tbuckley/cabot-search huggingface dataset:
Abstract PD4-08: Relationship between FDG-uptake and expression level of PD-L1 in primary ER positive/HER2 negative breast cancer
Authors: T Hirakata, T Fijii, K Kaira, S Kurozumi, A Katayama, R Yajima, S Obayashi, Y NaKazawa, S Tokuda, K Yanai, K Shirabe
Journal: Cancer Research (2019)

Abstract Background: 18F-Fluorodeoxyglucose-positron emission tomography (FDG-PET) is used to evaluate the glucose metabolic rates of cancers. Several studies have reported that high FDG uptake is predictive of poor prognosis and aggressive features in patients with breast cancer (BC). FDG-uptake is influenced by many factors including inflammation. In this study, we investigated the relationship between FDG uptake and immunological factors, including degrees of stromal tumor-infiltrating lymphocytes (TILs), CD8 and programmed cell death ligand 1 (PD-L1) in ER positive/HER2 negative (ER+/HER2-) BC. No published study, to our knowledge, has assessed the association between FDG uptake and PD-L1 in BC cases, even though both represent prognosis. Methods: Invasive carcinoma tissues of 79 ER+/HER2- BC patients who underwent surgery without preoperative therapy were examined. PD-L1, CD8 and TILs expression were evaluated by immunohistochemically (IHC) method. The evaluation of PET was determined by standardized uptake value max (SUVmax). Multivariate linear regression analysis, including expression of PD-L1, CD8 and TILs, was performed to identify independent variable correlation with SUVmax. Results: Among the 79 ER+/HER2- BC (T1-4, N0-2, M0) patients, the analysis revealed that PD-L1 (P=0.005), lymphovascular invasion (P=0.011), large tumor size (p=0.001), lymph node meatstasis (P=0.010), and high nuclear grade (P=0.011) and premenopasal status (P=0.014) were significantly associated with high SUVmax in the primary tumor. To define predictive value for the expression of PD-L1, SUVmax cut offwas determined using receiver operating characteristic (ROC) analysis; low (&amp;lt;3.0) and high (≥3.0). Among the 30 cases with high SUVmax, 10 cases (33.3%) had PD-L1 positive expression in the primary tumor, while only 2 (4.1%) of the 49 cases with low SUVmax had PD-L1 positive expression in the primary tumor. Conclusions: The present study demonstrated that the finding of preoperative FDG uptake is associated with the expression of PD-L1 in ER+/HER2- BC. In light of our results, FDG uptake may be predictive of the expression of PD-L1 and may be reflective of immunological features as well as prognostic features among patients with ER+/HER2- BC. Citation Format: Hirakata T, Fijii T, Kaira K, Kurozumi S, Katayama A, Yajima R, Obayashi S, NaKazawa Y, Tokuda S, Yanai K, Shirabe K. Relationship between FDG-uptake and expression level of PD-L1 in primary ER positive/HER2 negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD4-08.
GPs get fresh warning over “rife” mis-selling of financial products
Authors: Gareth Iacobucci
Journal: BMJ (2019)

General practices that have taken out fixed rate loans for their premises are at risk of “significant” financial losses and should scrutinise the terms of their deals, as they could have been victims of mis-selling, lawyers have warned.

The warning was issued amid concerns that the mis-selling of complex interest rate hedging products, or “swaps,” remained “rife” until at least 2016 and that many practices may have purchased products without their knowledge.

Lawyers said that mis-selling had continued in spite of a Financial Conduct Authority ruling in 2013 that there were “serious failings” in the way the products had been sold.

