tbuckley/cabot-search huggingface dataset:
Abstract P5-02-16: Is surgical excision of intraductal papillomas justified by the rate of upstaging to breast cancer?
Authors: Paolo Cotzia, Ugur Ozerdem, Jiyon Lee, Jennifer Chun, Elianna Kaplowitz, Freya Schnabel, Farbod Darvishian
Journal: Cancer Research (2020)

Abstract Introduction: The management of intraductal papilloma (IDP) diagnosed on core needle biopsy (CNB) is controversial. Some investigators advocate surgical excision based on an upgrade risk of as high as 24%. Others contend that after adjusting for confounders, including size, clinical presentation, presence of other accompanying high-risk lesions and radiologic correlation, the upgrade risk may be as low as 2.3%. The implications for patient care would be the avoidance of invasive surgical procedures. The purpose of our study was to investigate the upgrade rate of IDP diagnosed on CNB to ductal carcinoma in situ (DCIS) and invasive carcinoma on subsequent surgical excision and the impact of associated high-risk borderline lesions and other clinicopathologic and radiologic variables. Methods: Our institutional pathology database was queried for all women who had a CNB with a diagnosis of intraductal papilloma between 2005-2018. Two independent pathologists reviewed all the core biopsy slides and excisional biopsy slides. Variables of interest included clinical, imaging and pathologic characteristics. Statistical analyses included Pearson’s chi-square, Wilcoxon rank-sum and logistic regression. Results: Out of 216 women, 19 (8.8%) upgraded to breast cancer (BC), including 14 (74%) DCIS and 5 (26%) invasive carcinoma. Out of 161 pure IDP without any atypia, 5 (3.1%) upgraded to BC and out of 45 IDP with atypical ductal hyperplasia (ADH), 13 (28.9%) upgraded to BC. Only one patient who upgraded to BC from IDP with ADH had a discordant finding on imaging. When we evaluated the clinicopathologic and radiologic variables associated with upgrading from pure IDP to BC on final pathology, we found that older age (&amp;gt;53 years) at time of biopsy (OR=1.05, 95%CI 1.01-1.09, p=0.027) and concomitant ipsilateral atypical ductal hyperplasia (ADH) (OR=9.69, 95%CI 3.37-27.81, p&amp;lt;0.0001) were associated with a BC upgrade. There was no significant association of upgrading to BC after having a concomitant ipsilateral or contralateral breast cancer. Conclusions: Our results support surgical excision of IDP on CNB when associated with ADH or diagnosed in women older than 53 years of age. The upgrade rate of 3.1% for IDP without atypia on CNB in younger women does not justify a universal recommendation for routine surgical excision. Citation Format: Paolo Cotzia, Ugur Ozerdem, Jiyon Lee, Jennifer Chun, Elianna Kaplowitz, Freya Schnabel, Farbod Darvishian. Is surgical excision of intraductal papillomas justified by the rate of upstaging to breast cancer? [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-02-16.
Abstract P233: History of Myocardial Infarction and Functional Status: The Reasons for Geographic and Racial Differences in Stroke Study
Authors: Emily B Levitan, Joanna B Ringel, Parag Goyal, Orysya Soroka, Madeline R Sterling, Raegan W Durant, Todd M Brown, Monika M Safford
Journal: Circulation (2020)

Background: In addition to traditional measures of cardiovascular health, individuals value the ability to conduct activities of daily living (ADLs) and physical and mental function. Whether myocardial infarction (MI) contributes to declines in these patient-centered health priorities is not known. Objective: To evaluate the association of history of MI with impairments in ADLs and physical and mental function. Methods: We included participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study without history of stroke who completed a study visit and interview in 2013-2016. Participants reported whether they had no difficulty (assigned a valued of 0), some difficulty (assigned a value of 1), or would require help (assigned a value of 2) conducting 12 basic and instrumental ADLs. We summed values across the 12 ADLs to create a score. Higher ADL impairment scores indicate more impairment. We calculated Physical and Mental Component Summary (PCS and MCS) scores from the 12-Item Short Form Health Survey. Higher PCS and MCS scores represent better function. History of MI included clinician-adjudicated MI, self-reported MI, or evidence of MI on electrocardiogram. We used logistic regression to compare prevalence of at least one ADL impairment and linear regression to compare ADL, PCS, and MCS scores between participants with and without history of MI. Results: Among 12,221 participants, 16% (n = 1,960) had a history of MI. The average age at the time of the interview was 72 (SD 8) years, 56% of the population was female, and 36% was black. Compared to participants without a history of MI, participants with a history of MI were more likely to have at least one ADL impairment and had higher average ADL impairment scores and lower average PCS and MCS scores ( Table ). Conclusion: History of MI was associated with more impairments in ADLs and worse physical and mental function in this study population. These findings suggest that prevention of MI may help prevent or delay declines functional status.
Outbreak of gastroenteritis highlighting the diagnostic and epidemiological challenges of enteroinvasive Escherichia coli, County of Halland, Sweden, November 2017
Authors: Nina Lagerqvist, Emma Löf, Theresa Enkirch, Peter Nilsson, Adam Roth, Cecilia Jernberg
Journal: Eurosurveillance (2020)

