tbuckley/cabot-search huggingface dataset:
Tailored anti-TNF therapy during pregnancy in patients with IBD: maternal and fetal safety
Authors: A de Lima, Z Zelinkova, C van der Ent, E A P Steegers, C J van der Woude
Journal: Gut (2015)

<h3>Objective</h3> Antitumour necrosis factor (TNF) during pregnancy in patients with IBD is related to high fetal anti-TNF levels. We evaluated maternal and child safety on discontinuing anti-TNF in the second trimester of pregnancy. <h3>Design</h3> Two groups of women with IBD were prospectively followed-up during pregnancy: women in sustained remission stopped anti-TNF before week 25 (stop group) and the remaining group continued anti-TNF beyond week 30 (continue group). Maternal, birth and 1-year child outcomes were compared with children of non-IBD women. <h3>Results</h3> Overall, 106 patients with 83 completed pregnancies were included. Relapse rate after week 22 did not differ between the stop (n=51) and continue (n=32) groups (5 (9.8%) versus 5 (15.6%), p=0.14). There was no difference in allergic reactions (p=1.00) or loss of response (p=1.00) postpartum between the two groups. Birth outcomes were comparable. Infants from both groups had lower birth weight (p=0.001), shorter gestational term (p=0.0001), were more often delivered via caesarean section (p=0.0001) and were less often breastfed (p=0.0001) compared with infants from non-IBD controls. Growth, infection rate, allergies, eczema and adverse reactions to vaccines were comparable across the stop and the continue groups as well as the children of anti-TNF-exposed and non-IBD women at 1 year. <h3>Conclusions</h3> To limit anti-TNF exposure in utero, anti-TNF can be stopped safely in the second trimester in women with IBD in sustained remission. In patients not in sustained remission, anti-TNF may be continued without clear additional risks to the fetus. We observed excellent 1-year child outcomes compared with children from non-IBD controls.
Pregnancy Outcome After Methotrexate Treatment for Rheumatic Disease Prior to or During Early Pregnancy: A Prospective Multicenter Cohort Study
Authors: Corinna Weber‐Schoendorfer, Christina Chambers, Evelin Wacker, Delphine Beghin, Nathalie Bernard, Svetlana Shechtman, Diana Johnson, Benedikte Cuppers‐Maarschalkerweerd, Alessandra Pistelli, Maurizio Clementi, Ursula Winterfeld, Georgios Eleftheriou, Anna Pupco, Kelly Kao, Heli Malm, Elisabeth Elefant, Gideon Koren, Thierry Vial, Asher Ornoy, Reinhard Meister, Christof Schaefer
Journal: Arthritis & Rheumatology (2014)

Objective High‐dose methotrexate (MTX) exposure during pregnancy is associated with embryopathy. The teratogenic potential of MTX at dosages typically used in the treatment of rheumatic diseases remains uncertain. The aim of this study was to evaluate the risk of spontaneous abortion, major birth defects, elective termination of pregnancy, shortened gestational age at delivery, and reduced birth weight in women exposed to MTX. Methods Pregnancy outcome in women taking MTX (≤30 mg/week) either after conception or within the 12 weeks before conception was evaluated in a prospective observational multicenter cohort study. Pregnancy outcomes in the MTX group were compared to outcomes in a group of disease‐matched women and a group of women without autoimmune diseases (neither group was exposed to MTX). Results The study sample included 324 MTX‐exposed pregnancies (188 exposed post‐conception, 136 exposed pre‐conception), 459 disease‐matched comparison women, and 1,107 comparison women without autoimmune diseases. In the post‐conception cohort, the cumulative incidence of spontaneous abortion was 42.5% (95% confidence interval [95% CI] 29.2–58.7), which was significantly higher than the incidence of spontaneous abortion in either comparison group. The risk of major birth defects (7 of 106 [6.6%]) was elevated compared to both the cohort of women without autoimmune diseases (29 of 1,001 [2.9%]) (adjusted odds ratio [OR] 3.1 [95% CI 1.03–9.5]) and the disease‐matched cohort (14 of 393 [3.6%]) (adjusted OR 1.8 [95% CI 0.6–5.7]). None of the malformations were clearly consistent with MTX embryopathy. Neither the cumulative incidence of spontaneous abortion (14.4% [95% CI 8.0–25.3]) nor the risk of major birth defects (4 of 114 [3.5%]) was increased in the pre‐conception cohort. Elective termination rates were increased in both of the MTX‐exposed cohorts. There were no other significant differences among groups in other study end points. Conclusion Post‐conception administration of MTX at dosages typically used in the treatment of rheumatic diseases was associated with an increased risk of major birth defects and spontaneous abortion. Such evidence was not found among women in our pre‐conception cohort.
Host cell mTORC1 is required for HCV RNA replication
Authors: Stefanie Stöhr, Rui Costa, Lisa Sandmann, Sandra Westhaus, Stephanie Pfaender, None Anggakusuma, Eva Dazert, Philip Meuleman, Florian W R Vondran, Michael P Manns, Eike Steinmann, Thomas von Hahn, Sandra Ciesek
Journal: Gut (2015)

