tbuckley/cabot-search huggingface dataset:
Adjunctive Dexamethasone in HIV-Associated Cryptococcal Meningitis
Authors: Justin Beardsley, Marcel Wolbers, Freddie M. Kibengo, Abu-Baker M. Ggayi, Anatoli Kamali, Ngo Thi Kim Cuc, Tran Quang Binh, Nguyen Van Vinh Chau, Jeremy Farrar, Laura Merson, Lan Phuong, Guy Thwaites, Nguyen Van Kinh, Pham Thanh Thuy, Wirongrong Chierakul, Suwatthiya Siriboon, Ekkachai Thiansukhon, Satrirat Onsanit, Watthanapong Supphamongkholchaikul, Adrienne K. Chan, Robert Heyderman, Edson Mwinjiwa, Joep J. van Oosterhout, Darma Imran, Hasan Basri, Mayfong Mayxay, David Dance, Prasith Phimmasone, Sayaphet Rattanavong, David G. Lalloo, Jeremy N. Day
Journal: New England Journal of Medicine (2016)

Cryptococcal meningitis associated with human immunodeficiency virus (HIV) infection causes more than 600,000 deaths each year worldwide. Treatment has changed little in 20 years, and there are no imminent new anticryptococcal agents. The use of adjuvant glucocorticoids reduces mortality among patients with other forms of meningitis in some populations, but their use is untested in patients with cryptococcal meningitis.
A randomized study of arterial infusion chemotherapy for hepatocellular carcinoma: Low-dose 5-fluorouracil/cisplatin versus low-dose 5-fluorouracil/cisplatin/Interferon beta
Authors: H. Ueda, H. Tanaka, Y. Kida, H. Fukuchi, M. Ichinose
Journal: Journal of Clinical Oncology (2007)

15098 Background: Recently, efficacy of intraarterial infusion chemotherapy for advanced hepatocellular carcinoma (HCC) have been improved by combination with interferon(IFN)-alpha and 5-fluorouracil (5-FU) or 5-FU and cisplatin (FP). However, there is no report about combination chemotherapy with 5-FU, cisplatin and IFNbeta. Therefore, we examined to evaluate the efficacy and safety of combination intraarterial infusion chemotherapy with IFN-beta, 5-FU and cisplatin in patients with advanced HCC in comparison with a chemotherapy using 5- FU and cisplatin. Methods: Twelve HCC patients in advanced stage were enrolled in the study after informed consent was performed. Patients with WHO performance status greater than 2, belonging to Child-Pugh class C, or with platelet less 80 x 10 9 /l were not eligible. They were randomly assigned to FP group (n=6) and FP-IFN group (n=6). One cycle of both regimens lasted for 4 wk. 5-FU (500 mg/day) and cisplatin (10mg/day) were administered via the proper hepatic artery for 5 consecutive days per week for 3 wk. IFNbeta (1 x 10 6 units) was injected via the proper hepatic artery twice a week for 3 wk. Primary and secondary end points are efficacy and safety, respectively. The effect of combination chemotherapy was evaluated in each patient after one cycle based on the reduction of tumor volume. Adverse event was based on Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Results: The reduction rates in the FP group and FPI group were 16.5% and 36.2%, respectively. The response rates in the FP group and FPI group were 16.7%(CR:n=0, PR:n=1) and 66.7%(CR:n=0, PR:n=4), respectively. The efficacy in FPI group was significantly higher than that in FP group. As for safety, any severe adverse event was not observed in this study although neutropenia and thrombocytopenia were more common in FPI group than in FP group. Conclusions: These data indicate that arterial infusion chemotherapy with 5-FU/cisplatin/IFNbeta may be a promising treatment modality for advanced HCC. No significant financial relationships to disclose.
Effect of pazopanib on hair and skin hypopigmentation: A series of three patients.
Authors: K. Sideras, M. E. Menefee, J. K. Burton, S. P. Ivy, C. Erlichman, K. C. Bible
Journal: Journal of Clinical Oncology (2010)

