tbuckley/cabot-search huggingface dataset:
Abstract P4-06-18: Clinical application of multigene panel testing and genetic counseling for hereditary/familial breast cancer risk assessment: Prospective single center study
Authors: E-S Lee, W Han, Y Kim, J Rhu, JH Park, K-E Kim, YW Ju, R Kim, H-B Lee, H-G Moon, D-Y Noh
Journal: Cancer Research (2018)

Abstract Background The identification of individuals at elevated risk for hereditary cancers has allowed the development of consensus recommendations for cancer screening and prevention. The introduction of multigene panels may identify more individuals with breast cancer gene mutations than does testing for BRCA1/2 alone. Therefore, the multigenerational panel increase the need for genetic counseling suggesting preventive approach or cancer-specific screening to patients and family members. The rapid clinical introduction of multigene panel testing, however, have several issues such as low- to moderate-risk gene mutations and clinical recommendations. We collect the mutation results and clinical recommendations after testing with multigene panel and giving genetic counseling. Methods We had developed multigene panel consisted of 64 genes related to hereditary cancer through previous study and prospectively enrolled 104 individuals who were appropriate candidates for hereditary breast cancer evaluation. The patients were tested with 64-gene panel(Celemics) and results were provided by us 4˜10 weeks later. We checked the family history of cancer and made a pedigree before testing. Result Among 104 participants, 26 patients harbored deleterious mutations, most commonly in high to moderate-risk breast/ovarian cancer genes (BRCA1/2, BRIP, RAD51 and RAD51D), Lynch syndrome gene(MSH6) and other genes(FH, SPINK1). We recommended the cancer-specific screening and/or preventive approach for mutation-positive patients and suggested additional genetic test for the family members. Among them, 6 (23%) patients received Risk reducing procedures (Prophylactic mastectomy or oophorectomy) and most of them(19 patients(73%)) received cancer specific screening. Conclusion We demonstrate the use of multigene panel testing for hereditary breast cancer and will suggest the process of the genetic counseling including indication and results analysis with multigene panel testing. Citation Format: Lee E-S, Han W, Kim Y, Rhu J, Park JH, Kim K-E, Ju YW, Kim R, Lee H-B, Moon H-G, Noh D-Y. Clinical application of multigene panel testing and genetic counseling for hereditary/familial breast cancer risk assessment: Prospective single center study [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 P4-06-18.
Clinician engagement determines care quality and patient satisfaction, says CQC chair
Authors: Abi Rimmer
Journal: BMJ (2014)

Engagement of clinicians can help improve satisfaction among patients and the quality of care delivered in an organisation, the chairman of the Care Quality Commission has said.

The CQC began a new type of hospital inspection in January this year, using larger inspection teams that include clinical staff and trained members of the public. The inspections will focus on 19 acute trusts and will award CQC ratings for the first time. Two key indicators measured by the CQC are …
Credentialing could come in after changes to law governing regulators, says GMC
Authors: Abi Rimmer
Journal: BMJ (2014)

The General Medical Council has said that it could introduce credentialing once proposed changes to the law that governs healthcare regulators are introduced.

In a system of credentialing, doctors could receive certification or a “credential” for their knowledge, skills, and competence in providing a particular service or performing a specific procedure.