<h3>Objective</h3> Chronically HCV-infected orthotopic liver transplantation (OLT) recipients appear to have improved outcomes when their immunosuppressive regimen includes a mammalian target of rapamycin (mTOR) inhibitor. The mechanism underlying this observation is unknown. <h3>Design</h3> We used virological assays to investigate mTOR signalling on the HCV replication cycle. Furthermore, we analysed HCV RNA levels of 42 HCV-positive transplanted patients treated with an mTOR inhibitor as part of their immunosuppressive regimen. <h3>Results</h3> The mTOR inhibitor rapamycin was found to be a potent inhibitor for HCV RNA replication in Huh-7.5 cells as well as primary human hepatocytes. Half-maximal inhibition was observed at 0.01 µg/mL, a concentration that is in the range of serum levels seen in transplant recipients and does not affect cell proliferation. Early replication cycle steps such as cell entry and RNA translation were not affected. Knockdown of raptor, an essential component of mTORC1, but not rictor, an essential component of mTORC2, inhibited viral RNA replication. In addition, overexpression of raptor led to higher viral RNA replication, demonstrating that mTORC1, but not mTORC2, is required for HCV RNA replication. In 42 HCV-infected liver-transplanted or kidney-transplanted patients who were switched to an mTOR inhibitor, we could verify that mTOR inhibition decreased HCV RNA levels in vivo. <h3>Conclusions</h3> Our data identify mTORC1 as a novel HCV replication factor. These findings suggest an underlying mechanism for the observed benefits of mTOR inhibition in HCV-positive OLT recipients and potentiate further investigation of mTOR-containing regimens in HCV-positive recipients of solid organ transplants.
Neuroendocrine cells in anthracosilicotic lungs
Authors: HL Gubbelmans, BL Maesen, J Koudstaal, FB Thunnissen
Journal: European Respiratory Journal (1991)

In normal human lungs, neuroendocrine (NE) cells can be found as solitary NE cells and in corpuscular aggregates, the neuroepithelial bodies. By means of a quantitative morphometric method, we compared the number and distribution of chromogranin-reactive NE cells in anthracosilicotic and control lungs. After death, 14 pairs of control and 12 pairs of anthracosilicotic lungs were sampled. The extents of anthracosilicosis and emphysema were described for the right lung. The left upper lobe was used for quantitative determination of the number and distribution of NE cells, visualized by immunohistochemical staining for chromogranin. In contrast to expectations, we found no statistical difference in the numbers of chromogranin-reactive NE cells per 10 cm of epithelium between control (11.0) and anthracosilicotic (2.4) lungs. In both groups, there was a much greater number of chromogranin-reactive cells in the more peripheral compared to the central airways. Most peripheral NE cells were arranged in neuroepithelial bodies, which were not found in the central airways.
Survival of Patients With Resected N2 Non–Small-Cell Lung Cancer: Evidence for a Subclassification and Implications
Authors: Fabrice Andre, Dominique Grunenwald, Jean-Pierre Pignon, Antoine Dujon, Jean Louis Pujol, Pierre Yves Brichon, Laurent Brouchet, Elisabeth Quoix, Virginie Westeel, Thierry Le Chevalier
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Patients who suffer from non–small-cell lung cancer (NSCLC) with ipsilateral mediastinal lymph node involvement (N2) belong to a heterogeneous subgroup of patients. We analyzed the prognosis of patients with resected N2 NSCLC to propose homogeneous patient subgroups. PATIENTS AND METHODS: The present study comprised 702 consecutive patients from six French centers who underwent surgical resection of N2 NSCLC. Initially, two groups of patients were defined: patients with clinical N2 (cN2) and those with minimal N2 (mN2) disease were patients in whom N2 disease was and was not detected preoperatively at computed tomographic scan, respectively. RESULTS: The median duration of follow-up was 52 months (range, 18 to 120 months). A multivariate analysis using Cox regression identified four negative prognostic factors, namely, cN2 status (P &lt; .0001), involvement of multiple lymph node levels (L2+; P &lt; .0001), pT3 to T4 stage (P &lt; .0001), and no preoperative chemotherapy (P &lt; .01). For patients treated with primary surgery, 5-year survival rates were as follows: mN2, one level involved (mN2L1, n = 244): 34%; mN2, multiple level involvement (mN2L2+, n = 78): 11%; cN2L1 (n = 118): 8%; and cN2L2+ (n = 122): 3%. When only patients with mN2L1 disease were considered, the site of lymph node involvement according to the American Thoracic Society numbering system had no prognostic significance (P = .14). Preoperative chemotherapy was associated with a better prognosis for those with cN2 (P &lt; .0001). Five-year survival rates were 18% and 5% for cN2 patients treated with and without preoperative chemotherapy, respectively. CONCLUSION: This study has identified homogeneous N2 NSCLC prognostic subgroups and suggests different therapeutic approaches according to the subgroup profile.
Characterization of a Steroid Receptor Coactivator Small Molecule Stimulator that Overstimulates Cancer Cells and Leads to Cell Stress and Death
Authors: Lei Wang, Yang Yu, Dar-Chone Chow, Fei Yan, Chih-Chao Hsu, Fabio Stossi, Michael A Mancini, Timothy Palzkill, Lan Liao, Suoling Zhou, Jianming Xu, David M Lonard, Bert W O'Malley
Journal: Cancer Cell (2015)
IMMUNOLOGIC INJURY OF RENAL HOMOGRAFTS
Authors: F. Milgrom, J. Klassen, H. Fuji
Journal: The Journal of Experimental Medicine (1971)