e13602 Background: Pazopanib, an inhibitor of multiple kinases including VEGF-R, PDGF-R, and c-KIT, is the latest of a series of tyrosine kinase inhibitors (TKIs) to be FDA approved for the treatment of human cancers. Hair and skin hypopigmentation have been occasionally reported in response to therapy with c-Kit inhibitors, such as imatinib, but not with other TKIs. Methods: We report our experience with severe skin and hair hypopigmentation in 3 representative patients treated with pazopanib (800 mg daily continuously, 28 day cycles) for advanced and progressive thyroid cancers enrolled in an ongoing IRB and NCI/CTEP-approved phase II clinical trial. Results: More than 50% of patient's enrolled in our ongoing phase II trial, who have remained on study for >6 months, have experienced hair and skin hypopigmentation. The 3 patients presented here (1 African American, 2 Caucasians - Hürthle cell, medullary, follicular histology respectively) all responded to therapy - with maximal reduction of target lesions by 59%, 19%, and 35%, respectively, and reduction in respective tumor markers by 71%, 76%, and 51%. All 3 patients are still receiving pazopanib after 14 to 17 cycles of therapy. Hypopigmentation was first noted after 1 or 2 cycles, with maximal hypopigmentation noted after 6 to 10 cycles. Our African American patient experienced severe sunburn for the first time in her life, presumably due to profound hypopigmentation. She has now started to regain skin pigmentation in response to pazopanib dose reduction. The 2 Caucasian patients are hypopigmented to a degree otherwise expected only in albinism. One of the Caucasian patients is slowly regaining pigmentation while on pazopanib in the absence of a dose reduction. Conclusions: The precise incidence of pazopanib induced hypopigmentation is not yet known. However, severe hypopigmentation of the hair and skin has been commonly observed in our thyroid cancer trial. We postulate that dual potent inhibition of c-Kit and PDGF-R may be responsible. Whether pazopanib-induced hypopigmentation may represent a biomarker of response remains uncertain. Patients and physicians should be aware of this complication, and of its potential reversibility. Supported in part by NCI-CA15083 and NO1-CM62205. No significant financial relationships to disclose.
Comparison of complementary medicine use at genetic testing program enrollment and one-year following results disclosure
Authors: L. Digianni, M. Rue, K. Emmons, J. Garber
Journal: Journal of Clinical Oncology (2004)

1013 Background: We sought to compare change in complementary and alternative medicine (CAM) use from enrollment into a randomized BRCA1/2 testing project to CAM use one-year following results disclosure. We also explored factors influencing new CAM use at one-year by women not using CAM at program entry, including BRCA1/2 test result, anxiety, cancer-related surveillance behaviors, and prophylactic surgical choices. Methods: A matched cohort of 243 high-risk women completed questionnaires at enrollment into BRCA1/2 randomized control trial (with semi-structured counseling intervention) and one-year post results disclosure. Women were asked about their use of several types of CAM, including ingestible, behavioral and physical modalities. Assessment of the pattern of change in CAM use from baseline to one-year was done using McNemar's Test of Change for Paired Samples. Correlates of new CAM use at one-year were explored using logistic regression models for the subset of 113 women (46.5%) who did not report CAM use at enrollment into the testing program. Results: Among women that changed their CAM behavior from baseline enrollment to one-year following BRCA1/2 results disclosure, there was a significantly higher proportion that changed from no CAM use to CAM use among the overall cohort (p=. 01), women without cancer (p=. 003), BRCA1/2 carriers (p=. 03), and among women randomized to the genetic counseling intervention arm of the study (p=. 009). Additionally, new CAM use at one-year was positively associated with the reported number of cancer-related surveillance behaviors for both healthy women and cancer survivors. Conclusions: High-risk women who have received BRCA1/2 testing may adopt new CAM use in the first year post disclosure. Healthy high-risk women and cancer survivors may utilize both CAM and other cancer-related surveillance strategies. The correlation between CAM use and genetic counseling deserves further study. No significant financial relationships to disclose.
Association between severe bronchopulmonary dysplasia and serum HGF levels in premature infants during early postnatal life
Authors: Isamu Hokuto, Takeshi Arimitsu, Masayuki Miwa, Yohei Matsuzaki, Kazushige Ikeda
Journal: European Respiratory Journal (2011)

