tbuckley/cabot-search huggingface dataset:
Risk of rare adult-type carcinomas as a subsequent malignant neoplasm in survivors of childhood cancer: The Childhood Cancer Survivor Study
Authors: M. Bassal, N. S. Kadan-Lottick, J. Neglia, L. Taylor, Y. Yasui, D. L. Friedman, A. C. Mertens, L. L. Robison, A. T. Meadows
Journal: Journal of Clinical Oncology (2004)

8530 Background: Subsequent malignant neoplasms (SMNs) are a leading cause of late mortality in survivors of childhood cancer. Using the Childhood Cancer Survivor Study (CCSS) cohort, we determined the risk of carcinomas occurring as SMNs excepting breast, thyroid and skin cancers. Methods: A retrospective cohort of 14,352 five-year survivors of childhood cancers treated at 25 US and Canadian institutions was assembled. SMNs were ascertained through self-administered questionnaires and confirmed with pathology reports. Cumulative incidence, age- and gender-matched standardized incidence ratios (SIRs) were calculated. Results: In 71 individuals, 71 carcinomas of interest were found at a median age of 27 years (range 10–44 years) and a median elapsed time of 15 years (range 6–28 years) from first malignancy. Twenty-five (35%) SMNs occurred in the genitourinary system, 23 (32%) in the head and neck area, 16 (23%) in the digestive tract, 4 (6%) in the thorax and the remainder (4%) in other sites. Fifty-nine subjects (83%) had received radiation therapy, 49 (69%) had a history of alkylator therapy, and 8 (11%) had a history of epipodophyllotoxin therapy. Forty-two carcinomas (59%) arose in a radiation field. An excess of carcinomas was found following all childhood diagnoses, and was highest for neuroblastoma (SIR = 24.2 [95% confidence interval [CI] = 12.6–46.5]), soft tissue sarcomas (SIR = 6.2, [95% CI = 3.5–11]) and Wilms tumor (SIR = 4.8 [95% CI = 1.5–14.8]). There was a significant excess of carcinomas in most of the morphology types examined and was greatest for mucoepidermoid neoplasms (SIR=34.0 [95%CI= 19.3–59.9]) and renal cell carcinomas (SIR = 13.3 [95%CI = 6.7–26.7]). The 20-year cumulative incidence for all SMNs in this report is 0.45%. Conclusions: Childhood cancer survivors are at increased risk of developing subsequent adult-type carcinomas, but the cumulative incidence is low. Further analyses of the contribution of patient and treatment factors to the increased risk of carcinomas in this population are in progress. No significant financial relationships to disclose.
Taking stock of the first 133 MERS coronavirus cases globally – Is the epidemic changing?
Authors: P M Penttinen, K Kaasik-Aaslav, A Friaux, A Donachie, B Sudre, A J Amato-Gauci, Z A Memish, D Coulombier
Journal: Eurosurveillance (2013)

Since June 2012, 133 Middle East respiratory syndrome coronavirus (MERS-CoV) cases have been identified in nine countries. Two time periods in 2013 were compared to identify changes in the epidemiology. The case-fatality risk (CFR) is 45% and is decreasing. Men have a higher CFR (52%) and are over-represented among cases. Thirteen out of 14 known primary cases died. The sex-ratio is more balanced in the latter period. Nosocomial transmission was implied in 26% of the cases.
Abstract 762: 14-Aminocamptothecin: Synthesis, preclinical activity, and potential use for cancer treatment
Authors: Jian-Xin Duan, Xiaohong Cai, Jessica D. Sun, Fanying Meng, Qian Liu, Deepthi Bhupathi, Dharmendra Ahluwalia, Heli Huang, Don Jung, Charles Hart, Mark Matteucci
Journal: Cancer Research (2010)

