tbuckley/cabot-search huggingface dataset:
Detection of distant metastases in breast cancer patients: Comparison between [18F]-fluorodeoxyglucose positron emission tomography and conventional imaging
Authors: S. Mahner, S. Schirrmacher, V. Müller, C. Habermann, W. Brenner, J. Dose Schwarz
Journal: Journal of Clinical Oncology (2007)

1054 Background: The presence of distant metastases is a key prognostic factor in breast cancer patients and plays a central role in therapeutic decisions. To detect distant metastases, chest X-ray, abdominal ultrasound and bone scintigraphy are performed as standard of care in many centers. In various tumors, [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) detects metastatic disease with high accuracy, but the diagnostic value in breast cancer still needs to be defined. The aim of this study was to compare the diagnostic performance of FDG-PET with conventional imaging. Methods: In 119 breast cancer patients who presented for restaging, whole-body FDG-PET was compared with chest X-ray, bone scintigraphy and abdominal ultrasound. Each imaging modality was independently assessed and classified as ‘negative’, ‘equivocal’ and ‘positive’ for metastasis. The imaging results were compared with histopathology and clinical follow-up including follow-up imaging procedures which together served as the reference standard. Results: For findings classified as ‘positive’, FDG-PET detected distant metastases with a sensitivity of 87% and a specificity of 83%. In contrast, the sensitivity and specificity of combined conventional imaging procedures was 43% and 98%, respectively. The positive and negative predictive values were 89% and 82% for FDG-PET and 96% and 69% for conventional imaging. Combining ‘equivocal’ and ‘positive’ results, the sensitivity and specificity of FDG-PET was 93% and 76%, respectively, compared to 61% and 86% for conventional imaging. The positive and negative predictive values were 86% and 88% for FDG-PET versus 77% and 75% for conventional imaging. Conclusions: FDG-PET is superior to conventional imaging procedures for detection of distant breast cancer metastases. However, the use of computed tomography (CT), particularly in combined PET/CT, needs to be addressed in future studies comparing anatomical vs. metabolic staging procedures in breast cancer patients. No significant financial relationships to disclose.
Factors associated with long-term survival following stem cell transplantation (SCT) for non-Hodgkin lymphoma
Authors: R. P. McQuellon, G. B. Russell, M. T. Jesse, C. R. Thomas, Y. Keung
Journal: Journal of Clinical Oncology (2007)

18504 Background: Psychosocial variables have been associated with survival in stem cell transplantation recipients. The purpose of this study was to examine the relationship between clinical, psychosocial, and demographic variables and long-term survival. Methods: Autologous SCT recipients with NHL (n=315) from 1/92 - 4/05 (mean age = 51.6 yrs (±12); 35% F; 7% AA; median survival/follow-up = 4.4/ 6.1 yrs) completed the Center for Epidemiologic Studies-Depression Scale, Functional Assessment of Cancer Therapy- BMT (FACT-BMT; physical well-being, PWB), Profile of Mood States, and the Medical Outcomes Study Social Support Survey (MOS-SS) prior to transplantation. Clinical and demographic data were abstracted from the patient’s record. Cox’s proportional hazards regression models were used to assess the effect of the following variables on survival: clinical - histological subtypes (HS) [anaplastic large cell (ALC), diffuse large B-cell (DLBC), mantle cell (MC), indolent, and aggressive], grade, stage, type of conditioning regimen (TC), chemosensitivity (CS), number of chemotherapy regimens (1–7) prior to SCT (NCR); demographic - age, race, gender; and psychosocial - depressed mood, general distress, quality of life, and social support. Measures with a univariate p-value &lt;0.2 were fit in a backwards stepwise regression; remaining variables had a p-value &lt; 0.05. Results: The included univariate model variables (p-values) were: HS (0.0004), grade (0.004), TC (0.14), CS (0.0001), NCR (0.02), PWB (0.03), FACT-BMT subscale (0.16), SS-Emotional (0.05), SS-affection (0.13). In the regression model, predictors of survival were: HS (&lt;0.0001), median survival = ALC 1.9, DLBC 2.7, aggressive 3.3, MC 5.1, indolent 8.4 yrs; CS (0.008); NCR (0.03), and PWB(0.03). Conclusions: Clinical variables were the most predictive of survival. Psychosocial variables were not associated with survival. No significant financial relationships to disclose.
Abstract 11410: Occupations Associated With Poor Cardiovascular Health in Women
Authors: Bede N Nriagu, Adams A Ako, Conglong Wang, Anneclaire De Roos, Robert B Wallace, Matthew A Allison, Rebecca Seguin, Rami Nassir, Yvonne Michael
Journal: Circulation (2019)

