tbuckley/cabot-search huggingface dataset:
Percutaneous core biopsy in patients with a history of LCIS
Authors: N. L. Sroka, L. Sclafani, M. Stempel, S. Devore, L. Montgomery
Journal: Journal of Clinical Oncology (2008)

11555 Background: Patients with a history of lobular carcinoma in situ (LCIS) routinely undergo increased radiologic surveillance for early detection of breast cancer (BC). This screening often results in abnormal imaging and subsequent percutaneous core biopsy (PCB) for tissue diagnosis. If the PCB reveals LCIS, the standard of care is surgical excision (SE). The purpose of this study was to compare the pathology of PCB and final surgical excisional pathology in patients with LCIS. Methods: A retrospective review of the Breast Service Surgical Database was performed for patients with a previous surgical biopsy demonstrating LCIS. All patients with previous or simultaneous diagnosis of BC were excluded. All LCIS patients underwent yearly mammography and biannual clinical breast examination (CBE). Additional screening ultrasound or MRI was performed at the discretion of the physician. Each PCB was recorded as an individual event. All subsequent pathology was reviewed and recorded. Results: A total of 559 patients were identified with a diagnosis of LCIS. After receiving this diagnosis, 26 patients underwent bilateral total mastectomies. The remaining 533 patients were followed for a median of 36 months. During this time 89 PCB were performed for abnormal imaging. All patients had a normal CBE at the time of PCB. Conclusions: At a median follow-up of 36 months, PCB detected BC in 27/89 (30.3%) of patients who underwent PCB for abnormal imaging. Two of the 6 (33%) patients with ADH on PCB had BC at excision. While none of the patients with LCIS on PCB had BC at definitive excision, PCB remains an important aspect of LCIS management. Summary of Percutaneous Core Biopsy Pathology and Surgical Excision Pathology PCB Pathology Number SE Surgical Excision Pathology BC Benign ADH/ALH LCIS Benign (n=44) 4 0 0 1 3 ADH (n=6) 6 1 1 1 2 LCIS (n=12) 10 2 2 6 0 Cancer (n=27) 25 1 3 4 17 Total (n=89) 45 5 6 12 22 No significant financial relationships to disclose.
Persistent Efficacy of Vi Conjugate Vaccine against Typhoid Fever in Young Children
Authors: Mai Ngoc Lanh, Phan Van Bay, Vo Anh Ho, Tran Cong Thanh, Feng Ying C. Lin, Dolores A. Bryla, Chiayung Chu, Joseph Schiloach, John B. Robbins, Rachel Schneerson, Shousun C. Szu
Journal: New England Journal of Medicine (2003)

To the Editor: The limitations of the three licensed typhoid vaccines that precluded their use in children younger than five years old have been overcome by a Vi conjugate vaccine (Vi-rEPA, a conjugate of the capsular polysaccharide of Salmonella typhi, Vi, bound to nontoxic recombinant Pseudomonas aeruginosa exotoxin A [rEPA]).1–3 After 27 months of active surveillance in a double-blind, placebo-controlled, randomized trial involving 12,008 children two to five years old in the Mekong Delta region of Vietnam, Vi-rEPA was found to confer 91.1 percent protection against typhoid.3,4 Vi-rEPA induced an increase by a factor of 10 or more . . .
Iatrogenic Iron Overload in Dialysis Patients at the Beginning of the 21st Century
Authors: Guy Rostoker, Nosratola D. Vaziri, Steven Fishbane
Journal: Drugs (2016)

Iron overload used to be considered rare in hemodialysis patients but its clinical frequency is now increasingly realized. The liver is the main site of iron storage and the liver iron concentration (LIC) is closely correlated with total iron stores in patients with secondary hemosideroses and genetic hemochromatosis. Magnetic resonance imaging is now the gold standard method for LIC estimation and monitoring in non-renal patients. Studies of LIC in hemodialysis patients by quantitative magnetic resonance imaging and magnetic susceptometry have demonstrated a strong relation between the risk of iron overload and the use of intravenous (IV) iron products prescribed at doses determined by the iron biomarker cutoffs contained in current anemia management guidelines. These findings have challenged the validity of both iron biomarker cutoffs and current clinical guidelines, especially with respect to recommended IV iron doses. Three long-term observational studies have recently suggested that excessive IV iron doses may be associated with an increased risk of cardiovascular events and death in hemodialysis patients. We postulate that iatrogenic iron overload in the era of erythropoiesis-stimulating agents may silently increase complications in dialysis patients without creating frank clinical signs and symptoms. High hepcidin-25 levels were recently linked to fatal and nonfatal cardiovascular events in dialysis patients. It is therefore tempting to postulate that the main pathophysiological pathway leading to these events may involve the pleiotropic master hormone hepcidin (synergized by fibroblast growth factor 23), which regulates iron metabolism. Oxidative stress as a result of IV iron infusions and iron overload, by releasing labile non-transferrin-bound iron, might represent a ‘second hit’ on the vascular bed. Finally, iron deposition in the myocardium of patients with severe iron overload might also play a role in the pathogenesis of sudden death in some patients.
Complicated grief and bereavement-related depression as distinct disorders: preliminary empirical validation in elderly bereaved spouses
Authors: H G Prigerson, E Frank, S V Kasl, C F Reynolds, B Anderson, G S Zubenko, P R Houck, C J George, D J Kupfer
Journal: American Journal of Psychiatry (1995)

