bluuebunny/crossref_metadata_2025_split huggingface dataset:
Midline Carcinoma of Children and Young Adults With NUT Rearrangement
Authors: French Christopher A. , Kutok Jeffery L. , Faquin William C. , Toretsky Jeffrey A. , Antonescu Cristina R. , Griffin Constance A. , Nose Vania , Vargas Sara O. , Moschovi Mary , Tzortzatou-Stathopoulou Fotini , Miyoshi Isao , Perez-Atayde Antonio R. , Aster Jon C. , Fletcher Jonathan A. 
Published: October 2004

Purpose A balanced chromosomal translocation, t(15;19), resulting in the BRD4-NUT oncogene, has been identified in a lethal carcinoma of young people, a disease described primarily in case reports. We sought to amass a more definitive series of tumors with NUT and/or BRD4 gene rearrangements and to determine distinct clinicopathologic features. Patients and Methods Carcinomas (N = 98) in young individuals (median age, 32.5 years) were screened for NUT and BRD4 rearrangements using dual-color fluorescence in situ hybridization. Four published carcinomas with BRD4 and NUT rearrangements were also evaluated. Immunophenotypic analyses were performed. Results Eleven tumors had NUT gene rearrangements, including eight with BRD4-NUT fusions and three with novel rearrangements, which were designated as NUT variant. All NUT-rearranged carcinomas (NRCs) arose from midline epithelial structures, including the first example arising below the diaphragm. Patients were young (median age, 17.6 years). Squamous differentiation (seen in 82% of NRCs) was particularly striking in NUT-variant cases. In this first description of NUT-variant carcinomas, the average survival (96 weeks, n = 3) was longer than for BRD4-NUT carcinomas (28 weeks, n = 8). Strong CD34 expression was found in six of 11 NRCs but in zero of 45 NUT wild-type carcinomas. Conclusion NRCs arise from midline structures in young people, and NRCs with BRD4-NUT are highly lethal, despite intensive therapies. NUT-variant carcinomas might have a less fulminant clinical course than those with BRD4-NUT fusions. CD34 expression is characteristic in NRCs and, therefore, holds promise as a diagnostic test for this distinctive clinicopathologic entity.
Frequency and Heritability of WT1 Mutations in Nonsyndromic Wilms' Tumor Patients: A UK Children’s Cancer Study Group Study
Authors: Little Suzanne E. , Hanks Sandra P. , King-Underwood Linda , Jones Chris , Rapley Elizabeth A. , Rahman Nazneen , Pritchard-Jones Kathy 
Published: October 2004

Purpose Constitutional WT1 mutations in patients with Wilms' tumor (WT) have specifically been associated with genitourinary abnormalities, such as cryptorchidism and hypospadias. We sought to ascertain the frequency and heritability of constitutional WT1 mutations in nonsyndromic WT patients. Patients and Methods Constitutional DNA from 282 patients treated at seven United Kingdom Children's Cancer Study Group centers was screened for WT1 mutations using heteroduplex analysis. Bidirectional sequencing was used to confirm the mutation and to analyze the corresponding parental DNA samples. Results Five different constitutional WT1 mutations were identified in six children. Mutations in four patients were confirmed to be de novo, and all five mutations are predicted to produce truncated protein. The WT1 mutation group had a young median age at diagnosis of 13.8 months, compared with 34.9 months in the group in whom no WT1 mutations were found; four were female and two were male; and all tumors were of favorable histology. The three tumors with known histologic subtype were stromal-predominant. Contrary to expectation, four of six mutations occurred in children with unilateral tumors without any associated genitourinary abnormality. Conclusion Constitutional WT1 mutations occur with a low frequency (2.1%; 95% CI, 0.8% to 4.6%) in nonsyndromic WT patients. Most mutations occurred in children with unilateral WT without associated genitourinary abnormalities, creating difficulties in identifying individuals with germline mutations on phenotype alone. Two factors that may indicate that an individual is carrying a germline WT1 mutation are an early age of onset and stromal-predominant histology of the WT.
Is Eligibility for a Chemotherapy Protocol a Good Prognostic Factor for Invasive Bladder Cancer After Radical Cystectomy?
Authors: Madersbacher Stephan , Thalmann George N. , Fritsch Johannes C. , Studer Urs E. 
Published: October 2004