An outbreak of gastroenteritis with 83 cases occurred at a conference venue in November 2017 in Halland County, Sweden. Stool samples from two venue visitors and a symptomatic secondary case attributed to household transmission were PCR-positive for the ipaH gene, a target found in both Shigella spp. and enteroinvasive Escherichia coli (EIEC). EIEC was isolated from stool samples and whole genome sequencing analysis confirmed EIEC O96:H19 to be the aetiological agent. A cohort study was conducted among venue attendees and employees and the findings implicated contaminated leafy greens as the vehicle of infection, however, no microbiological evidence could support the study results. Here, we report the investigation into the first recorded EIEC outbreak in Sweden and illustrate the challenges associated with the differential laboratory diagnostics of Shigella/EIEC in an outbreak setting.
Abstract P512: Red Meat Intake and Risk of Coronary Heart Disease Among US Men
Authors: Laila Al-Shaar, Ambika Satija, Dong Wang, Eric Rimm, Stephanie A Smith-Warner, Meir J Stampfer, Frank Hu, Walter Willett
Journal: Circulation (2020)

Background: The relation of red meat to risk of coronary heart disease (CHD) is of great interest, but this is likely to depend on the foods to which red meat is compared. Objective: We investigated the associations between total, processed and unprocessed red meat consumption and CHD risk and also estimated the effects of substituting other protein sources for red meat. Methods: We prospectively followed 43,259 men in the Health Professionals Follow up Study (1986-2012) who had no known history of cancer or cardiovascular disease. Diet was assessed by a standardized and validated food frequency questionnaire that was updated every 4 years. Multivariate Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of CHD risk across categories of red meat consumption. Substitution analyses were done by comparing coefficients in models including alternative foods as continuous variables. Results: During 932,968 person-years of follow-up, we documented 4,148 incident CHD cases of which 1,680 were fatal CHD cases. After multivariate adjustment for dietary and nondietary risk factors, both total and processed red meat intake were associated with a modestly higher risk of CHD (HR for a one serving/day increment: 1.08; 95% CI, 1.01-1.14 for total and HR=1.13; 95% CI, 1.03-1.22 for processed red meat). Substitutions of 1-serving per day of other foods (including nuts, legumes, soy, whole grains, low- and high-fat dairy) for 1-serving per day of total red meat were associated with a 10%-47% lower CHD risk. Stronger inverse associations were observed between some of these substitutions for red meat and risk of fatal CHD [substituting nuts (-17%, -27% to -6%) or whole grains (-48%, -60% to -32%), and were more pronounced when replacing processed red meat. Conclusions: Our results suggest that red meat consumption, particularly processed red meat, is associated with higher risk of CHD. Substituting high-quality plant foods such as legumes, nuts, soy, and whole grains for red meat may substantially lower CHD risk.
Exercise-Related Acute Cardiovascular Events and Potential Deleterious Adaptations Following Long-Term Exercise Training: Placing the Risks Into Perspective–An Update: A Scientific Statement From the American Heart Association
Authors: Barry A. Franklin, Paul D. Thompson, Salah S. Al-Zaiti, Christine M. Albert, Marie-France Hivert, Benjamin D. Levine, Felipe Lobelo, Kushal Madan, Anjail Z. Sharrief, Thijs M.H. Eijsvogels
Journal: Circulation (2020)