This study sought to determine whether a set of symptoms interpreted as complicated grief could be identified and distinguished from bereavement-related depression and whether the presence of complicated grief would predict enduring functional impairments.Data were derived from a study group of 82 recently widowed elderly individuals recruited for an investigation of physiological changes in bereaved persons. Baseline data were collected 3-6 months after the deaths of the subjects' spouses, and follow-up data were collected from 56 of the subjects 18 months after the baseline assessments. Candidate items for assessing complicated grief came from a variety of scales used to evaluate emotional functioning (e.g., the Hamilton Depression Rating Scale, the Brief Symptom Inventory). The outcome variables measured were global functioning, medical illness burden, sleep, mood, self-esteem, and anxiety.A principal-components analysis conducted on intake data (N = 82) revealed a complicated grief factor and a bereavement-depression factor. Seven symptoms constituted complicated grief: searching, yearning, preoccupation with thoughts of the deceased, crying, disbelief regarding the death, feeling stunned by the death, and lack of acceptance of the death. Baseline complicated grief scores were significantly associated with impairments in global functioning, mood, sleep, and self-esteem in the 56 subjects available for follow-up.The symptoms of complicated grief may be distinct from depressive symptoms and appear to be associated with enduring functional impairments. The symptoms of complicated grief, therefore, appear to define a unique disorder deserving of specialized treatment.
Carboplatin hypersensitivity reaction in pediatric low grade glioma (LGG) patients: A national experience. On behalf of the Canadian Pediatric Brain Tumor Consortium
Authors: L. Lafay-Cousin, J. Hukin, A. Carret, B. Wilson, S. Zelcer, D. Strother, I. Odame, M. Silva, D. Johnson, E. Bouffet
Journal: Journal of Clinical Oncology (2006)

9053 Background: Carboplatin based regimens are widely used in the treatment of unresectable pediatric LGG. Carboplatin hypersensitivity reaction (CHSR) represents a main limiting factor. Objective: To analyse the incidence, characteristics, management and impact on outcome of CHSR. Methods: National retrospective review of children diagnosed with LGG between 1988 and 2004. Inclusion criteria were age &lt;18 years, pathology proven diagnosis of LGG except in NF1 patients, and no chemotherapy or radiotherapy prior to carboplatin chemotherapy. Results: 105 patients (61F/44M) from 10 Canadian centers were included in the study. Median age at diagnosis was 3.5y (0.3–16.8). 33 patients had NF1, 75 had diencephalic tumor. Carboplatin was given monthly or weekly respectively in 46 and 59 patients. 44 (41.9%) patients developed carboplatin HSR at a median time of 6.5 months (0.4–15.4), after a median number of 10.5 (3–39) injections. CHSR occurred significantly earlier with the weekly schedule (p=0.016). Cumulative incidence of CHSR increased with the number of injections with no plateau. Female had significant higher risk to develop CHSR (p=0.02) whereas age, NF1 status and schedule of administration were not significant risk factors. First allergic reaction was rated grade I, II in 36 patients (82%). 34 patients were reexposed to carboplatin with desensitization/premedication, allowing 14 patients (41.2%) to complete their treatment. But the majority (58.8%) had recurrent allergic reaction with a significant worsening of their symptoms (p=0.039). The median number of additional Carboplatin injections delivered was 4 (0.5–34). After Carboplatin discontinuation, 18 patients were switched to another chemotherapy regimen. 5 years PFS was not significantly different in allergic and non allergic patients (53.9% and 45.6%). Conclusions: In our experience, the incidence of CHSR is high (41.9%). Female have higher risk of CHSR. Desensitization/premedication has limited efficacy and does not prevent worsening of CHSR. CHSR did not impact the PFS. However many patients did switch to another chemotherapy regimen and the total duration of treatment was comparable in both groups. No significant financial relationships to disclose.
Thrombopoietin Does Not Induce Lineage-Restricted Commitment of Mpl-R Expressing Pluripotent Progenitors But Permits Their Complete Erythroid and Megakaryocytic Differentiation
Authors: Frédérique Goncalves, Catherine Lacout, Jean-Luc Villeval, Françoise Wendling, William Vainchenker, Dominique Duménil
Journal: Blood (1997)
Abstract 153: IL-10 Accelerates Re-Endothelialization and Inhibits Post-injury Intimal Hyperplasia following Carotid Artery Denudation by Attenuating TNF-alpha-induced Endothelial Cell Dysfunction
Authors: Suresh K Verma, Prasanna Krishnamurthy, Alexander R Mackie, Erin E Vaughan, Mohsin Khan, Garikipathy V Srikanth, Veronica Ramirez, Tatiana Abramova, Sol Misener, Gangjian Qin, Raj Kishore
Journal: Circulation Research (2014)

