tbuckley/cabot-search huggingface dataset:
Surgical ovarian ablation for hormone receptor positive primary breast cancer in premenopausal women.
Authors: Anton Oseledchyk, Mary Gemignani, Maura N. Dickler, Shari Beth Goldfarb, Alexia Iasonos, Qin Zhou, Jeanne Carter, Richard R. Barakat, Nadeem Abu-Rustum, Oliver Zivanovic
Journal: Journal of Clinical Oncology (2017)

e12536 Background: Ovarian ablation is increasingly used to complement endocrine therapy in select premenopausal women with hormone-receptor positive (HR+) breast cancer (BC). It can be achieved by either medical ovarian suppression (OS) or therapeutic bilateral salpingo-oophorectomy (BSO). We sought to investigate trends of therapeutic BSO in premenopausal patients at our institution. Methods: Premenopausal women with HR+ primary BC diagnosed from 2010-2014 were identified in our prospectively maintained BC database. Patients with confirmed BRCA1/2 mutations were excluded. Distribution of patient and disease characteristics between treatment groups were assessed using univariate logistic regression analyses. Surgical details and complications were extracted from our surgical database. Results: We identified 2,854 eligible patients; 2,113 (74%) received endocrine therapy without ovarian ablation, 246 (9%) received endocrine therapy plus medical OS, 180 (6%) underwent additional BSO, and 315 (11%) did not receive endocrine therapy at the time of analysis. Independent predictors for undergoing ovarian ablation were younger age (OR 0.98; 95%CI, 0.96-0.99; p &lt; 0.001), higher grade (grade 3 vs 1: OR 3.17; 95%CI, 1.70-5.90; grade 2 vs 1: OR 3.13; 95%CI, 1.64-5.95; p &lt; 0.001), lymph node involvement (OR 1.46; 95%CI, 1.19-1.80; p &lt; 0.001), and higher AJCC stage as well as de novo metastatic BC (II vs I: OR = 1.35; 95%CI, 1.03-1.76; III vs I: OR 2.57; 95%CI, 1.86-3.55; IV vs I: OR 19.69; 95%CI, 12.76-30.39; p &lt; 0.001). Among patients who underwent ovarian ablation, patients of younger age (1.04; 95%CI, 1.01-1.07; p = 0.009) and with metastatic BC (stage IV vs I: OR 0.36; 95%CI, 0.20-0.68; p = 0.007) were less likely to undergo BSO than OS. In 180 patients undergoing BSO, five adverse events were noted: two grade 1, two grade 2, and one grade 3 complication. Conclusions: Premenopausal women with HR+ BC with high-risk features or metastatic disease were more likely to undergo ovarian ablation at our institution. Surgical ovarian ablation is a safe alternative, with low complication rates. Understanding patient preferences, side effects, and quality of life implications will help guide personalized treatment decisions.
Cardiovascular disease incidence and mortality in breast cancer survivors compared to the general population: Systematic review and meta-analysis.
Authors: Marina Michelle Reeves, Yi Zhong, Jennifer Job, Robert Ware, Brigid Lynch
Journal: Journal of Clinical Oncology (2016)

1039 Background: Cardiovascular disease (CVD) is the most prevalent comorbidity among breast cancer survivors. In older breast cancer survivors, the risk of dying from CVD is similar to the risk of dying from breast cancer. In addition to pre-existing CVD, it has been suggested that breast cancer survivorship may be associated with increased risk of incident CVD due to direct and indirect effects of cancer treatments and shared risk factors between the diseases. The aim of this systematic review was to investigate the risk of CVD in breast cancer survivors, compared to the general population, in terms of both incidence and mortality. Methods: Relevant articles were identified by structured searches in Embase, Pubmed, CINAHL, and Web of Sciences up until January 22, 2016. Eligible studies were those reporting on CVD incidence and/or CVD mortality in women diagnosed with invasive breast cancer compared to a matched general population sample. Meta-analysis was performed by calculating a meta-rate ratio (mRR) for comparison of relative mortality and overall incidence of CVD using random-effects models. Meta-analysis of specific CVDs was conducted where possible. Results: Of 2,637 articles identified, 21 met the eligibility criteria. Compared to the general population, breast cancer survivors experienced significantly higher risk for overall CVD incidence (13 studies; mRR = 1.20 [95% CI: 1.10, 1.31]) but slightly lower risk of CVD mortality (6 studies; mRR = 0.94 [95% CI: 0.87, 1.03]). When specific CVDs were examined separately, stroke/venous thromboembolism was the only CVD category with significantly increased incidence (6 studies; mRR = 1.24 [95% CI: 1.02, 1.45]). Conclusions: Breast cancer survivors may be more likely to develop CVD but are less likely to die from CVD, compared with age-matched general population. Identifying breast cancer survivors at high risk of CVD incidence is important to inform follow-up care guidelines around screening and prevention strategies to reduce this additional burden on survivors and the health care system.
Immunotherapy for Brain Tumors
Authors: John H. Sampson, Marcela V. Maus, Carl H. June
Journal: Journal of Clinical Oncology (2017)