Richard Marchant, assistant director of GMC regulation policy, was speaking to an Academy of Medical Royal Colleges’ conference for specialty and associate specialist doctors on the topic of credentialing in London last month. He said that although the GMC had …
CD40 ligand deficiency causes functional defects of peripheral neutrophils that are improved by exogenous IFN-γ
Authors: Otavio Cabral-Marques, Tabata Takahashi França, Ashraf Al-Sbiei, Lena Friederike Schimke, Taj Ali Khan, Claudia Feriotti, Tania Alves da Costa, Osvaldo Reis Junior, Cristina Worm Weber, Janaíra Fernandes Ferreira, Fabiola Scancetti Tavares, Claudia Valente, Regina Sumiko Watanabe Di Gesu, Asif Iqbal, Gabriela Riemekasten, Gustavo Pessini Amarante-Mendes, José Alexandre Marzagão Barbuto, Beatriz Tavares Costa-Carvalho, Paulo Vitor Soeiro Pereira, Maria J. Fernandez-Cabezudo, Vera Lucia Garcia Calich, Luigi D. Notarangelo, Troy R. Torgerson, Basel K. al-Ramadi, Hans D. Ochs, Antonio Condino-Neto
Journal: Journal of Allergy and Clinical Immunology (2018)
EFFICACY OF INTRAVASCULAR ULTRASOUND-GUIDED PERCUTANEOUS CORONARY INTERVENTION IN PATIENTS WITH DIABETES MELLITUS AND CHRONIC KIDNEY DISEASE
Authors: Ryota Sato, Kenji Sakamoto, Seiji Hokimoto, Suguru Nagamatsu, Takayoshi Yamashita, Shuichi Oshima, Ryusuke Tsunoda, Koichi Nakao, Toshiyuki Matsumura, Kazuteru Fujimoto, Hideki Shimomura, Yasuhiro Izumiya, Sunao Kojima, Hisao Ogawa, Koichi Kaikita, Kenichi Tsujita
Journal: Journal of the American College of Cardiology (2018)
DIFFERENTIAL REGULATION OF CIRCULATING CARDIAC NATRIURETIC PEPTIDES IN HUMAN ACUTE DECOMPENSATED HEART FAILURE: EVIDENCE FOR A SELECTIVE AND RELATIVE ATRIAL NATRIURETIC PEPTIDE DEFICIENCY
Authors: Shawn Reginauld, Valentina Cannone, Denise Heublein, Seethalakshmi Iyer, Christopher Scott, Jeson Sangaralingham, John C. Burnett
Journal: Journal of the American College of Cardiology (2018)
I have an idea for a book related to general practice which is aimed at GP registrars. How do I go about trying to get it published, and how difficult is it to get any medical book published?
Authors: Tim Albert
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>
Editor’s Choice: From the ground up
Authors: Tom Moberly
Journal: BMJ (2015)

This week BMJ Careers looks at some of the building blocks supporting doctors’ work and careers, from academic research and ethics to ensuring equality of opportunity in careers.

Garth Funston and colleagues guide readers through the career path of a clinical academic (http://careers.bmj.com/careers/advice/view-article.html?id=20021103). As well as providing an insight into each stage of the path, they also deal with some of …
Abstract GS5-05: Primary endocrine therapy for ER-positive ductal carcinoma in situ (DCIS) CALGB 40903 (Alliance)
Authors: ES Hwang, S Duong, I Bedrosian, J Allred, D Wisner, T Hyslop, A Caudle, J Guenther, C Hudis, E Winer, L Esserman, N Hylton
Journal: Cancer Research (2018)

Abstract Background: Standard treatment for ductal carcinoma in situ (DCIS) consists of surgery, often followed by adjuvant radiation therapy or endocrine therapy. This current approach is thought to represent overtreatment for some patients. This study was undertaken to determine whether an alternate approach of primary endocrine therapy alone could result in measurable radiographic changes in unresected estrogen receptor (ER)-positive DCIS. Methods: A phase II open-label single arm multi-center cooperative group trial (CALGB 40903) was conducted for postmenopausal patients diagnosed with ER-positive DCIS. All eligible patients underwent baseline mammography and MRI, followed by 6 months of preoperative therapy with letrozole. Follow up breast MRI was obtained at 3 and 6 months of treatment. The primary endpoint was change in total MRI volume of DCIS enhancement from baseline to 3 months and from baseline to 6 months. Secondary endpoints were change in MRI maximum diameter over baseline and change in mammographic extent of disease over baseline. Endpoints were analyzed via 2-sided paired t-tests (a=0.05). Results: From 8/1/12 to 2/1/16 108 patients were enrolled; Of the 77 patients who completed letrozole treatment per protocol, 66 patients were assessable. 2 additional patients who did not complete treatment per protocol were considered assessable and thus included in the analysis for a total of 68 patients. Median age of the cohort was 62.7 years. DCIS nuclear grade was low in 10% of patients, intermediate in 49%, and high in 40%. 82% of patients had ER-positive, PR-positive DCIS. The total mean MRI volume decreased from baseline to 3 months by 1.93 cm3 (p&amp;lt;0.001) and from baseline to 6 months by 1.82 cm3 (p&amp;lt;0.001). There was no significant difference in tumor volume between 3 and 6 months. Mean total mammographic tumor diameter decreased from baseline to 6 months by 3.31 mm2 (p=0.078). Conclusions: In a cohort of postmenopausal women treated with 6 months of preoperative endocrine therapy for ER-positive DCIS, MRI volume decreased markedly by 3 months, while mammographic extent of disease was not altered significantly. Correlation of imaging changes with pathology and baseline biomarkers will be conducted. These results will help determine whether MRI could be an effective modality for monitoring treatment response in some patients treated with primary endocrine therapy for ER-positive DCIS. Citation Format: Hwang ES, Duong S, Bedrosian I, Allred J, Wisner D, Hyslop T, Caudle A, Guenther J, Hudis C, Winer E, Esserman L, Hylton N. Primary endocrine therapy for ER-positive ductal carcinoma in situ (DCIS) CALGB 40903 (Alliance) [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 GS5-05.
MD/MCh in orthopaedics
Authors: Farokh Wadia
Journal: BMJ (2007)

