tbuckley/cabot-search huggingface dataset:
Combined management of open tibial fractures course
Authors: Abhilash Jain, Patrick Tansley
Journal: BMJ (2010)

Lower limb trauma can present complex problems, and early correct management is crucial to optimise outcome. This can be difficult, however, especially in non-specialist centres where people with these injuries sometimes present. In an attempt to improve the delivery of surgical care, the British Association of Plastic, Reconstructive and Aesthetic Surgeons (BAPRAS) and the British Orthopaedic Association (BOA) have recently published updated management guidelines, the Standards for the Management of Open Fractures of the Lower Limb (2009; www.bapras.org.uk/downloaddoc.asp?id=141). The aims of these guidelines, and of the course, are to encourage cooperation between plastic surgeons and orthopaedic surgeons and to provide an evidence based rationale for treatment.

This course complements the recent updated guidelines, and four of its authors teach the course. They are recognised for their expertise in the field and come from a background of orthopaedics, plastic surgery, and infectious diseases. The course …
What do GP principals look for when selecting a new partner?
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>
What opportunities exist in organ transplant surgery in the United Kingdom? What are the pros and cons of a career in transplant surgery?
Authors: Zain Khalpey
Journal: BMJ (2004)

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 (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.
Relevant prognostic markers involved in apoptosis in colorectal cancer
Authors: Martin Gasser, Martin Grimm, Silke Hom, Marco Bueter, Mathias Koenigshausen, Andreas Thalheimer, Sabine Mueller, Arnulf Thiede, Heinz-Jochen Gassel, Detlef Meyer, Ana Maria Waaga-Gasser
Journal: Cancer Research (2005)

2254   One of the main goals in cancer therapy is the detection of markers enabling a prognosis before therapy in patients with cancer. In addition, there are no suitable markers for the detection of colorectal cancer so far. The aim of this study was to identify clinical relevant markers, which are involved in the apoptosis of tumor cells. 81 patients operated with curative intent were included and compared according to their stage (UICC I: 21%, II: 25.9%, III: 23.5%, IV: 29.6%). Assessment of different markers for (anti)apoptosis, tumor suppressor gene p53 and T-cell subpopulations were performed using immunohistological doublestaining and Real Time PCR. The results were correlated with the relevant clinical and histopathological data of our clinical database. In contrast to bcl-x L  (UICC I/II: 77.8%, III/IV: 63.6%), bcl-2 was weakly detected in all patients independent of their stage. The expression of Fas/FasL, TRAIL/TRAILII receptor, and TGF-β/TGF-β receptor II (DR4) was dependent on the stage of the patients (Fas/FasL: UICC I/II 77.8%, III/IV 45.5%; TRAIL/TRAILII R: UICC I/II 33.3%, III/IV 36.4%; TGF-β/TGF-β RII: UICC I/II 34.4%, III/IV 63.6% positive cells). Moreover, a significant increase of FasL expression was detected on tumor cells from UICC III and IV patients compared with their Fas expression (p53/FasL: UICC I/II 22.2%, III/IV 50% vs. p53/Fas: UICC I/II 55.5%, III/IV 9.1% pos. cells). During the progressive course of disease an increased number of infiltrating CD4+ (T helper cells), but not of CD8+ (cytotoxic T cells) or NK cells (natural killer), was detected in the tumor (p53/CD4: UICC I/II 18.2%, III/IV 33.3%; p53/CD8: UICC I/II 55,5%, III/IV 11,1%; p53/NK: UICC I/II 45,6%, III/IV 18,2% pos. cells). In addition, a marked decrease in the FasL expression was observed in CD8+ (4-fold) and NK cells (99%). These results were confirmed by the molecular analysis of Fas, FasL, p53, bcl-2, CD4, CD8, NK, and TGF-β. This study indicates that the tumor become less vulnerable to cytotoxic and NK cell response during tumor progression. The tumor develops a mechanism to protect from immunological killing. Moreover, high expression of TGF-β receptor II and p53 in the primary tumor correlates with the progressive course of disease and tumor relapses in these patients.
Bullying in health teams undermines patient care, finds study
Authors: Matthew Limb
Journal: BMJ (2016)

Bullying relationships between junior doctors and nurses are common and often interfere with patient care, researchers studying teamwork in healthcare settings in Ireland have found.

