tbuckley/cabot-search huggingface dataset:
Pamidronate Reduces Skeletal Morbidity in Women With Advanced Breast Cancer and Lytic Bone Lesions: A Randomized, Placebo-Controlled Trial
Authors: Richard L. Theriault, Allan Lipton, Gabriel N. Hortobagyi, Richard Leff, Stefan Glück, John F. Stewart, Sean Costello, Ian Kennedy, Joseph Simeone, John J. Seaman, Robert D. Knight, Kathleen Mellars, Maika Heffernan, Dirk J. Reitsma
Journal: Journal of Clinical Oncology (1999)

To assess whether pamidronate can reduce the frequency of skeletal morbidity in women with lytic bone metastases from breast cancer treated with hormone therapy.Three hundred seventy-two women with breast cancer who had at least one lytic bone lesion and who were receiving hormonal therapy were randomized to receive 90 mg of pamidronate or placebo as a 2-hour intravenous infusion given in double-blind fashion every 4 weeks for 24 cycles. Patients were evaluated for skeletal complications: pathologic fractures, spinal cord compression, irradiation of or surgery on bone, or hypercalcemia. The skeletal morbidity rate (the ratio of the number of skeletal complications to the time on trial) was the primary efficacy variable. Bone pain, use of analgesics, quality of life, performance status, bone tumor response, and biochemical parameters were also evaluated.One hundred eighty-two patients who received pamidronate and 189 who received placebo were assessable. The skeletal morbidity rate was significantly reduced at 12, 18, and 24 cycles in patients treated with 90 mg of pamidronate (P = .028, .023, and .008, respectively). At 24 cycles, the proportion of patients having had any skeletal complication was 56% in the pamidronate group and 67% in the placebo group (P = .027). The time to the first skeletal complication was longer for patients receiving pamidronate than for those given placebo (P = .049). There was no statistical difference in survival or in objective bone response rate. Pamidronate was well tolerated.Treatment with 90 mg of pamidronate as a 2-hour intravenous infusion every 4 weeks in addition to hormonal therapy significantly reduces skeletal morbidity from osteolytic metastases.
Why has induction chemotherapy for advanced head and neck cancer become a United States community standard of practice?
Authors: P M Harari
Journal: Journal of Clinical Oncology (1997)

PURPOSE Induction chemotherapy for advanced head and neck (H&amp;N) cancer has been studied in clinical trials for more than two decades without clear demonstration of benefit for locoregional tumor control or overall patient survival. Nonetheless, its use has become a common community standard of practice in the United States (US). This report examines some of the factors that may have contributed to this phenomenon. MATERIALS AND METHODS A mail survey was conducted of 300 US community cancer specialists (equally divided among otolaryngologists, radiation oncologists, and medical oncologists) to solicit their most frequent therapy approach for patients with locoregionally advanced, nonmetastatic H&amp;N cancer. The rationale for selection of treatment strategy was identified by each respondent. RESULTS Two hundred eighteen physicians (73%) completed and returned the survey, representing 47 US states. The single most common treatment approach reported for patients with locoregionally advanced H&amp;N cancer was that of sequential chemoradiation (61%), specifically, induction chemotherapy with fluorouracil (5-FU)/cisplatin followed by radiation therapy. Four percent of respondents indicated that induction chemotherapy was administered within the context of a controlled clinical trial, whereas 96% indicated that therapy was administered off study. The primary objectives cited by respondents for the use of induction chemotherapy included the desire to improve locoregional tumor control (67%), to improve overall survival (56%), to maintain a spirit of multidisciplinary care (34%), to improve quality of life (29%), and to decrease distant metastases (26%). CONCLUSION Review of the published trials between 1970 and 1995 and of the published meta-analyses show no clear evidence for an improvement in locoregional tumor control or survival for H&amp;N cancer patients treated with 5-FU/cisplatin induction chemotherapy regimens. Nonetheless, this induction chemotherapy approach for advanced H&amp;N cancer patients has become a dominant community practice in the US. Factors that may have contributed to this paradox are reviewed.
Reversing Vascular Dysfunction in Rheumatoid Arthritis: Improved Augmentation Index but Not Endothelial Function With Peroxisome Proliferator–Activated Receptor γ Agonist Therapy
Authors: Michelle J. Ormseth, Annette M. Oeser, Andrew Cunningham, Aihua Bian, Ayumi Shintani, Joseph Solus, S. Bobo Tanner, C. Michael Stein
Journal: Arthritis & Rheumatology (2014)

