tbuckley/cabot-search huggingface dataset:
Human Papillomavirus Vaccination and Cervical Cytology Outcomes Among Urban Low-Income Minority Females
Authors: Annika M. Hofstetter, Danielle C. Ompad, Melissa S. Stockwell, Susan L. Rosenthal, Karen Soren
Journal: JAMA Pediatrics (2016)

<h3>Importance</h3> The quadrivalent human papillomavirus (HPV) vaccine was licensed for use in 9- through 26-year-old females in 2006. Postlicensure studies in Australia, Denmark, and Canada have demonstrated vaccine effectiveness against abnormal cervical cytology results. However, there are limited data describing postlicensure effectiveness in the United States, particularly among minority females at higher risk for HPV infection and cervical cancer. <h3>Objective</h3> To examine the effect of HPV vaccination on abnormal cervical cytology results among minority females. <h3>Design, Setting, and Participants</h3> Retrospective cohort study conducted between January 2007 and January 2014 at 16 academically affiliated community clinics serving a low-income minority population. Included in this study was a population-based sample of 16 266 females aged 11 through 20 years as of January 1, 2007, who received care at a participating clinic on or after that date. <h3>Exposure</h3> Human papillomavirus vaccination, stratified by the number of doses. <h3>Main Outcomes and Measures</h3> Cervical cytology abnormality following either HPV vaccination or, if unvaccinated, the first missed opportunity for HPV vaccination after January 1, 2007. Abnormalities were defined as atypical glandular cells, atypical squamous cells of undetermined significance, atypical squamous cells, cannot exclude a high-grade squamous intraepithelial lesion, low-grade squamous intraepithelial lesions, or high-grade squamous intraepithelial lesions. <h3>Results</h3> There were 4127 female patients who initiated quadrivalent HPV vaccination or had their first missed HPV vaccination opportunity from 11 through 20 years of age and underwent subsequent cervical cytology screening. The patients were primarily Spanish speaking (n = 2297; 58.3%) and publicly insured (n = 3801; 92.1%). The detection rate for an abnormal cervical cytology result during the observation period was lower among vaccinated (≥1 dose) (79.1 per 1000 person-years) vs unvaccinated (125.7 per 1000 person-years) females. The risk for an abnormal cervical cytology result was lower among vaccinated vs unvaccinated females (hazard ratio [HR], 0.64; 95% CI, 0.57-0.73), particularly if the 3-dose series was completed (HR, 0.48; 95% CI, 0.41-0.56) or if the vaccine was administered from 11 through 14 years of age (≥1 dose: HR, 0.36; 95% CI, 0.16-0.79; 3 doses: HR, 0.27; 95% CI, 0.12-0.63). This protective effect remained after adjusting for demographics, clinic type, abnormal baseline cervical cytology result, and baseline<i>Chlamydia</i>screening (as proxy for sexual experience). <h3>Conclusions and Relevance</h3> This study demonstrated the HPV vaccine is effective in a real-world setting of high-risk patients with variable HPV vaccination patterns.
Effect of Some Anticancer Drugs on the Surface Membrane Electrical Properties of Differentiated Murine Neuroblastoma Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: S G Oakes, K S Santone, G Powis
Journal: JNCI Journal of the National Cancer Institute (1987)

