tbuckley/cabot-search huggingface dataset:
Abstract 2851: Temporal QT Variability from Bipolar Ventricular Tip-to-Ring Electrograms Predicts Sustained Ventricular Tachyarrhythmia.
Authors: Larisa G Tereshchenko, Barry J Fetics, Peter P Domitrovich, Ronald D Berger
Journal: Circulation (2007)

We assessed the hypothesis that ventricular tachycardia / ventricular fibrillation (VT/VF) risk stratification based on the repolarization assessment of intracardiac electrograms (EGMs) from implantable devices is feasible. Methods: Bipolar right ventricular tip-to-ring EGMs were recorded at rest (mean heart rate 66 ± 16 bpm) for 5.5 ± 2.6 minutes in 75 patients (58 ± 14 years, 72% men) with ischemic (60%) and non-ischemic (40%) cardiomyopathy who underwent single-chamber Medtronic ICD implantation for primary (77%) or secondary (23%) prevention of SCD. QT variability index (QTVI), variability of Tpeak-Tend area index, and T-wave alternans (TWA) were calculated as previously described elsewhere. Only 41 out of 75 recordings (55%) were eligible for analysis as determined by data quality requirements of the custom software (less than 10% non-analyzable beats or 5% ectopic beats). The endpoint was appropriate ICD therapy for VT/VF during follow-up &gt; 6 months. Results: During mean follow-up of 12 months (range 6–19 months), 12 patients had appropriate ICD therapy. The survival analysis showed that the top quartile of QTVI (&gt; - 0.5) predicts an event-free survival rate from appropriate ICD therapies (p = 0.027). Neither increased Tpeak-Tend area variability nor TWA was associated with a significant increased risk for VT/VF. Conclusions: In this prospective study, temporal QT variability measured from right ventricular tip-to-ring EGMs is associated with increased risk of sustained VT/VF events. Repolarization lability may be present throughout the ventricular myocardium, such that single-site EGMs may provide an effective means for VT/VF risk stratification.
Racial Differences in the Survival of Childhood B-Precursor Acute Lymphoblastic Leukemia: A Pediatric Oncology Group Study
Authors: Brad H. Pollock, Michael R. DeBaun, Bruce M. Camitta, Jonathan J. Shuster, Yaddanapudi Ravindranath, D. Jeanette Pullen, Vita J. Land, Donald H. Mahoney, Stephen J. Lauer, Sharon B. Murphy
Journal: Journal of Clinical Oncology (2000)

PURPOSE: We conducted a historic cohort study to test the hypothesis that, after adjustment for biologic factors, African-American (AA) children and Spanish surname (SS) children with newly diagnosed B-precursor acute lymphoblastic leukemia had lower survival than did comparable white children. PATIENTS AND METHODS: From 1981 to 1994, 4,061 white, 518 AA, and 507 SS children aged 1 to 20 years were treated on three successive Pediatric Oncology Group multicenter randomized clinical trials. RESULTS: AA and SS patients were more likely to have adverse prognostic features at diagnosis and lower survival than were white patients. The 5-year cumulative survival rates were (probability ± SE) 81.9% ± 0.6%, 68.6% ± 2.1%, and 74.9% ± 2.0% for white, AA, and SS children, respectively. Adjusting for age, leukocyte count, sex, era of treatment, and leukemia blast cell ploidy, we found that AA children had a 42% excess mortality rate compared with white children (proportional hazards ratio [PHR] = 1.42; 95% confidence interval [CI], 1.12 to 1.80), and SS children had a 33% excess mortality rate compared with white children (PHR = 1.33; 95% CI, 1.19 to 1.49). CONCLUSION: Clinical presentation, tumor biology, and deviations from prescribed therapy did not explain the differences in survival and event-free survival that we observed, although differences seem to be diminishing over time with improvements in therapy. The disparity in outcome for AA and SS children is most likely related to variations in chemotherapeutic response to therapy and not to compliance. Further improvements in outcome may require individualized dosing based on specific pharmacogenetic profiles, especially for AA and SS children.
Comparative analysis of antimicrobial susceptibility among organisms from France, Germany, Italy, Spain and the UK as part of the tigecycline evaluation and surveillance trial
Authors: A.C. Rodloff, R. Leclercq, E.A. Debbia, R. Cantón, B.A. Oppenheim, M.J. Dowzicky
Journal: Clinical Microbiology and Infection (2008)
Absolute Effect of Prostate Cancer Screening: Balance of Benefits and Harms by Center within the European Randomized Study of Prostate Cancer Screening
Authors: Anssi Auvinen, Sue M. Moss, Teuvo L.J. Tammela, Kimmo Taari, Monique J. Roobol, Fritz H. Schröder, Chris H. Bangma, Sigrid Carlsson, Gunnar Aus, Marco Zappa, Donella Puliti, Louis J. Denis, Vera Nelen, Maciej Kwiatkowski, Marco Randazzo, Alvaro Paez, Marcos Lujan, Jonas Hugosson
Journal: Clinical Cancer Research (2015)

