tbuckley/cabot-search huggingface dataset:
“Threadbare” approach to leadership needs radical change, says King’s Fund
Authors: Matthew Limb
Journal: BMJ (2016)

The NHS is “scrabbling” to find medical leaders to fill vacancies because of a “threadbare” approach to leadership development, the King’s Fund has said.

Michael West, head of thought leadership at the King’s Fund, said that leadership was the key to improving organisational cultures that affect the way staff treat patients and each other. “We’ve been able to identify the key elements in cultures that deliver high quality, continually improving, compassionate care,” he said. “The resounding answer from research is that . . . leadership has the most significant influence on culture.”

West told BMJ Careers, “It’s not just about getting leaders in post …
Differential expressions of PD-1, PD-L1, and PD-L2 between the primary and metastatic sites in renal cell carcinoma.
Authors: Xingming Zhang, Pengfei Shen, Hao Zeng
Journal: Journal of Clinical Oncology (2018)

616 Background: To evaluate the differential expressions of PD-1, PD-L1 and PD-L2 between the primary and metastatic sites of renal cell carcinoma (RCC), and to find potential factors influencing expression difference. Methods: We included cases of RCC histologically diagnosed at West China Hospital between January 2009 and November 2016. Clinicopathological data were retrospectively extracted. SPPS 22.0 and GraphPad Prism 6 statistical software were used for data analysis. Kaplan-Meier was used to analyze PFS and OS. R software was used to calculate predictive accuracy (PA). Results: A total of 163 patients were included in this study. Immunohistochemistry results suggested significant differential expressions of PD-1, PD-L1 and PD-L2 between the primary and metastasis, with a higher detection rate of the primary than metastasis. Meanwhile, the concordance rate of PD-L1 between the primary and metastasis was only 32.5% (27/83), with a significant statistically difference (χ2 = 4.664, p = 0.031) and poor consistency (Kappa = 0.229, p = 0.031). PD-1 and PD-L1 were highly expressed in the lung/lymph node and PD-L2 was highly expressed in visceral metastases. Survival analysis suggested that PD-1 positive either in the primary or metastasis was a poor prognostic factor for OS (HR: 1.59, 95% CI 1.08-2.36, P = 0.0195). The expression of PD-L1 in the primary was a poor prognostic factor for OS (HR 2.55, 95% CI 1.06-6.15, P = 0.0373). Although the predictive effect of PD-L1 expression on OS was not statistically significant in TKI treated patients, the OS time was shorter in PD-L1-positive patients than those negative (median OS 19.0 vs 41.0 months). In the whole cohort, the PA value of COX regression analysis was 0.683 for PFS, and the addition of PD-1 expression in the primary increased the PA value to 0.699. Conclusions: The assessment of immunological checkpoint-related protein in primary tumor may not be able to provide adequate information for clinicians to evaluate or predict the patient's treatment-related efficacy and prognosis. Biopsy or resection of the metastases may provide a more accurate biological information for clinician's decision-making and the patient's prognosis.
THE RANGE OF MICROVASCULAR PERFUSION PATTERNS OBSERVED IN THE ACUTE SETTING OF TAKOTSUBO CARDIOMYOPATHY: COMPARISON WITH REVASCULARIZED ACUTE ST SEGMENT ELEVATION MYOCARDIAL INFARCTION PATIENTS
Authors: Thomas Richard Porter, Sourabh Aggarwal, Chetaj A. Mahabir, Gregory Pavlides, Feng Xie
Journal: Journal of the American College of Cardiology (2018)
Abstract P1-07-34: Clinical outcomes of single versus double hormone receptor positive breast cancer patients treated with neoadjuvant chemotherapy
Authors: J Raphael, S Nofech-Mozes, ME Trudeau
Journal: Cancer Research (2018)