The association of inflammation with atherosclerosis and restenosis is now fairly well established. Restenosis, a persistent complication of percutaneous vascular interventions, is thought to be a complex response to injury, which includes early thrombus formation, neointimal growth and acute inflammation. Mononuclear phagocytes are likely participants in the host response to vascular injury, via the secretion of cytokines and chemokines, including TNF-alpha (TNF). Others and we have previously shown that IL-10 inhibits TNF and other inflammatory mediators produced in response to cardiovascular injuries. The specific effect of IL-10 on endothelial cell (EC) biology is not well elucidated. Here we report that in a mouse model of carotid denudation, IL-10 knock-out mice (IL10KO) displayed significantly delayed ReEndothelialization and enhanced neointimal growth compared to their WT counterparts. Exogenous treatment of recombinant IL-10 dramatically blunted the inflammatory cell infiltration and neointimal thickening while significantly accelerating the recovery of the injured endothelium both WT and IL10KO mice. In vitro, IL10 co-treatment reversed TNF-mediated growth arrest, EC cell cycle inhibition, EC-monocyte adhesion and EC apoptosis. At signaling level, IL-10 reduced TNF-induced activation of JNK MAP kinase while simultaneously activating PI3K/Akt pathway. Because IL-10 function and signaling are important components for control of inflammatory responses, these results may provide insights necessary to develop strategies for modulating vascular repair and other accelerated arteriopathies, including transplant vasculopathy and vein graft hyperplasia.
P195 Demographics and outcomes of NIV in MND: a frontline perspective
Authors: K Ward, V Ford, H Ashcroft, S Wordingham-Baker, B Chakrabarti, N Duffy, R Angus, R Parker
Journal: Thorax (2015)

<h3>Introduction</h3> Non-invasive ventilation (NIV) in motor neurone disease (MND) is an evidence-based therapy, recommended by NICE. A single centre randomised trial of 41 patients underpins much of current practice,<sup>1</sup> it was suggested our patient cohort may differ from those in the original trial work. <h3>Methods</h3> Retrospective review of all patients offered NIV from 01.01.2013 to 30.06.2015. Data was taken from the initial neurology referral, and NIV set-up. Demographics were compared with the Newcastle study<sup>1</sup> (Table 1). Twelve month survival, and/or death post NIV initiation were assessed. <h3>Results</h3> Sixty-three patients were offered trial of NIV; 5 declined admission, and 7 declined NIV. Fifty-one patients were discharged with NIV, of whom 4 rapidly discontinued ventilation. Forty-seven patients were followed as NIV users, 35 for at least a year or to death. Fifty-seven percent were documented as having bulbar symptoms, the severity of which were not formally assessed. Twenty-nine percent received formal carer support at NIV initiation. Of the 35, 24 (68.6%) died within one year of NIV commencement, and median survival for all deaths was 177 days (range 4–630 days). Patients who died were significantly more likely to have bulbar dysfunction (18/24, p = 0.003) with a trend to reduced survival, median 149 vs. 239.5 days non-bulbar (p = 0.09). Twenty patients are alive at data collection, current median survival 292 days (range 7–793 days) and this data will affect results. Those with carers in place had a significantly lower ALSFRS-R (26.3 vs 32.4, p = 0.008) and shorter median survival (135 days). Of those dying or surviving at least a year, 22/35 (63%) were issued with cough-assist support (18/22 mechanical in/exsufflation). <h3>Conclusions</h3> Our cohort and outcomes are similar to those in the Bourke trial. Patients with bulbar disease, and/or pre-existing care input may have worse survival. Current users will be followed up to complete the dataset for survival. The impact of bulbar disease, cough augmentation<sup>2</sup> and carer need remain uncertain. Ways to better assess and support these groups should be sought, and adequately powered randomised trials in these areas developed. <h3>References</h3> 1 Bourke SC, Tomlinson M, Williams TL. <i>et al.</i> Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomised controlled trial.<i> Lancet Neurol</i>. 2006;<b>5</b>:140–7 2 Rafiq MK, Bradburn M, Proctor AR. <i>et al.</i> A preliminary randomized trial of the mechanical insufflator-exsufflator versus breath-stacking technique in patients with amyotrophic lateral sclerosis.<i> Amyotroph Lateral Scler Frontotemporal Degener</i>. Published Online First: 3 Jul 2015. doi:10.3109/21678421.2015.1051992
Streptozocin Alone Compared with Streptozocin plus Fluorouracil in the Treatment of Advanced Islet-Cell Carcinoma
Authors: Charles G. Moertel, James A. Hanley, Lewis A. Johnson
Journal: New England Journal of Medicine (1980)