Researchers at the National University of Ireland, Galway, and Trinity College, Dublin, said that action should be taken to target key areas of poor teamwork performance, such as poor communication, that pose higher risks to patients.

The researchers collected and analysed examples of poor teamwork in the Republic of Ireland and published their findings in the International Journal for Quality in Healthcare .1

The study involved 28 interns in the …
Efficacy of antiangiogenic renal neoplasm with bone metastasis: A mono-institutional study in France.
Authors: Christophe Sajous, Julien Peron, Helen Jane Boyle, Sylvie Negrier, Guillaume Moriceau, Jean-Yves Blay, Aude Flechon
Journal: Journal of Clinical Oncology (2018)

610 Background: Although bone metastases occur frequently in metastatic renal cell carcinoma (mRCC) and represent approximatively 20-30% of the different sites of metastases, few studies have assessed the prognostic impact of these metastatic sites. In this context, the aim of our study was to evaluate the efficiency of antiangiogenic (AA) treatments in this particular site Methods: A retrospective review of patients with mRCC and bone metastases, treated with a first line of antiangiogenic therapy at the Centre Leon Berard (CLB) was conducted between January 2010 and November 2016. In order to identify a differential treatment effect according to the metastatic site, we assessed the bone progression-free survival (bPFS) defined as the time from the first day of 1 st line AA to the date of bone progression or death; and extra bone PFS (ebPFS), defined as the time from the 1st day of 1st line AA to the date of extra-bone progression or death. The association between survival and potential prognosis factor, including metastases location was assessed using log-rank test for univariate analysis Results: A total of 200 patients (146 men; mean age 57,9 years; range 21-86) were analysed and the most common first line AA used was Sunitinib (147; 73,5%). Median PFS at the first AA line was 7,4 months (95% confidence interval (CI) = 6,1-9,2months). Median bPFS was higher than the median of extra bone metastasis PFS (11 months (95% CI = 9-14 months) versus 9 months (95% CI = 8 to 12 months). Other factors have a pejorative impact on the PFS such as sarcomatoid component, non clear cell RCC, Karnofsky index, and the presence of renal thrombus Conclusions: The efficacy of AA was similar on bone and extra-bone metastases, among patients with at least one bone metastasis
Abstract 18901: Metabolic Regulation of Adipose Tissue Inflammation and Systemic Insulin Sensitivity: A Role for PFKFB3 in Macrophage Polarization
Authors: Hang Xu, Xin Guo, Honggui Li, Shih-Lung Woo, Chaodong Wu
Journal: Circulation (2013)