The MD (doctor of medicine)/MCh (master of surgery) can be done in ear, nose, and throat surgery, anaesthesia, and paediatrics as well as orthopaedics. It is the first “taught” MD programme in the United Kingdom as opposed to the traditional MD by research.

University of Central Lancashire, Preston.

It is mainly for doctors who have completed their basic surgical training and who wish to pursue a career in orthopaedics. The entry requirement for the MD/MCh is a professional qualification in medicine or health with relevant experience and evidence of aptitude to undertake this programme or a recent and relevant second class honours degree or equivalent.

September 2004. I was among the first 27 students to join this course, …
Coexisting genomic aberrations associated with lymph node metastasis in breast cancer
Authors: Li Bao, Zhaoyang Qian, Maria B. Lyng, Ling Wang, Yuan Yu, Ting Wang, Xiuqing Zhang, Huanming Yang, Nils Brünner, Jun Wang, Henrik J. Ditzel
Journal: Journal of Clinical Investigation (2018)

Single cancer cell–sequencing studies currently use randomly selected cells, limiting correlations among genomic aberrations, morphology, and spatial localization. We laser-captured microdissected single cells from morphologically distinct areas of primary breast cancer and corresponding lymph node metastasis and performed whole-exome or deep-target sequencing of more than 100 such cells. Two major subclones coexisted in different areas of the primary tumor, and the lymph node metastasis originated from a minor subclone in the invasive front of the primary tumor, with additional copy number changes, including chr8q gain, but no additional point mutations in driver genes. Lack of metastasis-specific driver events led us to assess whether other clonal and subclonal genomic aberrations preexisting in primary tumors contribute to lymph node metastasis. Gene mutations and copy number variations analyzed in 5 breast cancer tissue sample sets revealed that copy number variations in several genomic regions, including areas within chr1p, chr8q, chr9p, chr12q, and chr20q, harboring several metastasis-associated genes, were consistently associated with lymph node metastasis. Moreover, clonal expansion was observed in an area of morphologically normal breast epithelia, likely driven by a driver mutation and a subsequent amplification in chr1q. Our study illuminates the molecular evolution of breast cancer and genomic aberrations contributing to metastases.
Interim results of a phase 1/2 study of JNJ-63723283, an anti-PD-1 monoclonal antibody, in patients with advanced cancers.
Authors: Emiliano Calvo, Victor Moreno, Enriqueta Felip, Giuseppe Curigliano, Daniel Morgensztern, James Greger, Kyounghwa Bae, Christina Lourdes Mayer, Jennifer Marino, Edward F. Attiyeh, Hong Xie, James J. Lee
Journal: Journal of Clinical Oncology (2018)