The products were sold with bank loans to small businesses, including many general practices, from 2001 onwards as a way to mitigate fluctuations in interest rates. In 2017 The BMJ …
Abstract 2545: Response to a preventive HER2/<i>neu</i> peptide (E75) vaccine based on HER2/<i>neu</i> status
Authors: Linda C Benavides, Jeremy D Gates, Mark G Carmichael, Jarrod P Holmes, Matthew T Hueman, Elizabeth A Mittendorf, Ritesh Patil, Alexander Stojadinovic, Dianna Craig, Sathibalan Ponniah, George E Peoples
Journal: Cancer Research (2008)

Abstract Background: HER2/neu is a source of immunogenic peptides and is over-expressed in 30% of early stage breast cancer (BCa) patients. We have conducted clinical trials with the HER2/neu E75-peptide vaccine in node-positive and node-negative BCa patients demonstrating all levels of HER2/neu expression. Methods: A subset analysis review was performed of 165 BCa patients enrolled in our E75 vaccine trial based on the level of HER2/neu expression. Patients were HLA typed; HLA-A2+/A3+ patients were vaccinated (V); HLA-A2-/A3- patients served as controls (C). HER2/neu over-expressers (OE) were defined as FISH &amp;gt;2.0 and IHC 3+ HER2/neu tumors. Low-expressers (LE) included patients with IHC ranging from 0 to 2+. These 2 groups were assessed by clinicopathologic factors, immunologic response (in vivo DTH reactions and in vitro HLA-A2:IgG dimer assay) to the vaccine, and post-vaccine clinical responses (recurrence and survival). Results: Of 165 patients assessed; 94 were vaccinated (30 OE = 32%, 64 LE = 68%) and 71 were controls (22 OE = 31%, 49 LE = 69%). HER2/neu over-expressers were similar regarding prognostic and treatment factors, except a statistically larger number of V-OE patients were hormone receptor negative (ER/PR-; p=0.02) and node-negative (p=0.007). Clinicopathologic factors were not significantly different between control and V-LE patients. Immunologic responses were similar as measured by DTH reactions (post DTH V-OE=12.7+1.9 vs. V-LE=15.1+1.8; p=0.6), but V-OE demonstrated a decreased number of E75-specific CD8+ T cells when compared to V-LE post-vaccination (V-OE vs. V-LE Dimer: 0.6+0.06% vs. 0.8+0.07%; p=0.08; V-OE vs. V-LE Max Dimer: 1.5+0.1% 1.9+0.1%; p=0.04). At 30 months median follow-up, disease recurrence rates (RR) were similar between V-OE and C-OE patients (V-OE vs. C-OE RR: 4.3% vs. 5.6%; p=0.7); however there was a 50% reduction in mortality rate (MR) among patients that recurred (V-OE vs. C-OE MR: 25% vs. 50%; p=NS). RR was reduced for vaccinated patients with low HER2/neu expression (V-LE vs. C-LE RR: 6.4% vs. 11.3%; p=0.3). Importantly, MR among those that recurred was 0% vs. 38% (p=0.2) for V-LE and C-LE BCa patients, respectively. Conclusions: Patients with HER2/neu over-expressing breast cancer (FISH amplified (&amp;gt;2.0) and IHC 3+) respond well to the E75 vaccine immunologically and have a 50% absolute reduction in mortality compared to controls. Unexpectedly, patients with low-expressing (0 - 2+ on IHC) HER2/neu tumors show better response not only immunologically, but clinically with decreased breast cancer recurrence and 0% mortality following E75 peptide vaccination.
From one disaster to another
Authors: Matthew Billingsley
Journal: BMJ (2015)

It seems like we are never far off the next humanitarian crisis. The recent earthquakes in Nepal killed more than 3500 people, and injured over 4000, as well as destroying 95% of homes in some areas. In the wake of the devastation urgent aid is required to respond to the needs of the people affected to save lives and provide basics such as food and shelter. But who are the medics who offer help in these moments of crisis? Anna Sayburn interviews some of the doctors who have been involved in recent conflict and disaster situations to find out what it takes to work in this field (doi:10.1136/sbmj.h2843). A career in this area of medicine carries with it a certain …
Nearly All Medications Contain Potentially Allergenic Inactive Ingredients, Analysis Shows
Authors: Rebecca Voelker
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
High incidence of venous thromboembolism recurrence in patients with sickle cell disease
Authors: Ann Brunson, Theresa Keegan, Anjlee Mahajan, Richard White, Ted Wun
Journal: American Journal of Hematology (2019)