Much evidence demonstrates that macrophages play a pivotal role in the development of overnutrition-associated metabolic diseases, such as cardiovascular disease and type II diabetes. Macrophage inflammatory status (polarization) is a key determinant of systemic insulin resistance, which is under the control of bi-directional regulation: macrophage proinflammatory activation and macrophage alternative activation (anti-inflammatory). It has been previously shown that PFKFB3, a gene that encodes for a key regulatory enzyme of glycolysis, is crucial for the control of systemic insulin sensitivity. In the present study, if and how PFKFB3 alters macrophage polarization in relation to adipose tissue inflammation and systemic insulin sensitivity were examined. Bone marrow cells were isolated from wild-type mice and PFKFB3-disrupted mice and differentiated into macrophages which were referred to as bone marrow-derived macrophages (BMDM). Compared with control cells, the phosphorylation of NF-kB p65 and JNK1/2 is in PFKFB3-disrupted BMDM. Additionally, the expression of proinflammatory cytokines, such as TNF-α and IL-6, was increased in PFKFB3-disrupted BMDM under the stimulation of lipopolysaccharides (LPS, 100 ng/ml). Upon adoptive transfer of bone marrow cells to lethally irradiated wild-type mice, the recipients with PFKFB3-disrupted bone marrow cells displayed a decrease in systemic insulin sensitivity, which was accompanied by an increase in adipose tissue inflammatory responses. The later were evidenced by increases in adipose tissue macrophage infiltration, the phosphorylation of NF-kB p65, and mRNA levels of proinflammatory cytokines. Taken together, PFKFB3 is a metabolic regulator of macrophage polarization, which accounts for the effects of PFKFB3 on protecting against diet-induced adipose tissue inflammation and systemic insulin resistance.
DIFFERENT LEFT ATRIAL APPENDAGE OCCLUSION DEVICES FOR STROKE PREVENTION IN CHINESE PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION: A SINGLE-CENTER EIGHT-YEAR EXPERIENCE WITH AMPLATZER CARDIAC PLUG/AMULET AND WATCHMAN DEVICES
Authors: Chak Yu So, Gary S.H. Cheung, Christy K.Y. Chan, Kelvin K.H. Kam, Anna K.Y. Chan, Sylvia S.W. Au, Simon K.C. Chan, Y.Y. Lam, Alex P.W. Lee, Bryan P.Y. Yan
Journal: Journal of the American College of Cardiology (2018)
用量強化多剤化学療法と手術を用いた小児期にリスクの高い肝芽腫の治療奏効:SIOPEL-3HR試験の最終結果
Authors: Zsiros Jozsef, Maibach Rudolf, Shafford Elizabeth, Brugieres Laurence, Brock Penelope, Czauderna Piotr, Roebuck Derek, Childs Margaret, Zimmermann Arthur, Laithier Veronique, Otte Jean-Bernard, DE Camargo Beatriz, Mackinlay Gordon, Scopinaro Marcelo, Aronson Daniel, Plaschkes Jack, Perilongo Giorgio
Journal: Journal of Clinical Oncology (2010)
A retrospective review of clinical outcome and hippocampus dosimetry in patients treated with stereotactic radiosurgery for brain metastases in South Wales
Authors: Najmus Sahar Iqbal, Owen Tilsley, Andrew Bryant, Anthony Millin, David G Lewis, John Staffurth, James Powell
Journal: Neuro-Oncology (2018)

Stereotactic radiosurgery(SRS) has demonstrated improved survival, quality of life and neurocognitive function(NCF) for patients with 1–3 brain metastases compared to whole brain radiotherapy. Despite its precision, a significant proportion of patients experience neurocognitive decline: 63.5% of patients undergoing SRS alone had neurocognitive decline[1]. The hippocampus has been implicated in NCF impairment following radiation however, the tolerance dose of hippocampus remains unclear for SRS. In a study of fractionated radiotherapy, a dose of more than 7.3Gy delivered to >40% of the bilateral hippocampus is associated with significantly worse NCF[2]. In animal studies, doses as low as 2Gy has demonstrated increased cell apoptosis in hippocampus[3]. We performed a retrospective review of all patients treated with SRS without WBRT over 1year at Velindre Cancer Centre. Patients with 1–3 brain metastases and WHO performance status 0–2 were included. We studied dose delivered to hippocampi in our patient population. Bilateral hippocampi were outlined manually according to the RTOG0933 atlas[4] and dose volume histograms were recreated using BrainLab iPlan RT Dose4.5. We identified 30 patients between January 2015 and January 2016. Mean age was 61. The most common primary sites were lung, kidney and melanoma. 19 patients had a single metastasis. Median overall survival was 7.5months. Dose to 0.1cc of the hippocampus was >5Gy in 8 and 2–4.9Gy in 12 patients. Dose to 50% of the hippocampus was >5Gy in 6 patients and 2–4.9Gy in 8 patients. Objective neurocognitive assessment was not attempted in this study due to the challenges of collecting such data retrospectively. We have identified a considerable proportion of patients receiving significant radiation to the hippocampus. Overall survival of patients is in line with previously published studies. We will now conduct a prospective study in patients undergoing SRS to correlate detailed radiation dosimetry, NCF and functional MRI measurements of organs at risk.
Second malignancies in patients with myeloproliferative neoplasms: a population-based cohort study of 9379 patients
Authors: Anna Ravn Landtblom, Hannah Bower, Therese M.-L. Andersson, Paul W. Dickman, Jan Samuelsson, Magnus Björkholm, Sigurdur Yngvi Kristinsson, Malin Hultcrantz
Journal: Leukemia (2018)
BASELINE FRAGMENTED QRS IS ASSOCIATED WITH INCREASED OVERALL MORTALITY IN HEART FAILURE WITH REDUCED EJECTION FRACTION: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Chanavuth Kanitsoraphan, Pattara Rattanawong, Poemlarp Mekraksakit, Pakawat Chongsathidkiet, Tanawan Riangwiwat, Napatt Kanjanahattakij, Wasawat Vutthikraivit, Saranapoom Klomjit
Journal: Journal of the American College of Cardiology (2018)
Why don’t staff, associate specialist, and specialty doctors engage more fully with the CPD opportunities offered to them?
Authors: Umesh Dashora
Journal: BMJ (2014)