Abstract Topoisomerase I targeted camptothecin analogs are currently employed in a number of different anti-cancer therapeutic regimens. Although efficacious, there continue to be active efforts to develop new camptothecin analogs that avoid deficiencies of the current drugs. The extensive historical SAR efforts on camptothecin and its analogs have largely ignored the 14 position. Only the chloro derivative has been reported, and it is inactive, suggesting a lack of tolerance for substitution at that position. We have developed a highly regioselective process for the synthesis of 14-nitro and 14-aminocamptothecin. 14-aminocamptothecin (TH-1320) demonstrated comparable cytotoxic potency relative to the parent camptothecin, and to clinically relevant camptothecin analogs (topotecan, SN-38) when tested on a panel of human cancer cell lines in vitro (H460, PC3, HT29). Unlike most camptothecin analogs in clinical trials, TH-1320 is not a substrate for any of the major clinically relevant efflux pumps, (MDR1, MRP1, and BCRP). Unlike camptothecin, the potency of TH-1320 is minimally affected by the addition of human serum albumin to cell culture media. TH-1320 showed good bioavailability and brain penetration when dosed orally in mice. TH-1320 is tolerated up to 30 mg/kg with daily oral dosing (MTD). An H460 human NSCLC xenograft model in nude mice was produced by s.c. implantation of 1 ×106 cells into the flank of the animals. When tumor size was approximately 150mm3, animals were randomized into groups of 10 mice each for dosing. 30mg/kg of TH-1320 treatment yielded 79% tumor growth inhibition (TGI) and 15 days tumor growth delay (TGD), while the body weight loss was less than 4%, which suggested a good therapeutic index. Two out of 10 animals showed complete response in the study. However, in same model, Topotecan daily dose at 2mg/kg (MTD) showed only 46% TGI. A xenograft model of metastatic ovarian cancer was set up by the intraperitoneal (i.p.) injection of 3×106 IGROV1 human ovarian cancer cells in nude mice. Mice were evaluated twice a week for morbidity and mortality. Kaplan-Meier survival curves were plotted. Vehicle treated animals had a median survival time (MST) of 39 days. TH-1320 treatment significantly prolonged the survival time. MST of 2/3 MTD dose of TH-1320 (20mg/kg, QDx5/wk x 2wks) was 78 days (p&amp;lt;0.05 vs. vehicle by Logrank test), which was similar to the MTD dose of Topotecan (2mg/kg) or Karenitecin (1.5mg/kg) (MST was 72.5 and 71 days, respectively). Given the favorable properties of TH-1320, further effort is warranted. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 762.
FRI0408 Body mass index and depression are independently associated with knee pain and activity limitations in knee osteoarthritis: Results from the AMS-OA cohort
Authors: J.F.M. Holla, M. van der Leeden, L.D. Roorda, M. van der Esch, R.E. Voorneman, W.F. Lems, J. Dekker
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Body mass index (BMI) and depression are positively associated with each other (Rosemann et al. 2008), and positively associated with pain and activity limitations in knee osteoarthritis (OA) patients (Dekker et al. 2009). There is growing evidence that metabolic factors are involved in both the development of overweight and depression (McIntyre et al. 2007). This raises the question whether BMI and depression are related to knee pain and activity limitations independently of each other. <h3>Objectives</h3> To establish if BMI and depression are independently associated with knee pain and activity limitations in knee OA patients. <h3>Methods</h3> A cross-sectional study was conducted in a sample of 304 participants with knee OA from the Amsterdam Osteoarthritis Cohort. All patients fulfilled the American College of Rheumatology (ACR) clinical criteria for knee OA. Depression was measured with the Hospital Anxiety and Depression Scale. Pain was measured with a numeric rating scale for knee pain during the last week, and activity limitations were measured with the Western Ontario and McMaster Universities Osteoarthritis Index and the timed get up and go test. Multivariable regression analyses were performed with BMI and depression as independent variables, and pain and activity limitations as dependent variables. Regression models with only BMI or only depression as independent variable were compared with regression models with both BMI and depression as independent variables. All analyses were adjusted for age, gender, civil status, educational level and comorbidity count. <h3>Results</h3> BMI and depression were independently associated with knee pain. After adjustment for each other the regression coefficients (Bs) of BMI and depression changed with 20.5% and 16.4% respectively, and were still significantly associated with knee pain (p≤0.01). BMI and depression were independently associated with both self-reported and performance-based activity limitations (p≤0.01). After adjustment for each other the Bs of BMI and depression changed with 10.3% and 27.9% in the analyses with self-reported activity limitations as dependent variable, and with 4.7% and 40.6% in the analysis with performance-based activity limitations as dependent variable. <h3>Conclusions</h3> The association between overweight and knee pain and activity limitations is not explained by depression, and the association between depression and knee pain and activity limitations is not explained by overweight. Both BMI and depression are independently associated with knee pain and activity limitations. As a consequence, in treating patients with knee OA, overweight and depression should both be targeted. <h3>Disclosure of Interest</h3> None Declared
Cost-Effectiveness Analysis in a Setting of Budget Constraints — Is It Equitable?
Authors: Peter A. Ubel, Michael L. DeKay, Jonathan Baron, David A. Asch
Journal: New England Journal of Medicine (1996)

