tbuckley/cabot-search huggingface dataset:
Postoperative radiation and concurrent chemotherapy (RCT) with weekly docetaxel is feasible and effective in patients with oral and oropharyngeal cancer - long-term results
Authors: A. F. Kovács, S. Mose
Journal: Journal of Clinical Oncology (2005)

5545 Background: To examine the feasibility and efficacy of weekly docetaxel with concurrent radiation as postoperative treatment in a multimodality approach to oral and oropharyngeal cancer. Methods: Ninety-four patients with primary resectable squamous cell carcinoma of the oral cavity and oropharynx (UICC stage I 14%, II 15%, III 18%, IV 53%) were treated with a multimodality therapy program consisting of neoadjuvant intra-arterial high-dose chemotherapy (cisplatin 150 mg/m2 with parallel systemic sodium thiosulfate 9 g/m2 for neutralization), followed by surgery of the primary and neck, and postoperative RCT with weekly docetaxel (20–30 mg/m2). Chronic toxicities were followed over a period of 5 years. Results: At a median follow-up of 65 months, the 5-year survival rate for all 94 patients was 67%, disease-free survival 60%, and locoregional control 85%. Among patients with advanced disease (stage III and IV), survival was 86 and 50%, respectively. Grade 3 and 4 mucositis was the main acute toxicity necessitating supportive care. Long-term toxicity appeared to be moderate. The maximum tolerated dose of weekly docetaxel was 25 mg/m2. Conclusions: RCT with weekly docetaxel is a feasible postoperative treatment in a multimodality approach to oral and oropharyngeal cancer, resulting in high overall and disease-free survival. This approach warrants further evaluation in prospective randomized trials. No significant financial relationships to disclose.
Opening the Black Box of Ethics Policy Work: Evaluating a Covert Practice
Authors: Andrea Frolic, Katherine Drolet, Kim Bryanton, Carole Caron, Cynthia Cupido, Barb Flaherty, Sylvia Fung, Lori McCall
Journal: The American Journal of Bioethics (2012)

Hospital ethics committees (HECs) and ethicists generally describe themselves as engaged in four domains of practice: case consultation, research, education, and policy work. Despite the increasing attention to quality indicators, practice standards, and evaluation methods for the other domains, comparatively little is known or published about the policy work of HECs or ethicists. This article attempts to open the "black box" of this health care ethics practice by providing two detailed case examples of ethics policy reviews. We also describe the development and application of an evaluation strategy to assess the quality of ethics policy review work, and to enable continuous improvement of ethics policy review processes. Given the potential for policy work to impact entire patient populations and organizational systems, it is imperative that HECs and ethicists develop clearer roles, responsibilities, procedural standards, and evaluation methods to ensure the delivery of consistent, relevant, and high-quality ethics policy reviews.
<i>p53</i> and K-<i>ras</i> Gene Mutations Correlate With Tumor Aggressiveness But Are Not of Routine Prognostic Value in Colorectal Cancer
Authors: Silvia Tortola, Eugenio Marcuello, Isabel González, Germán Reyes, Rosa Arribas, Gemma Aiza, Francesc J. Sancho, Miguel A. Peinado, Gabriel Capella
Journal: Journal of Clinical Oncology (1999)

p53 gene and K-ras mutations are among the most common genetic alterations present in colorectal cancer. The prognostic utility of such mutations remains controversial. The purpose of this study was to prospectively evaluate the prognostic significance of p53 and K-ras gene mutations in colorectal cancer.One hundred forty patients were analyzed. Tumors belonging to the microsatellite mutator phenotype were excluded (n = 8). Mutations at the K-ras and p53 genes were detected and characterized by restriction fragment length polymorphism, single-strand conformation polymorphism, and sequencing, as appropriate.p53 mutations were detected in 66 (50%) and K-ras mutations were detected in 54 (41%) of the 132 patients. In 26 cases (20%), ras and p53 mutations coexisted; in 38 cases (29%), neither mutation was found. Multivariate analysis of the whole population analyzed (n = 132) showed that survival was strongly correlated with the presence of p53 mutations alone or in combination with K-ras mutations (P = .002; log-rank test). When only patients undergoing a radical resection were considered (R0; n = 101), p53 mutations were no longer of prognostic significance.p53 mutations alone or in combination with K-ras mutations are correlated with a worse outcome. However, the routine use of these mutations as prognostic markers in the clinical setting is not recommended.
Hospitalizations of Low-Income Children and Children With Severe Health Conditions
Authors: Jeffrey D. Colvin, Matt Hall, Laura Gottlieb, Jessica L. Bettenhausen, Samir S. Shah, Jay G. Berry, Paul J. Chung
Journal: JAMA Pediatrics (2015)