Background:  Severe bronchopulmonary dysplasia (BPD) in very low birth weight infants often poses a therapeutic challenge. Therefore, it is important to make a prognosis. In this study, we investigated the relationship between the severity of BPD and serum HGF levels in infants less than 30 weeks of gestational age.   Methods:  The subjects were 16 infants less than 30 weeks of gestational age born in our hospital. Cord blood was taken at delivery. Thereafter, blood was collected from the infants once a week. Serum HGF levels were measured by ELISA. Medical records were reviewed to collect information about the mothers and the clinical course of the infants.   Results:  In 7 of the 16 infants, the serum HGF level exceeded 1 ng/dL during the clinical course. All those infants received more than 30% oxygen, nasal-CPAP, or mechanical ventilation at a corrected age of 36 weeks. Nine infants showed a serum HGF level of less than 0.6 ng/dL, and only 1 received 30% oxygen at a corrected age of 36 weeks. Infants exhibited high serum HGF levels within 2 weeks of birth. Serum HGF levels were not significantly correlated with the presence of chorioamnionitis (CAM).   Discussion:  High serum HGF levels within 2 weeks of birth were associated with a significant increase in the risk of severe BPD. Serum HGF levels were not correlated with CAM, suggesting that fetal inflammation alone does not lead to the development of BPD. We speculate that some inflammation with or without CAM within 2 weeks of birth plays an important role in the development of severe BPD.   Conclusions:  The periodic measurement of serum HGF levels may allow the early diagnosis of severe BPD.
Penetration of Rat Skin by &lt;italic&gt;N&lt;/italic&gt;-Nitrosodiethanolamine and &lt;italic&gt;N&lt;/italic&gt;-Nitrosomorpholine&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: W Lijinsky, A M Losikoff, E B Sansone
Journal: JNCI Journal of the National Cancer Institute (1981)

N-Nitrosomorpholine (NMOR) and N-nitrosodiethanolamine (NDELA) were painted on the clipped upper dorsal skin of male F344 rats. NDELA was applied undiluted, dissolved in water, and dissolved in cutting oil; NMOR was applied dissolved in water and in ethyl acetate. Aqueous solutions of the nitrosamines were used for gavage. Rats were housed individually. Blood and urine samples were analyzed for nitrosamines by chromatography combined with a Thermal Energy Analyzer. Maximum penetration of NMOR was approximately equal to 34% 2 hours after application of 5 mg to the skin or by gavage; less than 1% appeared in the urine in 24 hours. Skin painting with NDELA in water (20 mg/100 microliters) and in cutting oil (25 mg/25 microliters) yielded small concentrations of NDELA (always < 25 micrograms/ml blood). When 50 mg of undiluted NDELA was painted on the skin, 130 to 220 micrograms/ml of blood was recovered after 1 hour. Administering 50 mg NDELA in water by gavage yielded similar blood concentrations. Maximum skin penetration observed with NDELA was 78% 1 hour after application of 50 mg. From 20 to 30% of the NDELA applied undiluted and by gavage appeared in the urine in 24 hours. Although animals and humans differ, skin exposure to NMOR or NDELA represents a risk due to absorption.
Publication bias in randomized controlled trials (RCTs) of colorectal cancer presented at ASCO Annual Meetings.
Authors: A. I. Leal, W. F. Barra, D. F. Saragiotto, E. D. Saad, P. M. Hoff
Journal: Journal of Clinical Oncology (2010)