Abstract Purpose: The balance of benefits and harms in prostate cancer screening has not been sufficiently characterized. We related indicators of mortality reduction and overdetection by center within the European Randomized Study of Prostate Cancer Screening (ERSPC). Experimental Design: We analyzed the absolute mortality reduction expressed as number needed to invite (NNI = 1/absolute risk reduction; indicating how many men had to be randomized to screening arm to avert a prostate cancer death) for screening and the absolute excess of prostate cancer detection as number needed for overdetection (NNO = 1/absolute excess incidence; indicating the number of men invited per additional prostate cancer case), and compared their relationship across the seven ERSPC centers. Results: Both absolute mortality reduction (NNI) and absolute overdetection (NNO) varied widely between the centers: NNI, 200–7,000 and NNO, 16–69. Extent of overdiagnosis and mortality reduction was closely associated [correlation coefficient, r = 0.76; weighted linear regression coefficient, β = 33; 95% confidence interval (CI), 5–62; R2 = 0.72]. For an averted prostate cancer death at 13 years of follow-up, 12 to 36 excess cases had to be detected in various centers. Conclusions: The differences between the ERSPC centers likely reflect variations in prostate cancer incidence and mortality, as well as in screening protocol and performance. The strong interrelation between the benefits and harms suggests that efforts to maximize the mortality effect are bound to increase overdiagnosis and might be improved by focusing on high-risk populations. The optimal balance between screening intensity and risk of overdiagnosis remains unclear. Clin Cancer Res; 22(1); 243–9. ©2015 AACR.
Identification and Management of Pump Thrombus in the HeartWare Left Ventricular Assist Device System
Authors: Ulrich P. Jorde, Keith D. Aaronson, Samer S. Najjar, Francis D. Pagani, Christopher Hayward, Daniel Zimpfer, Thomas Schlöglhofer, Duc T. Pham, Daniel J. Goldstein, Katrin Leadley, Ming-Jay Chow, Michael C. Brown, Nir Uriel
Journal: JACC Heart Failure (2015)
Comment on Hughes et al. An Early Pregnancy HbA1c ≥5.9% (41 mmol/mol) Is Optimal for Detecting Diabetes and Identifies Women at Increased Risk of Adverse Pregnancy Outcomes. Diabetes Care 2014;37:2953–2959
Authors: H. Bryan Anderson, Shadi Rezai, Anuradha Setlur, Cassandra E. Henderson
Journal: Diabetes Care (2015)

We welcome the article by Hughes et al. (1) on glycosylated hemoglobin A1c (HbA1c) as a readily available screening tool that the authors propose be used to identify undiagnosed diabetes during the early prenatal period. However, we submit that the low subject participation rate of 23% severely limits the validity of their findings.