Epidemiological and biological plausibility studies support a cause-and-effect relationship between increased levels of physical activity or cardiorespiratory fitness and reduced coronary heart disease events. These data, plus the well-documented anti-aging effects of exercise, have likely contributed to the escalating numbers of adults who have embraced the notion that "more exercise is better." As a result, worldwide participation in endurance training, competitive long distance endurance events, and high-intensity interval training has increased markedly since the previous American Heart Association statement on exercise risk. On the other hand, vigorous physical activity, particularly when performed by unfit individuals, can acutely increase the risk of sudden cardiac death and acute myocardial infarction in susceptible people. Recent studies have also shown that large exercise volumes and vigorous intensities are both associated with potential cardiac maladaptations, including accelerated coronary artery calcification, exercise-induced cardiac biomarker release, myocardial fibrosis, and atrial fibrillation. The relationship between these maladaptive responses and physical activity often forms a U- or reverse J-shaped dose-response curve. This scientific statement discusses the cardiovascular and health implications for moderate to vigorous physical activity, as well as high-volume, high-intensity exercise regimens, based on current understanding of the associated risks and benefits. The goal is to provide healthcare professionals with updated information to advise patients on appropriate preparticipation screening and the benefits and risks of physical activity or physical exertion in varied environments and during competitive events.
Small cell lung cancer in African Americans
Authors: J. Eads, P. Fu, L. Patrick, N. Levitan, A. Dowlati
Journal: Journal of Clinical Oncology (2007)

18194 Background: Several factors associated with prognosis in patients with small cell lung cancer (SCLC) have been established. The association between these known prognostic factors and race, in particular in African Americans has not been reported. This study was conducted to detect differences in presentation and prognostic factors among African Americans when compared to Caucasians. Methods: A retrospective chart review was performed identifying patients diagnosed with SCLC between July 1998 and December 2005. Data collected included demographic information (age, gender and race) as well as clinical information: stage at time of diagnosis, date of diagnosis, date of death, sites of metastases, response to chemotherapy as well as presenting symptoms and lab values including serum sodium, hemoglobin, WBC, platelets, LDH and any evidence of a neurological presentation. Results: Data was available for 198 patients. There was no significant association between race and stage (p=0.594), gender and stage (p=0.731), age and stage (p=0.505) or presence of a neurological symptom at time of diagnosis and stage (p=0.63). There was a trend that African Americans were more likely to present with a neurological symptom when compared to Caucasians (25% vs. 17% respectively) but this was not statistically significant (p=0.285). There was a significant association between race and gender (p=0.019). Of African Americans with SCLC, 71.4% were female while among Caucasians there was a more even distribution between sexes (51% female, 49% male). No significant difference was detected in overall survival when gender or race were examined (p=0.595 and p=0.953 respectively) and the difference when evaluating those with a neurological presentation was marginal (p=0.086). Other prognostic factors were similar amongst Caucasians and African Americans. Conclusions: When compared with Caucasian females, African American females are more likely to be diagnosed with SCLC than their male counterparts. Although not statistically significant, there is also a trend that African Americans with SCLC are more likely to present with neurological symptoms. No significant financial relationships to disclose.
Angiotensin II type 1 receptor antagonist candesartan is an angiogenic inhibitor in MDA-MB 468 human breast cancer cells
Authors: D. Herr, M. Rodewald, G. Hack, R. Konrad, R. Kreienberg, C. Wulff
Journal: Journal of Clinical Oncology (2007)

14114 Background: The present study examined the effect of angiotensin II on the regulation of different angiogenesis associated genes in human breast cancer cells and attempted to determine whether administration of At1R blocker candesartan could suppress the angiotensin II dependent gene regulation. Methods: Angiotensin II dependent expression of vascular endothelial growth factor (VEGF), tissue inhibitor of matrix metalloproteinases 1 (TIMP-1), and hypoxia inducible transcription factor 2alpha (HIF-2alpha) as well as administration of angiotensin II and At1R blocker candesartan was analyzed in MDA-MB 468 human breast cancer cells using immunofluorescence and TaqMan-Real-Time PCR analysis. Results: VEGF, TIMP-1, HIF-2alpha and the At1R were expressed in MDA-MB 468 human breast cancer cells. Angiotensin II significantly increased gene expression of VEGF, TIMP-1, and HIF-2alpha in these cells. This effect was completely inhibited by candesartan. Conclusion: It is hypothesized that angiotensin II is involved in regulation of tumor angiogenesis in breast cancer by regulation of angiogenesis associated genes via At1R. These findings are the first evidence for targeting tumor angiogenesis by inhibition of At1R in human breast cancer cells and may lead to new therapeutical anticancer strategies proposing administration of candesartan. No significant financial relationships to disclose.
Increase in Endogenous Glucose Production With SGLT2 Inhibition Is Unchanged by Renal Denervation and Correlates Strongly With the Increase in Urinary Glucose Excretion
Authors: Carolina Solis-Herrera, Giuseppe Daniele, Mariam Alatrach, Christina Agyin, Curtis Triplitt, John Adams, Rupal Patel, Amalia Gastaldelli, Henri Honka, Xi Chen, Muhammad Abdul-Ghani, Eugenio Cersosimo, Stephano Del Prato, Ralph DeFronzo
Journal: Diabetes Care (2020)