The effect of some anticancer agents that produce toxic effects on electrically excitable cells in vivo was studied in vitro with the use of differentiated N1E-115 murine neuroblastoma cells and single microelectrode electrical recording. In the presence of 10(-7) g/ml tetrodotoxin, following the release of 500-millisecond conditioning hyperpolarization, the cells exhibited Ca2+-dependent action potentials. Local application to N1E-115 neuroblastoma cells of cisplatin (cis-PDD) for 30 seconds from a drug-containing effusion pipette produced a dose-dependent reversible inhibition of the Ca2+-dependent action potential, with a 61% inhibition at 1.7 microM and 67% inhibition at 17 microM cis-PDD. trans-Dichlorodiammineplatinum(II) and platinic(IV) chloride, both of which lacked the growth inhibitory properties of cis-PDD against N1E-115 neuroblastoma cells, at concentrations of 170 and 120 microM produced only an 11 and 19% inhibition of the Ca2+-dependent action potential, respectively. Vincristine at a concentration of 1 microM reversibly inhibited the Ca2+-dependent action potential by 48%. 3'-Deamino-3'-(3''-cyano-4''-morpholinyl)doxorubicin, a more potent experimental antitumor agent than doxorubicin, at 10(-8) M inhibited the Ca2+-dependent action potential by 22%, similar to the inhibition previously reported for doxorubicin. None of the agents affected the cell transmembrane potential, which suggests a lack of an effect on the mechanisms responsible for maintaining the resting cell membrane potential difference. The effects of the agents on the Ca2+-dependent action potential might reflect a direct effect on a plasma membrane Ca2+ channel or on the lipid domain around the channels, or they might be produced by changes in intracellular Ca2+ homeostasis, among other mechanisms. It is not known whether a change in the membrane Ca2+ current is related to the antitumor effects of the agents, but such a change may contribute to the neurotoxicity of cis-PDD and vincristine and the cardiac toxicity of the anthracycline.
True patient participation is difficult and takes dialogue
Authors: J Ditters
Journal: BMJ (2016)

What does participation really mean? J Ditters reflects

I felt tense driving to the conference. My neurologist and I had been asked to speak about the potential benefits of technology for neurology patients. My tenseness puzzled me: this should have been a routine task for someone who works as an innovation manager in a health centre, empowering patients and their families with social and technological advances.

I fumbled at the parking meter, and in the cloakroom I dropped my umbrella for the third time that day. I have muscular dystrophy with myotonia. I often have cold, stiff hands, but today this upset me. I felt as if all of the doctors there would identify me as a patient.

As an optimist, I’ve always let myself be guided by possibilities rather than …
Long-term non-cancer mortality among 39,657 one-year testicular cancer survivors (TCSs)
Authors: S. D. Fosså, J. Chen, G. M. Dores, K. A. McGlynn, S. J. Schonfeld, L. B. Travis
Journal: Journal of Clinical Oncology (2006)

4508 Background: Multiple reports address the incidence of second cancer (SC) and long-term morbidity in TCSs, yet few data analyze the impact of non-malignant late sequelae on mortality. Methods: 39,657 one-year TCSs were identified in 14 population-based cancer registries in North America and Europe, with 17,856, 13,084 and 6,298 men followed for 10, 20 and 30 years, respectively. Standardized mortality ratios (SMRs), comparing TCSs to the general population, were calculated for deaths due to all non-cancer causes (n = 2,942) and specific sites. Further, absolute mortality due to TC, non-TC SC and all non-cancer disorders was estimated. Results: The SMR for all non-malignant diseases combined was 0.99 (95% CI: 0.95–1.02), with a significant reduction of deaths due to circulatory diseases (SMR: 0.92, n = 1,117). However, following initial treatment with chemotherapy and radiotherapy, the SMR for circulatory diseases was significantly elevated (SMR: 1.76), with a non-significant 29% excess after chemotherapy alone. Mortality due to digestive diseases was significantly increased (SMR: 1.32, n = 222), including gastric and duodenal ulcers (SMR = 1.52; excess deaths were observed between 10 and 25 years after initial radiotherapy). For the first 20 years after TC diagnosis, deaths due to infection were significantly elevated (SMR: 1.52, n=211). Absolute mortality due to non-cancer disorders always exceeded that due to SC, and was 15% after 30 years in a TCS diagnosed at age 35 compared with about 11% for SC. Conclusions: Compared with the general population, the overall risk of mortality due to all non-cancer causes combined does not appear to be increased in TCSs. However, they experience excess non-cancer deaths due to infection and digestive diseases, but not circulatory diseases. Additional analytic studies with detailed data on treatment and co-morbidities are required to further evaluate associations with specific causes of death. No significant financial relationships to disclose.
Longitudinal Evaluation Of Health Status In Aging Pediatric Hodgkin Lymphoma Survivors: Report From The Childhood Cancer Survivor Study
Authors: Karen E. Effinger, Wendy M. Leisenring, Kevin C. Oeffinger, Melissa M. Hudson, Kirsten K. Ness, Neyssa Marina, Marilyn Stovall, Gregory T. Armstrong, Leslie L. Robison, Kristin Sainani, Alice S. Whittemore
Journal: Blood (2013)
Immune Tolerance Induction Following AIT Is Associated with Induction of Circulating CD4+CXCR5+PD-1+FoxP3+ T Follicular Regulatory Cells
Authors: Hjh Hanisah Hj Awg Sharif, Rebecca Parkin, Constance Ito, Guy Scadding, Stephen R. Durham, Mohamed H. Shamji
Journal: Journal of Allergy and Clinical Immunology (2016)
A single arm, multicenter, open label, phase II study of lapatinib as 2L treatment of pts with locally advanced/metastatic transitional cell carcinoma (TCC) of the urothelial tract
Authors: C. Wülfing, J.-P. Machiels, D. Richel, M.-O. Grimm, U. Treiber, M. de Groot, P. Beuzeboc, J. Farrell, N. L. Stone, L. Leopold, I. El-Hariry
Journal: Journal of Clinical Oncology (2005)