Objective To examine the hypothesis that improving insulin sensitivity improves vascular function in rheumatoid arthritis (RA). Methods We performed a 20‐week, single center, randomized, double‐blind, placebo‐controlled crossover study. Patients with RA (n = 34) with moderate disease activity who were receiving stable disease‐modifying antirheumatic drug therapy were randomized to drug sequence, receiving either pioglitazone 45 mg/day or matching placebo for 8 weeks, followed by a 4‐week washout period and the alternative treatment for 8 weeks. We measured changes in vascular stiffness (augmentation index and aortic pulse wave velocity [PWV]), endothelial function (reactive hyperemia index), and blood pressure. High‐sensitivity C‐reactive protein levels and the homeostatic model assessment of insulin resistance were also measured. The treatment effect of pioglitazone on outcomes was analyzed using linear mixed‐effects models. Results Pioglitazone treatment resulted in a change in augmentation index of −4.7% units (95% confidence interval [95% CI] −7.9, −1.5) ( P = 0.004) and in diastolic blood pressure of −3.0 mm Hg (95% CI −5.7, −0.2) ( P = 0.03), but did not significantly change aortic PWV ( P = 0.33) or reactive hyperemia index ( P = 0.46). The improvements in augmentation index and diastolic blood pressure were not mediated by the effect of pioglitazone on insulin resistance or inflammation. Conclusion Our findings indicate that pioglitazone improves some indices of vascular function, including augmentation index and diastolic blood pressure, in patients with RA. This is not mediated by improved insulin sensitivity.
Mediastinal tumor size and response to chemotherapy are the only prognostic factors in supradiaphragmatic Hodgkin's disease treated by ABVD plus radiotherapy: ten-year results of the Paris-Ouest-France 81/12 trial, including 262 patients.
Authors: P Colonna, J P Jais, B Desablens, J L Harousseau, J Brière, M Boasson, A Lemevel, P Casassus, P Y Le Prisé, F Guilhot, C Ghandour, F Lejeune, J M Andrieu
Journal: Journal of Clinical Oncology (1996)

PURPOSE To identify prognostic factors in 262 patients with supradiaphragmatic Hodgkin's disease (HD), clinical stages (CS) I and II, prospectively treated between 1981 and 1988 according to the Paris-Ouest-France (POF) 81/12 protocol by three 1-month cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus methylprednisone (ABVD-MP) followed by subtotal nodal irradiation (RT). PATIENTS AND METHODS The size of mediastinal tumor (MT) was measured in all patients: 66 did not have MT (NoMT); 105 had a small-size MT (SSMT), ie, mediastinal mass ratio (MMR) less than 0.33; 58 had a medium-size MT (MSMT), ie, MMR &gt; or = 0.33 and less than 0.45; and 33 had a bulky MT (BuMT), ie, MMR &gt; or = 0.45. All patients received three cycles (CS IA, one cycle only) of ABVD-MP; patients in partial remission (PR) or complete remission (CR) after chemotherapy (CT) received supradiaphragmatic RT (involved fields, 40 Gy; adjacent fields, 30 Gy) plus lumboaortic and splenic RT (30 Gy); patients not in CR or PR after CT received salvage CT. RESULTS Two hundred seventeen patients (82.8%) entered CR after CT and 258 (98.5%) after RT. Ten-year freedom-from-progression (FFP) and survival rateswere 88.6% and 89.4%, respectively. According to univariate analysis, MT size and post-CT status were the only factors to influence both FFP and survival. For patients with NoMT or SSMT, those with MSMT, and those with BuMT, FFP rates were 94.1%, 87.0%, and 63.0% (P &lt; .001), respectively, while corresponding survival rates were 92.6%, 87.2%, and 78.2% (P &lt; .05). FFP rates were significantly different between the patients who achieved CR and those who did not achieve CR after CT: 94.6% versus 65.3% (P &lt; .001); corresponding survival rates were 89.9% and 73.7% (P &lt; .01). Multivariate analysis confirmed that MT size and post-CT status were the only two prognostic factors for FFP; for survival, the same two characteristics, as well as age (&lt; 40 v &gt; or = 40 years), significantly affected prognosis. We were thus able to identify three groups. The 33 patients (12.6%) with a BuMT had 10-year FFP and survival rates of 63.0% and 78.2%, respectively. Of 229 patients without BuMT, the 195 who attained CR after CT had an optimal prognosis (FFP, 96.6%; survival, 93.6%), while those who failed to achieve CR after CT had an intermediate prognosis (FFP, 68.8%; survival, 77.6%). CONCLUSION These results demonstrate the independent impact on HD prognosis of tumor burden and post-CT status.
Correlation of IgVH somatic mutation and disease course in chronic lymphocytic leukemia
Authors: M. S. Kaufman, R. Damle, X. Yan, Y. Lebowicz, C. Johnson, N. Driscoll, N. Kohn, K. R. Rai, N. Chiorazzi
Journal: Journal of Clinical Oncology (2008)