Abstract Previous reports show increased incidence of venous thromboembolism [VTE, deep‐vein thrombosis (DVT) and pulmonary embolus (PE)] in sickle cell disease (SCD) patients. The incidence, time course, and risk factors for VTE recurrence have been less well described. We determined the cumulative incidence of first VTE recurrence and bleeding in a cohort of SCD patients with incident VTE. Risk factors for recurrence and bleeding were also determined using multivariable Cox regression models, adjusting for gender, race/ethnicity, era of incident VTE, location and hospitalization‐associated status of incident VTE, and SCD‐related complications. Results are presented as adjusted hazard ratios (HR) and 95% confidence intervals (CI). Among 877 SCD patients with an incident VTE, the 1‐year and 5‐year cumulative incidence of recurrence was 13.2% (95% CI 11.0%‐15.5%) and 24.1% (95% CI 21.2%‐27.1%). Risk factors for VTE recurrence included more severe SCD (HR = 2.41; CI: 1.67‐3.47), lower extremity DVT as the incident event (HR = 1.64; CI: 1.17‐2.30), and pneumonia/acute chest syndrome (HR = 1.68; CI: 1.15‐2.45). The cumulative incidence of bleeding was 4.9% (CI 3.5%‐6.4%) at 6 months and 7.9% (CI: 6.2%‐9.8%) at 1 year. More severe SCD (HR = 1.61; CI: 1.11‐2.35) was associated with bleeding. The high incidence of VTE recurrence in patients with SCD suggests that extended anticoagulation may be indicated; however, this must be weighed against a relatively high risk of bleeding. Prospective, randomized studies of anticoagulation in SCD patients with VTE are needed.
Help is here
Authors: Prizzi Zarsadias
Journal: BMJ (2010)

“No man is an island,” said the poet John Donne, but when you’re a junior doctor whose patient’s vital signs are spiralling in a worrying direction you’ll have never felt more alone, says an article in this month’s Education section. The truth is that help is always just a bleep away (doi:10.1136/sbmj.c900). When your team goes home and the on-call doctors are tied up with an emergency, leaving you stranded with an increasingly ill patient, you can call the critical care outreach team. These …
Abstract P3-12-02: Intraoperative radiotherapy outcomes in early-stage breast cancer: A study in elderly Canadian women
Authors: M Elmi, A Tigert, J Escallon, B Zagorski, W Leong, M Vranic, A Fyles, A Vitkin, T Cil, D McCready
Journal: Cancer Research (2019)

Abstract Objective. Breast-conserving therapy with external beam radiotherapy (EBRT) is currently the standard of care for women with early breast cancer. Our aim was to determine if early-stage breast cancers treated with lumpectomy and primary intraoperative radiotherapy (IORT) have comparable local recurrence rates. This is the first study examining the Canadian experience with IORT. Methods. Patients who underwent breast-conserving therapy with pre-pathology IORT between 2007- 2017 were retrospectively identified. The primary outcome measure was ipsilateral breast tumor recurrence (IBRT). A time to event analysis was performed; Kaplan-Meier estimates report the fraction of patients living free of recurrence. Secondary outcomes included acute and chronic wound complications. Results. 106 patients with a median age of 70 (IQR 65-75) were included. Median follow-up was 33 months. The majority of patients had screen-detected (94.3%), estrogen-receptor positive (96.2%), HER2neu negative (93.4%), invasive ductal carcinomas (92.5%). Only 50 (47.6%) were prescribed adjuvant endocrine blockade. IBTR occurred in 5 (4.7%) patients. Five and ten-year local recurrence-free rates were 0.95 and 0.81, respectively. The superficial skin infection rate was 9.4%. Acute symptomatic seromas occurred in 23 (21.7%), while only 10 (9.4%) persisted chronically. Conclusion. In this cohort of Canadian post-menopausal women treated with breast-conserving surgery and IORT, the IBTR approached 5%. Despite selection of low-risk patients, the local recurrence rate is higher than what is reported in the literature with EBRT. The low rates of prescribed adjuvant systemic therapy may have contributed to this outcome. Citation Format: Elmi M, Tigert A, Escallon J, Zagorski B, Leong W, Vranic M, Fyles A, Vitkin A, Cil T, McCready D. Intraoperative radiotherapy outcomes in early-stage breast cancer: A study in elderly Canadian women [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-02.
Going to extremes: determinants of extraordinary response and survival in patients with cancer
Authors: Flurina A. M. Saner, Alan Herschtal, Brad H. Nelson, Anna deFazio, Ellen L. Goode, Susan J. Ramus, Ahwan Pandey, Jessica A. Beach, Sian Fereday, Andrew Berchuck, Stephanie Lheureux, Celeste Leigh Pearce, Paul D. Pharoah, Malcolm C. Pike, Dale W. Garsed, David D. L. Bowtell
Journal: Nature reviews. Cancer (2019)
Body art is still taboo in healthcare
Authors: Sarah Winfield
Journal: BMJ (2014)