Purpose To assess whether eligibility to an adjuvant chemotherapy protocol in itself represents a good prognostic factor after radical cystectomy for bladder cancer. Patients and Methods Between April 1984 and May 1989, our institution entered 35 patients with invasive bladder cancer into the Swiss Group for Clinical and Epidemiological Cancer Research (SAKK) study 09/84. They were randomly assigned to either observation or three postoperative courses of cisplatin monotherapy after cystectomy. This study had a negative result. The outcome of these 35 patients (protocol group) was compared with an age- and tumor-stage–matched cohort (matched group; n = 35) who also underwent cystectomy during the same period, but were not entered into the SAKK study, as well as the remaining 57 patients treated during the study period for the same indication (remaining group). Results Median overall survival decreased from 76.3 months in the protocol group to 52.1 months in the matched group and to 20.3 months in the remaining group. The respective times of median recurrence-free survival were 67.2, 16.0, and 9.4 months. Tumor progression occurred in 46% of the protocol group compared with 69% in the matched group and 65% in the remaining group (P < .05). Cancer-related death was noted in 40% of the protocol group, 57% in the matched group, and 56% in the remaining group. Conclusion These data suggest that being willing and fit enough for a chemotherapy protocol is a good prognostic factor for invasive bladder cancer. This eligibility bias emphasizes the need for prospective, randomized trials, and indicates that single-group studies using historical or matched controls have to be interpreted with caution.
Quality of Life After Transhiatal Compared With Extended Transthoracic Resection for Adenocarcinoma of the Esophagus
Authors: de Boer A.G.E.M. , van Lanschot J.J.B. , van Sandick J.W. , Hulscher J.B.F. , Stalmeier P.F.M. , de Haes J.C.J.M. , Tilanus H.W. , Obertop H. , Sprangers M.A.G. 
Published: October 2004

Purpose To assess 3 years of quality of life in patients with esophageal cancer in a randomized trial comparing limited transhiatal resection with extended transthoracic resection. Patients and Methods Quality-of-life questionnaires were sent at baseline and at 5 weeks; 3, 6, 9, and 12 months; and 1.5, 2, 2.5, and 3 years after surgery. Physical and psychological symptoms, activity level, and global quality of life were assessed with the disease-specific Rotterdam Symptom Checklist. Generic quality of life was measured with the Medical Outcomes Study Short Form-20. Results A total of 199 patients participated. Physical symptoms and activity level declined after the operation and gradually returned toward baseline within the first year (P < .01). Psychological well-being consistently improved after baseline (P < .01), whereas global quality of life showed a small initial decline followed by continuous gradual improvement (P < .01). Quality of life stabilized in the second and third year. Three months after the operation, patients in the transhiatal esophagectomy group (n = 96) reported fewer physical symptoms (P = .01) and better activity levels (P < .01) than patients in the transthoracic group (n = 103), but no differences were found at any other measurement point. For psychological symptoms and global quality of life, no differences were found at any follow-up measurement. A similar pattern was found for generic quality of life. Conclusion No lasting differences in quality of life of patients who underwent either transhiatal or transthoracic resection were found. Compared with baseline, quality of life declined after the operation but was restored within a year in both groups.
Health-Related Quality of Life and Psychosocial Status in Breast Cancer Prognosis: Analysis of Multiple Variables
Authors: Goodwin Pamela J. , Ennis Marguerite , Bordeleau Louise J. , Pritchard Kathleen I. , Trudeau Maureen E. , Koo Jarley , Hood Nicky 
Published: October 2004