7068 Background: IgVH mutation status is a well accepted prognostic marker in chronic lymphocytic leukemia (CLL). Typically >98% of the germline sequence homology is considered unmutated, and =98% is considered mutated. The 98% cutoff was originally chosen to account for undefined IgVH polymorphisms that could be responsible for DNA sequence disparity. Prior data showed that mutated patients have a more benign course of disease vs unmutated patients . However an unanswered question is whether IgVH somatic mutations correlate to disease course in a linear, continuous fashion. Methods: Using a Cox proportional hazards model, we evaluated 146 patients and examined the relationship between time to first treatment (TTT) and percentage of mutation as a continuum. Results: Patients with higher mutation percentages were less likely to start treatment (p<0.0002). See table below. For each unit increase in mutation percent, the patient was 0.829 times less likely to start treatment. So, for example, a patient with a mutation percent of 3% is 0.829 times as likely to start treatment as a patient with a mutation percentage of 2%, and a patient with a mutation percent of 8% is 0.829 times as likely to start treatment as a patient with a mutation percentage of 7%, (i.e. any 1 unit increase in mutation percent). Similarly, a patient with mutation rate 3 percentage points higher than another patient is 0.570 times as likely to need treatment, and a patient with a mutation rate 5 percentage points higher than another patient is 0.392 times as likely to need treatment. Conclusion: These data suggest that as the percentage of mutation in IgVH increases, the time to first treatment increases. This has implications as to the role of the CLL B-cell receptor (BCR) and its specificity in clinical outcome. Assuming that in vivo BCR stimulation causes CLL cell proliferation, increased IgVH mutations may result in narrowed specificity of the BCR, thereby limiting the diversity of antigens capable of delivering a stimulatory signal. % Mutation and corresponding hazard ratios for requiring treatment Mutation % Hazard ratio 1 0.829 2 0.687 3 0.570 4 0.472 5 0.392 10 0.153 15 0.060 No significant financial relationships to disclose.
Target Engagement, Pathway Inhibition, and Efficacy Of The Bruton’s Tyrosine Kinase (Btk) Inhibitor CC-292
Authors: Daniel W Pierce, Sabine Ponader, Kumudha Balakrishnan, Varsha Gandhi, William G. Wierda, Susan O'Brien, Carla Heise, Mariana Nacht, Sharon Aslanian, Xiping Liu, Sean Hong, Shijuan Wu, Marianna Zavodovskaya, Jeffrey Marine, Evelyn Barnett, Pilar Nava-Parada, Jay Mei, Rajesh Chopra, Jan A. Burger, Juswinder Singh
Journal: Blood (2013)
Abstract P065: Effects of Palm Oil Consumption on Blood Lipids: A Meta-Analysis of Clinical Trials
Authors: Ye Sun, Nithya Neelakantan, Yi Wu, Rob M van Dam
Journal: Circulation (2014)