Introduction: Women’s participation in the workforce grew substantially since 1950. Among women, older women have been projected to have the largest percentage increase in labor force participation...
Role of MDM2 in DNA repair
Authors: Laura Paternoster, Anupama Munshi, Raymond E. Meyn
Journal: Cancer Research (2006)

2311  The p53 tumor suppressor protein plays a critical role in preventing tumorigenesis and the activation of p53 by stresses such as DNA damage or oncogene activation results in either cell cycle arrest or apoptotic cell death. MDM2, the mdm2 gene product, is an E3 ligase that plays a central role in regulating p53 stability, targeting both p53 and itself for ubiquitination. p53 activates expression of MDM2, which keeps p53 levels low during normal growth and development, creating a feed-back auto-regulatory loop between p53 and MDM2. Amplification of mdm2 or increased expression by unknown mechanisms occurs in many tumors that retain wild-type p53, leading to the hypothesis that overexpression of MDM2 is an important mechanism by which the cell inactivates p53 in the process of transformation. At the same time, some tumors contain both high levels of MDM2 and mutation in the p53 gene. The reasons for disrupting two components of the same pathway are unclear but suggest that MDM2 may have other p53-independent functions and the pathways that mediate these functions are unresolved. Recently, studies described a novel interaction of MDM2 with the DNA repair protein Nbs1. The binding between MDM2 and Nbs1 was direct and independent of p53 and occurred at Nbs1 nuclear foci following γ-irradiation. In light of these recent observations, we decided to investigate the possible involvement of MDM2 in DNA repair following γ-irradiation. We examined MDM2 nuclear localization following γ-irradiation in two different tumor cell lines, A549 and H1299, the former expressing wild-type p53 and the latter being p53 null. Our results indicate that MDM2 localization in nuclear foci follows different kinetics in the two cell lines. In A549 cells, a relatively small number of foci were observed at 1 hour after irradiation, but these disappeared at 2 hours. Then, MDM2 foci reappeared at 4 hours and increased through 24 hours. This pattern while evident was not as dramatic in the H1299 cells which had a relatively high background in unirradiated cells. These new observations suggest that MDM2 can play a role in the DNA repair response which can be distinct from the DNA damage checkpoint response regulated by p53.
Infusion-related reactions (IRR) associated with cetuximab plus irinotecan treatment in patients with irinotecan-resistant metastatic colorectal cancer (mCRC): Findings from the MABEL study
Authors: S. Siena, R. Glynne-Jones, J. Thaler, A. Adenis, P. Preusser, E. Aranda Aguilar, M. Aapro, A. Loos, R. Esser, H. Wilke
Journal: Journal of Clinical Oncology (2007)

4137 Background: Cetuximab is an IgG1 anti-EGFR monoclonal antibody, active alone and in combination with irinotecan in mCRC patients (pts) who have failed prior irinotecan therapy. In previous studies with cetuximab, IRRs were observed in a small proportion of pts especially at the first infusion. Methods: MABEL investigated cetuximab plus irinotecan in pts with EGFR-detectable mCRC whose last treatment regimen contained irinotecan. A secondary objective of MABEL was to further study cetuximab-related adverse events. Study treatment was cetuximab, initial dose 400 mg/m 2 , weekly 250 mg/m 2 , plus irinotecan with dose and schedule as pre-study. Data analyzed included prophylactic pre-medication, IRRs and medication for IRRs. Prophylactic medication given before the first cetuximab infusion was categorized as chlorphenamine antihistamines, antihistamines other than chlorphenamine, and any antihistamines plus corticosteroids. Results: Overall, 1147 pts were treated in this study: median age was 62 years [25–84], Karnofsky performance status was =70% and 64% pts were male. 1,122 patients were pre-treated with antihistamines. The frequency of IRRs was lower in pts who received antihistamines plus corticosteroids than in pts who received antihistamines alone (9.6% vs 25.6% any grade, 1% vs 4.7% grade 3/4 IRRs). The primary efficacy variable of MABEL was the 12-weeks progression-free survival (PFS) status. Efficacy results by pre-medication groups for PFS (see table ) and overall survival do not suggest differences related to prophylactic pre-medication. Conclusions: The data suggest that the type of pre-medication impacts on the occurrence of IRRs, and that the addition of corticosteroids to antihistamines reduces IRRs without altering antitumor efficacy in the analyzed pre-medication groups. [Table: see text] No significant financial relationships to disclose.
Increased foxp3+ regulatory T cells predicts for superior relapse-free and overall survival in early stage hepatocelullar carcinoma
Authors: H. Toh, Y. P. Phoon, R. Quek, A. H. Banham, S. Y. Tan
Journal: Journal of Clinical Oncology (2007)