Purpose Evidence that psychosocial status and health-related quality of life (HRQOL) are associated with breast cancer (BC) outcomes is weak and inconsistent. We examined prognostic effects of these factors in a prospective cohort study. Patients and Methods Three hundred ninety-seven women with surgically resected T1 to T3, N0/N1, M0 BC completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (Core 30 items), Profile of Mood States, Psychosocial Adjustment to Illness Scale, Impact of Events Scale, Mental Adjustment to Cancer Scale, and the Courtauld Emotional Control Scale 2 months after diagnosis and 1 year later. Data on tumor-related factors, treatment, and outcomes were obtained prospectively from medical records, and Cox survival analyses were performed. Results Mean age was 52.0 ± 9.9 years. Two hundred twenty-five women had T1, 136 women had T2, 16 women had T3, and 20 women had TX tumors; 127 were N1. One hundred thirteen women received adjuvant chemotherapy, 130 received hormone therapy, 45 received both, and 109 received neither. We investigated 140 prognostic associations; four were found to be statistically significant at a P value of ≤ .05 (three fewer than expected by chance). Two were in the hypothesized direction of effect, and two were in the opposite direction. All arose from measurements 1 year after diagnosis, which were most susceptible to confounding by treatment. There was no evidence of consistency of associations across outcomes or questionnaires. These results are in keeping with chance as the explanation for our statistically significant findings. Conclusion HRQOL and psychosocial status at diagnosis and 1 year later are not associated with medical outcome in women with early-stage BC.
Clinical Decisions Associated With Positron Emission Tomography in a Prospective Cohort of Patients With Suspected or Known Cancer at One United States Center
Authors: Hillner Bruce E. , Tunuguntla Renuka , Fratkin Melvin 
Published: October 2004

Purpose In 2001, Medicare approved reimbursement of F-18 fluorodeoxyglucose positron emission tomography (PET) for a variety of cancers. PET has been observed to be more accurate than other imaging in cancer patients, but the impact of PET on management in routine practice is uncertain. Patients and Methods We studied a prospective cohort having noninvestigational PET at one university center. Before and after PET, a questionnaire was administered to solicit information regarding each physician's preceding actions, intended management, and probability estimates. Results Seventy-one physicians provided data on 248 patients, of whom 40% had new or suspected cancer and 60% were undergoing restaging or had suspected recurrence. Lung, lymphoma, and head/neck cancers accounted for two thirds of cases. Sixteen physicians made 64% of requests. Physicians changed their intended management in 61% of patients (95% CI, 54% to 66%). For individual physicians ordering at least 10 scans, the average kappa was 0.16 (range, −0.04 to 0.36), reflecting only slight level of agreement between their before and after PET plan. PET was associated with a change in 90 (79%) of 114 patients if the pre-PET intended plan involved more testing or biopsy. In 32% of cases, physicians changed to a treatment from a nontreatment strategy. The therapeutic goal and mode changed in 22 (7%) and 21 cases (8%), respectively. Conclusion This study confirms that physicians often change their decision making based on PET. This impact is likely due to combined effects of PET's improved accuracy and reduced physician uncertainty. Physicians may also be overconfident in interpreting PET and use it as the final arbiter after an extensive evaluation in lieu of tissue biopsy.
Selectionism and Learning in Projects with Complexity and Unforeseeable Uncertainty
Authors: Sommer Svenja C. , Loch Christoph H. 
Published: October 2004

Companies innovating in dynamic environments face the combined challenge of unforeseeable uncertainty (the inability to recognize the relevant influence variables and their functional relationships; thus, events and actions cannot be planned ahead of time) and high complexity (large number of variables and interactions; this leads to difficulty in assessing optimal actions beforehand).There are two fundamental strategies to manage innovation with unforeseeable uncertainty and complexity: trial and error learning and selectionism. Trial and error learning involves a flexible (unplanned) adjustment of the considered actions and targets to new information about the relevant environment as it emerges. Selectionism involves pursuing several approaches independently of one another and picking the best one ex post.Neither strategy nor project management literatures have compared the relative advantages of the two approaches in the presence of unforeseeable uncertainty and complexity. We build a model of a complex project with unforeseeable uncertainty, simulating problem solving as a local search on a rugged landscape. We compare the project payoff performance under trial and error learning and selectionism, based on a priori identifiable project characteristics: whether unforeseeable uncertainty is present, how high the complexity is, and how much trial and error learning and parallel trials cost. We find that if unforeseeable uncertainty is present and the team cannot run trials in a realistic user environment (indicating the project's true market performance), trial and error learning is preferred over selectionism. Moreover, the presence of unforeseeable uncertainty can reverse an established result from computational optimization: Without unforeseeable uncertainty, the optimal number of parallel trials increases in complexity. But with unforeseeable uncertainty, the optimal number of trials might decrease because the unforeseeable factors make the trials less and less informative as complexity grows.
Calcimimetics and the Treatment of Primary and Secondary Hyperparathyroidism
Authors: Joy Melanie S , Kshirsagar Abhijit V , Franceschini Nora 
Published: October 2004

