tbuckley/cabot-search huggingface dataset:
Osteoprotegerin in breast cancer: beyond bone remodeling
Authors: Michael Weichhaus, Stephanie Tsang Mui Chung, Linda Connelly
Journal: Molecular Cancer (2015)

Osteoprotegerin (OPG) is a secreted protein and member of the Tumor Necrosis Factor (TNF) Receptor superfamily. OPG has been well characterized as a regulator of bone metabolism which acts by blocking osteoclast maturation and preventing bone breakdown. Given this role, early studies on OPG in breast cancer focused on the administration of OPG in order to prevent the osteolysis observed with bone metastases. However OPG is also produced by the breast tumor cells themselves. Research focusing on OPG produced by breast tumor cells has revealed actions of OPG which promote tumor progression. In vitro studies into the role of OPG produced by breast tumor cells have demonstrated that OPG can block TNF-related apoptosis inducing ligand (TRAIL)-mediated apoptosis. Furthermore, in vivo studies show that OPG expression by breast tumors can promote tumor growth and metastasis. In addition it has been shown that OPG stimulates endothelial cell survival and tube formation thus it may indirectly promote breast tumor progression through impacting angiogenesis. This article will present a summary of the data concerning the tumor-promoting effects of OPG in breast cancer.
Effect of training in educational programs at the level of control and quality of life of patients with bronchial asthma
Authors: Olena Semendyayeva, Nadiya Monogarova, Denys Stupachenko, Alexandr Le
Journal: European Respiratory Journal (2011)

Objective:  To study the effect of educational programs, training in asthma-school on the level of control and quality of life in patients with persistent asthma, detection of comorbidity.   Materials and methods:  The study summarizes the results of the survey 57 patients with bronchial asthma, which for 5 years regularly attending classes in the asthma-school. Of the 24 examined patients with severe asthma. To assess the quality of life questionnaires were used AQLQ, ACQ. The direction of the educational program on asthma involves several steps: asthma visiting schools for physicians, asthma school for patients, creating Web sites for patients, listening to lectures. The most effective training methods were group sessions of 5-7 patients, round table, individual sessions with the doctor. Before the training of 40 patients had not received basic therapy regularly. Currently, all of these patients have a high commitment to treatment, through monitoring of their condition (filling questionnaires of quality of life, regular spirometry advice specialist doctor). The most frequently diagnosed gastroesophageal reflux disease (65%), drug intolerance (23%), cardiovascular disease (30%), depression (26%). Treatment of comorbidity improved control and adherence to treatment.   Conclusion:  The long-term (over 5 years) studies of patients with persistent asthma to an increase in adherence to treatment, improve disease control and quality of life.We need to continue the search for new forms of patient education, not only with asthma but also with chronic obstructive pulmonary disease.
Treatment of refractory non-Hodgkin's lymphoma with radiolabeled MB-1 (anti-CD37) antibody.
Authors: O W Press, J F Eary, C C Badger, P J Martin, F R Appelbaum, R Levy, R Miller, S Brown, W B Nelp, K A Krohn
Journal: Journal of Clinical Oncology (1989)

The biodistribution, toxicity, and therapeutic potential of anti-CD37 monoclonal antibody (MoAb) MB-1 labeled with iodine 131 (131I) was evaluated in ten patients with advanced-, low- or intermediate-grade non-Hodgkin's lymphomas who failed conventional treatment. Sequential dosimetric studies were performed with escalating amounts of antibody MB-1 (0.5, 2.5, 10 mg/kg) trace-labeled with 5 to 10 mCi 131I. Serial tumor biopsies and gamma camera imaging showed that the 10 mg/kg MoAb dose yielded the best MoAb biodistribution in the ten patients studied. Biodistribution studies in the five patients with splenomegaly and tumor burdens greater than 1 kg indicated that not all tumor sites would receive more radiation than normal organs, and these patients were therefore not treated with high-dose radioimmunotherapy. The other five patients did not have splenomegaly and had tumor burdens less than 0.5 kg; all five patients in this group showed preferential localization and retention of MoAb at tumor sites. Four of these patients have been treated with 131I (232 to 608 mCi) conjugated to anti-CD37 MoAb MB-1, delivering 850 to 4,260 Gy to tumor sites. Each of these four patients attained a complete tumor remission (lasting 4, 6, 11+, and 8+ months). A fifth patient, whose tumor did not express the CD37 antigen, was treated with 131I-labeled anti-CD20 MoAb 1F5 and achieved a partial response. Myelosuppression occurred 3 to 5 weeks after treatment in all cases, but there were no other significant acute toxicities. Normal B cells were transiently depleted from the bloodstream, but immunoglobulin (Ig) levels were not affected, and no serious infections occurred. Two patients required reinfusion of previously stored autologous, purged bone marrow. Two patients developed asymptomatic hypothyroidism 1 year after therapy. The tolerable toxicity and encouraging efficacy warrant further dose escalation in this phase I trial.
Phase I Clinical Trial of Ipilimumab in Pediatric Patients with Advanced Solid Tumors
Authors: Melinda S. Merchant, Matthew Wright, Kristin Baird, Leonard H. Wexler, Carlos Rodriguez-Galindo, Donna Bernstein, Cindy Delbrook, Maya Lodish, Rachel Bishop, Jedd D. Wolchok, Howard Streicher, Crystal L. Mackall
Journal: Clinical Cancer Research (2015)

