tbuckley/cabot-search huggingface dataset:
FRI0095 Subclinical Hypothyroidism is Associated with an Increased Risk of Cardiovascular Events in Patients with Rheumatoid Arthritis
Authors: R. Agca, H.G. Raterman, S. Simsek, A.E. Voskuyl, M.T. Nurmohamed
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) have an increased risk of developing cardiovascular disease (CVD). This risk is only partially explained by classic risk factors for CVD. Autoimmune thyroid disease often coexists with RA and has been associated with an elevated cardiovascular (CV) risk, especially in hypothyroid patients. However, the existing studies show conflicting results. <h3>Objectives</h3> To investigate whether patients with thyroid dysfunction at baseline have an increased incidence of CVD compared to euthyroid RA patients. <h3>Methods</h3> In this study thyroid function was assessed in 353 RA patients participating in an ongoing prospective cohort study to assess cardiovascular morbidity and mortality (CARRΈ study). Cardiovascular end points were defined as a verified medical history of coronary, cerebral or peripheral arterial disease. Cox regression analyses were performed to calculate hazard rates (HR) and to adjust for confounders. <h3>Results</h3> The participants were predominantly females (65.7%) with a mean age of 63±6 years and a mean disease duration of 8±4 years. At baseline 4.6% was hypothyroid, 4.0% was hyperthyroid, 2.6% had subclinical hyperthyroidism and 2.9% had subclinical hypothyroidism. 85.9% of the patients was euthyroid. In the total population 58 patients (16.4%) had developed CVD after 5 years of follow up. Compared with euthyroid patients crude HR were 1.20 (95%CI 0.37 – 3.89; P=0.76) for hyperthyroid patients, 0.83 (95% CI 0.20 – 3.43; P=0.80) for hypothyroid patients, 0.59 (95%CI 0.89 – 5.92; P=0.61) for subclinical hyperthyroidism and 2.30 (95%CI 0.89-5.92; P=0.084) for subclinical hypothyroidism. Intriguingly, only subclinical hypothyroidism was associated with incident CVD compared to euthyroid patients in the adjusted models. The age and gender adjusted HR for CV events in this group was 3.36 (95% CI 1.29 – 8.77; P=0.013). The HR was 3.85 (95% CI 1.45 – 10.19; P=0.007) after adjustment for prevalent CVD and metabolic syndrome. The final model corrected for RA duration, and disease activity showed a HR of 3.23 (95% CI 1.09 – 9.58; P=0.035). <h3>Conclusions</h3> Coexistence of subclinical hypothyroidism with RA was associated with incident CVD. If external validation can confirm this amplified CVD risk, thyroxine supplementation and cardiovascular risk management may be warranted in this subgroup of patients. <h3>Disclosure of Interest</h3> None declared
Strategy for Incorporating Molecular and Cytogenetic Markers into Acute Myeloid Leukemia Therapy
Authors: Mark G. Frattini, Peter G. Maslak
Journal: Journal of the National Comprehensive Cancer Network (2008)

Acute myeloid leukemia is a heterogeneous disease. Standard treatments may be applied to biologically distinct subgroups, resulting in different treatment outcomes. The concept of risk-adapted therapy allows for recognition of this biologic diversity by incorporating key biologic features, such as cytogenetic and molecular markers, when formulating treatment regimens and investigating emerging targeted therapies based on disease characteristics.
Cat-Scratch Fever
Authors: William E. R. Greer, Chester S. Keefer
Journal: New England Journal of Medicine (1951)

THE domestic cat has long been known as a carrier of disease. Unfortunately, perhaps, cats have long enjoyed intimate companionship with human beings and their households. Many homeless cats are accepted in homes out of sympathy, with no investigation or consideration of their disease status. The occurrence of a disease entity incurred through cat scratches in a young adult male has prompted this report.There are no reports in the English literature concerning "cat-scratch fever."§ It is a term first used by Dr. Lee Foshay,1 of Cincinnati, to describe lymphadenitis of unknown etiology following cat scratches. The disease is suggestive . . .
Treatment for children of volatile psychotic adults in the adult psychiatric setting
Authors: R Rosenheck, P Nathan
Journal: American Journal of Psychiatry (1984)

The authors describe a unique program for the treatment of troubled children of adult psychiatric patients at a Veterans Administration hospital. The location of this program within the adult setting greatly facilitated the successful treatment of these children. The program can also be a valuable addition to the treatment of adult patients, especially patients who are chronically ill and emotionally volatile and have been particularly difficult to treat.
Wearable Fitness Trackers and Heart Disease
Authors: Daniel W. Kaiser, Robert A. Harrington, Mintu P. Turakhia
Journal: JAMA Cardiology (2016)