Glioblastoma (GBM) is the most lethal form of brain tumor and remains a large, unmet medical need. This review focuses on recent advances in the neurosciences that converge with the broader field of immuno-oncology. Recent findings in neuroanatomy provide a basis for new approaches of cellular therapies for tumors that involve the CNS. The ultimate success of immunotherapy in the CNS will require improved imaging technologies and methods for analysis of the tumor microenvironment in patients with GBM. It is likely that combinatorial approaches with targeted immunotherapies will be required to exploit the vulnerabilities of GBM and other brain tumors.
Can radiation therapy adequately address positive surgical margins in elderly women (≥70 years) with stage I ER+ breast cancer?
Authors: Kaelen Medeiros, Prakash Peddi, Meijiao Zhou, Quyen Chu
Journal: Journal of Clinical Oncology (2016)

1045 Background: Re-excision for positive margin(s) following a lumpectomy for breast cancer is generally recommended. Whether radiation therapy can adequately address positive margins and thereby preclude a reoperation in elderly women with small breast cancer is not known. Methods: We evaluated a cohort of 71,607 women age ≥ 70 years with Stage I, ER+ breast cancer with lumpectomy and hormone therapy diagnosed between 1998 and 2012 in the National Cancer Data Base. Patients were divided into three groups: (1) positive margins (2) negative margins, and (3) positive margins with radiation therapy (RT). Clinicopathological and sociodemographic variables were compared among these groups. Univariate and multivariate analysis were employed, as was inverse propensity of treatment weighting (IPTW) methods to create both a weighted and unweighted analysis based on propensity score methods assigning probability of being treated. Results: The positive margin rate for the entire group was 1.81%. The 5-yr overall survival (OS) rates for the unweighted positive margins group, negative margins group, and positive margins + RT group were 57.75%, 83.81%, and 83.66%, respectively (P < 0.0001). The median survival time (months) was 76.16, 130.23, and 133.45, respectively. Significant predictors (P < 0.01) in both the unweighted and weighted analyses of OS include treatment groups, age, and comorbidities. Conclusions: Radiation therapy for positive surgical margins is a viable option for elderly women with small ER+ tumor treated with lumpectomy and hormonal therapy.
Regulation of Energy Homeostasis After Gastric Bypass Surgery
Authors: Martin L. Yarmush, Matthew D'Alessandro, Nima Saeidi
Journal: Annual Review of Biomedical Engineering (2017)

The obesity epidemic continues to escalate each year in the United States more than anywhere else in the world. The existing pharmaceutical and other nonsurgical treatments for morbid obesity produce suboptimal physiologic outcomes compared with those of Roux-en-Y gastric bypass (RYGB) surgery. RYGB has been the gold standard of bariatric surgery because the beneficial long-term outcomes, which include sustainable weight loss and type 2 diabetes mellitus (T2DM) resolution, are far superior to those obtained with other bariatric surgeries. However, the current understanding of RYGB's mechanisms of actions remains limited and incomplete. There is an urgent need to understand these mechanisms as gaining this knowledge may lead to the development of innovative and less invasive procedures and/or medical devices, which can mirror the favorable outcomes of RYGB surgery. In this review, we highlight current observations of the metabolic and physiologic events following RYGB, with a particular focus on the role of the anatomical reconfiguration of the gastrointestinal tract after RYGB.
Family history is strong risk factor in <i>BRCA1</i> and <i>BRCA2</i> carriers, study finds
Authors: Jacqui Wise
Journal: BMJ (2017)