Rejection of renal allografts in man and animals is most frequently induced by cell-mediated immunity, the morphologic hallmark of which is the infiltration of the graft by mononuclear cells. In some presensitized recipients rejection may be mediated by humoral transplantation antibodies, and this is characterized clinically by a rapid tempo of rejection and morphologically by accumulation of polymorphonuclear neutrophils and renal cortical necrosis. In recipients treated with immunosuppressive drugs, most renal allografts function well for over 1 yr. However, late deterioration is observed in many grafts. This may take the form of proliferative glomerulonephritis with accumulation of immunoglobulin and complement along glomerular basement membranes. This glomerular lesion of the graft may be of immunologic nature without being rejection. In many instances the glomerular lesion may be due to recurrence of the original disease of the recipient. In other instances it may represent a de novo immunologic process induced by the response to antigens shared by the graft and recipient as evidenced by animal experiments. The glomerular lesion in the graft may also be caused by humoral transplantation antibodies. Therefore, the final outcome of the renal transplantation may to a great extent depend on the strength of transplantation antibody response, being more favorable for low than high responders.
Abstract #2338: 17-\#946; Estradiol impairs the growth of selective estrogen receptor modulator (SERM)-resistant endometrial tumors
Authors: Gregor Balaburski, Rita Dardes, V Jordan
Journal: Cancer Research (2009)

Previous studies in SERM resistant breast cancer models have suggested that an estrogen induced tumor regression and estrogen induced apoptosis of anti-hormonal resistance are potentially universal principles of drug resistance in estrogen target tissues. We hypothesize that estrogen induced tumor regression is a universal principle of SERM anti-hormonal resistance and therefore, estrogen treatments will significantly impede the growth of SERM resistant endometrial tumors. To test our hypothesis, we developed raloxifene resistant cell lines  in vitro  and tumor models  in vivo . First, we developed a SERM resistant endometrial cell line, ECC1-RAL. The ECC1-RAL cells were developed by continuously passaging the endometrial ECC1 cells in media containing 1 \#956;M raloxifene (RAL) for at least one year. The ECC1-RAL cell growth is stimulated by both E 2  and RAL treatments as determined by growth assays. The ECC1-RAL cells express ER\#945; which appears to be similarly regulated as in the parental ECC1 cells and based on transcriptional assays, ER\#945; remains functional. Moreover, the basal levels of the estrogen regulated gene  tff1  was up regulated 3-fold,  ebag-9  4.1-fold and  c-myc  3-fold, indicating significant ligand independent activities of ER\#945; in the ECC1-RAL cells The  in vivo  ECC1-RAL tumor xenograft model was established by injecting 10 million ECC1-RAL cells into the mammary fat pads of ovariectomized athymic nude female mice that were treated with 1.5 mg daily RAL, orally administered. The ECC1-RAL tumors were then continuously passaged in naive animals for at least 5 years. The growth of the RAL stimulated and spontaneously growing ECC1-RAL tumors was retarded by E 2  treatments. In addition, E 2  treatments impaired the growth of established ECC1-RAL tumors. Long term E 2  treatments of the estrogen treated ECC1-RAL tumors resulted in reversal of tumor phenotype from RAL stimulated and E 2  sensitive into RAL sensitive and E 2  stimulated. Continuous RAL treatments of the newly RAL sensitive tumors resulted in reversion to the original ECC1-RAL tumor phenotype, RAL stimulated and E 2  sensitive. Importantly, the initial E 2  treatments reduced the growth of the spontaneously growing ECC1-RAL tumors in the placebo groups of all subsequent experiments. Our data demonstrate that the estrogen induced tumor regression of SERM anti- hormonal resistance in estrogen target tissues previously observed in breast cancer also applies to endometrial tissues and that it is indeed a universal principle. The ability of E 2  to retard the growth of raloxifene resistant endometrial tumors and its immediate and considerable impact on the tumors in the no estrogen state provide significant clues for clinical treatment of SERM resistant endometrial tumors.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2338.
Evidence of Clozapine’s Effectiveness in Schizophrenia: A Systematic Review and Meta-Analysis of Randomized Trials
Authors: Kristian Wahlbeck, Maxim Cheine, Adib Essali, Clive Adams
Journal: American Journal of Psychiatry (1999)