Wearable Fitness Trackers and Heart DiseaseWhat Are Fitness Trackers?Fitness or activity trackers are devices with special sensors that can monitor your movement.Often referred to as "wearables," these devices are typically worn around the wrist as a bracelet or embedded in a mobile phone or wristwatch.They can measure footsteps taken, distance traveled, type of movement (walk, run, or jog), and quality and duration of sleep.Some wearables have additional sensors to monitor heart rate, blood pressure, blood oxygen levels, and perspiration.Data from wearables can be transferred to a smartphone, computer, database, or website.Connected smartphones and wearables can alarm or vibrate to encourage behaviors, such as exercise or sleep.As wearable technology matures, these devices will likely cost less, and it may become easier to share data from them with your health care professional, clinic, or hospital.Can Fitness Trackers Prevent or Treat Heart Disease?
Role of Surgery in Hodgkin's Disease
Authors: Mortimer J. Lacher
Journal: New England Journal of Medicine (1963)

The discovery of 4 cases of Hodgkin's disease that A had been treated surgically with long-term survival without recurrence led Slaughter and Craver1 (in 1942) to speculate about "unicentric" Hodgkin's disease and the possibility that early detection would result in a "cure" through surgery.In 1951 Craver2 came to the following conclusion:If the disease is detected while still apparently restricted to one site, and if this early focus is accessible for surgical removal, one may always consider radical surgery as the primary treatment. Not many such cases are seen, except by the general practitioners, and relatively few attempts have . . .
Characterization of Th2 Induced Bronchial Associated Lymphoid Tissue (BALT) in a Mouse Model of Asthma
Authors: David M. Kemeny, Yen L. Chua, Chiung-Hui Huang, Ka Hang Liong, Kenneth Wong, Sophie Q. Zhou, Yafang Tang, Michelle C.P. Low, Yongliang Zhang, Fred W.S. Wong
Journal: Journal of Allergy and Clinical Immunology (2016)
Stroke Following Coronary-Artery Bypass Surgery
Authors: Guy L. Reed, Daniel E. Singer, Ernest H. Picard, Roman W. DeSanctis
Journal: New England Journal of Medicine (1988)