Specific provisions of the Patient Protection and Affordable Care Act may pose a disproportionate risk to children's hospitals because they carry the greatest burden of care costs of any type of hospital.
High‐Resolution Projection Microstereolithography for Patterning of Neovasculature
Authors: Ritu Raman, Basanta Bhaduri, Mustafa Mir, Artem Shkumatov, Min Kyung Lee, Gabriel Popescu, Hyunjoon Kong, Rashid Bashir
Journal: Advanced Healthcare Materials (2015)

To gain a quantitative understanding of the way cells sense, process, and respond to dynamic environmental signals in real‐time requires developing in vitro model systems that accurately replicate the 3D structure and function of native tissue. A high‐resolution projection stereolithography apparatus (μSLA) capable of multimaterial and grayscale 3D patterning of cells and biomaterials at &lt;5 μm resolution is presented. Murine cells (fibroblasts, myoblasts, endothelial, and bone marrow stromal cells) encapsulated within photosensitive hydrogels using the μSLA remain viable up to two weeks after fabrication. Harnessing the high‐resolution fabrication capabilities of this machine, sub‐millimeter scale angiogenic cell‐encapsulating patches designed to promote targeted growth of neovasculature are printed, as assessed in vitro via enzyme‐linked immunosorbent assay (ELISA) and in ovo via a chick chorioallantoic membrane assay (CAM). This application establishes the μSLA as an enabling technology that is widely adaptable to any application that requires high‐resolution patterning of cells and cells signals. By providing an efficient and robust method of engineering microscale tissues with encapsulated cells, this apparatus has a range of applications including fundamental studies of extracellular matrix interactions, high throughput drug testing of physiologically relevant substitutes for native tissue, and programmable tissue engineering for applications in regenerative medicine.
The Role of Appropriate Use Criteria for Coronary Revascularization⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: W. Douglas Weaver, Timothy J. Gardner, Joseph D. Babb
Journal: Journal of the American College of Cardiology (2009)
Lack of effect of palifermin on the anti-tumor activity of cisplatin, cetuximab or panitumumab in the FaDu human head and neck carcinoma model
Authors: L. Borges, R. Brake, R. Radinsky, C. Starnes
Journal: Journal of Clinical Oncology (2007)

6060 Background: The FaDu human pharyngeal carcinoma cell line expresses the receptors for both KGF and EGF. Palifermin is a recombinant form of human KGF. The objective of this study was to determine whether the combination of palifermin with cisplatin and the EGFR inhibitors cetuximab or panitumumab interferes with the anti-tumor activities of these agents in the FaDu head and neck xenograft model. Methods: FaDu tumor cells were implanted subcutaneously in CD1 nude mice. For the combination of palifermin with cetuximab and cisplatin, treatment began on day 9 and for the combination of palifermin with panitumumab and cisplatin, treatment began on day 10. The primary endpoint was the measure of tumor volume. Results: There was no statistically significant difference in tumor volume between the control arm and palifermin alone (p = 0.9993, 0.9831). Neither was there a statistically significant difference between the combination of palifermin, cisplatin and cetuximab compared to the combination of cisplatin and cetuximab (p = 0.7730). Similarly, there was no significant difference between the combination of palifermin, cisplatin and panitumumab compared to the combination of cisplatin and panitumumab (p = 0.9739). Conclusions: In drug combination settings, the addition of palifermin did not affect the therapeutic efficacy of cisplatin, cetuximab or panitumumab in any of the two- or three-way drug combinations. When used alone, palifermin did not promote the growth of the FaDu human xenograft despite the fact that these tumors express KGFR. The lack of interference of palifermin with the anti-tumor activity of cisplatin and the anti-EGFR target therapeutics suggests it is appropriate to move forward clinically investigating the use of palifermin in solid tumor settings in which these therapeutic modalities are used. No significant financial relationships to disclose.
Daytime measurements underestimate nocturnal oxygen desaturations in pulmonary arterial and chronic thromboembolic pulmonary hypertension
Authors: Florian Hildenbrand, Konrad E. Bloch, Rudolf Speich, Silvia Ulrich
Journal: European Respiratory Journal (2012)

Background: Nocturnal hypoxemia is important in precapillary pulmonary hypertension (pPH) as it worsens pulmonary hemodynamics. Whether daytime oxygen saturation (SpO2) predicts nocturnal hypoxemia in pPH patients has not been conclusively studied. Therefore, we investigated the prevalence of nocturnal hypoxemia in ambulatory pPH patients in comparison to daytime SpO2 and disease severity.