The purpose of this study was to evaluate all available trial-based evidence on the effectiveness of clozapine in schizophrenia as compared with conventional neuroleptics.All randomized, controlled trials comparing clozapine with a conventional neuroleptic in which there was satisfactory concealment of patients' treatment allocation were located through electronic searches in all languages of several databases and through contacting authors of recent trials as well as the manufacturer of clozapine. At least two independent reviewers assessed trials for inclusion in the study and extracted data for meta-analysis.The review included 2,530 randomly assigned participants in 30 trials, most of them short-term. Clozapine-treated patients showed more clinical improvement and experienced significantly fewer relapses during treatment, although the risk of blood dyscrasias in long-term treatment may be as high as 7%. Scores on symptom rating scales showed greater improvement among clozapine-treated patients, who were also more satisfied with their treatment. However, there was no evidence that the superior clinical effect of clozapine is reflected in levels of functioning; on the other hand, global functional and pragmatic outcomes were frequently not reported. Clinical improvement was most pronounced in patients with treatment-resistant illness.This meta-analysis confirms that clozapine is more effective than conventional neuroleptics in reducing symptoms of patients with both treatment-resistant and nonresistant schizophrenia. Future trials should be long-term pragmatic community trials or should address the effectiveness of clozapine in special patient populations. An international standard set of outcomes, including pragmatic assessments of functioning, would greatly enhance the comparison and summation of trials and future assessments of effectiveness.
Trimethoprim-sulfamethoxazole versus vancomycin for severe infections caused by meticillin resistant Staphylococcus aureus: randomised controlled trial
Authors: M. Paul, J. Bishara, D. Yahav, E. Goldberg, A. Neuberger, N. Ghanem-Zoubi, Y. Dickstein, W. Nseir, M. Dan, L. Leibovici
Journal: BMJ (2015)