Abstract Purpose This study aimed to evaluate and compare tumor response rates and survival outcomes between single and double hormone receptor (HR) positive (+) [Estrogen Receptor (ER+)/Progesterone Receptor (PR) negative (-) or ER-/PR+ versus ER+/PR+] breast cancer (BC) patients with any HER2 status treated with neoadjuvant chemotherapy at a single institution Methods A retrospective review was conducted using the Sunnybrook “Biomatrix” database to identify eligible patients. A multivariable logistic regression analysis (MLR) was performed to assess the association between HR status (single or double HR+) and pathologic complete response (pCR) rates at surgery. A Kaplan-Meier method was used to estimate Disease Free Survival (DFS) and a log-rank test was used to compare DFS between 3 subgroups of patients: single or double HR+ and HR negative patients Results Three hundred and four BC patients were identified and included in the analysis with a median follow up of 43.3months (Q1-Q3: 28.7-61.1) and a mean age of 49.7 years (Standard deviation 10.9). Forty seven percent (47/101), 31% (11/36) and 14% (24/167) of patients with HR negative, single HR+ and double HR+ disease achieved a pCR respectively (X2 test &amp;lt;0.0001). In a MLR analysis, HR status and HER2 status were associated with pCR rates. Compared to HR negative patients, patients with double HR+ disease were less likely to achieve pCR (Odd ratio (OR):0.14, 95%CI 0.06-0.31, p&amp;lt;0.0001) while single HR+ patients did not differ (OR:0.51, 95%CI 0.19-1.4). The association between HR+ status (single versus double HR+) and pCR rates compared to HR negative patients remained the same in subgroup analyses of HER2+ and HER2 negative patients separately. No difference in survival (DFS) was seen between the 3 subgroups of patients: HR negative, single and double HR+ patients. Conclusion BC patients with single HR+ disease behave differently than double HR+ patients in terms of likelihood of achieving pCR after neoadjuvant chemotherapy and do not differ from HR negative patients. This difference does not translate into a difference in DFS. Prospective studies are needed to validate these findings before considering different treatment strategies for these 2 subgroups of HR+ BC patients. Citation Format: Raphael J, Nofech-Mozes S, Trudeau ME. Clinical outcomes of single versus double hormone receptor positive breast cancer patients treated with neoadjuvant chemotherapy [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 P1-07-34.
ADOLESCENTS AND ADULTS WITH FONTAN CIRCULATION: BASELINE CHARACTERISTICS FROM THE PREPARE FONTAN REGISTRY
Authors: Lars Søndergaard, Jamil Aboulhosn, Yves d'Udekem, Wayne Franklin, Alfred Hager, Philippe Huot-Marchand, Yuli Kim, Erwan Muros-Le Rouzic, Markus Schwerzmann, Barbara Schwierin, Paul Clift
Journal: Journal of the American College of Cardiology (2018)
Quality-of-life analysis of the MITO-8, MaNGO, BGOG-Ov1, AGO-Ovar2.16, ENGOT-Ov1, GCIG study comparing platinum-based versus non-platinum-based chemotherapy in patients with partially platinum-sensitive recurrent ovarian cancer
Authors: M.C. Piccirillo, G. Scambia, A. Bologna, S. Signoriello, I. Vergote, K. Baumann, D. Lorusso, V. Murgia, R. Sorio, G. Ferrandina, C. Sacco, G. Cormio, E. Breda, S. Cinieri, D. Natale, G. Mangili, C. Pisano, S.C. Cecere, M. Di Napoli, V. Salutari, F. Raspagliesi, L. Arenare, A. Bergamini, J. Bryce, G. Daniele, C. Gallo, S. Pignata, F. Perrone
Journal: Annals of Oncology (2018)
Fairness at work affects employees’ health, research finds
Authors: Matt Limb
Journal: BMJ (2016)

Employees’ experiences of fairness at work may affect their health, new research has shown.

A study of 5800 workers found that, when their perceptions of fairness changed, so did their self rated health. On average, those who experienced more fairness over time reported better health, results published on 11 May showed.1

Constanze Eib, coauthor, said, “People who feel fairly treated are not only more likely to be motivated at work and go the extra mile for their organisation, but they are also more likely to be healthy, have an active …
Consultants trained in adult care should not be compelled to treat children, says BMA
Authors: Abi Rimmer
Journal: BMJ (2015)

Consultants who have trained in adult medicine should not be compelled to provide care to children unless they have the skills to do so, the BMA has said.