Methods: Consecutive patients diagnosed with pPH classified as either pulmonary arterial (PAH) or chronic thromboembolic pPH (CTEPH) had daytime resting and exercise SpO2 (at the end of 6-minute walk test), thereafter they underwent overnight pulse oximetry at home. Functional class, pro-BNP and tricuspid pressure gradient were assessed.

Results: 63 patients (mean age±SD 60±15, 43 females) with PAH (44) and CTEPH (19) were included. The resting SpO2, exercise SpO2 and mean nocturnal SpO2 were 94±3, 87±9 and 89±4 %. 49 patients (77%) spent >10% of the night with SpO2  50% of the night with SpO2 <90% (sustained desaturators). The positive predictive values of a daytime SpO2 ≥91% to predict nocturnal desaturation or sustained desaturation were 75 resp. 47%. Nocturnal SpO2 was negatively correlated with the tricuspid pressure gradient, but not with functional class, 6MWT and pro-BNP.

Conclusion: Nocturnal hypoxemia is very common in PAH and CTEPH despite often normal daytime SpO2 and reflects disease severity. Nocturnal pulse oximetry should be considered in routine evaluation of pPH patients and research be directed to the treatment of nocturnal desaturation in pPH.
Outcome in surgically staged papillary serous and clear cell carcinoma of the uterus: A single institution experience
Authors: S. L. Harris, M. E. Randall, K. Y. Look, D. H. Moore, A. J. Fakiris, S. Lo, H. Cardenes
Journal: Journal of Clinical Oncology (2005)

5108 Objective To determine the outcomes of surgically staged patients with I-IIIA uterine papillary serous carcinoma (UPSC) and clear cell carcinoma (CCC) of the uterus treated at Indiana University and compare their outcomes to patients treated on the Hoosier Oncology Group (HOG) 97–01 protocol involving intraperitoneal 32P and vaginal brachytherapy for a similar patient population. Methods Twenty-six patients with surgically staged FIGO stage I-IIIA UPSC or CCC were treated with standard, non-protocol adjuvant therapies at Indiana University Cancer Center between 1997 and 2003. Modality and distribution of therapies given to these patients included: no therapy (6), whole abdomen radiotherapy (WAR) (9), pelvic radiotherapy (4), intraperitoneal 32P with vaginal brachytherapy per HOG 97–01 protocol (3), and unsure (4). An additional 21 patients were treated on the Hoosier Oncology Group 97–01 protocol during the same time period. Patients treated on protocol received, in addition to complete surgical staging, 15 mCi of 32P administered intraperitoneally, followed by high dose-rate or low dose-rate vaginal cuff brachytherapy. Clinic charts, hospital records and pathology reports were reviewed for each patient. Results A total of 26 patients treated off HOG 97–01 protocol were reviewed and compared with the 21 patients who were treated on protocol. Patient characteristics and survival and recurrence data are listed in the following table. Conclusion In this population of limited-stage UPSC and CCC patients, recurrences in the abdomen and pelvis were much less common in the group treated with intraperitoneal 32P and vaginal brachytherapy. Therefore, further investigation using intraperitoneal radiocolloids combined with intracavitary brachytherapy in the adjuvant setting as an alternative to radiation therapy or chemotherapy is warranted in this group of patients after comprehensive surgical staging. No significant financial relationships to disclose.
MicroRNA-155 controls affinity-based selection by protecting c-MYC+ B cells from apoptosis
Authors: Rinako Nakagawa, Rebecca Leyland, Michael Meyer-Hermann, Dong Lu, Martin Turner, Giuseppina Arbore, Tri Giang Phan, Robert Brink, Elena Vigorito
Journal: Journal of Clinical Investigation (2015)