One of the promises of cost-effectiveness analysis is that it can demonstrate how to maximize health benefits attainable within a specific limited budget. Many people argue, however, that when there are budget limitations, the use of cost-effectiveness analysis leads to health care policies that are inequitable.
Heal the Burn: Pepper and Lasers in Cancer Pain Therapy
Authors: C. Nelson
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Heal the Burn: Pepper and Lasers in Cancer Pain Therapy Get access Corinna Nelson Corinna Nelson Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 18, 21 September 1994, Pages 1381–1382, https://doi.org/10.1093/jnci/86.18.1381 Published: 21 September 1994
Aberrant Interleukin-1 Receptors in a Cortisol-Secreting Adrenal Adenoma Causing Cushing's Syndrome
Authors: Holger S. Willenberg, Constantine A. Stratakis, Christian Marx, Monika Ehrhart-Bornstein, George P. Chrousos, Stefan R. Bornstein
Journal: New England Journal of Medicine (1998)

Cortisol-secreting adrenal adenomas are an uncommon cause of Cushing's syndrome. Little is known about the events leading to the formation of these tumors, but molecular defects, including activating mutations of receptors for corticotropic factors, have been suspected in this process. Structural mutations of the corticotropin-receptor gene have not been detected in these tumors,1 but some have had gastric inhibitory polypeptide,2,3 vasopressin,4 and more recently, β-adrenergic receptors.5 In this report, we provide evidence of the involvement of immune cells and one of their cytokine products in the formation of an adrenocortical adenoma in a patient with Cushing's syndrome. A striking . . .
FRI0449 Retro-Orbital Granuloma in Granulomatosis with Polyangiitis
Authors: B. Bitik, L. Kilic, O. Kucuksahin, K. Sahin, R. Mercan, A. Tufan, S. Pay, O. Karadag, A. Ates, S. Haznedaroglu, B. Goker
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Retro-orbital granuloma is a rare and devastating component of granulomatosis with poliangiitis (GPA). Current medical treatment protocols are falling short and outcomes are poor [1-2]. <h3>Objectives</h3> To investigate the frequency, clinical features and treatment outcomes of retro-orbital granuloma in patients with GPA. <h3>Methods</h3> This is a retrospective, multi-center study, which involves GPA cohorts from five different clinics. Data were extracted from patient charts including history, physical examination, radiologic-laboratory-histological findings and treatment protocols. Major clinical outcome measures were changes in the volume of the granuloma on comparative MRI, and visual acuity on repeated ophthalmologic examinations. <h3>Results</h3> Among 153 GPA patients, 9 (5 female, 4 male) were diagnosed with a retro-orbital granuloma. Average duration of disease was 8 years. Proptosis and diplopia were the dominant presenting symptoms (77%), followed by orbital pain (55%). Three out of nine patients had isolated retro-orbital granulomas, without other organ involvement of GPA. Three patients had already been diagnosed with GPA, prior to the development of the retro-orbital granuloma. Seven patients received conventional pulse steroid and pulse cyclophosphamide as the first line remission induction therapy. Six of these patients had progressive disease and one had stable disease. Seven patients received rituximab (1 as the first-line, 6 as the second-line) as a remission induction therapy. None of these patients had progression following rituximab therapy. In four of these patients mass size on MRI remained stable while in the remaining three it decreased. 3 patients underwent orbital decompression surgery. The indication for the decision for surgery was either progressive loss of vision or intractable pain. <h3>Conclusions</h3> Standard first-line chemotherapy (cyclophosphamide and steroids) was ineffective against retro-orbital granuloma associated with GPA. Rituximab could be an alternative in these cases. Surgical intervention may help to decrease the morbidity. Further prospective studies with greater patient numbers are needed to test the clinical efficiency of Rituximab as a first-line remission induction chemotherapy. <h3>References</h3> Pagnoux, C., et al., Wegener9s granulomatosis strictly and persistently localized to one organ is rare: assessment of 16 patients from the French Vasculitis Study Group database. J Rheumatol, 2011. 38(3): p. 475-8. Holle, J.U., et al., Orbital masses in granulomatosis with polyangiitis are associated with a refractory course and a high burden of local damage. Rheumatology (Oxford), 2013. 52(5): p. 875-82. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2372
Compelling Evidence for Coronary-Bypass Surgery in Patients with Diabetes
Authors: Mark A. Hlatky
Journal: New England Journal of Medicine (2012)