Delegates at the BMA’s annual UK consultants’ conference in London on Wednesday 4 March voted unanimously in favour of a motion saying that consultants should not be compelled to care for children “unless …
PDGFRB mutation and tyrosine kinase inhibitor resistance in Ph-like acute lymphoblastic leukemia
Authors: Yingchi Zhang, Yufeng Gao, Hui Zhang, Jingliao Zhang, Fuhong He, Aleš Hnízda, Maoxiang Qian, Xiaoming Liu, Yoshihiro Gocho, Ching-Hon Pui, Tao Cheng, Qianfei Wang, Jun J. Yang, Xiaofan Zhu, Xin Liu
Journal: Blood (2018)
Using evidence based design to produce healthier hospital buildings
Authors: Diana C Anderson, D Kirk Hamilton
Journal: BMJ (2013)

Evidence about how architecture affects healthcare staff and patients is increasingly influencing the design of hospitals. <b>Diana Anderson</b>, a qualified architect and a doctor in a major urban tertiary hospital, and <b>Kirk Hamilton</b>, an architect now working in academia after 30 years of practice, provide an international perspective on the issues involved
Primary resistance in docetaxel and androgen deprivation therapy in metastatic castrate sensitive prostate cancer patients.
Authors: Athanasios Pouptsis, Styliani Germanou, Nick Waldron, Thomas Young, Madeha Khan, Simon Hughes, Debra Hannah Josephs, Sarah Maria Rudman, Deborah Enting, Simon Chowdhury
Journal: Journal of Clinical Oncology (2018)

342 Background: Docetaxel chemotherapy combined with androgen deprivation therapy (ADT) has become the new standard of care in patients with metastatic castrate sensitive prostate cancer as it has shown significant benefit in terms of overall survival (OS) and response rates (Sweeney 2015, James 2016). However a subgroup of patients still experience early progression. Methods: We searched the hospital database for patients treated with docetaxel in the castrate sensitive setting. Eligible patients included those with newly diagnosed metastatic prostate adenocarcinoma and also patients with relapsed metastatic disease post radical radiotherapy or radical prostatectomy. Patients starting chemotherapy &gt; 12 weeks after commencing ADT were excluded. Results: We identified 72 patients treated with docetaxel and ADT between August 2014 and September 2017. The median age was 66 years (49-84 years). Of the 72 patients, 63 (88%) had bone metastases, 5 (7%) had visceral metastases and 45 (63%) had pelvic lymph node disease. Seven patients (9.7%) had relapsed metastatic disease post radical treatment. All patients had ≤6 cycles of docetaxel. Median time from diagnosis of metastatic disease to commencing castrate resistant treatment was 13 months (2-41 months). Median duration of follow-up was 16 months (5-39 months). Six patients (8%) had biochemical, radiological or clinical progression during, or at completion of docetaxel chemotherapy. One patient terminated treatment before completion of six cycles due to disease progression. The median presenting PSA in this group was 49.5 ug/L (9.04-2290 ug/L) and 2 patients had visceral disease. Of these 6 patients, 2 have died, and the median OS for the group was 11.5 months (8-22 months). Five patients were subsequently treated with enzalutamide and 1 with abiraterone. Conclusions: Despite the improvement in OS and response rates with the use of early docetaxel, a clinically significant number of patients developed disease progression during treatment, and these patients have a particularly poor prognosis. These patients should be the focus of future clinical trials.
Air Pollution Is Greatest Environmental Threat to Health
Authors: M.J. Friedrich
Journal: JAMA (2018)

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The Diagnosis and Management of Thyroid Nodules
Authors: Cosimo Durante, Giorgio Grani, Livia Lamartina, Sebastiano Filetti, Susan J. Mandel, David S. Cooper
Journal: JAMA (2018)

<h3>Importance</h3> Thyroid nodules are common, being detected in up to 65% of the general population. This is likely due to the increased use of diagnostic imaging for purposes unrelated to the thyroid. Most thyroid nodules are benign, clinically insignificant, and safely managed with a surveillance program. The main goal of initial and long-term follow-up is identification of the small subgroup of nodules that harbor a clinically significant cancer (≈10%), cause compressive symptoms (≈5%), or progress to functional disease (≈5%). <h3>Observations</h3> Thyroid function testing and ultrasonographic characteristics guide the initial management of thyroid nodules. Certain ultrasound features, such as a cystic or spongiform appearance, suggest a benign process that does not require additional testing. Suspicious sonographic patterns including solid composition, hypoechogenicity, irregular margins, and microcalcifications should prompt cytological evaluation. Additional diagnostic procedures, such as molecular testing, are indicated only in selected cases, such as indeterminate cytology (≈20%-30% of all biopsies). The initial risk estimate, derived from ultrasound and, if performed, cytology report, should determine the need for treatment and the type, frequency, and length of subsequent follow-up. Management includes simple observation, local treatments, and surgery and should be based on the estimated risk of malignancy and the presence and severity of compressive symptoms. <h3>Conclusions and Relevance</h3> Most thyroid nodules are benign. A diagnostic approach that uses ultrasound and, when indicated, fine-needle aspiration biopsy and molecular testing, facilitates a personalized, risk-based protocol that promotes high-quality care and minimizes cost and unnecessary testing.
Abstract MS1-2: New clinical approaches for TNBC
Authors: M Telli
Journal: Cancer Research (2018)