The production of high-affinity antibodies by B cells is essential for pathogen clearance. Antibody affinity for antigen is increased through the affinity maturation in germinal centers (GCs). This is an iterative process in which B cells cycle between proliferation coupled with the acquisition of mutations and antigen-based positive selection, resulting in retention of the highest-affinity B cell clones. The posttranscriptional regulator microRNA-155 (miR-155) is critical for efficient affinity maturation and the maintenance of the GCs; however, the cellular and molecular mechanism by which miR-155 regulates GC responses is not well understood. Here, we utilized a miR-155 reporter mouse strain and showed that miR-155 is coexpressed with the proto-oncogene encoding c-MYC in positively selected B cells. Functionally, miR-155 protected positively selected c-MYC+ B cells from apoptosis, allowing clonal expansion of this population, providing an explanation as to why Mir155 deletion impairs affinity maturation and promotes the premature collapse of GCs. We determined that miR-155 directly inhibits the Jumonji family member JARID2, which enhances B cell apoptosis when overexpressed, and thereby promotes GC B cell survival. Our findings also suggest that there is cooperation between c-MYC and miR-155 during the normal GC response, a cooperation that may explain how c-MYC and miR-155 can collaboratively function as oncogenes.
Frequency of discrepancies in retracted clinical trial reports versus unretracted reports: blinded case-control study
Authors: Graham D Cole, Alexandra N Nowbar, Michael Mielewczik, Matthew J Shun-Shin, Darrel P Francis
Journal: BMJ (2015)

<b>Objectives</b> To compare the frequency of discrepancies in retracted reports of clinical trials with those in adjacent unretracted reports in the same journal. <b>Design</b> Blinded case-control study. <b>Setting</b> Journals in PubMed. <b>Population </b>50 manuscripts, classified on PubMed as retracted clinical trials, paired with 50 adjacent unretracted manuscripts from the same journals. Reports were randomly selected from PubMed in December 2012, with no restriction on publication date. Controls were the preceding unretracted clinical trial published in the same journal. All traces of retraction were removed. Three scientists, blinded to the retraction status of individual reports, reviewed all 100 trial reports for discrepancies. Discrepancies were pooled and cross checked before being counted into prespecified categories. Only then was the retraction status unblinded for analysis. <b>Main outcome measure</b> Total number of discrepancies (defined as mathematically or logically contradictory statements) in each clinical trial report. <b>Results</b> Of 479 discrepancies found in the 100 trial reports, 348 were in the 50 retracted reports and 131 in the 50 unretracted reports. On average, individual retracted reports had a greater number of discrepancies than unretracted reports (median 4 (interquartile range 2-8.75) <i>v</i> 0 (0-5); P&lt;0.001). Papers with a discrepancy were significantly more likely to be retracted than those without a discrepancy (odds ratio 5.7 (95% confidence interval 2.2 to 14.5); P&lt;0.001). In particular, three types of discrepancy arose significantly more frequently in retracted than unretracted reports: factual discrepancies (P=0.002), arithmetical errors (P=0.01), and missed P values (P=0.02). Results from a retrospective analysis indicated that citations and journal impact factor were unlikely to affect the result. <b>Conclusions</b> Discrepancies in published trial reports should no longer be assumed to be unimportant. Scientists, blinded to retraction status and with no specialist skill in the field, identify significantly more discrepancies in retracted than unretracted reports of clinical trials. Discrepancies could be an early and accessible signal of unreliability in clinical trial reports.
Fundholding reduces dependence on private sector
Authors: R A Smith
Journal: BMJ (1996)

EDITOR,—As a general practitioner in one of the first wave fundholding practices involved in the prospective study of trends in referral patterns in fundholding and non-fundholding practices in the Oxford region,1 I am not surprised that many of the suppositions which this study set out to investigate have been shown to be “unfounded.” The researchers may have expected to see an increase in private referrals but we did not, as our aim …
Phase I trial to determine the dose range for the c-Met inhibitor ARQ 197 that inhibits c-Met and FAK phosphorylation, when administered by an oral twice-a-day schedule
Authors: T. A. Yap, D. Harris, J. Barriuso, M. Wright, R. Riisnaes, J. Clark, I. Ledaki, R. Savage, T. Chen, J. S. De Bono
Journal: Journal of Clinical Oncology (2008)