OBJECTIVE Sodium–glucose cotransporter 2 (SGLT2) inhibition causes an increase in endogenous glucose production (EGP). However, the mechanisms are unclear. We studied the effect of SGLT2 inhibitors on EGP in subjects with type 2 diabetes (T2D) and without diabetes (non-DM) in kidney transplant recipients with renal denervation. RESEARCH DESIGN AND METHODS Fourteen subjects who received a renal transplant (six with T2D [A1C 7.2 ± 0.1%] and eight non-DM [A1C 5.6 ± 0.1%) underwent measurement of EGP with [3-3H]glucose infusion following dapagliflozin (DAPA) 10 mg or placebo. Plasma glucose, insulin, C-peptide, glucagon, and titrated glucose-specific activity were measured. RESULTS Following placebo in T2D, fasting plasma glucose (FPG) (143 ± 14 to 124 ± 10 mg/dL; P = 0.02) and fasting plasma insulin (12 ± 2 to 10 ± 1.1 μU/mL; P &amp;lt; 0.05) decreased; plasma glucagon was unchanged, and EGP declined. After DAPA in T2D, FPG (143 ± 15 to 112 ± 9 mg/dL; P = 0.01) and fasting plasma insulin (14 ± 3 to 11 ± 2 μU/mL; P = 0.02) decreased, and plasma glucagon increased (all P &amp;lt; 0.05 vs. placebo). EGP was unchanged from baseline (2.21 ± 0.19 vs. 1.96 ± 0.14 mg/kg/min) in T2D (P &amp;lt; 0.001 vs. placebo). In non-DM following DAPA, FPG and fasting plasma insulin decreased, and plasma glucagon was unchanged. EGP was unchanged from baseline (1.85 ± 0.10 to 1.78 ± 0.10 mg/kg/min) after DAPA, whereas EGP declined significantly with placebo. When the increase in EGP production following DAPA versus placebo was plotted against the difference in urinary glucose excretion (UGE) for all patients, a strong correlation (r = 0.824; P &amp;lt; 0.001) was observed. CONCLUSIONS Renal denervation in patients who received a kidney transplant failed to block the DAPA-mediated stimulation of EGP in both individuals with T2D and non-DM subjects. The DAPA-stimulated rise in EGP is strongly related to the increase in UGE, blunting the decline in FPG.
Landmark article Jan 28, 1956: Successful homotransplantation of the human kidney between identical twins. By John P. Merrill, Joseph E. Murray, J. Hartwell Harrison, and Warren R. Guild
Authors: J. P. Merrill
Journal: JAMA (1984)

A patient whose illness had begun with edema and hypertension was found to have suffered extreme atrophy of both kidneys. Because of the steady worsening of the condition and the appearance of uremia with other unfavorable prognostic signs, transplantation of one kidney from the patient's healthy identical twin brother was undertaken. Preparations included collection of evidence of monozygosity and experimental transplantation of a skin graft from the twin. During the transfer of the healthy kidney it was totally ischemic for 82 minutes. Evidence of functional activity in the transplanted kidney was obtained. The hypertension persisted until the patient's diseased kidneys were both removed. The homograft has survived for 11 months, and the marked clinical improvement in the patient has included disappearance of the signs of malignant hypertension.
Temozolomide combined with the PI3K inhibitor LY294002 or the mTOR inhibitor rapamycin inhibits melanoma cell growth, survival and invasion
Authors: F. E. Meier, K. Lasithiotakis, B. Schittek, T. Sinnberg, C. Garbe
Journal: Journal of Clinical Oncology (2007)