The causes of stroke following coronary-artery bypass surgery are largely unknown. To determine whether carotid bruits increase the risk of these events, we compared 54 patients with postoperative stroke or transient ischemic attacks with 54 randomly selected control patients. Both groups were drawn from 5915 consecutive patients who had coronary bypass surgery at our hospital from 1970 to 1984. Carotid bruits were noted preoperatively in 13 patients with postoperative stroke and in 4 control patients. case-control analysis showed that the presence of carotid bruits increased the risk of stroke or transient ischemic attacks by 3.9-fold (95 percent confidence interval, 1.2 to 12.8; P<0.05). This increased risk remained essentially unchanged after adjustment for potentially confounding variables in a multiple logistic regression analysis. Other factors associated with a significantly increased risk (P<0.05) of these neurologic deficits were a history of stroke or transient ischemic attack (odds ratio, 6.0; 95 percent confidence interval, 1.6 to 22.1), a history of congestive heart failure (odds ratio, 5.3; confidence interval, 1.6 to 17.0), mitral regurgitation (odds ratio, 4.3; confidence interval, 1.4 to 12.9), postoperative atrial fibrillation (odds ratio, 3.0; confidence interval, 1.4 to 6.7), a cardiopulmonary-bypass pump time of more than two hours (odds ratio, 2.7; confidence interval, 1.1 to 6.7), and a previous myocardial infarction (odds ratio, 2.3; confidence interval, 1.1 to 5.1). We conclude that the presence of carotid bruits increases the risk of stroke after coronary-artery bypass surgery. However, the absolute magnitude of this risk, 2.9 percent, is small and comparable to the reported risk of stroke from carotid endarterectomy. (N Engl J Med 1988; 319:1246–50.)
THU0421 Secukinumab is Effective in Reducing Dactylitis and Enthesitis Using Multiple Measures in Patients with Psoriatic Arthritis: Data from a Phase 3 Randomized, Multicenter, Double-Blind, Placebo-Controlled Study (Future 2)
Authors: B. Kirkham, I.B. McInnes, P. Mease, J. Kremer, S. Kandala, L. Pricop, S. Mpofu
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Dactylitis and enthesitis are common disabling manifestations of psoriatic arthritis (PsA) that have been reported according to multiple methods of assessment. Several measures of dactylitis and enthesitis were utilized in the phase 3 FUTURE 2 secukinumab study (NCT01752634)<sup>1</sup> and are reported here. <h3>Objectives</h3> To evaluate the effects of subcutaneous (s.c.) secukinumab on dactylitis and enthesitis through Week (Wk) 24 in FUTURE 2. <h3>Methods</h3> 397 adults with active PsA were randomized to s.c. secukinumab (300, 150 or 75 mg) or PBO at baseline, Wk 1, 2, 3, 4 and then every 4 wks thereafter. The primary endpoint was ACR20 response at Wk 24. The proportions of pts with resolution of dactylitis and enthesitis at Wk 24 (of those with these conditions at baseline) were secondary endpoints. Additional measures utilized in this study were dactylitis counts, Leeds Dactylitis Index (LDI), and Leeds Enthesitis Index (LEI). <h3>Results</h3> At baseline, 138 pts (35%) had dactylitis and 253 pts (64%) had enthesitis. At Wk 24, comparing secukinumab 300 mg and 150 mg vs PBO respectively, 56.5% and 50.0% vs 14.8% of pts had complete resolution of dactylitis, and 48.2% and 42.2% vs 21.5% had complete resolution of enthesitis. Corresponding reductions in LDI, LEI and mean dactylitis counts were observed (Table). <h3>Conclusions</h3> Across multiple methods of assessment, secukinumab 300 and 150 mg s.c. reduced the number of dactylitic digits and enthesitis sites in pts with PsA and was associated with a greater proportion of patients achieving complete resolution of dactylitis/enthesitis compared with PBO. <h3>References</h3> McInnes IB, et al. Presented at ACR 2014; L1 <h3>Acknowledgements</h3> Medical writing support was provided by Rachel Mason at Seren Communications (Tytherington, UK), and was funded by Novartis. <h3>Disclosure of Interest</h3> B. Kirkham Grant/research support from: AbbVie and UCB, Consultant for: Novartis, AbbVie, BMS, Lilly, and MSD, Speakers bureau: BMS, MSD, and UCB, I. McInnes Consultant for: Novartis, Amgen, Janssen, BMS, Pfizer, UCB, Abbvie, Celgene, and Lilly, P. Mease Grant/research support from: AbbVie, Amgen, Biogen Idec, BMS, Celgene, Crescendo, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, and Vertex, Consultant for: AbbVie, Amgen, Biogen Idec, BMS, Celgene, Covagen, Crescendo, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, and Vertex, Speakers bureau: AbbVie, Amgen, Biogen Idec, BMS, Crescendo, Janssen, Lilly, Pfizer, and UCB, J. Kremer Grant/research support from: Novartis, Lilly, BMS, Janssen, Pfizer, and UCB, S. Kandala Employee of: Novartis, L. Pricop Shareholder of: Novartis, Employee of: Novartis, S. Mpofu Shareholder of: Novartis, Employee of: Novartis
A novel antifolate 10-propargyl-10-deazaaminopterin (PDX) displays synergistic effects with gemcitabine in non-Hodgkin's lymphoma models <b><i>in vitro</i></b> and <b><i>in vivo</i></b>
Authors: R. Vrhovac, L. E. Toner, E. A. Smith, O. A. O'Connor
Journal: Journal of Clinical Oncology (2004)