3584 Background: ARQ 197 is a non-ATP competitive small molecule inhibitor of c-Met, a receptor tyrosine kinase activated by hepatocyte growth factor/scatter factor and implicated in cell migration, invasion, proliferation and angiogenesis. Methods: Patients (pt) with advanced, safely biopsiable, solid tumors were enrolled to determine safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics and preliminary antitumor activity. Pre and post therapy tumor biopsies were mandated for immunohistochemical studies (IHC) for total and phosphorylated (p) c-Met and its downstream target p-FAK. Tumor biopsies were analyzed for c-Met amplification by FISH and c-Met mutation by sequencing. Circulating endothelial cell (CEC) and circulating tumor cell enumeration were undertaken. Results: To date 14 pt have been treated (8 M; median age 64y) at 100, 200, 300 and 400mg bid continuously. A dose limiting toxicity (DLT) of CTCAEv3 grade (G) 3 fatigue was reported at 200mg bid, which resolved ≤ 24 h of drug cessation and no other DLT was seen after cohort expansion to 6 pt. Other adverse events were ≤ G2 such as fatigue, nausea, vomiting, diarrhea and anorexia. AUC and Cmax increased linearly with dose, but each increase was less than dose proportional. Mean values for t1/2, Cl/F and Vd/F were relatively constant and mean plasma drug concentrations were above the in vitro IC50. Baseline tumor biopsies from 3 of 11 pt had high p-c-Met expression (Aperio digital scanning IHC score > 50) and 6 had high p-FAK (score > 50). Post therapy, 3 of these pt (at 100, 200, 300mg bid) had 72, 73, 66% declines in p-c-Met and 69, 73, 30% declines in p-FAK expression. Another pt at 200mg bid with advanced melanoma and c-Met mutation T276T/A had declines in p-c-Met (21%) and p-FAK (29%) expression and RECIST stable disease (SD) for 20+ weeks (w). Total c-Met expression did not alter significantly. CEC counts declined by a mean of 60% (range 6 - 100%) post therapy in 6 of 9 pt. The best tumor efficacy response has been SD in 5 pt for up to 20+ w. Conclusions: ARQ 197 can inhibit c-Met and FAK phosphorylation in serial tumor biopsies with minimal toxicity up to 300 mg bid, decreasing CEC counts. MTD has not been reached and dose escalation continues. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration ArQule ArQule ArQule
THE MEDICAL PROFESSION AND THE PUBLIC
Authors: H J van Norden
Journal: JAMA (1921)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Ground-level ozone levels are associated with acute hospital admissions and emergency room visits in Reykjavík, Iceland
Authors: Hanne Krage Carlsen, Bertil Forsbert, Kadri Meister, Thorarinn Gíslason, Anna Oudin
Journal: European Respiratory Journal (2012)

Background: Air pollution levels in Reykjavik, Iceland, are generally low, but follow a different pattern than in most other cities. Intercorrelations are low, a large fraction of particulate matter with aerodynamic diameter ≤ 10µm (PM10) is from natural sources, and ozone (O3) peaks in early in spring. This study aimed to study short-term associations between pollution levels and daily emergency room visits and hospital admissions (ERV/HA) for cardiopulmonary causes.

Methods: A time series of daily cardiopulmonary ERV/HAs between the years 2003 and 2009 was made from hospital register data. Three-day moving averages of exposure variables PM10, nitrogen dioxide (NO2), O3, and weather variables were calculated. The ERV/HA counts were regressed on the exposure variables with Generalized Additive Models assuming Poisson distribution, and time trend adjustment using Cubic splines. The relative increase in number of events per interquartile (IQR) increase in pollutant level was calculated from the model coefficients with a 95% confidence interval (CI).

Results: Mean daily number of ERV/HAs was ten, 76% were cardiac and 60.8% in people older than 70 years of age. Pollution was characterized by seasonality and large PM10 fluctuations. Daily ERV/HA's were associated with O3 levels, we estimated a 4.6% increase in ERV/HA's per IQR change in three-day moving average (95% CI 1.9-5.5). The association was stronger in women; 7.2% (95% CI 3.3-11.4). In elderly, NO2 was associated with an increase of 3.4% (95% CI 0.1-6.8). We found no associations with PM10.

Conclusion: In this study, O3 was associated with cardiopulmonary ERV/HAs. NO2 was associated with ERV/HAs in the elderly.