58 Background: JNJ-63723283 (JNJ-283), an anti-programmed cell death protein-1 antibody, enhances T cell-mediated cytokine induction and reduces tumor volume in preclinical models. A phase 1/2 study is ongoing to evaluate the safety and efficacy of JNJ-283 in patients (pts) with advanced cancers. Methods: Eligible pts have advanced or refractory solid tumor malignancies. Phase 1 dose escalation starting from 80 mg Q2W was supported by a modified continual reassessment method to identify the recommended phase 2 dose(s) (RP2D). Safety and efficacy of the RP2D(s) will be evaluated in phase 2. Pharmacokinetics (PK), receptor occupancy (RO) and other pharmacodynamic parameters were assessed. Results: As of data cut-off, 32 pts were treated with JNJ-283 80 mg (n = 4), 240 mg (n = 16) or 460 mg (n = 4) Q2W, or 480 mg (n = 8) Q4W; 16 pts remain on study drug. Median duration of treatment was 58 days (range 16 – 240). Median age was 56 years (range 27 - 80) and median prior lines of therapy was 3 (range 1 - 12). One dose-limiting toxicity of grade 3 pleural effusion was reported at 240 mg Q2W. An RP2D of 240 mg Q2W is being evaluated in phase 2. Most common adverse events (AEs) were anemia (28.1%), hypertension (28.1%), diarrhea (21.9%) and hyponatremia (21.9%). Observed serious AEs were pleural effusion, pneumonia and chest pain (6.3% each). Infusion-related AEs of nausea and rash occurred in 6.3% of pts each. Immune-related AEs (irAEs) were reported in 21.8% of pts and were mostly grade 1-2; grade 3 irAEs included pleural effusion, pneumonitis, AST increased and ALT increased. One pt discontinued treatment due to a treatment-related AE. Three pts achieved a partial response at 240 mg Q2W; 18 pts achieved stable disease or better. Preliminary serum JNJ-283 concentrations demonstrated linear PK with dose-proportional increases and interpatient variability generally consistent with monoclonal antibody therapeutics. Preliminary circulating T cell RO demonstrated dose-independent saturation. Conclusions: JNJ-283 displayed a well-tolerated safety profile with preliminary antitumor activity in pts with advanced cancers. The trial is ongoing to further characterize the safety, PK and clinical activity of JNJ-283. Clinical trial information: 2016-002017-22.
Abstract P2-11-06: Analysis of cardiac events among node positive breast cancer (NPBC) patients treated with three-dimensional conformal radiation therapy (3D-CRT)
Authors: JA Bradley, I Sparks, P Prior, C Bergom, A Walker, JF Wilson, XA Li, J White
Journal: Cancer Research (2018)

Abstract Background: Regional nodal irradiation (RNI) in addition to the chest wall and/or breast can maximize local regional control and improve overall survival, but has been associated with late cardiac morbidity. We examined NPBC patients treated with RNI using 3D-CT based radiation therapy (RT) to evaluate incidence and type of cardiac events. Methods: Between 2000 and 2007, 156 NPBC patients were treated with RNI following lumpectomy or mastectomy using 3D-CRT. In all cases, treatment target and normal tissue volumes were delineated on treatment CT scans. The heart contour included the left ventricle and the atria. Prescription dose was typically 50Gy in 25 fractions (range 44-54 Gy) to the chest wall and/or breast PTVeval. 37% received a boost to the chest wall and 73% to the lumpectomy cavity. The mean prescription dose to the axilla and supraclavicular lymph nodes was 47.6 Gy (range 43.2 – 54 Gy) and 46.8 Gy to the IMN (range 35.3 – 50.4 Gy). The dose-volume cardiac data and incidence of cardiac events is reported. Results: Median follow-up of surviving patients was 7 years (range, 0.3-10.6). Median patient age was 50 (range, 27-91), 52% were premenopausal, 76% estrogen receptor positive, and 18% were HER-2 positive. The IMN received &amp;gt; 40 Gy in 66%. Chemotherapy was used in 94% of patients, and it was anthracycline-based in 82.3%. At the time of RT, 12.5% smoked, 9% had diabetes, 33% with HTN, and 4.4% had a history of CAD. Average mean heart dose for the cohort was 5.2 Gy (range, 0.2 - 25.3 Gy). Mean cardiac V25 was 5.4% (range, 0-20%), mean cardiac V45 was 1.7% (range, 0-13.3%), and mean maximum cardiac point dose was 45.4 Gy. There was 1 (0.7% of cohort) right sided patient with cardiac events and 8 (5.1% of cohort) left experiencing cardiac events. A total of 18 cardiac diagnoses were experienced among the 9 patients: Coronary artery disease with or without myocardial infarction (4), congestive heart failure (6), cardiomyopathy (3), and arrhythmia (5). Conclusions: The cardiac event rate among these NPBC patients treated with RNI and anthracycline-based chemotherapy was low, but more common in women with left-sided breast cancer compared to right. Additional analysis using 3DCRT volumes are important to validate these findings and better define the dose-volume parameters for cardiac toxicity. Citation Format: Bradley JA, Sparks I, Prior P, Bergom C, Walker A, Wilson JF, Li XA, White J. Analysis of cardiac events among node positive breast cancer (NPBC) patients treated with three-dimensional conformal radiation therapy (3D-CRT) [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 P2-11-06.
Revalidation will cost nearly £100m a year
Authors: Caroline White
Journal: BMJ (2012)

The cost of implementing revalidation in England is likely to come to around £97m a year over the next decade, indicates a cost-benefit analysis of the scheme published by the Department of Health.