To evaluate the treatment of advanced islet-cell carcinoma, we randomly assigned 84 patients to streptozocin alone or streptozocin plus fluorouracil. Each regimen was given in five-day courses. The most frequent toxic effects were nausea and vomiting, mild and reversible renal toxicity, and bone-marrow depression with the combination regimen. The combination had advantages over streptozocin alone in overall rate of response (63 vs. 36 per cent) and in rates of complete response (33 vs. 12 per cent). There was no evidence of a preferential response among types of functional tumors. Objective responses were generally of long duration (median, 17 months) and of substantive clinical benefit. Treatment with the combination also yielded a survival advantage over treatment with streptozocin alone (medians, 26 and 16 1/2 months), but this difference is not statistically significant. In spite of gastrointestinal side effects, streptozocin combined with fluorouracil appears to be a valuable treatment for advanced islet-cell carcinoma. (N Engl J Med. 1980; 303:1189–94.)
Screening for Fetal Down's Syndrome in Pregnancy by Measuring Maternal Serum Alpha-Fetoprotein Levels
Authors: Miriam Schoenfeld DiMaio, Alexander Baumgarten, Robert M. Greenstein, Howard M. Saal, Maurice J. Mahoney
Journal: New England Journal of Medicine (1987)

Although the risk of Down's syndrome increases with maternal age, women under 35 bear about 80 percent of the infants born with this condition. We prospectively investigated the utility of measuring maternal serum alpha-fetoprotein during the second trimester in women under 35 in order to identify pregnancies in which the fetus was affected with Down's syndrome. Over a two-year period, 34,354 women in this age group were screened. Amniocentesis was offered when the risk of Down's syndrome, calculated as a function of maternal age and maternal serum alpha-fetoprotein concentration adjusted for maternal weight and race, was 1:270 or higher, the risk for a 35-year-old woman. This threshold was exceeded in 1451 women in whom gestational age was confirmed by ultrasound; 9 women in this group had a fetus with the syndrome. In three women whose fetuses had trisomy 18 and one whose fetus had trisomy 13, the calculated risk of Down's syndrome was 1:270 or higher. Thus, among women in whom the risk exceeded our cutoff point, 1 in 161 were found to have a pregnancy in which the fetus was affected with Down's syndrome; the figure was 1 in 112 for all autosomal trisomies. Eighteen pregnancies involving Down's syndrome, three involving trisomy 18, and two involving trisomy 13 were not associated with a calculated risk above the cutoff point. The available data indicate that in our population, using a cutoff for risk at which 5 percent of women under 35 are offered amniocentesis, we will detect one quarter to one third of pregnancies in which the fetus has Down's syndrome.
Preclinical efficacy data of MGN1601, a tumor vaccine comprising 4-fold gene-modified and irradiated allogeneic tumor cells in combination with a DNA-based immunomodulator for the treatment of metastatic renal carcinoma.
Authors: B. Volz, M. Schmidt, K. Kapp, M. Schroff, M. Tschaika, B. Wittig
Journal: Journal of Clinical Oncology (2010)