Abstract Over the last decade, triple-negative breast cancer (TNBC) has been the subject of intense clinical investigation. Importantly, an improved understanding of the critical role of DNA damage repair deficiency in TNBC has led to effective therapeutic strategies to target BRCA1 and BRCA2 mutation-associated TNBCs with platinum chemotherapy agents and PARP inhibitors. A major area of increasing clinical relevance focuses on the treatment of BRCA1 and BRCA2 mutation-associated breast cancers after the development of resistance to platinum and PARP inhibitor therapy. Lurbinectedin, a novel marine derived DNA damaging agent, has shown activity in BRCA1 and BRCA2 mutation-associated cancers, including those with platinum resistance. While therapeutic strategies for TNBC patients with BRCA1 and BRCA2 mutations have increased, most TNBC patients lack an underlying germline mutation in these genes and continue to have high unmet clinical need. Multiple lines of investigation are currently underway. Androgen receptor (AR) blockade has shown preliminary proof-of-concept in AR expressing TNBCs. While monotherapy with PD-1/PD-L1 checkpoint inhibitors has shown modest activity in metastatic TNBC, multiple studies are exploring the role of these agents in combination with chemotherapy, targeted therapies and other immunotherapeutic agents. Given the high prevalence of TP53 mutations in TNBC, strategies to target additional cell cycle checkpoints including ATR, ATM, Wee1 and others may hold promise. Antibody-drug conjugates targeting Trop-2, LIV-1 and GPNMB expressing TNBCs have also shown clinical activity and are advancing in clinical development. Citation Format: Telli M. New clinical approaches for TNBC [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 MS1-2.
NOVEL CYP2C19 GENETIC VARIANTS ASSOCIATED WITH STENT THROMBOSIS: A NEXT GENERATION SEQUENCING STUDY
Authors: Kashish Goel, Saurabh Baheti, Axel Åkerblom, Niclas Eriksson, Lars Wallentin, Shaun Goodman, Greg Jenkins, Suzette Bielinski, Veronique Roger, Charanjit Rihal, Naveen Pereira
Journal: Journal of the American College of Cardiology (2018)
PULMONARY ARTERIAL CAPACITANCE AND RENAL FUNCTION IN PATIENTS WITH HEART FAILURE WITH PRESERVED AND REDUCED EJECTION FRACTION
Authors: Hesam Mostafavi Toroghi, Kevin Lo, Benjamin Horn, Napatt Kanjanahattakij, Erum Malik, Jorge Luis Penalver, Mary Rodriguez, Janani Rangaswami, Kamran Mohiuddin, Shuchita Gupta, Aman Amanullah
Journal: Journal of the American College of Cardiology (2018)
99mTc-Methionine Hybrid SPECT/CT for Detection of Recurrent Glioma
Authors: Geetanjali Arora, Punit Sharma, Anshul Sharma, Anil Kumar Mishra, Puja Panwar Hazari, Ahitagni Biswas, Ajay Garg, Deepak Aheer, Rakesh Kumar
Journal: Clinical Nuclear Medicine (2018)