Ipilimumab is a first-in-class immune checkpoint inhibitor approved for treatment of metastatic melanoma but not studied in children until this phase I protocol.This study examined safety, pharmacokinetics, and immunogenicity, and immune correlates of ipilimumab administered to subjects ≤21 years old with recurrent or progressive solid tumors. Dose escalation cohorts received 1, 3, 5, or 10 mg/m(2) intravenously every 3 weeks in a 3 + 3 design. Response was assessed after 6 weeks and 12 weeks, and then every 3 months. Treatment was continued until disease progression or unacceptable toxicity.Thirty-three patients received 72 doses of ipilimumab. Patients enrolled had melanoma (n = 12), sarcoma (n = 17), or other refractory solid tumors (n = 4). Immune-related adverse events included pancreatitis, pneumonitis, colitis, endocrinopathies, and transaminitis with dose-limiting toxicities observed at 5 and 10 mg/kg dose levels. Pharmacokinetics revealed a half-life of 8 to 15 days. At day 21, subjects had increased levels of cycling T cells, but no change in regulatory T-cell populations. Six subjects had confirmed stable disease for 4 to 10 cycles (melanoma, osteosarcoma, clear cell sarcoma, and synovial sarcoma).Ipilimumab was safely administered to pediatric patients using management algorithms for immune-related toxicities. The spectrum of immune-related adverse events is similar to those described in adults; however, many of the pediatric toxicities were evident after a single dose. Although no objective tumor regressions were observed with ipilimumab as a single agent, subjects with immune-related toxicities had an increased overall survival compared with those who showed no evidence of breaking tolerance.
Hepatitis C Virus-Associated Glomerular Disease in Patients with Human Immunodeficiency Virus Coinfection
Authors: JEN-TSE CHENG, HERMAN L. ANDERSON, GLEN S. MARKOWITZ, GERALD B. APPEL, VELVIE A. POGUE, VIVETTE D. D'AGATI
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Chronic infection with hepatitis C virus (HCV) has been linked to the development of glomerular disease. HCV infection is highly prevalent among intravenous drug users, a population that is also at risk for HIV coinfection. This study reports the clinical-pathologic features and outcome of HCV-associated glomerular disease (HCV-GD) in 14 patients with HIV coinfection. All were intravenous drug users and all but one were African-Americans. Renal presentations included renal insufficiency, microscopic hematuria with active urine sediment, hypertension, and nephrotic syndrome or nephrotic-range proteinuria without hypercholesterolemia. Hypocomplementemia and cryoglobulinemia were present in 46 and 33% of patients, respectively. The predominant renal biopsy findings were membranoproliferative glomerulonephritis type 1 or type 3 (Burkholder subtype) in 79% of patients and membranous glomerulopathy with atypical features in 21% (including overlap with collapsing glomerulopathy in one patient). The clinical course was characterized by rapid progression to renal failure requiring dialysis. The overall morbidity and mortality were high with median time of 5.8 mo to dialysis or death. Although most patients died in renal failure, cause of death was primarily attributable to long-term immunosuppression and advanced AIDS. Patients with AIDS had shorter survival than those without (median survival time of 6.1 mo versus 45.9 mo, log-rank test P = 0.02). Only two patients were alive with stable renal function at follow-up of 28.5 mo. In patients with HCV-GD, coinfection with HIV leads to an aggressive form of renal disease that can be easily confused with HIV-associated nephropathy. Although hypocomplementemia, cryoglobulinemia, and more prominent hypertension and microscopic hematuria may provide clues to the presence of HCV-GD, renal biopsy is essential to differentiate HCV-GD from HIV-associated nephropathy.
Survival outcomes of secondary cancers in patients with waldenström macroglobulinemia: An analysis of the SEER database
Authors: Jorge J. Castillo, Adam J. Olszewski, Sandra Kanan, Kirsten Meid, Zachary R. Hunter, Steven P. Treon
Journal: American Journal of Hematology (2015)