Introduction: Palm oil is among the most commonly consumed cooking oils worldwide and, in contrast to most other vegetable oils, contains a high amount of saturated fatty acids. It has been suggested that palm oil has unique characteristics resulting in less detrimental effects on blood lipids than expected from its fat content. We therefore evaluated the effect of palm oil consumption on blood lipid concentrations as compared with vegetable oils high in natural unsaturated fatty acids, partially hydrogenated vegetable oils (rich in trans -fat), or animal fats. Methods: We searched PubMed, the Cochrane Library, Scopus, ProQuest, and Web of Science databases up to 31 October 2012 for trials of at least 2 weeks that compared the effects of palm oil consumption with at least one of the aforementioned comparison oils. Data on effects on total, LDL and HDL cholesterols and triglycerides were pooled using random effects meta-analysis. Results: A total of 25 studies were identified comparing palm oil with natural highly unsaturated vegetable oils. Palm oil significantly increased total cholesterol by 0.32 mmol/L (95% CI: 0.19, 0.44; I 2 =85.9%), increased LDL cholesterol by 0.20 mmol/L (95% CI: 0.09, 0.32; I 2 =82.9%), and increased HDL cholesterol by 0.02 mmol/L (95% CI: 0.01, 0.04; I 2 =56%) as compared with control oils. The considerable amount of heterogeneity in study results were partly explained by the type of control oil used, funding source, geographical location, and level of intake of test oil. Statistical tests suggested that this meta-analysis might be subject to publication bias. Eight studies were identified comparing palm oil with partially hydrogenated vegetable oils. When compared to trans -fat rich oils, palm oil significantly increased HDL cholesterol by 0.07 mmol/L (95% CI: 0.05, 0.09; I 2 =19.2%). However, palm oil did not significantly change total cholesterol (0.15 mmol/L, 95% CI: -0.04, 0.33), LDL cholesterol (0.11 mmol/L, 95% CI: -0.04, 0.27), or triglycerides (-0.02 mmol/L, 95% CI: -0.12, 0.07). Geographical location, method of preparation of test oils, and level of intake of trans -fat in control intervention were contributors to the heterogeneity in the study results. The pooled results from the 2 studies on comparison between palm oil and animal fats did not show a significant difference between the two dietary groups for total cholesterol (0.00 mmol/L, 95% CI: -0.08, 0.08), LDL cholesterol (-0.01 mmol/L, 95% CI: -0.08, 0.07), HDL cholesterol (0.00 mmol/L, 95% CI: -0.03, 0.04), or triglycerides (0.02 mmol/L, 95% CI: -0.15, 0.17). Conclusions: Palm oil consumption results in higher LDL cholesterol levels than other natural unsaturated vegetable oils. However, palm oil may be preferable to trans -fat rich oils based on its effect on HDL cholesterol. More studies are needed to evaluate the effects of palm oil consumption on incidence of coronary heart diseases.
The impact of an inverse correlation between plasma B-type natriuretic peptide levels and insulin resistance on the diabetic condition in patients with heart failure
Authors: Yasunori Inoue, Makoto Kawai, Kosuke Minai, Kazuo Ogawa, Tomohisa Nagoshi, Takayuki Ogawa, Michihiro Yoshimura
Journal: Metabolism (2015)

A diabetic state is causally related to heart failure (HF); therefore, there should be a close correlation between the severity of diabetes and HF. However, a direct relationship between these conditions has rarely been reported and remains unclear. This study was designed to precisely examine this relationship, taking into consideration the possible association between natriuretic peptide (NP) levels and insulin resistance.We examined various hemodynamic parameters and simultaneously performed blood biochemical analyses of consecutive patients who underwent cardiac catheterization at our institution (n=840).Simple regression analyses showed that hemoglobin A1c (HbA1c) levels were not significantly changed by the left ventricular end-diastolic pressure (LVEDP) and left ventricular ejection fraction (LVEF), which were correlated with a low cardiac index. Rather, there was a negative correlation between the HbA1c levels and plasma BNP levels as a marker of HF. A multivariate analysis showed no correlations between the HbA1c levels and cardiac functional parameters (LVEDP, LVEF or the plasma BNP levels), suggesting that the trend toward high HbA1c levels in HF cases is likely to be limited for unknown reasons. To search for an explanation of this finding, we examined the potential biological interactions between BNP and insulin resistance. A multivariate analysis revealed that the plasma BNP levels were positively correlated with age, creatinine levels and LVEDP and inversely correlated with the male gender, body mass index and HOMA-IR (homeostasis model assessment-insulin resistance) (P<0.001, respectively), but not HbA1c levels. This analysis indicated a close correlation between plasma BNP levels and insulin effectiveness in HF.HF and diabetes tend to worsen with each other; however, the appearance of an association between them was likely blunted due to the considerable effect of NP in counteracting insulin resistance, even during the metabolically harmful condition of HF.
Getting in early: primary skin cancer prevention at 55 German kindergartens
Authors: L.A. Stöver, B. Hinrichs, U. Petzold, H. Kuhlmei, J. Baumgart, C. Parpart, O. Rademacher, E. Stockfleth
Journal: British Journal of Dermatology (2012)