Data obtained from only 23% of the study participants do not allow one to have confidence that the selected 5.9% (41 mmol/mol) HbA1c cutoff correlates …
IL32 expression in induced sputum of COPD subjects
Authors: Maria Cristina Scarpa, Kim Lokar Oliani, Filippo Liviero, Simonetta Baraldo, Graziella Turato, Fiorella Calabrese, Marina Saetta, Piero Maestrelli
Journal: European Respiratory Journal (2013)

IL32 is a cytokine produced by T lymphocytes, natural killers cells, lung epithelial cells, monocytes and macrophages, involved in some chronic inflammatory diseases characterized by an autoimmune pathogenesis. A recent study demonstrated increased expression of IL32 in peripheral lung of COPD subjects.  The present research investigated whether induced sputum, being a non-invasive methods, could be useful to study IL32 expression levels in COPD subjects.  Sputum was induced in 20 COPD patients, 20 smokers without airflow limitation, 20 non-smokers with normal respiratory function and 20 systemic sclerosis (SS) subjects, as disease control. IL32 expression was evaluated by immunocytochemistry. Immunoreactivity was quantified in alveolar macrophages as a score obtained multiplying the % of positive cells for the staining intensity (0-3). The mRNA for IL32 isoform α, β and e was evaluated by RT-PCR.  Adequate number of macrophages for immunocytochemistry was obtained in 50% COPD subjects only. Macrophages % was decreased significantly in COPD subjects (median 19, [interquartile range: 9.4-29.2]) compared to smokers (52.2, [23.3-66.7], p  In conclusion, IL32 expression in induced sputum samples do not reflect that observed in peripheral lung tissue.
Prognostic importance of thymidylate synthase expression in early breast cancer.
Authors: B C Pestalozzi, H F Peterson, R D Gelber, A Goldhirsch, B A Gusterson, H Trihia, J Lindtner, H Cortés-Funes, E Simmoncini, M J Byrne, R Golouh, C M Rudenstam, M Castiglione-Gertsch, C J Allegra, P G Johnston
Journal: Journal of Clinical Oncology (1997)

PURPOSE To assess the prognostic importance of thymidylate synthase (TS) expression in breast tumors of patients with early-stage breast cancer, and to determine whether the benefit of chemotherapy (CT) is associated with TS expression. PATIENTS AND METHODS The level of TS expression was evaluated in 210 node-negative and 278 node-positive patients enrolled onto Trial V of the International Breast Cancer Study Group ([IBCSG] formerly the Ludwig Breast Cancer Study Group) with a median follow-up time of 8.5 years. TS expression was assessed using the immunohistochemical method with the monoclonal antibody TS 106 on paraffin-embedded tissue specimens. RESULTS High TS expression was associated with a significantly worse prognosis in node-positive but not in node-negative breast cancer patients. Twenty-seven percent of node-positive patients with high TS expression were disease-free at 10 years, compared with 44% of node-positive patients with low TS expression (P = .03). Forty-one percent of patients with node-positive high-TS-expressing tumors were alive after 10 years, compared with 49% of those with low TS expression (P = .06). The association between TS and disease-free survival (DFS) and overall survival (OS) was independent of other prognostic factors such as tumor size, tumor grade, nodal status, vessel invasion, estrogen receptor (ER)/ progestin receptor (PR) status, c-erb B-2, or Ki-67 expression. In node-positive patients, six cycles of standard adjuvant cyclophosphamide, methotrexate, and fluorouracil ([5-FU] CMF) CT improved DFS and OS compared with one cycle of perioperative CMF therapy. The magnitude of this benefit was greatest in patients whose tumors had high TS expression (P &lt; .01 for DFS; P &lt; .01 for OS). Node-negative patients demonstrated no difference in outcome to CT based on TS expression; however, the power to detect differences was limited by the small number of events in this group. CONCLUSION In early-stage breast cancer, high TS expression is associated with a significantly worse prognosis in node-positive patients. Node-positive patients with high TS levels demonstrate the most significant improvement in DFS and OS when treated with six cycles of conventional adjuvant CMF therapy.
Evaluation of vitamin D replacement in the tuberculosis patients
Authors: Karanvir Singh, Adeel Tariq Sahal, Joyutpal Das, Chris Bond, Alice Turner, Martin Dedicoat, Heinke Kunst
Journal: European Respiratory Journal (2012)