We hypothesized that survival outcomes of WM patients who develop SM is distinct from the general population of individuals who develop those same malignancies. Using the SEER-18 data (2000-2011), we identified patients with cancers of the breast, prostate, lung, colorectum, bladder, melanoma, non-Hodgkin lymphoma (NHL), and acute leukemia, and compared their outcomes according to having antecedent WM or not. The outcome of interest was overall survival (OS), which was analyzed in proportional-hazard models adjusted for age, sex, race, and stage. We found that patients with WM who developed SM were older than population controls with those same cancers. In the multivariate analysis, WM cases with colorectal cancer (HR 1.97; P < 0.001), melanoma (HR 2.63; P < 0.001) and NHL (HR = 1.35; P = 0.02) had worse OS than controls with those respective cancers. WM patients with diffuse large B-cell lymphoma also had worse OS (HR = 1.86; P = 0.008). The utilization of surgery and radiation was similar between WM cases and controls, except lower rates of prostatectomy and melanoma surgery among WM patients. The survival of WM patients with colorectal cancer, melanoma, and NHL is worse than among general population controls, arguing in favor of age-appropriate cancer screening.
Health-related quality of life after automated or protocol-based weaning from mechanical ventilation
Authors: Dirk Schädler, Laura Kaiser, Björn Malchow, Gunnar Elke, Sven Pulletz, Inez Frerichs, Jens Scholz, Thomas Küchler, Norbert Weiler
Journal: European Respiratory Journal (2011)

Introduction:  Although automated weaning systems have shown to be safe and more efficient than a conventional approach, it is unknown whether they influence health-related quality of life (HRQOL).   Objective:  We hypothesized that automated weaning with SmartCare/PS compared with a standardized weaning protocol has a positive effect on HRQOL.   Methods:  Patients were systematically followed-up one year after participation in a randomized controlled trial investigating the effect of automated versus protocol-driven weaning from mechanical ventilation (ASOPI-trial; clinicaltrials.gov ID 00445289). Quality of life was assessed using QLQ C-30 3.0 questionnaire. Mean differences of equal or more than 10 score points were considered to be clinically relevant.   Results:  300 patients were initially included, 232 patients were alive one year later. We were able to get into contact with 143 patients, 127 patients gave consent to fill out the questionnaire. 81 questionnaires were sent back and included into this analysis. Regarding the function-related scales we found clinically significant higher mean score values for “emotion” and “global health status” in the automated weaning group (Figure 1, Panel A). Symptom-related scales like “fatique” and “diarrhoea” were clinically significant lower in the SmartCare/PS-group (Figure 1, Panel B).   Conclusions:  This study shows an improved HRQOL in the automated weaning group.
Bone marrow transplantation
Authors: S. A J Rule, S. G O'Brien, A. Spencer, J. Apperley, J. M Goldman
Journal: BMJ (1995)

nappy was being changed; there was a "crack," and he was distressed.In our view it is unwise to label these fractures as spontaneous, although the force required may be less than that needed to fracture well mineralised bones.A difficulty arises if a non-accidental injury has occurred: if the fracture has been accepted as spontaneous the child is left unprotected.Children with disability are at greater risk of abuse than their peers, and some of these fractures will be the result of abuse.23 Have Lingam and Joester considered why the school attended by the subjects of their reports apparently has such a high incidence of fracture of the femur?
Barrett's oesophagus: size does matter
Authors: Pieter J F de Jonge, Frederik Hvid-Jensen
Journal: Gut (2015)