e15067 Background: MGN1601 is a cell-based tumor vaccine for the treatment of mRCC. MGN1601 consists of two active pharmaceutical ingredients. One consists of allogeneic, human tumor cells, derived from RCC tissue, and transfected in-vitro with four different MIDGE vectors for transient expression of human IL-7, GM-CSF, CD80 and CD154. The other ingredient is the DNA-based immunomodulator dSLIM-30L1, mainly a TLR-9 agonist. Methods: Murine tumor models were used to evaluate the efficacy of a murine homologue of MGN1601 (mMGN1601). mMGN1601 was set up from Renca cells and transfected with 4 different MIDGE vectors for transient expression of mouse IL-7, GM-CSF, CD80 and CD154. For tumor inoculation in syngenic BALB/c mice Renca cells were used. For efficacy of the vaccine in a prophylactic setting, mice were vaccinated with mMGN1601 and thereafter challenged with Renca cells. In therapeutic settings Balb/c mice first received naïve Renca cells and were subsequently vaccinated four times with different test items, either the complete mMGN1601 or one out of three lacking different components. To address the mode of action, modulations of the immune system were monitored in NMRI mice (allogeneic setting). Results: Prophylactic setting: None of the vaccinated mice showed tumor growth, whereas all of the tumor-bearing mice of the control group died due to the tumor growth. Efficacy evaluation in the therapeutic setting revealed, that the complete tumor vaccine clearly achieved the most pronounced effects in tumor reduction, showing a survival of 92%, compared to 25% survival in the control group. The incomplete derivatives led to less pronounced therapeutic efficacy. The immunomodulatory effects of mMGN1601 in allogeneic NMRI mice generated a more than 3-fold increase of the cytotoxic activity of spleen cells, an augmented T-cell proliferation (> 6-fold) and an increase of CD4+, CD8+ and CD86+ cells at the site of vaccination (up to 20-fold). Conclusions: The murine homologue of MGN1601 showed excellent antitumor efficacy and significant pharmacological effects in murine models. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MOLOGEN AG MOLOGEN AG MOLOGEN AG
P217 Chronic mucus hypersecretion may represent a biomarker of airways disease activity rather than simply a phenotype: A longitudinal study of a nationally representative British birth cohort
Authors: JP Allinson, R Hardy, GC Donaldson, SO Shaheen, D Kuh, JA Wedzicha
Journal: Thorax (2015)

<h3>Introduction</h3> Chronic mucus hypersecretion (CMH) is associated with COPD development and progression. CMH presence across adult life is dynamic, influenced by factors such as smoking behaviour. CMH is usually considered a binary phenotype and the potential influence of longitudinal CMH pattern on concurrent FEV<sub>1</sub> decline has not been explored. We investigated how longitudinal prevalence of CMH relates to concurrent FEV<sub>1</sub> decline. <h3>Methods</h3> The MRC National Survey of Health and Development consists of a sample of men and women born in one week in March 1946 within England, Scotland and Wales. Smoking behaviour, MRC questionnaire defined CMH, height, weight and pre-bronchodilator spirometry were recorded at three ages: 43, 53 and (60–64) years. We used the number occasions that CMH was positively reported (0–3) as a measure of longitudinal prevalence of CMH. Multilevel models adjusted for sex were used to analyse the relationship between longitudinal prevalence of CMH and concurrent FEV<sub>1</sub> decline (between ages 43 and (60–64)), allowing both intercept and slope to vary according to the longitudinal prevalence of CMH score. Height, weight and mean FEV<sub>1</sub> at age 43 years were then included in the model. Smoking status (current, ex and never-smoker) and number of cigarettes smoked daily were included as time-varying covariates capable of influencing both intercept and slope. <h3>Results</h3> 1960 individuals contributed data to the multilevel model: 46% male; 59% ever-smoker and mean FEV<sub>1 </sub>at age 43 years = 3.00 L. 13% reported CMH ≥ once between ages 43 and 60–64 years. After full adjustment, longitudinal prevalence of CMH was significantly associated with both a lower FEV<sub>1</sub> at age 43 (intercept p &lt; 0.001) and a faster decline (slope p = 0.003) (See Table 1). For each additional occasion CMH was reported there was an additional 3.2 ml/yr decline in FEV<sub>1</sub> (p = 0.003) i.e. presence of CMH on all three occasions was associated with an additional 9.6 ml/year FEV<sub>1</sub> decline compared with those without CMH on any occasion. <h3>Conclusion</h3> Longitudinal prevalence of CMH is associated with concurrent FEV<sub>1 </sub>decline independent of concurrent smoking history. Rather than CMH being solely an airway disease phenotype, the longitudinal course of CMH may represent a biomarker of concurrent disease activity.