Introduction    One hypothesis is that low serum vitamin D (25[OH]D) level is a risk factor for tuberculosis infection. Historically, 25[OH]D supplementation had been used as a treatment for Tuberculosis. In our study we have assessed the effect of two commonly used 25[OH]D supplements on the 25[OH]D levels in active TB (TB) patients.   Methods and results    We reviewed 113 TB cases from 2010 in our retrospective study. The study population was consisted of 68 males and 45 females. 25[OH]D levels were checked in 96% (65/68) and 98% (44/45) of male and female patients respectively. 56/65 males were 25[OH]D deficient (   Conclusions    Consistent with other studies, we have noticed that most of the TB patients had low 25[OH]D levels. Majority of these patients responded to supplementation, regardless of the gender or the therapeutic agent(s).
Nonadrenergic, noncholinergic responses stabilize smooth muscle tone, with and without parasympathetic activation, in guinea-pig isolated airways
Authors: A Linden, CG Lofdahl, A Ullman, BE Skoogh
Journal: European Respiratory Journal (1993)

In guinea-pig isolated airways, nonadrenergic, noncholinergic (NANC) neural responses converge towards a similar level of smooth muscle tone, via a contraction when the tone is low prior to stimulation, and via a relaxation when the tone is high prior to stimulation. We wanted to assess the effect of simultaneous parasympathetic activation on these converging NANC responses, with and without the addition of sympathetic activation. In guinea-pig isolated airways, the spontaneous airway tone was initially abolished by indomethacin (10 microM). In one series, adrenergic depletion by guanethidine (10 microM) was then established, with and without cholinergic blockade by atropine (1 microM). In another series, either cholinergic blockade by atropine (1 microM) or no blockade was utilized. Responses to electrical field stimulation (1,200 mA, 0.5 ms, 3 Hz for 240 s) were studied with no induced tone, at a moderate (0.3 microM) and at a near-maximum (6 microM), histamine-induced tone. The mean level of the tonus equilibrium (% of maximum tone) was higher with the simultaneous NANC and parasympathetic activation than with NANC activation alone (75% compared with 44%, in the main bronchus, n = 8). The level of the tonus equilibrium was also higher with the simultaneous NANC, sympathetic and parasympathetic activation than with NANC and sympathetic activation only (49% compared with 21%, in the main bronchus, n = 8). The pattern was similar in the distal trachea. In conclusion, NANC neural responses can stabilize smooth muscle tone, and this stabilizing effect can be modulated by both parasympathetic and sympathetic activation, in guinea-pig isolated airways.
Use of “Immunological Enhancement” in the Study of Histocompatibility Mutations2
Authors: S. S. Dhaliwal
Journal: JNCI Journal of the National Cancer Institute (1964)