For several decades, the incidence of oesophageal adenocarcinoma (OAC) has shown the highest proportional rise among all cancers in the Western world. In order to detect neoplasia at a curable stage, endoscopic surveillance of patients with its precursor lesion Barrett's oesophagus (BO) is recommended by various societal guidelines and as such has been widely implemented over the past decades. However, although surveillance endoscopy is intuitively rational, there is currently no proof from randomised trials that this strategy reduces OAC mortality, and its cost-effectiveness has been questioned. The observation that <8% of OAC is preceded by a BO diagnosis further undermines the impact of surveillance. Recent population-based studies have shown a much lower overall cancer risk in BO than previously anticipated, and together with the growing emphasis on healthcare cost containment, the rationale for endoscopic surveillance has come under greater scrutiny.1 ,2 A 2014 cost-utility analysis of current surveillance protocols, incorporating progression estimates from large population-based studies, suggests that surveillance of patients with non-dysplastic BO is unlikely to be cost-effective.3 Alternative strategies such as ablation have raised hope to omit surveillance in patients; however, in reality considerable recurrence rates of both BO and carcinomas in particularly long segment BO (LSBO) still require …
The estimation of respiratory muscles (RM) status by echodensitometry in men with chronic obstructive pulmonary disease (COPD)
Authors: Alexandr Lemeschewskij, Mikhail Nedzvedz, Alexander Pochtavcev, Alexander Makarevich, Sviatlana Lemiasheuskaya
Journal: European Respiratory Journal (2012)

Aim: Investigate the RM status.  Material, Methods: We obtained the indices: homogenity (H), structural density (SD), echogenicity (E) and dispersion (D) of the internal oblique abdominal muscle (intOAM) by ultrasonic scanner. We carried out histological research of intOAM. Research was made in 20 COPD pts: 1st group (10 – 1st stage); 2nd group (10 – 2nd stage). Control - 12 healthy subjects.  Results: There have been areas of myolysis, cell proliferation of perimiysium, ingrowth of fatty tissue between myofibrils (MF). There is interstitial sclerosis, sections “contractions” of MF. Among the relatively preserved MF was found deep dystrophic one with protein granules of different sizes in the appearance of the sarcoplasm. The H in pts of the 1st and 2nd groups was 20.8 and 19.3 respectively (p  Conclusion: The proposed echodensitometric parameters reflect the degenerative processes occurring in the RM.
Single-breath lung diffusion capacity for carbon monoxide in children and young adults born extremely preterm
Authors: Emma Satrell, Ola Røksund, Einar Thorsen, Thomas Halvorsen
Journal: European Respiratory Journal (2011)

Introduction: Extreme preterm (EP) birth is associated with acinar developmental alterations, potentially influencing lung diffusing capacity (DLCO) and gas exchange. Techniques of measurement are complex and feasibility in children needs to be addressed.

Aims: To study repeatability of DLCO in children and young adults, and to compare results of subjects born EP and at term in two different decades.

Methods: Two area-based cohorts of subjects born at gestational age (GA) ≤ 28 weeks or with birth weight (BW) ≤ 1000 grams in the two periods 1991-1992 (n=35) and 1982-1985 (n=46) and matched controls born at term performed single-breath DLCO tests twice within two weeks. Mean ages (SD) were 10.6 (0.4) and 17.7 (1.2) years.

Results: The coefficient of variation for intersession measurements of DLCO for subjects born preterm and at term in the 1991-92 and 1982-85 birth-cohorts were 8.2 and 7.7%, and 9.5 and 7.6%, respectively. EP birth was associated with significantly reduced height adjusted DLCO and with lower KCO**. Deficits were similar in the two birth-cohorts (test of interaction, p = 0.410).

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Conclusions: Repeatability of DLCO was acceptable for all subgroups. Compared to controls born at term, lung diffusion capacity was significantly and similarly reduced for subjects born preterm in the two decades studied.
The PRECIS-2 tool: designing trials that are fit for purpose
Authors: K. Loudon, S. Treweek, F. Sullivan, P. Donnan, K. E. Thorpe, M. Zwarenstein
Journal: BMJ (2015)

PRECIS is a tool to help trialists make design decisions consistent with the intended purpose of their trial. This paper gives guidance on how to use an improved, validated version, PRECIS-2, which has been developed with the help of over 80 international trialists, clinicians, and policymakers. Keeping the original simple wheel format, PRECIS-2 has nine domains—eligibility criteria, recruitment, setting, organisation, flexibility (delivery), flexibility (adherence), follow-up, primary outcome, and primary analysis—scored from 1 (very explanatory) to 5 (very pragmatic) to facilitate domain discussion and consensus. It is hoped PRECIS-2 will be valuable in supporting the explicit matching of design decisions to how the trial results are intended to be used
Mantel-Haenszel Analysis of Oxford Data. I. Independent Effects of Several Birth Factors Including Fetal Irradiation2
Authors: G. W. Kneale, A. M. Stewart
Journal: JNCI Journal of the National Cancer Institute (1976)