The risk of developing breast cancer in women who carry BRCA1 or BRCA2 mutations increases with the number of relatives who have a breast cancer diagnosis, a large prospective cohort study published in JAMA has found.1

The study also found that cancer risk varied by mutation position within the BRCA1 or BRCA2 mutations. The findings suggest that individualised counselling for women with either mutation should incorporate family history profiles and the mutation site, the researchers said. …
Comparative analysis of various targeted enrichment methodologies to identify actionable mutations in lung cancer.
Authors: Anup Madan, Kellie Howard, Fang Yin Lo, Sharon Austin, Amanda Leonti, Lindsey Maassel, Christopher Subia, Tuuli Saloranta, Nicole Heying, Kathryn Shiji, Shradha Patil, Saman Tahir, Sally Dow, Evan Anderson, Jon Oblad, Kerry Deutsch, Steven Anderson
Journal: Journal of Clinical Oncology (2016)

e13110 Background: The recent expansion of knowledge about genetic changes associated with various diseases including cancers, using whole genome or exome sequencing has led to the development of focused or targeted gene panels. Such panels can be used to characterize both germ-line and somatic changes with a high degree of specificity and sensitivity. Two different approaches-hybridization capture and PCR-have been widely used to generate target specific libraries covering relevant loci. The limited amount of sample available, particularly in tissue biopsies and FFPE specimens, can restrict the use of both approaches for investigating a large number of gene targets. In addition, false positives may occur during the early steps of PCR or during whole genome amplification introducing potential errors. Methods: We used probes specific for the coding regions of 215 genes from Nimblegen (capture approach), NuGEN (AMP approach) and Illumina (PCR approach) to identify clinically actionable mutations and gene fusions in lung cancer. Various control DNAs were sequenced at 10,000X coverage and the data was analyzed at different depths. DNA isolated from 32 FFPE lung tumor samples of varying quality were interrogated by these three approaches. Results: A minimum coverage of 500X was required for identifying genomic aberrations with a high degree of confidence. The majority of identified variants (90%) were called by all three approaches. In these experiments, samples older than 5 years showed a high duplication rate and required greater coverage to call variants. We found on average 3 pathogenic mutations to be present in genes such as TP53, ATM and ATR in the 32 analyzed samples. Conclusions: All three methods can be used to profile DNA isolated from FFPE samples. It is expected 10% of the variants will be unique to each method. Some of this is likely due to coverage of target region and the ability of the bio-informatics tools to detect variants. To identify any false positives, uniquely identified variants from each approach are being confirmed by pyrosequencing. These datasets are also being further analyzed by various pathway analysis tools to define possible pathogenic mechanisms in lung cancer.
Soundings: Of free condoms
Authors: Imre Loefler
Journal: BMJ (2004)

The Lancet has broadcast the ultimate socialist message: “The lesson: even in the world's richest country, the right price for condoms is zero” (Lancet 2004;364: 13. [PubMed]).

The first step will be the erection of thousands of condom factories, financed by the Bretton Wood Sisters—the International Monetary Fund and the World Bank.

The United Nations will need to discuss how to calculate the numbers of condoms required. Applying human rights criteria, every male capable of penile erection (including those who achieve this by means of mechanical props or chemicals) is entitled to condoms.

Of the six billion world citizens there are a little less than three billion males, and perhaps one and a half to two billion of these are capable of erection.

As to the annual requirement in sheathing this penile force, the Lancet should invite global studies such as “Cultural and health determinants of the frequency of coitus according to age sets.” It can be assumed that the highest requirement occurs in the third decade in life when the annual demand can reach, in certain countries (such as Hungary), a thousand pieces. In the second decade erection is frequent, but, for the lack of opportunity and courage, coitus is not. The World Health Organization might advise young people to practise condom use when masturbating. From the fourth decade onwards the frequency of erection declines. It is unlikely that any male would be capable of more than 25 000 copulations in his life.