The use of immunological enhancement in the detection of histocompatibility mutations at the histocompatibility-2 (H-2) locus was investigated. C57BL/10Sn (C57BL) and its isogenic resistant (IR) strains were used. Previous studies showed that enhancement of a tumor is antigenically specific and the enhancing antibody is a product of the H-2 antigens. The specificity of enhancement for the IR strains and the particular host-tumor combination best suited for enhancement were first investigated. DBA/1 strain as hosts gave the best results. No difference was found between various sarcomas. Complete specificity was lacking for strains C57BL and B10.D2 with active immunization. With passive immunization anti-B10.D2 serum enhanced tumors of B10.D2 strain and, partially, tumors of C57BL strain, whereas anti-C57BL serum enhanced only C57BL tumors. Mixture of tumor cells showed that anti-C57BL serum could enhance a small number of C57BL tumor cells in a large inoculum of B10.D2 cells; anti-B10.D2 serum enhanced both C57BL and B10.D2 tumor cells. The reason for this is discussed in relation to the antigenic constitution of the strains. Unlike B10.D2 strain, a third IR strain, B10.M, showed complete specificity for enhancement. Hybrid tumors of (C57BL × B10.D2)F1 were enhanced with anti-B10.D2 serum and not anti-C57BL serum. Hybrid tumors of (C57BL × B10.M)F1 were enhanced only when host mice were conditioned with antisera to both strains. The method of detection of mutations with enhancement is presented. By this method a large number of tumor cells were tested for mutant variants. No mutant variants could be isolated. The possible reason for lack of mutant variants at the H-2 locus is discussed. The lack of complete specificity for enhancement between some of the IR strains indicates that enhancement is not suitable for the study of mutations at the H-2 locus.
Lung involvement in multiple myeloma - study case
Authors: Mimi Floarea Nitu, Mihai Olteanu, Cristina Calarasu, Madalina Olteanu, Alina Miulescu, Damaris Ardelean, Iulia Vasilache
Journal: European Respiratory Journal (2013)

Background: Mutiple mieloma (MM) cells are rarely found in extramedullary sites. Lung involvement in MM is rarely diagnosed antemortem. We report a case in which the myeloma was diagnosed after we discovered the presence of monoclonal plasma cells in the bronchoalveolar lavage fluid (BAL).  Case-study: A 60 years old man, smoker, with no history of respiratory hospitalization was admitted in our hospital with fever, chronic cough, significant weight loss and progressive dyspnea in the previous two months. Chest x-ray: diffuse, bilateral lower-zone reticulo-nodular shadowing. Repeated exams of sputum smear were negative for Mycobacterium tuberculosis (both microscopy and culture). Thorax CT scan: scattered ground glass opacities in both lungs suggestive of interstitial lung disease, no suspect thoracic lymph nodes. Bronchoscopy was performed and bronchoalveolar lavage (BAL) fluid revealed the presence of monoclonal plasmatic cells in BAL. The diagnosis was Multiple myeloma IgG type stage III subclass A. In time the pacient had a rapid decrease of cardiac and respiratory function and the chest x-ray after 4 months showed the extension of the interstitial infiltrates in lower fields of both lungs. Because of his cardiac condition (ischemic heart disease, cardiomyopathy and sinus tachycardia) he couldn’t start specific chemotherapy for MM so his prognosis is severe.  Conclusions: Diffuse parenchymal infiltrates in the lung due to MM are rare but should be considered when finding pulmonary infiltrates. Analysis of BAL fluid for plasma cells is a noninvasive method to establish a diagnosis. Pulmonary MM with comorbidities is associated with rapid progression of the disease unlike primary pulmonary plasmacytomas with a good prognosis.
Stereotactic Approach in Brain Tumors
Authors: F. Giunta, V. Scipione, F. Zorzi, G. Marini
Journal: Neuro-Oncology (1991)

The stereotactic approach to intracranial expansive lesions is to be considered complementary to the traditional "free hand" surgery. With both techniques it is possible to explore or remove any kind of lesion sited everywhere into the cranial space. When an intraparenchimatous lesion is to be approached the only help to the surgeon is the possibility to distinguish normal from pathological tissue. This is not always possible. A surgical approach with the stereotactic frame not only helps to guide exactely the position of the surgical instrument into the tumor, but also to recognize the volume of the lesion when removal is acheavable (open-stereotaxis). 362 (26%) out of 1385 patients with intracranial expansive lesions were approached with stereotactic guide from May 1983 to May 1990. In 96% of these patients serial stereotactic samples were sufficient to reach an histopathological diagnosis. The most important result is that about 20% of all patients had not neoplasms, 35% had slow growing tumors and 45% had fast growing or malignant tumors. Stereoguided histopathology helps in making decision for a more adequate further treatment.
What you don't know can hurt you: adverse psychologic effects in members of BRCA1-linked and BRCA2-linked families who decline genetic testing.
Authors: C Lerman, C Hughes, S J Lemon, D Main, C Snyder, C Durham, S Narod, H T Lynch
Journal: Journal of Clinical Oncology (1998)