Data from the Oxford Survey of Childhood Cancers were subjected to the Mantel-Haenszel procedures to recognize independent effects of associated factors in retrospective data. Our results showed that several birth factors, including fetal irradiation, social class, maternal age, and sibship position, exerted separate effects on childhood cancers in general, and reticuloendothelial system neoplasms in particular.
The effect of right atrial catheters on infectious complications of chemotherapy in children.
Authors: J van Hoff, A T Berg, J H Seashore
Journal: Journal of Clinical Oncology (1990)

Rates of infections and catheter complications in children with right atrial catheters (RACs) receiving chemotherapy were compared with those without RACs in a retrospective cohort study. One hundred sixty-five children presenting to Yale-New Haven Hospital with a malignancy diagnosed between January 1, 1981 and December 31, 1985 were followed through June 30, 1986 for the number of treatment-related complications resulting in hospitalization. The time on therapy totaled 80,089 person-days that were divided into 510 periods of observation defined by the presence or absence of a RAC, disease status (remission, partial remission, or relapse), intensity of chemotherapy (using a 0 to 4 scale), and use of radiation therapy. Children with RACs experienced markedly higher rates of sepsis (14-fold higher, P less than .0001) and catheter-site infection or other catheter complications requiring hospitalization (both greater than 30-fold higher, P less than .0001). These effects persisted after controlling for other risk factors, ie, disease status, chemotherapy intensity, and age. Children with RACs also had higher rates of fever and neutropenia and other infections requiring hospitalization that were more strongly influenced by the other risk factors. The association of RACs with sepsis, fever and neutropenia, and days hospitalized for treatment-related complications was assessed using multivariable analysis methods to control for disease status, intensity of chemotherapy, radiation therapy, type of cancer, age, and sex. The presence of a RAC (rate ratio [RR], 6.39; P less than .0001) and the disease status (RR, 2.45; P = .0004) were the only factors that predicted sepsis. Fever and neutropenia rates were most influenced by chemotherapy intensity (RR, 2.31; P = .0001) and age (RR, 0.94; P = .013 per year of age) and less by the presence of a RAC (RR, 1.56; P = .053). Controlling for other risk factors, children with RACs experienced a 6.4-times higher rate of sepsis and spent an average of 15.4 more days per year in the hospital for treatment-related complications.
Abstract 2255: Plaque With Calcified Nodule in the Culprit Lesion is Prone to Develop a Smaller Myocardial Infarction Size
Authors: Takahiro Hayashi, Hiroshi Yabushita, Kenji Yamaji, Toshikazu Tsujimoto, Kentaro Ohe, Takuo Ishise, Yukiko Miyamura, Masafumi Ueno, Naoya Kobayashi, Atsuhiro Kurooka, Mitsugu Taniguchi, Akio Kimura, Shunichi Miyazaki
Journal: Circulation (2006)

Introduction: Coronary artery calcification is associated with plaque disruption of culprit lesion in the patient with acute myocardial infarction (MI). However, the impact of calcification in the ...
Eosinophilia as marker of outcome in hospitalised patients with AECOPD
Authors: H.J. Prins, D. Snijders, J.M.A. Daniels, W.G. Boersma
Journal: European Respiratory Journal (2013)

Background:  blood eosinophilia > 2% has been promising marker for outcome in AECOPD treated with 14 days course of prednisolone.    1  Methods:  Patients included in an ongoing randomised controlled intervention trial (the CATCH study) patients were grouped based on blood eosinophil count >2% and ≤ 2% on admission, respectively. Treatment was standardised in the trial and consisted of prednisolone therapy, bronchodilators and based on the allocated treatment algorithm patients were treated with antibiotics or not. The two groups were analysed with respect to baseline characteristics and outcome parameters.   Results:  Ninety patients hospitalised for AECOPD were included. All three types  of Anthonisen AECOPD were included. Each patient could be included once.   Conclusions :  subanalysis of the results of the CATCH study showed that eosinophilia (>2%) is associated with lower LOS. These patients used more often inhalation CS than those with low eosinophil count.   1  Bafehei M, et al. Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2012;186:48-55.