In what proportion of the grand total of penile exertion is it appropriate—to use President Bush's words—to use a condom? What proportion of the total takes place in stable monogamous or polygamous relationships, the only situations when condom use may not be required? More research is needed.

Condom distribution will be the duty of WHO. The UN will bear the cost of production. There is only one remaining problem: disposal. Without draconic legal measures, the world will be littered with discarded condoms within a decade, and every hole, natural or artificial, will be plugged up. Recycling may be an option. To encourage men to save and surrender used condoms they will have to be paid. One way to recover costs would be to find a use for the contents.
Early mortality rate (EMR) and complications in adults with acute myeloid leukemia (AML) in California.
Authors: Gwendolyn Ho, Brian Andrew Jonas, Qian Li, Ann Brunson, Theodore Wun, Theresa H.M. Keegan
Journal: Journal of Clinical Oncology (2016)

e13091 Background: Early mortality (defined here as death ≤ 60 days from diagnosis) continues to be a barrier to improving overall survival in AML patients. There are few population-based studies that have evaluated the impact of complications on EMR in the modern treatment era. Methods: Using a retrospective observational study design, we analyzed linked data from the California Cancer Registry and hospital discharge records in California from 1999-2012. We identified patients ≥ 15 years of age diagnosed with AML who received inpatient treatment (N = 5798). Multivariable logistic regression analyses were used to determine the association of complications with EMR (overall and by age group), adjusting for sociodemographic factors, comorbidities and hospital type. Results are presented as adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: EMR decreased over time (22.9%, 1999-2000; 16.7%, 2011-2012). There was consistent positive association of overall EMR with increasing age (6.7%, 15-39, 11.4%, 40-54, 19.1% 55-65, and 35.3%, > 65 years). Complications did not vary substantially by age, except that older patients had higher rates of sepsis, renal failure and respiratory failure. In multivariable models, major bleeding (OR 1.7, CI 1.4-2.1), liver failure (OR 2.4, CI 1.2-3.8), renal failure (OR 2.4, CI 2.0-2.9), respiratory failure (OR 7.3, CI 5.9-9.2) and cardiac arrest (OR 14.1, CI 7.7-26.0) were associated with EMR. Undergoing surgery was associated with lower EMR (OR 0.56, CI 0.41-0.77). Results were similar by age, except bleeding and respiratory failure had higher odds of EMR in patients < 55. Higher EMR also was associated with low neighborhood socioeconomic status, lack of health insurance (vs. private) and comorbidities. Treatment at a NCI-designated cancer center was associated with lower EMR (OR 0.49, CI 0.40-0.61). Conclusions: Major organ dysfunction and sepsis are substantial drivers of EMR in AML. Newer disease-directed therapies may minimally impact EMR without more robust initiatives to address these complications. Other strategies to improve outcomes include wider insurance coverage and treatment at specialty centers, where lower EMR may result from better supportive care.
Heart failure with mid‐range ejection fraction: a distinct clinical entity? Insights from the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (<scp>TIME‐CHF</scp>)
Authors: Peter Rickenbacher, Beat A. Kaufmann, Micha T. Maeder, Alain Bernheim, Kaatje Goetschalckx, Otmar Pfister, Matthias Pfisterer, Hans‐Peter Brunner‐La Rocca
Journal: European Journal of Heart Failure (2017)
Impact of albumin and calcium in multiple myeloma: An analysis from India.
Authors: Chepsy Cherian Philip, Amrith Mathew, Maria Ghosh, Naveen Kakkar, M Joseph John
Journal: Journal of Clinical Oncology (2016)