4642 Background: Hepatocellular carcinoma (HCC) endemic in Asia is aggressive and mainly hepatitis B-related. In ovarian and breast cancer, higher levels of foxp3+ regulatory T cells predicts for a poorer clinical outcome. The reverse is true with follicular lymphoma and Hodgkin’s disease. We hypothesize that foxp3+ CD4+ regulatory T lymphocyte (Treg) frequency predicts for clinical outcome in HCC. We also examined the recently identified IL17-producing, RORγt-expressing, CD4+ pathogenic Th17 cells in HCC. Methods: We analyzed Treg cells (n=116) and CD8+ T cells (n=24) expression by CD3/Foxp3 double immunoenzymatic using a anti-Foxp3 murine monoclonal antibody (Nuffield Department of Clinical Laboratory Sciences, Oxford University, UK) and CD3/CD8 double immunofluorescence, respectively. Treg cells and CD8 cells expression were reported as a percentage of CD3+ T cells. RORγt (for Th17) and Foxp3 mRNA were measured using real-time PCR. Results: Median age (n=116) was 62 years, 65.5% were hepatitis B+ (n=76), 4.3% were hepatitis C+ (n=5), 1.7% were both hepatitis B+ and C+ (n=2) and 28.4% were not virus-related (n=33). Treg numbers were significantly higher in all 116 HCC (median 9.3% of CD3+ T cells) compared to paired adjacent liver (median 1.9%) (p&lt;0.001). Conversely, CD8 + T cell numbers were significantly lower in 24 HCC (median 21.1%) vs paired liver (median 49.5%) (p&lt;0.001). Stage 1 and II HCC patients (n=24) with superior overall survival (= 6 years) compared with stage I and II patients (n=29) with inferior survival (≤ 1 year) had a significantly higher Treg frequency (median 10.9% versus 8.4%) (p=0.035). Stage I and II HCC patients (n=66) who were relapse-free at ≥ 1 year vs Stage I and II HCC patients (n=21) who were relapse-free at ≤ 0.5 years had higher Treg frequency (median 10.2% vs 6.8%) (p = 0.005). Hepatitis B+ HCC patients (n=76) had significantly higher Treg (median 10.2%) compared to non-viral associated HCC patients (n=33) (p=0.013). No correlation was seen between ROR and foxp3 mRNA. ROR mRNA was over-expressed (&gt; 1 fold) in 20 (54%) HCC (analysis ongoing). Conclusions: Treg expression was significantly higher in HCC compared to paired liver. Increased Treg frequency predicts for a superior relapse-free and overall survival in HCC. No significant financial relationships to disclose.
Abstract P553: The Association of Social Engagement With Cardiovascular Disease Risk Depends on the Risk Horizon: Comparing 10-year, 30-year and Lifetime Risk Estimates
Authors: Steven D Barger
Journal: Circulation (2020)