4594 Background: Lapatinib is an oral reversible inhibitor of ErbB1 (EGFR) and ErbB2 (HER-2/neu) receptor tyrosine kinases. Methods: The primary endpoint was RECIST response rate. Key eligibility criteria included stage IIIB/IV TCC of the bladder, progression following a first-line platinum regimen, expression of ErbB1 and or ErbB2 (1, 2 or 3+ by IHC) and KPS ≥ 70. Lapatinib (1250 mg, qd) was administered until disease progression or unacceptable toxicity. Tumor and safety assessments were performed every 8 and 4 wks, respectively. Cardiac function was monitored at baseline and every 8 wks. Tumor tissue was analyzed for biomarkers (TUNEL, p53, pAkt, Her3, pHer3, pErk, IGF-1R, Rb, pS6). Results: Fifty-nine pts were enrolled. Investigators reported 2 (3%) PRs and 12 (20%) SD; independent radiologic review (IRR) reported 1 (2%) PR and 18 (31%) SD. Based upon investigator and IRR, six and three pts had durable SD lasting 4 and 6 mos, respectively. At wk 8, 10 pts had some degree of cytoreduction; however, most was short-lived. One pt remains on study for > 56 wks. The median TTP was 8.6 wks (95% CI, 8.00, 11.29) and median OS was 17.9 wks (95% CI, 13.14, 30.29). A trend towards clinical benefit was observed in pts with 2+/3+ ErbB1 or ErbB2. Preliminary analysis of biomarkers suggests high pHer3, high pErk and both mutant p53 and high pHer3 predicts resistance, and high pAkt and high IGF-1R predicts sensitivity to lapatinib. Adverse events (AEs) with ≥ 10% frequency were diarrhea (39%), rash (32%), nausea (27%), vomiting (22%), asthenia (12%) and fatigue (10%). Grade 3/4 AEs occurring in more than one pt were vomiting (7%) and diarrhea (3%). One pt had an asymptomatic, Grade 2 decrease in LVEF. Conclusions: Lapatinib was well-tolerated and exhibits activity in pts with relapsed, advanced/metastatic TCC of the bladder, demonstrated by clinical benefit (CR + PR + SD≥ 16 wks) in 14% and 12% of pts by investigator and IRR, respectively. The median TTP of 8.6 wks is comparable to reports of various 2L chemotherapies. There was a trend toward clinical benefit in pts with ErbB1 or ErbB2 2+/3+ by IHC. Multivariate analysis of the biomarker data is planned. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline
Validation of a Three-Dimensional Method for Counting and Sizing Podocytes in Whole Glomeruli
Authors: Victor G. Puelles, James W. van der Wolde, Keith E. Schulze, Kieran M. Short, Milagros N. Wong, Jonathan G. Bensley, Luise A. Cullen-McEwen, Georgina Caruana, Stacey N. Hokke, Jinhua Li, Stephen D. Firth, Ian S. Harper, David J. Nikolic-Paterson, John F. Bertram
Journal: Journal of the American Society of Nephrology (2016)