e13087 Background: Emerging therapies and molecular investigations are redefining outcomes in myeloma treatment. With 60% of new cases with cancer residing in the developing world, with challenges in affordability and access to treatment; these advances are beyond the reach of the majority. It is then important to analyze the impact of available predictive factors to optimize resources. Methods: We undertook a retrospective analysis of outcomes on new patients with multiple myeloma over a 2year period from Jan 1st 2013 till December 31st 2015. Diagnosis was established as per IMWG .A linear regression analysis to evaluate the association between patient characteristics and OS was done. The significant variables of calcium and albumin were then grouped by quartiles and compared by the log-rank test to estimate the probability of survival with the use of the product-limit method of Kaplan and Meier. Results: 54 patients were newly diagnosed during this period. In a univariate analysis of factors at diagnosis (Table), albumin and calcium had a statistically significant impact on OS. The OS at 1 year was 92.9% ± 6.9%, 91.7% ± 8.0%, 73.8 ± 17.5% and 71.4% ± 12.1% when grouped by calcium quartiles . A significant difference was observed in relation to to quartiles of albumin with OS at 1 year of 44.0% ± 19.8% , 83.9% ± 10.4% ,100% and 100% respectively, P = 0.004. Conclusions: Serum albumin and calcium are predictors of survival in Indian patients with multiple myeloma. The patient numbers and single centric data limit the nature of these findings. However in developing economies the utility of these universal tests might be valuable in resource allocation. Baseline characteristics. Variable PATIENTS ( N = 54) n (%)/ Median ( IQR)/Mean (±SD) Impact on OS, P Age ( Years) 60 (38-94) NS Expenditure ( Out-of –pocket) 30 (63.8) NS Transplant Status (Yes) 6 (11.1) NS Hemoglobin (g/L) 88.6 (± 24.7) NS White blood cell count (x10 9/ L) 5.6 (1.5-17.8) NS Platelet count (x10 9/ L) 191.0 (36.0-601.0) NS Albumin (g/dL) 3.2 (2.0-5.0) 0.009 Creatinine (mg/dL) 1.7 (0.5-13.1) NS Calcium (mg/dL) 9.9 (7.7-15.0) 0.003 Beta2microglobulin (mg/L) 9.9 (6.0-23.5) NS ISS ( III) 41 (80.4) NS Plasma cells (%) 60.0 (35-85) NS
Abstract 14741: Ambulatory Arterial Stiffness Index Predicts Responder of Renal Denervation
Authors: Yusuke Sata, Geoffrey A Head, Murray D Esler, Markus P Schlaich
Journal: Circulation (2016)

Introduction:  Renal denervation (RDN) can reduce blood pressure in patients with resistant hypertension, particularly those with the highest office blood pressure, but less so in patients with isolated systolic hypertension). A possible explanation is that patients with stiffer arteries may have lesser neural contribution to their hypertension.   Hypothesis and Methods:  We hypothesized that arterial stiffness predicts the response to RDN. From ambulatory BP monitoring (ABPM), ambulatory arterial stiffness index (AASI) was calculated as 1 minus the regression slope of ambulatory diastolic BP plotted against ambulatory systolic BP (SBP).   Results:  In 111 patients with resistant hypertension, RDN reduced office and ambulatory 24h SBP after 3, 6, and 12 months (by 12/11/16 and 4/5/7 mmHg, P 0.50, median) showed no change in 24h SBP 6 month after denervation (0.6±11.4 mmHg, P>0.05). Those with AASI less than 0.50 showed a marked reduction in 24h SBP (-9.4±10.6 mmHg, P   Conclusions:  We conclude that AASI is a strong and independent predictor of the anti-hypertensive response to RDN, which suggests that resistant hypertension with compliant vasculature may have a greater neural rather than structural contribution to their hypertension.
A Phase 1b Study of Vadastuximab Talirine As Maintenance and in Combination with Standard Consolidation for Patients with Acute Myeloid Leukemia (AML)
Authors: Jay Yang, Farhad Ravandi, Anjali Advani, Sumithira Vasu, Roland B. Walter, Stefan Faderl, Anthony S. Stein, Harry P. Erba, Amir T. Fathi, William B. Donnellan, Moshe Y Levy, Scott E. Smith, Brent L. Wood, Eric J. Feldman, Jenna L Voellinger, Michael B. Maris
Journal: Blood (2016)
Human Placenta-Derived Stromal Cells Rescue Mice from Radiation-Induced Bone Marrow Failure: A Cytof-Based Mechanistic Analysis
Authors: Hoshea Allen, Noa Sher, Shiran Rekhes, Lena Pinzur, Tal Prezma, Raphael Gorodetsky, Hans Dieter Volk, Zami Aberman, Racheli Ofir
Journal: Blood (2016)