OBJECTIVE To review the mechanism of action, development, and clinical application of the calcimimetic compounds being investigated for the treatment of primary and secondary hyperparathyroidism (HPT). DATA SOURCES A MEDLINE search (1990–April 2004) was performed to identify all published articles related to calcimimetics. Published abstracts over the previous 5 years from various scientific meetings (American Society of Nephrology, American Society for Clinical Pharmacology and Therapeutics, American Society of Bone and Mineral Research) were also searched for reports regarding investigational calcimimetic agents. Data on cinacalcet HCI were provided by Amgen, Inc. STUDY SELECTION AND DATA EXTRACTION Studies were selected based on number of patients included, relevance to the approved indications, and inclusion of pharmacokinetic and drug interaction information. DATA SYNTHESIS The investigational calcimimetic compounds directly modulate the calcium-sensing receptor and can produce at least a 30% reduction in parathyroid hormone (PTH) secretion in secondary HPT. Cinacalcet appears to have more predictable pharmacokinetics and a lower risk of symptomatic hypocalcemia than the older agent, R-568. The safety profile and effective reduction in PTH and simultaneous reductions in calcium and phosphorus (and the calcium–phosphorus product) induced by cinacalcet make this agent advantageous over previously used therapies, such as vitamin D and phosphate-binding agents. More studies are required to determine additional uses of cinacalcet. CONCLUSIONS Cinacalcet has a unique mechanism for reducing PTH concentration and appears to be a safe and effective oral therapy for both primary and secondary HPT.
Possible Reduction in Posttraumatic Stress Disorder Symptoms with Oxcarbazepine in a Patient with Bipolar Disorder
Authors: Malek-Ahmadi Parviz , Hanretta Allan T 
Published: October 2004

OBJECTIVE To report the effect of oxcarbazepine in a patient with bipolar illness and posttraumatic stress disorder (PTSD). CASE SUMMARY A 38-year-old white woman with PTSD and bipolar disorder who had partially responded to carbamazepine was treated with oxcarbazepine. Within a month of initiation of treatment with oxcarbazepine, she reported progressive improvement in her PTSD symptoms. As oxcarbazepine monotherapy with 750 mg twice daily continued, she reported significant reduction of her PTSD symptoms and stabilization of her mood. She tolerated oxcarbazepine without adverse effects. DISCUSSION PTSD symptoms tend to wax and wane. Spontaneous remission also occurs in some patients with PTSD. There are a few reports indicating that carbamazepine alleviates PTSD symptoms. Since oxcarbazepine is an analog of carbamazepine, it is theorized that oxcarbazepine also has efficacy in significantly reducing PTSD symptoms. CONCLUSIONS There are case reports and uncontrolled studies suggesting that antiepileptic drugs (AEDs) alleviate PTSD symptoms. Oxcarbazepine may also benefit patients with PTSD. However, controlled studies are needed to investigate the use of AEDs in patients with PTSD and bipolar disorder.
Insulin Strategies for Type 2 Diabetes Mellitus
Authors: Vivian Eva M , Olarte Sophia V , Gutierrez Ann M 
Published: October 2004