8559 Background: Potential therapeutic targets in the treatment of metastatic melanoma have emerged, to which pharmacological inhibitors have been designed, which may enhance tumor chemosensitivity. In melanoma, dacarbazine is considered to be the most effective agent although total responses do not exceed 20% The clinical activity of temozolomide is similar to that of dacarbazine, but temozolomide has the advantages of being absorbed orally and of crossing the blood-brain barrier. Many clinical trials of targeted therapy and chemotherapy combinations lack rigorous preclinical evaluation and may neglect relevant mechanistic interactions. The PI3K-AKT-mTOR (AKT) and RAS-RAF- MEK-ERK (MAPK) signaling pathways are constitutively activated in melanoma, and appear to play a role in chemoresistance. Methods: In this study, a panel of pharmacological inhibitors was utilized in order to block the AKT and MAPK signaling pathways at different levels (AKT: PI3K, mTOR; MAPK: RAF, MEK) in 5 human metastatic melanoma cell lines. The effects on chemosensitivity to temozolomide and cisplatin was then investigated. Results: The effects of most inhibitors on chemosensitivity varied significantly between the different cell lines. However, LY294002, a PI3K inhibitor and rapamycin, an mTOR inhibitor, consistently enhanced chemosensitivity. Treatment of melanoma cells with temozolomide or cisplatin combined with LY294002 or rapamycin had a strong effect on melanoma cell growth and survival. Invasive melanoma growth in organotypic cultures of human skin was suppressed completely. The most pronounced potentiation of efficacy was seen with temozolomide in combination with rapamycin. Conclusions: These data suggest that LY294002 and rapamycin can render melanoma cells susceptible to apoptosis, induced by chemotherapeutic agents such as temozolomide and cisplatin. Since both temozolomide and rapamycin are used clinically, the combination of temozolomide with rapamycin might potentially be utilized as an approach in melanoma treatment. This combination merits clinical investigation. No significant financial relationships to disclose.
Quantifying the Survival Benefits of Oncology Drugs With a Focus on Immunotherapy Using Restricted Mean Survival Time
Authors: Amanda Putri Rahmadian, Seanthel Delos Santos, Shruti Parshad, Louis Everest, Matthew C. Cheung, Kelvin K. Chan
Journal: Journal of the National Comprehensive Cancer Network (2020)

Restricted mean survival time (RMST) overcomes limitations of current measures of survival benefits because it directly captures information of the entire area under Kaplan-Meier survival curves. Using RMST difference (absolute survival benefit) and RMST ratio (relative survival benefit), we quantified the magnitude of survival benefits of recent oncology drugs and compared immunotherapies with nonimmunotherapies.Kaplan-Meier curves were extracted from phase II/III randomized controlled trials used by the FDA for oncology drug approvals from January 2011 through November 2017 with overall survival (OS) or progression-free survival (PFS) as primary endpoints. RMST differences, ratios, and their 95% confidence intervals were meta-analyzed to estimate absolute and relative survival benefits of contemporary oncology drugs and to compare immunotherapies with nonimmunotherapies. Meta-regression was conducted to adjust for potential confounders.Ninety-four trials with a total of 51,639 patients were included. Overall absolute survival benefits (RMST differences) were 1.55 months for OS (95% CI, 1.32-1.77) and 2.99 months for PFS (95% CI, 2.65-3.33). Overall relative survival benefits (RMST ratios) were 1.11 for OS (95% CI, 1.09-1.13) and 1.42 for PFS (95% CI, 1.36-1.48). Immunotherapy absolute PFS benefit was less than that of nonimmunotherapy (1.56 vs 3.23 months), whereas immunotherapy absolute OS benefit was larger than that of nonimmunotherapy by 0.59 months (2.02 vs 1.43 months). Adjusted OS RMST difference was 0.91 months greater for immunotherapy than for nonimmunotherapy after adjusting for confounders.Absolute survival benefits of recent oncology drugs are modest. Survival benefits of immunotherapies are not dramatically superior to those of nonimmunotherapies. Routine reporting and use of RMST may help patients, physicians, and payers make more informed and responsible decisions regarding the care of patients with cancer.
Enasidenib in patients with mutant IDH2 myelodysplastic syndromes: a phase 1 subgroup analysis of the multicentre, AG221-C-001 trial
Authors: Eytan M Stein, Amir T Fathi, Courtney D DiNardo, Daniel A Pollyea, Gail J Roboz, Robert Collins, Mikkael A Sekeres, Richard M Stone, Eyal C Attar, Mark G Frattini, Alessandra Tosolini, Qiang Xu, Wendy L See, Kyle J MacBeth, Stéphane de Botton, Martin S Tallman, Hagop M Kantarjian
Journal: The Lancet Haematology (2020)