Seventeen years ago, the National Heart, Lung, and Blood Institute issued a clinical alert1 that coronary-artery bypass grafting (CABG) had better rates of survival than percutaneous coronary intervention (PCI) in patients with diabetes. The alert was based on the results of the Bypass Angioplasty Revascularization Investigation (BARI) trial,2 in which patients with multivessel coronary artery disease were randomly assigned to undergo either CABG or PCI.This recommendation has been controversial ever since, largely because subsequent trials comparing CABG and PCI have enrolled only small numbers of patients with diabetes. A pooled analysis of 10 randomized trials involving 1233 patients with . . .
FRI0392 The specific role of glutaredoxin2 isoform B (GLRX2B) in rankl-induced osteoclastogenesis through activation of the P38-MAPK signaling pathway
Authors: M.-S. Lee, J.-T. Yeon, J.-M. Oh, J.-U. Choi, W.-H. Yoo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Recently, reactive oxygen species (ROS) and antioxidant enzymes were shown to be closely associated with RANKL-mediated osteoclast differentiation. Although glutaredoxin2 (Glrx2) plays a role in cellular redox homeostasis, its role in RANKL-mediated osteoclastogenesis is unclear. <h3>Objectives</h3> The aim of this study was to examine the effect of Glrx2 on osteoclast differentiation <h3>Methods</h3> Osteoclast formation was evaluated in bone marrow cells (BMC) in specific condition with over-expression of Glrx2 or down- regulation of Glrx2 during receptor activator of NF-κB ligand (RANKL)- mediated osteoclastogenesis. The expression of c-fos and NFATc1 mRNA in osteoclast precursor were assessed by RT-PCR. The levels of c-fos and NFATc1 protein were assessed by western blot. Also the mitogen-activated protein (MAPK)s pathways were measured using Western blot analysis. <h3>Results</h3> We found that Glrx2 isoform b (Glrx2b) expression is induced during RANKL-mediated osteoclastogenesis. Over-expression of Glrx2b strongly enhanced RANKL-mediated osteoclastogenesis. In addition, Glrx2b-transduced BMMs enhanced the expression of key transcription factors c-Fos and NFATc1, but pre-treatment with SB203580, a p38-specific inhibitor, completely blocked this enhancement. Conversely, down-regulation of Glrx2b decreased RANKL-mediated osteoclastogenesis and the expression of c-Fos and NFATc1 proteins. Also, Glrx2b down-regulation attenuated the RANKL-induced activation of p38. <h3>Conclusions</h3> Taken together, these results suggest that Glrx2b enhances RANKL-induced osteoclastogenesis via p38 activation. It may bevery useful information for treatment of bone-resorbing disorders, such as rheumatoid arthritis and osteoporosis. <h3>Disclosure of Interest</h3> None Declared
A Comparison of Physical Therapy, Chiropractic Manipulation, and Provision of an Educational Booklet for the Treatment of Patients with Low Back Pain
Authors: Daniel C. Cherkin, Richard A. Deyo, Michele Battié, Janet Street, William Barlow
Journal: New England Journal of Medicine (1998)

There are few data on the relative effectiveness and costs of treatments for low back pain. We randomly assigned 321 adults with low back pain that persisted for seven days after a primary care visit to the McKenzie method of physical therapy, chiropractic manipulation, or a minimal intervention (provision of an educational booklet). Patients with sciatica were excluded. Physical therapy or chiropractic manipulation was provided for one month (the number of visits was determined by the practitioner but was limited to a maximum of nine); patients were followed for a total of two years. The bothersomeness of symptoms was measured on an 11-point scale, and the level of dysfunction was measured on the 24-point Roland Disability Scale.
Simple, Effective, but Out of Reach? Public Health Implications of HCV Drugs
Authors: John W. Ward, Jonathan H. Mermin
Journal: New England Journal of Medicine (2015)

The results of four clinical trials showing the excellent safety and efficacy of a 12-week course of sofosbuvir (an NS5B inhibitor licensed in the United States in 2013) and velpatasvir (a new NS5A inhibitor) in treating patients with hepatitis C infection (HCV) are reported now in the Journal.13 In two of these studies, ASTRAL-1 and ASTRAL-2, 97 to 100% of patients with HCV genotype 1a, 1b, 2, 4, 5, or 6 had a sustained virologic response at 12 weeks after the end of therapy, a marker that is indicative of virologic cure. Similar efficacy was observed among patients . . .
Former Scottish chief medical officer resigns from BMA over junior doctors’ action
Authors: Zosia Kmietowicz
Journal: BMJ (2016)

The former chief medical officer for Scotland, Mac Armstrong, has resigned from the BMA after more than 40 years because of the decision by junior doctors in England to hold an all-out strike over the government’s intention to impose a new contract on them.

