharmacodynamic biomarker of response to DNA damage
Authors: Jay Jiuping Ji, Ravithat Putvatana, Yiping Zhang, Christophe Redon, Olga Sedelnikova, Sherry Yang, Yves Pommier, William Bonner, Robert Kinders, Ralph Parchment, Melinda Hollingshead, Jennifer Low, Anthony Murgo, Joseph Tomaszewski, James Doroshow
Journal: Cancer Research (2007)

4027  Phosphorylated histone H2AX (also called gamma-H2AX) occurs in response to DNA double-strand breaks induced by a variety of genotoxic treatments. The number of resulting microscopic gamma-H2AX foci detected by immunofluorescence has been correlated directly with DNA damage severity and genomic repair. Our primary goal has been to develop and validate gamma-H2AX immunocytochemical assays to monitor response to DNA damage in human blood and tumor biopsies during Phase-0 clinical trials (eIND) conducted at the National Cancer Institute. Breast carcinoma (MCF-7), prostatic carcinoma (PC-3), melanoma (A375 and Colo 829) and monocytic leukemia (THP-1) cell lines were chosen for assay development, test optimization and biomarker quantitation. Slides from PBMC cytospins, cell culture coverslips and tumor touch preps were prepared and processed for the gamma-H2AX focus formation assay. Various doses of ionizing radiation, DNA topoisomerase I (Topo 1) inhibitors including camptothecin and indenoisoquinoline derivatives, as well as combinations of these agents with polyADP-ribose (PAR) polymerase inhibitors were tested in several cancer cell lines by quantifying gamma-H2AX foci. We developed positive and negative controls for the assay as well as quantitative panels for analysis of gamma-H2AX staining. We evaluated other biomarkers of DNA damage including p53BP1, Chk2 and ATM. Multiplexed fluorescent immunoassays for gamma-H2AX and p53BP1 were analyzed after ionizing radiation, treatment with Topo 1 or PARP inhibitors and combinations of these therapies. We found that gamma-H2AX foci were quantitative to DNA damage dosing and detected earlier than other biomarkers. Touch preps of Topotecan-treated nu/nu mouse/Colo 829 xenografts established that H2AX phosphorylation was upregulated within 2 hours of treatments. Assay performance in PBMCs of human bloods and needle biopsies of xenografts supports gamma-H2AX as a robust pharmacodynamic biomarker with substantial potential for clinical monitoring of DNA damage in PBMC and tumor specimens from early clinical trial patients.  Funded by NCI Contract N01-CO-12400.
NO REDUCTION IN BLEEDING ASSOCIATED WITH BIVALIRUDIN USE WHEN COMPARED TO UNFRACTIONATED HEPARIN AMONG PATIENTS WITH STABLE ISCHEMIC HEART DISEASE UNDERGOING PERCUTANEOUS CORONARY INTERVENTION
Authors: Morgan Kellogg, Yi-Ling Huang, Todd A. MacKenzie, Bina Ahmed, Matthew Watkins, Patrick Magnus, Jim Flynn, Peter N. Ver Lee, David Malenka, Samip C. Vasaiwala
Journal: Journal of the American College of Cardiology (2018)