Podocyte depletion is sufficient for the development of numerous glomerular diseases and can be absolute (loss of podocytes) or relative (reduced number of podocytes per volume of glomerulus). Commonly used methods to quantify podocyte depletion introduce bias, whereas gold standard stereologic methodologies are time consuming and impractical. We developed a novel approach for assessing podocyte depletion in whole glomeruli that combines immunofluorescence, optical clearing, confocal microscopy, and three-dimensional analysis. We validated this method in a transgenic mouse model of selective podocyte depletion, in which we determined dose-dependent alterations in several quantitative indices of podocyte depletion. This new approach provides a quantitative tool for the comprehensive and time-efficient analysis of podocyte depletion in whole glomeruli.
Cross-activity of various established antineoplastic regimens in primary breast cancer cells evaluated by the ex vivo ATP tumor chemosensitivity assay
Authors: W. J. Nagel, J. Luecke, I. A. Cree, U. Reinhold, J. A. Kurbacher, R. Reichelt, H. R. Bruch, C. M. Kurbacher
Journal: Journal of Clinical Oncology (2006)

20086 Recently, various chemotherapy (Ctx) regimens are established in operable breast cancer (BC). Whereas anthracylines are now standard in high-risk patients (pts), the future role of taxanes or classical CMF is still controversial. Moreover, little is known which Ctx will be individually beneficial. This particular information is unlikely to be obtained from randomized trials because simultaneous treatment of one single pt with different competing protocols is inappropriate. Thus, we used ex vivo sensitivity profiles from native primary BC assessed with the ATP tumor chemosensitivity assay (ATP-TCA) to analyze the cross-activity of different standard regimens in individual pts. Each Ctx was tested at six different levels over 1.5 log range including both therapeutical and supra-therapeutical concentrations. Resistance, complete, and incomplete sensitivity were determined using a semiquantitative score. The following head-to-head comparisons of ex vivo activity were made: CMF, 4-OOH-cyclophosphamide (4-HC)+methotrexate (MTX)+5-Fluorouracil (5-FU) vs. EC, epirubicin (EPI)+4-HC, n = 56; CMF vs. paclitaxel (PCT), n = 34; CMF vs. docetaxel (DCT), n = 49; EC vs. PCT, n = 51; EC vs. DCT, n = 35; EC vs. EPI+PCT (ET), n = 45; PCT vs. DCT, n = 34. The ex vivo response rates were in good agreement with the expected clinical activity: CMF 52%, EC 63%, ET 85%, PCT 52%, DCT 49%. CMF and EC were equally active (=) in 68% BCs, CMF was superior (&gt;) to EC in 16% and inferior (&lt;) in 16%. The corresponding proportions (=/&gt;/&lt;) for the other comparisons were: CMF vs. PCT, 45%/31%/24%; CMF vs. DCT, 40%/40%/20%; EC vs. PCT, 49%/31%/20%; EC vs. DCT, 40%/40%/20%; EC vs. ET, 53%/ 9%/38%; PCT vs. DCT 55%/21%/24%. Generally, ET was the most active regimen, being equal or superior to EC in the majority of cases. However, CMF is clearly not inferior to EC or single agent taxanes. PCT and DCT are apparently not always the same. Facing the broad heterogeneity of chemosensitivity demonstrated in this study, we were able to show that the results of randomized trials cannot always be translated to an individual pt. Cross-activity analyses using the ATP-TCA may thus prove useful to allow for a more rational design of clinical trials in primary BC. [Table: see text]
LDH in solid tumors as a surrogate marker for tumor burden and response to treatment
Authors: S. G. Naik, C. Rathnasabapathy, H. Chenthil, A. Sangal, T. Dumlao, S. Kodali, Z. He, M. Kalavar
Journal: Journal of Clinical Oncology (2008)