6596 Background: PDX is a rationally designed antifolate aimed at improving membrane transport and polyglutamylation in tumor cells. Previous studies have shown that PDX has better activity and a better hematological toxicity profile than MTX against human NHL. PDX as single agent is currently in phase I and II clinical trials for patients with NHL. Methods: The combination of PDX (2nM) and gemcitabine (20nM) was tested in vitro in 4 NHL cell lines. Cells were exposed to one drug for 24h, then exposed to the same or other drug for additional 24h or exposed to both drugs for 24h, then cultured in RPMI alone for 24h. Efficacy was measured at 48h by Alamar Blue and Trypan Blue assays. The same combination was evaluated in vivo in a model of human NHL in irradiated NOD/SCID mice. Mice were inoculated with 10x106 SKI-DLCL cells via a sc. route. When tumors approached 300 mm3, mice were divided into 4 groups of 5 and treated twice weekly for 4 doses i.p. with normal saline (control), MTD of PDX (60 mg/kg) and gemcitabine (60 mg/kg) or a combination of the drugs, each given at 30 mg/kg. Results: PDX displayed synergistic effects with gemcitabine in vitro in all cell lines, with strongest synergy observed in cells first treated with PDX and subsequently exposed to gemcitabine. This combination produced 10.9±4.1% greater effects in SKI-DLCL, 13.5±5.4% in HT, 25.5±7.2 % in DOHH2, and 28.4±8.7 % in RL compared to the additive effects of both drugs given as monotherapy. Animals in the control group had rapid POD and were sacrificed. PDX or gemcitabine treated animals initially responded to treatment but by day 44 regrew tumors to 739.0% and 317.7% of their initial tumor volumes, respectively. Animals in the PDX+gemcitabine arm had significant reduction (63.1%) of their initial tumor volume, with 3 animals in CR, 1 in PR and 1 with POD. Conclusions: The potential of the PDX-gemcitabine combination is very promissing. Future experiments are planned in order to: 1) determine the optimal schedule of these drugs, and 2) compare the eficacy of the optimal combination to the “standard” antifolate-pyrimidine analog combination (methotrexate-Ara-C). No significant financial relationships to disclose.
Case 46-1992
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, G.A. Patterson, H.C. Grillo, E.J. Mark
Journal: New England Journal of Medicine (1992)

Presentation of CaseA 48-year-old woman was admitted to the hospital because of increasing dyspnea, choking spells, and inability to cough up secretions.There was a 20-year history of exertional dyspnea that worsened during the 10 years before admission. Five and a half months before entry the patient received a triple coronary-artery-bypass graft at another hospital because of unstable angina pectoris. Intra-operative tracheal intubation was difficult, and a 6-French pediatric cuffed endotracheal tube was finally used. It was removed on the first postoperative day. The chest pain improved, but the dyspnea worsened and was provoked by climbing one flight of . . .
Abstract 236: Sirt6 Heterozygosity Exacerbates Atherosclerosis in Apolipoprotein E Deficient Mice
Authors: De-Pei Liu, Zhu-Qin Zhang, Si-Cong Ren, Zuo-Zhi Li, Ying Tan, Xiao-Qiang Tang, De-Long Hao, Zhi-Chen Guo, Xiang Zhao, Hou-Zao Chen
Journal: Circulation Research (2014)

Sirt6 is a member of the class III histone deacetylase family and is reported to promote longevity. Whether Sirt6 is involved in atherosclerosis, one aging associated disease and the major cause of cardiovascular diseases, is unknown. We investigated effects of Sirt6 on atherosclerosis development. We found that in human atherosclerotic plaques, Sirt6 expression was decreased. Sirt6+/-ApoE-/- mice exhibited increased atherosclerosis development and decreased plaque stability than ApoE-/- mice. We found that Sirt6 downregulation showed increased expression of NKG2D ligands (H60b in mice and MICA/B in human). Sirt6 bound to promoters of these genes and regulated the H3K9 acetylation levels. Thus, atherosclerosis development was promoted by Sirt6 heterozygosity and epigenetic modification of NKG2D ligand expression is involved in this process.
Phase II study of dulanermin plus rituximab in patients with relapsed follicular non-Hodgkin's lymphoma (NHL).
Authors: D. Belada, J. Mayer, M. S. Czuczman, I. W. Flinn, B. Durbin-Johnson, G. L. Bray
Journal: Journal of Clinical Oncology (2010)