In a letter to Mark Porter, chairman of the BMA council, Armstrong said that he could “no longer continue to be associated with an organisation which . …
A5.20 Low vitamin D status is associated with avascular necrosis: an atherosclerosis prevention in paediatric lupus erythematosus substudy
Authors: R Gurion, V Tangpricha, E Yow, LE Schanberg, GA McComsey, AB Robinson
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Avascular necrosis (AVN) can result in significant morbidity. Previous studies suggest that AVN is associated with systemic lupus erythematosus (SLE) and corticosteroid treatment. Hypovitaminosis D has been postulated to play a role in bisphosphonate-associated osteonecrosis of the jaw. Using frozen serum and demographic data from the Atherosclerosis Prevention in Paediatric Lupus Erythematosus (APPLE) trial, we conducted an exploratory analysis to assess associations between AVN and demographics, SLE disease activity and vitamin D deficiency, defined as serum 25-hydroxyvitamin D [25(OH)D] &lt; 20 ng/mL. <h3>Methods</h3> APPLE trial participants were randomised to placebo or atorvastatin. Frozen serum collected at baseline was used to measure 25(OH)D levels by chemiluminescent assay (IDS, LTD). Univariable analysis of APPLE data at baseline to 3 years was performed using chi- squared test for categorical baseline variables and Wilcoxon signed rank test for continuous variables. <h3>Results</h3> Samples were available for 201/221 APPLE participants. 17/201 (8.4%) either had a history of (n = 9) or developed AVN during the study period (n = 8). Vitamin D deficiency, minority status, southern latitude, elevated triglycerides, and a history of hypertension and/or glomerulonephritis were associated with the presence or development of AVN (table). Body mass index, presence of antiphospholipid antibodies, SLEDAI, SLE disease duration and corticosteroid use were not associated with AVN. <h3>Conclusion</h3> This is the first report of vitamin D deficiency associated with AVN in paediatric lupus. There was a trend towards lower vitamin D levels in subjects who developed AVN during the 3 years of the trial, but this was not statistically significant likely due to low numbers. AVN has devastating consequences, and its pathogenesis is likely multi-factorial. Unlike other studies, no association was seen between steroid use and AVN. This association does not prove causation, but suggests future avenues of study and may suggest a method of prevention for AVN.
NT-16 * NANOPARTICLE-MEDIATED DELIVERY OF ANTI-Ape1 siRNA SENSITIZES PEDIATRIC BRAIN TUMOR CELLS TO RADIATION THERAPY BY INHIBITING DNA REPAIR
Authors: F. Kievit, Z. Stephen, K. Wang, C. Dayringer, R. Ellenbogen, J. Silber, M. Zhang
Journal: Neuro-Oncology (2014)

Pediatric brain tumors are the leading cause of death in children, and survival is frequently accompanied by one or more radiation-induced adverse developmental and psychosocial sequelae. Radiotherapy (RT) is an integral component of the treatment for medulloblastoma (MB) and the only effective adjuvant therapy for ependymoma (EP). Therefore, there is an urgent need to develop strategies to enhance the tumoricidal action of RT while sparing adjacent normal tissue. The multifunctional DNA repair protein Ape1/Ref-1 has been implicated in conferring radiation resistance in pediatric brain tumors. However, inhibiting Ape1 activity in the clinic has been hindered by the lack of safe and effective drugs and siRNA delivery vehicles. We have previously developed a nanoparticle that can deliver siRNA specifically to brain tumors for efficient knockdown of GFP. Here, we aimed to deliver siRNA against Ape1 to improve tumor cell kill after RT. Nanoparticles were loaded with siApe1, or siGFP as a control, and used to treat UW228 (MB) and Res196 (EP) cells. Ape1 expression levels were measured using PCR and Western blot, and the abasic endonuclease activity of Ape1 was determined using an Ape activity assay. Cells were then treated with 137Cs-γ-rays and cell survival monitored using clonogenic assays. DNA repair in cells was assessed though quantification of abasic sites, and resulting double-strand breaks were imaged by γH2AX foci immunostaining. We found that nanoparticle-mediated siApe1 delivery reduced Ape1 expression and activity by greater than 80%. This diminished the shoulder of resistance in survival curves decreasing survival to ∼50% at 1 Gy, and was accompanied by inhibition of DNA repair. Sensitization was specific to abasic site generating treatments as response to paclitaxel was not affected. Therefore, siApe1 loaded nanoparticles may help enhance the therapeutic effect of RT in pediatric brain tumor patients by inhibiting DNA repair.