For centuries body piercing has been part of ritualistic and cultural practices, but it is now becoming mainstream.1 A survey published in The BMJ in 2008 of 10 503 adults in England found that out of the 659 women aged 16 to 24 included in the survey, 46.2% (n=305) admitted having a piercing at a site other than their earlobe2—a category that I also fall into. Likewise, tattoos—once a marker of someone on the fringes of society—are so common that one in five people has one,3 including the UK prime minister’s wife Samantha Cameron.4

Yet, while the General Medical Council encourages medical schools to select students from a diverse range of backgrounds, the medical profession maintains a conservative stance towards the display of body art. Hospitals in the United Kingdom vary in their rules on what is acceptable to display in clinical practice. East Cheshire NHS guidance, for example, strictly states …
Abstract P2-03-08: Preclinical evaluation of the PI3Kα/δ inhibitor, copanlisib in HER2+ breast cancer: A proof of concept study
Authors: P De, JH Carlson, N Dey, B Leyland-Jones
Journal: Cancer Research (2019)

Abstract Purpose: The PI3K-AKT-mTORC1/C2 pathway is frequently activated in HER2+ breast cancer and upregulation of this pathway is a key mechanism of trastuzumab resistance. However, attempts to indirectly target this pathway by using the allosteric mTOR inhibitor everolimus have had limited clinical success. Here, we present the results of a preclinical study of the PI3K α/δ (dominant) inhibitor copanlisib alone and in combination with T-DM1, in HER2 amplified cell lines including a model with acquired resistance to trastuzumab. Method: Anti-proliferative, apoptotic, cell cycle, and intracellular signaling effects of copanlisib alone and in combination with T-DM1 were evaluated in a panel of HER2 amplified (ER+ or ER-), and HER2 amplified/PIK3CA mutated cell lines, as well as trastuzumab-resistant breast cancer cell lines. Results: 1) Copanlisib inhibited PI3K, mTOR and their downstream signaling molecules in HER2 amplified/PIK3CA WT or PIK3CA mutated as well as in trastuzumab-resistant cell lines, 2) interestingly, copanlisib also inhibited RAS-MAPK signaling in the earlier time points, 3) copanlisib caused a strong differential growth inhibition in HER2 amplified BC cell lines by 3D-ON-TOP clonogenic assay and real-time monitoring in an IncuCyte Zoom. Inhibition was greater when copanlisib was combined with T-DM1, 4) administration of copanlisib induced cell cycle G0/G1 arrest and resulted in increased apoptosis in a dose-dependent manner, 5) unlike everolimus copanlisib blocked HIF1α accumulation in hypoxic condition and this blocking effect was reversed by prior treatment with the proteasome inhibitor, carfilzomib and 6) copanlisib also attenuated HER2 amplified cell migration, an important phenotypic feature for metastasis. Conclusions: Copanlisib is highly effective (blocks proliferation, induces apoptosis, and inhibits PI3K and its downstream signaling targets) in HER2 amplified breast cancer cell lines including trastuzumab-resistant and PIK3CA mutated cell lines. The addition of copanlisib to T-DM1 might represent an improved treatment strategy for patients with refractory metastatic HER2+ breast cancer. Citation Format: De P, Carlson JH, Dey N, Leyland-Jones B. Preclinical evaluation of the PI3Kα/δ inhibitor, copanlisib in HER2+ breast cancer: A proof of concept study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-03-08.
Uterine Glands: Developmental Biology and Functional Roles in Pregnancy
Authors: Andrew M Kelleher, Francesco J DeMayo, Thomas E Spencer
Journal: Endocrine Reviews (2019)