Continuing professional development programmes have been developed to make the most of the funding available for specialty and associate specialist doctors, but uptake of many programmes has been poor. <b>Umesh Dashora</b> discusses his research into what might be affecting doctors' uptake of these new opportunities
Blast phase myeloproliferative neoplasm: Mayo-AGIMM study of 410 patients from two separate cohorts
Authors: Ayalew Tefferi, Mythri Mudireddy, Francesco Mannelli, Kebede H. Begna, Mrinal M. Patnaik, Curtis A. Hanson, Rhett P. Ketterling, Naseema Gangat, Meera Yogarajah, Valerio De Stefano, Francesco Passamonti, Vittorio Rosti, Maria Chiara Finazzi, Alessandro Rambaldi, Alberto Bosi, Paola Guglielmelli, Animesh Pardanani, Alessandro M. Vannucchi
Journal: Leukemia (2018)

A total of 410 patients with blast phase myeloproliferative neoplasm (MPN-BP) were retrospectively reviewed: 248 from the Mayo Clinic and 162 from Italy. Median survival was 3.6 months, with no improvement over the last 15 years. Multivariable analysis performed on the Mayo cohort identified high risk karyotype, platelet count < 100 × 109/L, age > 65 years and transfusion need as independent risk factors for survival. Also in the Mayo cohort, intensive chemotherapy resulted in complete remission (CR) or CR with incomplete count recovery (CRi) rates of 35 and 24%, respectively; treatment-specified 3-year/5-year survival rates were 32/10% for patients receiving allogeneic stem cell transplant (AlloSCT) (n = 24), 19/13% for patients achieving CR/CRi but were not transplanted (n = 24), and 1/1% in the absence of both AlloSCT and CR/CRi (n = 200) (p < 0.01). The survival impact of AlloSCT (HR 0.2, 95% CI 0.1–0.3), CR/CRi without AlloSCT (HR 0.3, 95% CI 0.2–0.5), high risk karyotype (HR 1.6, 95% CI 1.1–2.2) and platelet count < 100 × 109/L (HR 1.6, 95% CI 1.1–2.2) were confirmed to be inter-independent. Similar observations were made in the Italian cohort. The current study identifies the setting for improved short-term survival in MPN-BP, but also highlights the limited value of current therapy, including AlloSCT, in securing long-term survival.
Royal College launches “chief registrar” role
Authors: Thomas Cassidy
Journal: BMJ (2016)

A role of “chief registrar” has been developed by the Royal College of Physicians to improve junior doctors’ clinical leadership skills.

The role was designed to allow junior doctors who are nearing consultancy to gain management experience while working less than full time in their normal clinical roles.