22164 Background: LDH is a biomarker of cellular turn over. The purpose of our study was to identify serum LDH as a surrogate marker of tumor burden and site of metastatic disease in cancer patients. Methods: Data from 245 cancer patients (mean age: 63.7 years, 53% F, 61.6% adenoca) were retrieved who were treated between July 2005 and December 2007. The pts were risk stratified as stage: stage I: 25, II: 23, III: 92, IV: 105. ECOG performance status was 0–2 in 142 pts, 3–4in 103 pts. All pts had CT scans for tumor staging. LDH, hemoglobin, uric acid, and renal functions were measured at the baseline. Relations between LDH and tumor burden were studied using multivariate analysis. Results: A total of 87 pts (35.5%) had normal LDH (300–600). High LDH was seen in pts as follows: 600–1,000: 80 pts (32.6%), 1,000–2,000: 53 pts (21.6%), 2,000–4,000: 15 pts (6.1%), 4,000–8,000: 7 pts (2.8%), 8,000–16,000: 3 patients (1.2%). The median baseline Hemoglobin, LDH and uric acid levels were 11g/dl, 740IU/L, 5.9mg/dl respectively. None of the pts with normal LDH had liver, brain or lung metastatic disease. Elevated uric acid levels were seen in 41 (16.7%) pts, elevated creatinine >1.5 were seen in 38 pts (15.5%) with high LDH. Increased LDH was the associated with tumor masses: colorectal: 12 pts, kidney: 2 pts, gastric: 8 pts, pelvic: 11 pts. High LDH was associated with extranodal metastatic disease: Liver: 26 pts, lung: 26 pts, and brain: in 6 pts. Elevated LDH did not correlate with stage: Stage 1: 14 pts, stage 2: 11 pts, stage III: 62 pts, stage IV: 70 pts. 90% of long term remitters (30/33) and 80% of pts with stable disease had pretreatment LDH <1000. In contrast, 37.9% of pts with progressive disease had LDH >1,000. No pts received prophylactic allopurinol. Incidence of tumor lysis was 2.8% in all pts (7/245), but with 4.4% (7/158) with high LDH. Conclusions: Incidence of liver and lung metastases was increased in pts with elevated LDH. A pretreatment LDH should always be measured in these pts. Extranodal metastatic sites LDH (IU/L) No.: % pts Liver mets (26) Lung mets (26) Brain mets (7) <600 87 (35.5%) 0 (0%) 0 (0%) 0 (0%) 600-1,000 80 (32.65%) 12 (46.2%) 14 (53.8%) 1 (14.3%) 1,000-2,000 53 (21.6%) 7 (26.9%) 11 (42.3%) 4 (57.1%) 2,000-4,000 15 (6.12%) 3 (11.5%) 0 (0%) 2 (28.6%) >4,000 10 (4.08%) 4 (15.4%) 1 (3.8%) 0 (0%) No significant financial relationships to disclose.
Screening for prostate cancer: A systematic review and meta-analysis.
Authors: M. Djulbegovic, M. M. Neuberger, T. L. Stoffs, P. Dahm
Journal: Journal of Clinical Oncology (2010)

e15038 Background: The value of prostate cancer (PCa) screening remains the subject of considerable controversy as reflected by varying recommendations by professional organizations. Only recently, several large randomized controlled trials (RCTs) on PCa screening were published. We conducted a systematic review and meta-analysis to characterize the totality of evidence on the benefits and harms of PCa screening to support current, evidence based recommendations on PCa screening. Methods: A systematic search using both electronic databases (MEDLINE, EMBASE, CENTRAL) and abstract proceedings of major meetings and bibliographies was conducted. All RCTs on screening versus no screening or routine care for PCa were eligible for inclusion. The screening intervention was defined as the use of prostate specific antigen (PSA) with or without digital rectal examination (DRE). Data abstraction and assessment of methodological quality was conducted by two independent reviewers. Analysis was performed on an intention-to-screen basis. Results were pooled using a random-effects model and expressed as relative risks (RR) with 95% confidence intervals. Results: Five RCTs with a total of 379,229 participants met inclusion criteria and were analyzed. PCa screening was associated with an increased probability of being diagnosed with PCa [Rr=1.39 (1.12-1.73); p=0.003] and being diagnosed with early stage PCa [Rr=1.63 (1.06-2.52); p=0.03]. There was no statistically significant effect of screening on PCa mortality [Rr=0.92 (0.78-1.09); p=0.33] or overall mortality [Rr=0.99 (0.94-1.04); p=0.60]. None of the studies addressed the effect of PCa screening on patients' quality of life or on cost-effectiveness. All trials had one or more substantial methodological limitation. Conclusions: The existing evidence questions the appropriateness of recommendations for the routine use of PCa screening. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration The Dennis W. Jahnigen Career Development Scholars Award by the American Geriatrics Society
The role of respiratory virus infection in COPD exacerbations
Authors: Xavier Pomares, Silvia Capilla, Concepciόn Montόn, Dolors Mariscal, M.A. Marcos, Mateu Espasa, Eduard Monsό, Miguel Gallego
Journal: European Respiratory Journal (2011)