Doctors’ time will be the largest expense, accounting for almost two thirds of the total. But within a few years the costs will be offset by fewer litigation payouts, better quality of care, fewer suspensions, and many other unquantifiable knock-on benefits, including improved public trust in doctors, says the analysis.

The detailed breakdown of costs indicates that training appraisers as well as those appraised will cost £22m over the …
Monitoring the effect of first-line treatment in RAS/RAF mutated metastatic colorectal cancer by serial analysis of tumor specific DNA in plasma.
Authors: Caroline Brenner Thomsen, Torben Hansen, Rikke Fredslund Andersen, Jan Lindebjerg, Lars Henrik Jensen, Anders Kristian Moeller Jakobsen
Journal: Journal of Clinical Oncology (2017)

3593 Background: Personalized medicine calls for an early indicator of treatment failure. Circulating tumor DNA (ctDNA) is a promising marker in this setting and our prospective study explored the association between disease control and change of ctDNA during first line chemotherapy in patients with RAS/RAF mutated metastatic colorectal cancer (mCRC). Methods: The present study included 138 mCRC patients receiving standard first line combination chemotherapy. In patients with a RAS/RAF mutated tumor the same mutation was quantified in the plasma using droplet digital PCR (ddPCR). The fractional abundance of ctDNA (ctDNA level) was assessed in plasma before treatment start and at every treatment cycle until radiologically defined progressive disease (PD). Results: RAS/RAF mutations were detected in the plasma from 77 patients (94% of patients with a tumor mutation). Twenty patients progressed on treatment and 57 stopped treatment without progression. The presence of a RAS/RAF mutation in plasma correlated to overall survival (OS) with a median of 24.2 months for patients with a wild-type tumor compared to 12.7 months for patients with a mution in plasma. A substantial increase in ctDNA level was highly associated with progression on treatment (risk ratio = 4.58, 95%CI = 1.99-10.51, p &lt; 0.0001). Furthermore, with a stable ctDNA level the chance of non-progression was 88.2% (range 76.1-95.6%). The first substantial increase in ctDNA level occurred at a median of 51 days (range 14-133 days) before radiologically confirmed PD. Conclusions: The results indicate that ctDNA level may be predictive of treatment effect in patients with mCRC. An increase was observed to correlate with high risk of progression with a relevant lead time, whereas an unchanging ctDNA level related to stable disease.
Liver regeneration after hemihepatectomy in patients with hepatocellular carcinoma.
Authors: Wen-Feng Gong, Jian-Hong Zhong, Liang Ma, Bang-De Xiang, Le-Qun Li
Journal: Journal of Clinical Oncology (2018)

339 Background: We explored clinical factors associated with extent of liver regeneration after hemihepatectomy to treat hepatocellular carcinoma (HCC), as well as how the extent of regeneration influences postoperative recovery of liver function. Methods: In this prospective study of 125 patients who underwent hemihepatectomy, future liver remnant volume (as a percentage of functional liver volume, %FLRV) and remnant liver volume were measured preoperatively and at 1, 5, 9 and 13 weeks postoperatively. Logistic regression was used to identify clinical factors associated with liver regeneration. Influence of liver regeneration on postoperative liver function was evaluated. Results: After hepatectomy, 1 of 125 patients (0.8%) died within 3 months, 13 (10.4%) experienced liver failure and 99 (79.2%) experienced complications. %FLRV was able to predict liver failure with an area under the receiver operating characteristic curve of 0.900, and a cut-off value of 42.7% showed sensitivity of 85.7% and specificity of 88.6%. Postoperative median growth ratio was 21.3% at 1 week, 30.9% at 5 weeks, 34.6% at 9 weeks and 37.1% at 13 weeks. Multivariate analysis identified three predictors associated with liver regeneration: FLRV &lt; 601 cm 3 (OR 0.230, 95%CI 0.074-0.717), %FLRV (OR 0.271, 95%CI 0.077-0.960) and liver cirrhosis (OR 7.740, 95%CI 2.748-21.798). At postoperative weeks 1 and 5, liver function indicators were significantly better among patients showing high extent of regeneration than among those showing low extent, but these differences disappeared by postoperative week 9. Conclusions: FLRV, %FLRV and liver cirrhosis strongly influence extent of liver regeneration after hepatectomy. %FLRV values below 42.7% are associated with greater risk of post-hepatectomy liver failure.