The college is piloting the role at a number of sites over the next 18 months and it will commission an independent …
OUTCOMES OF SWITCHING P2Y12 INHIBITORS IN PATIENTS WHO UNDERWENT PERCUTANEOUS CORONARY INTERVENTION: A RETROSPECTIVE COHORT STUDY
Authors: Angel Yi Nam Fu, Dylan Perry-Nguyen, Uyen Tran, Trevor Simard, Michel Le May, Marino Labinaz, Alexander Dick, Chris Glover, Michael Froeschl, Benjamin Hibbert, Aun-Yeong Chong, Derek So
Journal: Journal of the American College of Cardiology (2018)
Review of clinical excellence awards has been delayed for over a year
Authors: Caroline White
Journal: BMJ (2012)

Publication of the independent review of clinical excellence and distinction award schemes for NHS consultants has now been delayed for more than a year, causing “unnecessary uncertainty” for consultants, the BMA has said.

The report of the Review Body on Doctors’ and Dentists’ Remuneration (DDRB) on senior doctors’ bonus schemes, submitted to the government on 7 July 2011, will, however, be published later this year, the Department of Health has confirmed. 

But doctors’ leaders have demanded a concrete date for publication to end the uncertainty over the long term future of the …
Phase II trial of panitumumab plus FOLFOX4 or FOLFIRI in subjects with KRAS wild-type colorectal cancer and liver-limited disease: The PLANET study.
Authors: Albert Abad, Bartomeu Massuti, Cristina Gravalos, Pilar Escudero, Carmen Guillen, Jose Luis Manzano, M.Auxiliadora Gomez, Maria Jose Safont, Javier Gallego Plazas, Javier Sastre, Carles Pericay, Rosario Dueñas, Carlos López-López, Ferran Losa, Manuel Valladares Ayerbes, Encarnación González, Ana Yuste, Alfredo Carrato, Enrique Aranda
Journal: Journal of Clinical Oncology (2014)

3560 Background: Downsizing with chemotherapy (CT) unresectable liver-limited disease (LLD) can permit resection and prolonged survival in patients (pts) with colorectal cancer (CRC). We assessed the value of adding panitumumab (P) to standard CT in this setting. Methods: This was a phase II, open-label, randomized, multicenter study which included pts≥18 years with wild-type (WT) KRAS exon 2 metastatic CRC and LLD fulfilling one of the following criteria: ≥4 metastases; at least 1 metastasis>10 cm in diameter; or technically not resectable. Pts were randomized 1:1 to receive P-FOLFOX4 or P-FOLFIRI every two weeks. The primary endpoint was the objective response rate. Results: There were77 pts analyzed (38 received P-FOLFOX4 and 39 P-FOLFIRI). Not confirmed response was noted in 70.1% pts (73.7% with P-FOLFOX4 and 66.7% with P-FOLFIRI). After a median of 8 P infusions in both groups, 51.9% underwent surgical resection of liver metastases (44.7% and 59.0%, respectively). The resection rate (R0+R1) was 77.5% (76.5% and 78.3%). Median progression-free survival was 12.5 months with P-FOLFOX4 and 12.6 months with P-FOLFIRI (p=0.943). Preliminary median overall survival was 32.5 and 42.4 months. Median pre-surgery relative dose-intensity (RDI) for panitumumab was 79.8% with P-FOLFOX4 and 87.5% with P-FOLFIRI, and RDI for CT was 83.0% and 88.7%. Peri-operative safety was similar between groups (22.2% and 18.5% of pts with any adverse event). Neutropenia grade 3/4 (P-FOLFOX4 39.5% vs P-FOLFIRI 10.3%; p=0.0029) and neuropathy (P-FOLFOX4 13.2% vs P-FOLFIRI 0%;p=0.025), were the only statistically significant differences in grade 3/4 adverse events. It was possible to determine the RAS status (exon 2,3,4 of KRAS/NRAS) in 83.1% of the pts. In the subset of pts with RAS WT the response rate increases to 75.5% pts (77.8% with P-FOLFOX4 and 73.1% with P-FOLFIRI). Conclusions: In this selected population with WT KRAS CRC and LLD, panitumumab plus CT offers the possibility of rapid tumour shrinkage and potentially curative hepatic resection. Similar efficacy and safety results were obtained with either P-FOLFOX4 or P-FOLFIRI schema. Clinical trial information: NCT00885885.
Multivariate Associations Among Behavioral, Clinical, and Multimodal Imaging Phenotypes in Patients With Psychosis
Authors: Dominik A. Moser, Gaelle E. Doucet, Won Hee Lee, Alexander Rasgon, Hannah Krinsky, Evan Leibu, Alex Ing, Gunter Schumann, Natalie Rasgon, Sophia Frangou
Journal: JAMA Psychiatry (2018)