Aim:  To determine the prevalence of viral infection in a cohort of severe COPD patients.   Methods:  We conducted a prospective observational study in a cohort of severe COPD patients from 2005 to 2007. We recorded for each exacerbation: etiological agent, prior antibiotic prescription, corticosteroid treatment and days of hospitalization. Sputum samples were collected and the Gram staining Murray-Washington9s grade was done. A multiplex retrotranscriptase-nested PCR assay was used for simultaneous detection of Parainfluenza virus (1, 2, 3, 4AB), human Coronavirus 229E and OC43, Enterovirus, Rhinovirus, Influenza virus A, B, C, Respiratory syncytial virus and Adenovirus following the procedure described by Coiras  et al . (J Med Virol 72:484-95).   Results:  A total of 118 patients were registered with a mean age of 69±8 years. The 60% were in GOLD stage IV. Among the 307 respiratory samples processed 89.6% (275) were Murray grade IV-V and 66.1% (203) of them had potentially respiratory bacterial pathogen (positive cultures). Overall, virus were detected in 110/307 (35.8%) of analyzed samples, being Rhinovirus the most common of them (22%). In 51.5% (37/72) of bacterial negative culture samples virus were detected, while in 31% (63/203) of bacterial positive cultures virus co-infection was observed (p   Conclusions:   The prevalence of virus infection in our cohort was 36%, being Rhinovirus the most common virus.  A respiratory viral infection may be suspected in COPD exacerbations among patients with negative bacterial culture.  Granted by Fundaciό Maratό TV3
Lymphoid Cells Infiltrating Human Pulmonary Tumors: Effect of Intralesional BCG Injection&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: M Niitsuma, S H Golub, R Edelstein, E C Holmes
Journal: JNCI Journal of the National Cancer Institute (1981)

Tumor-infiltrating lymphocytes (TIL) and regional lymph node lymphocytes (LNL) were isolated by mechanical disaggregation and density gradient centrifugation from 30 untreated human lung tumors and 12 BCG-injected human lung tumors. Lymphocyte populations were characterized by their ability to form erythrocyte (E)-rosettes, erythrocyte-antibody-complement, and erythrocyte-antibody gamma-rosettes, by their proportion of esterase-staining cells, and by their responses in mixed lymphocyte culture (MLC), cell-mediated lympholysis (CML). and natural killer (NK) assays. TIL from untreated tumors had low proportions of E-rosetting cells (mean, 27.3%), relatively high proportions of "null" cells, and poor responses in MLC-CML and NK assays. There were no significant differences between primary lung tumors and lung metastases in rosettes, MLC-CML responses, or NK activity. In contrast, TIL from tumors injected with BCG 14 days before resection had higher proportions of E-rosetting cells (47.8%) and vigorous MLC-CML and NK responses. LNL from 11 patients with untreated tumors had higher proportions of E-rosetting cells (40.5%) than LNL from 9 patients with BCG-injected tumors (35.0%) and LNL from patients with untreated tumors had higher responses than LNL from treated patients in MLC-CML assays. These results suggest that the BCG injection induced an infiltration of functionally reactive NK and T-cells at the tumor site without an associated increased activity of T-cells from regional lymph nodes.