Posttherapy changes in treated glioma patients cannot be reliably differentiated from tumor recurrence. We evaluated the role of Tc-methionine SPECT/CT for the detection of recurrent glioma and compared the same with F-FDG PET/CT and contrast-enhanced MRI (CeMRI).Forty-four patients with histologically proven, previously treated glioma and clinical suspicion of recurrence were prospectively enrolled in the study. Of these 44 patients, 39 (28 male and 11 female subjects; age, 38.05 ± 9.7 years) underwent Tc-methionine SPECT/CT, F-FDG PET/CT, and CeMRI of the brain and were included for final analysis. Combination of repeat imaging, biopsy, and/or clinical follow-up (6-36 months) was taken as reference standard. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated. Diagnostic values among modalities were compared.Positive predictive value and negative predictive value for Tc-methionine SPECT/CT, F-FDG PET/CT, and CeMRI were 95.6% and 56.2%, 92.3% and 61.5%, and 79.4% and 42.9%, respectively. Sensitivity and specificity for the 3 modalities were 75.9% and 90%, 82.8% and 80%, and 87.1% and 30%. Specificity of Tc-methionine SPECT/CT was significantly higher than that of CeMRI (P < 0.0001) but not of F-FDG PET/CT (P = 0.36). No significant difference was seen between the modalities for sensitivity and accuracy.Tc-methionine is a promising tracer for detection of recurrent glioma. Diagnostic values of Tc-methionine SPECT/CT are similar to F-FDG, although it is more specific than CeMRI. So it may be used as a cost-effective alternative and also where PET/CT is not available.
Epigenome-Wide Assessment on DNA Methylation Change with Asthma Transition in Adolescence
Authors: Hongmei Zhang, Alemayehu Z. Wolde, Wilfried Karmaus, Faisal I. Rezwan, Cory H. White, Sabrina Iqbal, Syed H. Arshad, Susan Ewart, John W. Holloway
Journal: Journal of Allergy and Clinical Immunology (2018)
Abstract P6-08-06: Association of body mass index (BMI) with chemotherapy administration and emergency room (ER) visits among breast cancer patients
Authors: SH Giordano, J Niu, H Zhao, D Zorzi, M Chavez-Mac Gregor
Journal: Cancer Research (2018)

Abstract Background: Obese patients may be more likely to have treatment-related complications. Little is known about the association between BMI and chemotherapy-related ER visits and hospitalizations among breast cancer patients. In this study we evaluated the association between BMI and ER visits/hospitalizations in a large sample of breast cancer patients.Methods: We identified beneficiaries from the commercial MarketScan Health Risk Assessment database with breast cancer-specific claims between 2009-2014. All patients underwent mastectomy or lumpectomy and had BMI data available. BMI was categorized as normal (&amp;lt;25), overweight (≥25 and &amp;lt;30) and obese (≥30). Descriptive statistics were used to compare patient and treatment variables by BMI. Chemotherapy-related ER visits/hospitalizations in the 6 months after diagnosis were identified. Cox regression models were used to identify factors associated with ER visits and hospitalizations. Results: Among 7,830 patients included, 33.2% were classified as normal/underweight, 29.5% as overweight and 37.2% as obese. 2,928 (37%) patients were treated with chemotherapy. BMI differed significantly according to age, geographic region, comorbidity score, and treatment received. Among patients not treated with chemotherapy, the rates of ER visits/hospitalizations were: 11.4% for normal patients, 13.7% for overweight and 15.2% for obese patients (p=0.004). For chemotherapy-treated patients, the rates of ER visit/hospitalization were: 22.6% for normal patients, 24.3% for overweight and 30.2% for obese patients (p&amp;lt;0.001). In the multivariable model, chemotherapy-treated patients with obesity had higher risk to have ER visits/hospitalizations (HR=1.37, 95%CI 1.14–1.64) than patients with normal BMI. No significant increase was seen among overweight patients (OR=1.09; 95%CI 0.90-1.33). Conclusions: In this cohort of patients, obesity was associated with increased risk of ER visits/hospitalizations, suggesting that careful follow–up is warranted in these patients, particularly among those receiving chemotherapy. Citation Format: Giordano SH, Niu J, Zhao H, Zorzi D, Chavez-Mac Gregor M. Association of body mass index (BMI) with chemotherapy administration and emergency room (ER) visits among breast cancer patients [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 P6-08-06.
GENDER DIFFERENCES IN DISEASE PROFILE AND IN-HOSPITAL OUTCOMES OF PATIENTS WITH TAKAYASU ARTERITIS
Authors: Amitoj Singh, Sahil Agrawal, Sabir Saluja, Munveer Thind, Aman Rajpal, Sumit Gupta, Simranjit S. Randhawa, Efstathia Andrikopoulou, Jamshid Shirani
Journal: Journal of the American College of Cardiology (2018)