Introduction: Social engagement, or the extent to which people enact social ties in real life, is inversely associated with survival. However, less is known about how persons with low vs. high levels of social engagement differ across intermediate health pathways such as cardiovascular disease (CVD) risk. CVD risk comparisons that examine both short and long-term risk are particularly important because age is heavily weighted in short term CVD risk estimates whereas it is absent from lifetime risk estimates. Comparing across CVD risk epochs (10-year, 30-year and lifetime) more clearly partitions the influence of nonmodifiable (age) versus modifiable (blood pressure; lipids, etc.) disease risk elements with respect to social relationship resources. Hypothesis: Are risk differences for low vs. high social engagement consistent across three CVD risk definitions? Methods: Data are from adults free of baseline CVD who participated in in the Third National Health and Nutrition Examination Survey. Six activities comprised the social engagement score: talking on the phone with family, friends or neighbors; getting together with friends or relatives; visiting neighbors; attending church or religious services; belonging to a club or group; attendance at club or group activities. Participation was scored as present/absent; the 0 and 1 categories were combined. CVD risk was assessed using 1) the pooled cohort equations for 10-year risk (ages 40-79; N = 7195); 2) Framingham 30-year hard CVD risk (ages 20-59; N = 10,626); and 3) lifetime risk using established modifiable risk factors but excluding age (ages 20-79; N = 19,320). As per previous literature the latter was collapsed into low (&lt; 39%) and high (&gt;= 39%) lifetime risk. Results: Among the youngest age group common to all three risk estimates (40-49 years old) the 10 year risk difference was 2% across the lowest (0/1) versus highest (6) social engagement scores (4.3% vs. 2.3%, respectively), 6.6% for 30-year hard CVD risk (21.3% vs. 14.7%, respectively) and 19.7% (79.8% vs. 60.1%, respectively) for high lifetime risk. Among younger age groups (20-29 years) the social engagement score risk difference was very small for 30-year risk (0.5%; 3.3% vs. 2.8%) but was large (15.9%) for lifetime risk (60.7% vs.44.8%). A large social engagement score difference for lifetime CVD risk (26.3%) was also observed for persons aged 30-39 years (81.2% vs. 54.9%). In contrast, small ten-year (2.6%) and lifetime risk (2.9%) differences across low vs. high social engagement were observed among persons aged 70-79. Conclusions: CVD risk differences across high and low social engagement are smaller when using age-dependent risk estimates but are substantially larger when comparing lifetime risk, which is not age-dependent. Low social engagement is a marker of substantial modifiable lifetime CVD risk for persons under age 50.
Pattern of malignancies in geriatric patients
Authors: L. S. Maddali, S. Maddali
Journal: Journal of Clinical Oncology (2007)

19650 Background: Information regarding pattern of malignancies in geriatric patients in India is not readily available. Methods: Between 1st January 1999 and 31st December 2006 we encountered 832 geriatric patients among a total of 3748 cases. Analysis was done with respect to age, sex and disease. Results: Geriatric patients constituted 832/3748 (22.20%) of our work load. Males 432 (51.92%) Females 400 (48.08%). Hematologic malignancies 214 (25.72%) Solid tumors 618 (74.28%). male preponderance in Hematologic malignancies 141/214 (66.89%); female preponderance in solid tumors 327/618 (52.91%). Top 7 malignancies: Males (432)-NSCLC 60 (13.89%) Prostate 57 (13.19%) NHL 48 (11.11%) Myeloma 39 (9.03%) CLL 31 (7.18%) HNSCC 30 (6.94%) Colon 26 (6.02%); Females (400)- Breast 147 (36.75%) Ovary 50 (12.50%) Uterus 44 (11.00%) NHL 25 (6.25%) Colon 20 (5.00%) NSCLC 11 (2.75%) CML 10 (2.50%). Age groups: (65–70) yrs-517 (62.13%) males 254, females 263; (71–80) yrs-264 (31.73%) males 152 females 112; (81–90) yrs-48 (5.78%) males 24, females 24; &gt;91yrs-3 (0.36%) males 2 female 1. Top 5 malignancies in each age &amp; sex group: Males, (65–70) yrs, 254: NSCLC 39 NHL 30 Prostate 29 Myeloma 24 Colon 19; (71–80) yrs, 152: Prostate 20 NSCLC 19 NHL 17 CLL 15 HNSCC 14; (81–90) yrs, 24: Prostate 7 Myeloma 2 CLL 2 CML 2 AML 2; Females, (65–70) yrs, 263: Breast 99 Ovary 37 Uterus 30 colon 13 NHL 13; (71–80) yrs, 112: Breast 41 Ovary 12 NHL 11 Uterus 10 CLL 9; (81–90) yrs, 24: Breast 7 Uterus 4 CLL 2 Renal cell carcinoma 2 Ovary 1. Conclusions: Solid tumors are the predominant malignancies in geriatric patients 618/832 (74.28%). B Cell neoplasms constitute bulk of the hematologic neoplasms 173/214 (80.84%). Sarcomas are uncommon 20/832 (2.40%). Important solid tumors: Prostate, NSCLC, Colon and HNSCC in males; Breast, Ovary, Uterus and colon in females. Age group (65–70) yrs is the major group 517/832 (62.13%) followed by significant age group (71–80) yrs 264/832 (31.73%). It is imperative to employ curative strategies for malignancies in this ever expanding population. No significant financial relationships to disclose.
Covid-19: What’s the current advice for UK doctors?
Authors: Abi Rimmer
Journal: BMJ (2020)