All mammalian uteri contain glands in the endometrium that develop only or primarily after birth. Gland development or adenogenesis in the postnatal uterus is intrinsically regulated by proliferation, cell-cell interactions, growth factors and their inhibitors, as well as transcription factors, including forkhead box A2 (FOXA2) and estrogen receptor α (ESR1). Extrinsic factors regulating adenogenesis originate from other organs, including the ovary, pituitary, and mammary gland. The infertility and recurrent pregnancy loss observed in uterine gland knockout sheep and mouse models support a primary role for secretions and products of the glands in pregnancy success. Recent studies in mice revealed that uterine glandular epithelia govern postimplantation pregnancy establishment through effects on stromal cell decidualization and placental development. In humans, uterine glands and, by inference, their secretions and products are hypothesized to be critical for blastocyst survival and implantation as well as embryo and placental development during the first trimester before the onset of fetal-maternal circulation. A variety of hormones and other factors from the ovary, placenta, and stromal cells impact secretory function of the uterine glands during pregnancy. This review summarizes new information related to the developmental biology of uterine glands and discusses novel perspectives on their functional roles in pregnancy establishment and success.
A Prospective Study of Serum Vitamin E and 28-Year Risk of Lung Cancer
Authors: Jiaqi Huang, Stephanie J Weinstein, Kai Yu, Satu Männistö, Demetrius Albanes
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract Background Epidemiologic data are inconsistent regarding the vitamin E-lung cancer association, and no study to our knowledge has examined serologic changes in vitamin E status in relation to subsequent risk. Methods In a cohort of 22 781 male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, we ascertained 3184 lung cancer cases during up to 28 years of observation. Cox proportional hazards models examined whether higher serum alpha-tocopherol concentrations at baseline, 3 years, or the interval change were associated with lower lung cancer risk. All statistical tests were two-sided. Results After adjustment for age, body mass index, smoking intensity and duration, serum total cholesterol, and trial intervention group, we found lower lung cancer risk in men with high baseline alpha-tocopherol (fifth quintile [Q5] vs Q1, hazard ratio [HR] = 0.76, 95% confidence interval [CI] = 0.66 to 0.87, Ptrend &amp;lt; .001). A similar reduction in risk was seen for serum alpha-tocopherol at 3 years (Q5 vs Q1, HR = 0.78, 95% CI = 0.67 to 0.91, Ptrend = .004). The inverse risk association appeared stronger for younger men and those who had smoked fewer years but was similar across trial intervention groups. We also found reduced risk among men not supplemented with vitamin E who had a lower serum alpha-tocopherol at baseline and greater increases in concentrations at 3 years (third tertile vs first tertile of serum alpha-tocopherol change, HR = 0.74, 95% CI = 0.59 to 0.91, P = .005). Conclusions Higher vitamin E status, as measured by serum alpha-tocopherol concentration, as well as repletion of a low vitamin E state, was related to decreased lung cancer risk during a 28-year period. Our findings provide evidence supporting the importance of adequate physiological vitamin E status for lung cancer risk reduction.