8104 Background: Dulanermin is a pro-apoptotic receptor agonist that induces apoptosis via the extrinsic apoptotic pathway by binding to pro-apoptotic receptors DR4 and DR5. In preclinical studies, adding dulanermin to rituximab enhanced inhibition of NHL tumor xenografts in mice. In a phase Ib study, the combination of rituximab + dulanermin was well tolerated (ASCO 2007 abstract 8078). The present study assessed the safety and activity of multiple doses of rituximab + dulanermin vs. rituximab alone in patients (pts) with follicular NHL who progressed after previous rituximab therapy. Methods: This multicenter, open-label, randomized phase II trial compared rituximab (375 mg/m2/wk × 8) + dulanermin (8 mg/kg for 5 days every 3 wks × 4) (n=26) vs. rituximab alone (n=22). Adverse event (AE) and laboratory data were monitored. The primary efficacy endpoint was objective response rate (ORR) as assessed by blinded, independent review; progression-free survival (PFS) was a key secondary endpoint. Results: Grade 3-5 AEs were more frequent among rituximab + dulanermin pts (n=6) than among rituximab pts (n=2), although most were single occurrences. Among rituximab + dulanermin pts, Grade 3 serum lipase elevation and Grade 4 neutropenia were noted in 2 and 1 pts, respectively. Neither event was dose limiting. ORR results are shown below. PFS data are immature (only 27% of pts have progressed). Conclusions: The rituximab-dulanermin combination was well tolerated. Asymptomatic, transient serum lipase elevations observed in phase II were consistent with findings in phase Ib. Adding dulanermin to rituximab did not improve ORR in these relapsed pts with follicular NHL. Rituximab(n = 22) Rituximab + dulanermin(n = 26) No. (%) of pts with OR 14 (63.6%) 16 (61.5%) 95% CI for ORR (41.8%, 81.3%) (42.1%, 78.8%) Complete response 5 3 Complete response, unconfirmed 0 1 Partial response 9 12 Abbreviation: CI, confidence interval. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Abbott Laboratories Roche Genentech Abbott Laboratories, Genentech
Persistent immunity and survival after immunization with a HER2/neu (HER2) vaccine
Authors: L. G. Salazar, V. Goodell, M. O'Meara, K. Knutson, Y. Dang, C. dela Rosa, K. A. Guthrie, M. L. Disis
Journal: Journal of Clinical Oncology (2009)

3010 Background: Our initial vaccine studies showed that optimally treated breast cancer patients can be immunized against HER2 during active immunization. The majority of patients developed T-cell immunity to HER2 peptides and protein and also epitope spreading (ES). The goal of this study was to determine if patients previously immunized with a HER2 vaccine had persistent immunity years after active immunization and to assess their clinical outcome in terms of overall survival (OS). Methods: Subjects eligible for this IRB-approved long term follow-up (LTFU) study: (1) had HER2+ breast cancer and were immunized between 1996–1999 in a phase I HER2 peptide vaccine trial, (2) were at least 1 year out from their last vaccine, and (3) if donating blood samples could not be receiving chemotherapy. 52 patients (37 stage IV, 15 stage III) were identified and 21/52 patients (12 stage IV, 9 stage III) were determined to be living. All 21 subjects were contacted by letter and sent a LTFU Questionnaire. OS was defined as the time between date of vaccine study entry and death or last follow-up and was estimated using the Kaplan-Meier method. Cox proportional hazards were used to determine associations between OS and known clinical and vaccine-related immunologic factors; analyses included all 52 subjects. Long-term T-cell immunity was evaluated using IFN-γ ELISPOT assay. Results: Median follow-up time for the 21 patients still alive was 112 months (range, 104–126 months). Blood samples were collected in 10/21 subjects and 6/8 (75%) evaluble patients had persistent T-cell immunity to immunizing HER2 peptides; and 7/8 patients (88%) had T-cell immunity specific for HER2 protein and peptides not contained in their immunizing mix (defined as ES). In multivariate analysis, number of chemotherapy regimens prior to vaccination (HR=5.7 (CI 95%, 1.5–23; p=&lt;0.001)), and development of ES after HER2 vaccination (HR=0.34 (CI 95%, 0.12–1.0; p=0.05)) were independent predictors of OS. Median OS for 33 subjects who developed ES was 84 months vs 25 months for 16 subjects who did not develop ES. Conclusions: HER2-specific T-cell immunity elicited with active immunization is durable years after vaccination has ended and the generation of ES is an independent predictor of OS. No significant financial relationships to disclose.
Pathogenesis of Hypofibrinogenemia in Placental Abruption
Authors: Jack A. Pritchard, Marjorie R. Wright
Journal: New England Journal of Medicine (1959)

THE pathogenesis of hypofibrinogenemia associated with placental abruption continues to be a subject of much conjecture. The most commonly proposed explanation has been intravascular coagulation due to the escape of thromboplastin from the products of gestation into the maternal circulation.1 2 3 4 5 6 Fibrinogen destruction resulting from the activation of circulating plasminogen has also been proposed to account for the fall in circulating fibrinogen.7 8 9 Recently, Stefanini and Turpini10 reported hypofibrinogenemia to follow massive hemorrhage in laboratory animals.Dieckmann,11 who in 1936 first clearly demonstrated that a coagulation defect with severe hypofibrinogenemia occurred with some cases of premature separation of the placenta, suggested that . . .