<b>Objective</b> To show non-inferiority of trimethoprim-sulfamethoxazole compared with vancomycin for the treatment of severe infections due to meticillin resistant <i>Staphylococcus aureus</i> (MRSA). <b>Design</b> Parallel, open label, randomised controlled trial. <b>Setting</b> Four acute care hospitals in Israel. <b>Participants </b>Adults with severe infections caused by MRSA susceptible to trimethoprim-sulfamethoxazole and vancomycin. Patients with left sided endocarditis, meningitis, chronic haemodialysis, and prolonged neutropenia were excluded. <b>Interventions </b>Trimethoprim-sulfamethoxazole 320 mg/1600 mg twice daily versus vancomycin 1 g twice daily for a minimum of seven days and then by indication. <b>Main outcome measures </b>The primary efficacy outcome was treatment failure assessed at day 7, consisting of death, persistence of haemodynamic instability or fever, stable or worsening Sequential Organ Failure Assessment score, and persistence of bacteraemia. The primary safety outcome was all cause mortality at day 30. Non-inferiority was defined by a difference of less than 15% for treatment failure. <b>Results </b>252 patients were included in the trial, of whom 91 (36%) had bacteraemia. No significant difference in treatment failure was seen for trimethoprim-sulfamethoxazole (51/135, 38%) versus vancomycin (32/117, 27%)—risk ratio 1.38 (95% confidence interval 0.96 to 1.99). However, trimethoprim-sulfamethoxazole did not meet the non-inferiority criterion—absolute difference 10.4% (95% confidence interval −1.2% to 21.5%). For patients with bacteraemia, the risk ratio was 1.40 (0.91 to 2.16). In a multivariable logistic regression analysis, trimethoprim-sulfamethoxazole was significantly associated with treatment failure (adjusted odds ratio 2.00, 1.09 to 3.65). The 30 day mortality rate was 32/252 (13%), with no significant difference between arms. Among patients with bacteraemia, 14/41 (34%) treated with trimethoprim-sulfamethoxazole and 9/50 (18%) with vancomycin died (risk ratio 1.90, 0.92 to 3.93). <b>Conclusions </b>High dose trimethoprim-sulfamethoxazole did not achieve non-inferiority to vancomycin in the treatment of severe MRSA infections. The difference was particularly marked for patients with bacteraemia. <b>Trial registration</b> Clinical trials NCT00427076.
Preoperative Aspirin Therapy Is Associated With Improved Postoperative Outcomes in Patients Undergoing Coronary Artery Bypass Grafting
Authors: Kevin A. Bybee, Brian D. Powell, Uma Valeti, A. Gabriela Rosales, Stephen L. Kopecky, Charles Mullany, R. Scott Wright
Journal: Circulation (2005)

Background— Aspirin is beneficial in the setting of atherosclerotic cardiovascular disease. There are limited data evaluating preoperative aspirin administration preceding coronary artery bypass grafting and associated postoperative outcomes. Methods and Results— Using prospectively collected data from 1636 consecutive patients undergoing first-time isolated coronary artery bypass surgery at our institution from January 2000 through December 2002, we evaluated the association between aspirin usage within the 5 days preceding coronary bypass surgery and risk of adverse in-hospital postoperative events. A logistic regression model, which included propensity scores, was used to adjust for remaining differences between groups. Overall, there were 36 deaths (2.2%) and 48 adverse cerebrovascular events (2.9%) in the postoperative hospitalization period. Patients receiving preoperative aspirin (n=1316) had significantly lower postoperative in-hospital mortality compared with those not receiving preoperative aspirin [1.7% versus 4.4%; adjusted odds ratio (OR), 0.34; 95% CI, 0.15 to 0.75; P =0.007]. Rates of postoperative cerebrovascular events were similar between groups (2.7% versus 3.8%; adjusted OR, 0.67; 95% CI, 0.32 to 1.50; P =0.31). Preoperative aspirin therapy was not associated with an increased risk of reoperation for bleeding (3.5% versus 3.4%; P =0.96) or requirement for postoperative blood product transfusion (adjusted OR, 1.17; 95% CI, 0.88 to 1.54; P =0.28). Conclusions— Aspirin usage within the 5 days preceding coronary artery bypass surgery is associated with a lower risk of postoperative in-hospital mortality and appears to be safe without an associated increased risk of reoperation for bleeding or need for blood product transfusion.
Abstract 17696: Characteristics and Outcome of Percutanous Transluminal Angioplasty in Smokers
Authors: Seung Woon Rha, Amro Elnagar, Byoung Geol Choi, Sung Il Im, Sun Won Kim, Jin Oh Na, Seong Woo Han, Cheol Ung Choi, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Chang Gyu Park, Hong Seog Seo, Dong Joo Oh
Journal: Circulation (2011)

Background: Smoking is a known risk factor for peripheral vascular disease (PVD).The aim of this study to determine characteristics and outcome of percutanous transluminal angioplasty (PTA) in smokers. Methods: A total 187 patients (pts) with 350 lesions who underwent PTA were enrolled. Pts were divided into 2 groups (non smokers: n=127 pts, smokers: n=60 pts) Results: baseline characteristics were similar except that smokers had more males (95% vs. 68.5 %, p&lt;0.001), alcoholic (51.7% vs.14.2%, p&lt;0.001), dyslipidemic (21.7% vs. 11%.p=0.053).While non smokers were more hypertensive (73.2% vs.56.7%, p=0.024). Non smokers had significant higher Rutherford grade &amp; category, other clinical presentations were similar between 2 groups. Smokers had more ostial &amp; longer lesions, while non smokers had more De novo lesions. However procedural &amp; 1 year clinical outcomes were similar between the 2 groups. (table 1). Conclusions: In our study, despite longer &amp; ostial lesions in smokers, procedural &amp;1 year clinical outcomes were similar between the 2 groups.