PURPOSE To identify members of hereditary breast and ovarian cancer families who are at risk for adverse psychologic effects of genetic testing. PATIENTS AND METHODS A prospective cohort study with baseline (preeducation) assessments of predictor variables (ie, sociodemographic factors, cancer history, and cancer-related stress symptoms) was performed. The primary outcome variable (presence of depressive symptoms) was assessed at baseline and at 1- and 6-month follow-up evaluations. Participants were 327 adult male and female members of BRCA1- and BRCA2-linked hereditary breast and ovarian cancer families, who were identified as carriers, noncarriers, or decliners of genetic testing. RESULTS The presence of cancer-related stress symptoms at baseline was strongly predictive of the onset of depressive symptoms in family members who were invited but declined testing. Among persons who reported high baseline levels of stress, depression rates in decliners increased from 26% at baseline to 47% at 1-month follow-up; depression rates in noncarriers decreased and in carriers showed no change (odds ratio [OR] for decliners v noncarriers=8.0; 95% confidence interval [CI], 1.9 to 33.5; P=.0004). These significant differences in depression rates were still evident at the 6-month follow-up evaluation (P=.04). CONCLUSION In BRCA1/2-linked families, persons with high levels of cancer-related stress who decline genetic testing may be at risk for depression. These family members may benefit from education and counseling, even if they ultimately elect not to be tested, and should be monitored for potential adverse effects.
Temozolomide for the treatment of recurrent glioma: Results of a compassionate use program in Belgium
Authors: B. Neyns, E. Everaert, E. Joosens, T. Strauven, F. Branle, J. Menten
Journal: Journal of Clinical Oncology (2004)

1541 Background: Temozolomide (TMZ) is an oral alkylating agent that has demonstrated objective activity and an acceptable toxicity profile for the treatment of recurrent high-grade gliomas in phase II trials. Only limited information is available on the activity and toxicity of TMZ when prescribed outside a clinical trial. Methods: We conducted a retrospective study to evaluate the activity and safety of TMZ that was prescribed for the treatment of recurrent glioma in the context of a compassionate use program in Belgium. Data were obtained on 117 adult patients (from 5 hospitals) who received TMZ as first or second line chemotherapy. The recommended starting dose of TMZ was 200 mg/m2 x5d q28d for chemonaïve patients and 150 mg/m2 x5d q28d for pretreated patients. Results: Toxicity was generally mild although grade 3/4 toxicity was observed in 22 % of patients. Thrombocytopenia was the most frequent encountered toxicity (grade 3/4 in 17% of patients) and its occurrence was correlated with a starting dose of 200 mg/m2/d. The overall RR (CR + PR) was 29% and 34 % of patients achieved a SD. The median PFS was 104 days (95% CI 85–123) and the median OS was 215 days (95% CI 161–269). In multivariate analysis a "deep localization" of the glioma (as opposed to a cortico-subcortical localization) and the preceding history of a low-grade glioma were identified as independent prognostic variables with regard to TTP & OS. Administration of TMZ as first line chemotherapy was an independent prognostic variable for TTP only. Absence of disease progression at the end of TMZ cycle 3 was significantly correlated with a superior overall survival (landmark analysis, P<0.0001). Conclusions: This retrospective study indicates that the reported activity and toxicity profile of TMZ for the treatment of patients with recurrent glioma is reproducible outside the setting of a prospective clinical trial. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering-Plough (Benelux)