Alterations in multiple neuroimaging phenotypes have been reported in psychotic disorders. However, neuroimaging measures can be influenced by factors that are not directly related to psychosis and may confound the interpretation of case-control differences. Therefore, a detailed characterization of the contribution of these factors to neuroimaging phenotypes in psychosis is warranted.To quantify the association between neuroimaging measures and behavioral, health, and demographic variables in psychosis using an integrated multivariate approach.This imaging study was conducted at a university research hospital from June 26, 2014, to March 9, 2017. High-resolution multimodal magnetic resonance imaging data were obtained from 100 patients with schizophrenia, 40 patients with bipolar disorder, and 50 healthy volunteers; computed were cortical thickness, subcortical volumes, white matter fractional anisotropy, task-related brain activation (during working memory and emotional recognition), and resting-state functional connectivity. Ascertained in all participants were nonimaging measures pertaining to clinical features, cognition, substance use, psychological trauma, physical activity, and body mass index. The association between imaging and nonimaging measures was modeled using sparse canonical correlation analysis with robust reliability testing.Multivariate patterns of the association between nonimaging and neuroimaging measures in patients with psychosis and healthy volunteers.The analyses were performed in 92 patients with schizophrenia (23 female [25.0%]; mean [SD] age, 27.0 [7.6] years), 37 patients with bipolar disorder (12 female [32.4%]; mean [SD] age, 27.5 [8.1] years), and 48 healthy volunteers (20 female [41.7%]; mean [SD] age, 29.8 [8.5] years). The imaging and nonimaging data sets showed significant covariation (r = 0.63, P < .001), which was independent of diagnosis. Among the nonimaging variables examined, age (r = -0.53), IQ (r = 0.36), and body mass index (r = -0.25) were associated with multiple imaging phenotypes; cannabis use (r = 0.23) and other substance use (r = 0.33) were associated with subcortical volumes, and alcohol use was associated with white matter integrity (r = -0.15). Within the multivariate models, positive symptoms retained associations with the global neuroimaging (r = -0.13), the cortical thickness (r = -0.22), and the task-related activation variates (r = -0.18); negative symptoms were mostly associated with measures of subcortical volume (r = 0.23), and depression/anxiety was associated with measures of white matter integrity (r = 0.12).Multivariate analyses provide a more accurate characterization of the association between brain alterations and psychosis because they enable the modeling of other key factors that influence neuroimaging phenotypes.
PREDICTION OF MODE OF DEATH BY DIURETIC RESISTANCE IN PATIENTS ADMITTED FOR ACUTE DECOMPENSATED HEART FAILURE WITH REDUCED AND PRESERVED LEFT VENTRICULAR EJECTION FRACTION: A PROSPECTIVE STUDY
Authors: Eiji Fukuhara, Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Yusuke Iwasaki, Atsushi Kikuchi, Tsutomu Kawai, Masahiro Seo, Iyo Ikeda, Makoto Abe, Jyun Nakamura, Kiyomi Kayama, Masatsugu Kawahira, Kazuya Tanabe, Masatake Fukunami
Journal: Journal of the American College of Cardiology (2018)