UK employers have a legal obligation under the Health and Safety at Work Act 1974 to protect staff from harm. And the Control of Substances Hazardous to Health Regulations place a duty to carry out individual risk assessments to identify hazards, quantify risks, and put suitable controls in place, says Steven Nimmo, editor of the Occupational Medicine Journal . “If the risk assessment establishes that personal protective equipment (PPE) is required then your employer must provide it, properly fit it, and provide suitable instruction and training in its use,” he says.

Public Health England’s guidance says that clinicians preparing to assess a patient with suspected covid-19 must wear PPE, which as a minimum should be a correctly fitted FFP3 respirator, gown, gloves, and eye protection.1 Doctors seeing patients with confirmed covid-19 must wear full PPE, including a FFP3 respirator, disposable eye protection, and preferably a visor, a long sleeved disposable gown, and gloves, PHE says. For symptomatic, unconfirmed patients, doctors should wear a fluid resistant surgical mask, gloves, apron and eye protection if there is a risk of splashing into the eyes, PHE recommends.2

“Pregnant women and children are not at high risk,” Nimmo says. “But the above legal obligations still apply. Immunosuppressed people may well be at increased risk, depending on the reason for the immunosuppression, and drug type and dosage, and so on. The risk assessment should take this into account. The advice may well be to avoid exposure to covid-19, which could mean redeployment to a non-frontline role.”

People with chronic heart …
Should We Train Female and Male Residents Slightly Differently?
Authors: Oksana Babchenko, Katherine Gast
Journal: JAMA Surgery (2020)

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Abstract P121: Multidimensional Allostatic Load Score Directly Associates With Coronary Artery Disease Burden in Psoriasis
Authors: Sundus S Lateef, Mariyam Batool, Nina Prakash, Domingo E Uceda, Amit K Dey, Khaled M Abdelrahman, Youssef Elnabawi, Aarthi S Reddy, Maryia D Svirydava, Navya Nanda, Justin A Rodante, Andrew Keel, Heather L Teague, Mina Al Najafi, Wunan Zhou, Martin P Playford, Marcus Y Chen, Tiffany M Powell-Wiley, Nehal N Mehta
Journal: Circulation (2020)

Introduction: Psoriasis is a chronic inflammatory skin disease associated with accelerated development of asymptomatic coronary artery disease (CAD) by coronary computed tomography angiography (CCTA). Allostatic load score is a multidimensional measure related to chronic stress which incorporates cardiovascular, metabolic and inflammatory indices. To better understand the physiologic impact of chronic stress in psoriasis, we studied the association between allostatic load score and subclinical CAD. Hypothesis: We hypothesized that allostatic load score would associate with coronary artery disease burden beyond traditional risk factors in an ongoing psoriasis cohort study. Methods: Consecutive psoriasis patients (n=275) underwent CCTA for assessment of coronary artery disease burden (QAngio, Medis). Allostatic load score was determined using established methods (see Table 1 footnote). The association between coronary artery disease burden and allostatic load score was characterized by multivariable regression (STATA 12). Results: Psoriasis patients were middle-aged, predominantly male and white, with low cardiovascular risk by Framingham risk score and moderate-severe psoriasis severity (Table 1) . Allostatic load score associated with total coronary burden (β=0.39; p&lt;0.001) and non-calcified coronary burden (β=0.40; p&lt;0.001) in unadjusted analyses. In multivariable models, allostatic load score was still associated with total coronary burden (β=0.30; p&lt;0.001) and non-calcified coronary burden (β=0.31; p&lt;0.001) independent of race, Framingham risk score and waist-hip ratio. Conclusions: Allostatic load score positively associated with both total and non-calcified coronary artery burden beyond traditional risk factors, suggesting multisystem physiologic dysregulation related to chronic stress may drive subclinical atherosclerosis in psoriasis. Efforts to understand stress effects and its reduction are critical in this population at high-risk for cardiovascular disease.