Background Skin neoplasms are the most frequent types of neoplasms in white populations, and their incidence is increasing. Epidemiological studies have shown that the major environmental aetiological factor for their development is sunlight exposure. Sun protection programmes are urgently needed to raise awareness of the health hazards of ultraviolet radiation. In 2010 the 'SunPass' project was implemented at 55 kindergartens in Germany. This is the first nationwide environmental education programme for sun safety designed to teach children in kindergartens and their caregivers how to protect themselves from overexposure to the sun. Objectives An interventional lecture, site inspections and a certification were part of the programme. Effects of these interventions were studied. Methods The gain in knowledge and changed sun‐behavioural attributes were quantified by questionnaires administered before and after the 'SunPass' interventions. Results The total number of children was 5424. Sun‐protection behaviour after the intervention improved significantly (P <0·001). Among parents, 22·2% reported one to five sunburns of their child since birth. There was a significant increase in hat use by children in kindergartens (P =0·029), as well as some significantly improved shade practices. There was a significantly increased demand for protective clothing for children (P <0·001). The change in sunscreen use in kindergartens was not significant. Conclusions Although some aims of the 'SunPass' project were not fulfilled, such as the precise knowledge of skin types and a change of sunscreen use, the study had some positive outcomes in increasing the awareness of skin cancer and its prevention possibilities. The findings of the present study suggest that relatively brief interventions in kindergartens lead to improved sun protection of children. The whole investigation reaching over 5400 children and their parents underlines the importance of learning appropriate sun‐protective behaviour in early childhood in order to decrease the risk for skin cancer.
Acute renal dysfunction during interleukin-2 treatment: suggestion of an intrinsic renal lesion.
Authors: C L Shalmi, J P Dutcher, D A Feinfeld, K J Chun, K R Saleemi, L M Freeman, R I Lynn, P H Wiernik
Journal: Journal of Clinical Oncology (1990)

Adoptive immunotherapy with interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells has been effective in treating some advanced malignancies in animals and humans. One complication of this treatment is a reversible, oliguric, acute renal failure, which has been ascribed to renal hypoperfusion and resultant prerenal azotemia. We serially studied renal function in 10 patients receiving high-dose regimens of recombinant interleukin-2 (rIL-2) to attempt to delineate further the nature of the renal dysfunction caused by IL-2 treatment. Renal plasma flow was computed from iodine 131 (I-131 Hippuran; Mediphysics, Paramus, NJ) orthoiodohippurate, excretion curves, and glomerular filtration rate (GFR) was determined by creatinine clearance. Studies done prior to and on day 4 of treatment showed that GFR fell in nine of 10 patients, with a mean decrease of 43% +/- 8%, and renal plasma flow fell in five of the 10 patients with a mean decrease of 5% +/- 10%. The average pretherapy filtration fraction was calculated to be 23% +/- 1% and after 4 days of treatment, decreased to a mean value of 15 +/- 2%. The BUN to creatinine ratio also declined in all patients. These findings collectively suggest that IL-2 nephrotoxicity may result from an intrarenal defect in addition to the previously described prerenal azotemia. Additionally, radionuclide studies of renal function are a reliable and reproducible noninvasive method of assessing these changes in renal function.
Sleep disordered breathing in Prader Willi syndrome post recombinant human growth hormone therapy
Authors: Arun Kumar Pugalenthi, Sadasivam Suresh, Pat Wales, Gordon Williams, Margaret Harris
Journal: European Respiratory Journal (2011)

Introduction: Recombinant human growth hormone (rhGH) is licensed for treatment in Prader Willi Syndrome (PWS) for improvement of body composition, height velocity, mobility, behaviour and quality of life. Sleep disordered breathing (SDB) disorders are common in individuals with PWS. It has been suggested that rhGH exacerbates SDB.

Aim: To identify PWS children who have changes in SDB on polysomnography (PSG) at 6 weeks of commencement of rhGH in a tertiary paediatric sleep setting.

Methods: We retrospectively reviewed PWS patients who underwent PSG pre and 6 weeks post commencement of rhGH. The PSG was conducted in a sleep lab using standardized procedure and reported by a sleep physician.

Results: We studied 26 patients (13 Boys and 13 Girls) with age range between 1.6 to 17.9 years. 16 patients (61.5%) had normal PSG study indicating no deterioration in SDB since commencing on rhGH, 5 patients (19.2%) had mild increase in Apnoea Hypopnoea Index (AHI). 1 patient (3.8%) required an increase in support of non-invasive ventilation (NIV) and 4 patients (15.4%) were advised to cease rhGH treatment as PSG showed significant increase in AHI since rhGH commencement.

Discussion: 80% of our PWS patients on rhGH had either no evidence of change in SDB six weeks post rhGH treatment or mild increase in AHI. 19.2% (5 Patients) in which 4 patients (15.4%) studied ceased rhGH and in 1 (3.8%) NIV support was increased.

Conclusion: As we have no predictors of who will have SDB deterioration with rhGH, patients with PWS should have PSG before and after starting rhGH and monitoring of children with pre and post growth hormone PSG studies and clinical evaluation is essential in treatment.