OBJECTIVE To review the currently available insulin analogs and the benefits of insulin therapy in the treatment of type 2 diabetes mellitus. DATA SOURCES A MEDLINE search (1990–March 2004) was conducted using insulin and type 2 diabetes mellitus as search terms to identify clinical trials and review articles. The bibliographies of identified articles were reviewed. STUDY SELECTION AND DATA EXTRACTION All articles identified from the data sources were evaluated and deemed relevant if they included and assessed clinical outcomes. DATA SYNTHESIS Since its discovery in 1922, insulin therapy has been the only available pharmacologic treatment for type 1 diabetes and a mainstay therapy for patients with type 2 diabetes who fail to obtain glycemic control with oral antidiabetic agents. This article reviews the current insulin analogs available on the market and insulin regimens that are designed to mimic the pancreatic β-cells’ response to a glucose load. CONCLUSIONS Insulin therapy is often withheld until late in the disease process for patients with type 2 diabetes mellitus. This results in an enormous burden of disease for patients. Insulin therapy is beneficial in obtaining glycemic control and may attenuate the complications associated with diabetes.
Pharmacologic Perspectives for Once-Daily Antiretroviral Therapy
Authors: Anderson Peter L 
Published: October 2004

OBJECTIVE To contrast available once-daily antiretroviral agents and combinations of these agents from a clinical pharmacologic viewpoint. DATA SOURCES Data were extracted from publications and major HIV conference proceedings cited in MEDLINE (1966–March 2004) using the search terms antiretroviral therapy, combination therapy, once-daily therapy, and pharmacokinetics. Additional references were obtained from the bibliographies of these sources. STUDY SELECTION AND DATA EXTRACTION Information pertaining to pharmacologic perspectives for once-daily antiretroviral agents was selected. DATA SYNTHESIS Maximal and durable suppression of plasma HIV RNA, the principal goal of therapy, depends on the intrinsic antiviral activity of the antiretroviral regimen. A favorable tolerability/toxicity profile is also fundamentally important. All once-daily agents exhibit some pharmacologic limitations or lack adequate long-term follow-up. Of available agents, efavirenz has a long and distinguished efficacy record, with reasonable safety and moderate tolerability. Lamivudine, and newer agents such as atazanavir (or atazanavir/ritonavir), emtricitabine, fosamprenavir/ritonavir, and tenofovir, may offer pharmacologic advantages in the current state of once-daily therapy. Important considerations exist for coadministering once-daily agents including drug–drug interactions, drug–food incompatibilities, and synergistic toxicities. Few controlled studies have compared once-daily regimens with conventional regimens. CONCLUSIONS Progress has been made toward once-daily therapy, but more clinical experience with available agents is needed, including comparative studies of entirely once-daily regimens versus conventional regimens. Limitations of currently available agents signify a need for improved antiretroviral utilization or new alternative agents.
Comparing Hyperlipidemia Control with Daily Versus Twice-Weekly Simvastatin
Authors: Mangin Emmanuelle FM , Robles Gisela I , Jones William N , Ford Marjorie A , Thomson Steven P 
Published: October 2004

BACKGROUND Costs associated with the use of hydroxymethylglutaryl coenzyme A reductase inhibitors are increasing. Finding ways to manage hyperlipidemia at lower costs is critical to all healthcare systems. OBJECTIVE To assess effectiveness, safety, cost, and patients’ satisfaction when converting hyperlipemic patients taking simvastatin daily to simvastatin twice weekly. METHODS This nonrandomized, open-label, proof-of-concept study converted patients treated with simvastatin 10 or 20 mg daily to 40 or 80 mg twice weekly, respectively, for 12 weeks. The lipid profiles at enrollment, week 6, and week 12 were compared using repeated-measures ANOVA. The percentage of patients attaining the appropriate low-density lipoprotein cholesterol (LDL-C) goal was determined. RESULTS Thirty-one patients completed the study. The proportion of patients at the LDL-C goal was not statistically different between enrollment and week 12 (87% vs 68%; p = 0.068). The mean LDL-C value ± SD at weeks 6 and 12 increased compared with enrollment (112 ± 20, 111 ±17, and 97 ± 17 mg/dL, respectively; p < 0.001). Three (10%) patients reported nonadherence to the twice-weekly regimen. Seventeen (55%) patients reported that both regimens were equally convenient or preferred the twice-weekly regimen. Estimated cost-savings at our institution associated with this regimen would be $32 000 per 1000 patients per year. CONCLUSIONS The twice-weekly regimen safely maintained most of the patients at their LDL-C goal level, and over half the patients found this regimen to be the same or easier to follow than a daily regimen. Large outcome studies evaluating this approach are needed.