6116 Background: Full publication of RCTs presented as abstracts in scientific meetings may reduce publication bias, facilitate systematic reviews, and expedite implementation of therapeutic interventions in guidelines and clinical practice. We sought to compare the publication rates of positive and negative RCTs presented at recent ASCO Annual Meetings. Methods: We used the ASCO Website to identify all phase III RCTs in colorectal cancer accepted for ASCO Annual Meetings 1999-2006. We searched for full publications using PubMed (1999-current) and Google Scholar. Exclusion criteria were systematic reviews, combined/post-hoc analysis and interim/preliminary results. For each trial, data were summarized for presentation status, sample size, endpoints, type of analysis, participating organizations, pharmaceutical sponsorship, time to publication, journal impact factor (JCR 2008) of published trials and citations by Google Scholar. A positive trial was defined when the primary endpoint rejected the null hypothesis. Results: Wefound 199 phase III abstracts during the 8-year period, 102 of which met the eligibility criteria. By Kaplan-Meier, the 5-year cumulative publication rates were 73,1% and 59,3% for positive and negative trials (p = 0.009). The median time to publication for pharmaceutical industry-sponsored and government-funded trials were 21 and 40 months (p = 0.023). Studies conducted by cooperative groups were published later than noncooperative group trials (31 versus 17 months; p = 0.023). There was no significant difference between journal impact factor for positive and negative published studies. However, North American trials were more likely to be published in high impact factor journals (p = 0.020). Numbers of citations shown on Google Scholar were equivalent between positive and negative trials (p = 0.625). Conclusions: There is publication bias in colorectal cancer studies. Almost one-third of colorectal cancer RCTs presented at ASCO Annual Meetings remain unpublished after several years. Negative trials have a lower cumulative publication rate. However, negative RCTs are also published in high-impact journals and are frequently cited in the literature. No significant financial relationships to disclose.
Phase II trial of weekly docetaxel and oral capecitabine in metastatic hormone-refractory prostate cancer
Authors: S. Marur, L. Heilbrun, O. Kucuk, M. L. Cher, J. Forman, E. Heath, U. Vaishampayan
Journal: Journal of Clinical Oncology (2006)

4634 Background: Docetaxel based chemotherapy for hormone-refractory prostate cancer (HRPC) has demonstrated survival benefit. The combination of docetaxel-capecitabine has demonstrated synergistic anti-tumor effect, which is attributable to docetaxel-mediated up-regulation of thymidine phosphorylase (TP). Hence, a phase II trial is being conducted to assess efficacy and tolerability of weekly docetaxel and capecitabine in metastatic HRPC. Methods: Patients with metastatic HRPC, who have not received prior chemotherapy for metastatic disease were eligible to receive docetaxel 36 mg/m 2 /week IV on days 1,8, and 15 and Capecitabine 1250 mg/m 2 /day in two divided doses on days 5–18. Cycles were repeated every 28 days and response was assessed every 2 cycles. The primary end point was response rate. A two stage Simon study design required 15 patients to be accrued in first stage and additional 13 patients in second stage. Results: First stage was completed and response was adequate to proceed to second stage. 21 patients have been registered to this ongoing trial. Baseline characteristics included median age of 71 (range 47–80 years); median performance status of 1; median PSA at study entry of 60.6 ng/ml (range 1.2–3716.9); Of the 21 patients, 16 had bone pain pretherapy, Gleason score ≥ 8 in 14; 8 had measurable disease; 8 had new bone metastases and 14 had PSA progression. 83 cycles have been administered (median 4, range 1–10 cycles). To date 18 patients were assessable for toxicity and response. Grade 3 and 4 neutropenia was noted in 3 patients and Grade 3 hand-foot syndrome in 2 patients. There were no treatment related deaths. A PSA partial response (PR) defined as ≥ 50% decline sustained for ≥ 4 weeks was observed in 14/18 (77%) with ≥90% PSA decline in 7/18 (39%) patients. PR noted in 5/8 measurable disease patients. Stable disease by bone metastases in 15/18. Median time to PSA progression was 5 months (95% CI of 3.5–7.2+ month). Conclusions: The combination of capecitabine and weekly docetaxel demonstrated encouraging activity and acceptable toxicity profile. [Table: see text]
Practical Guidelines for Ethical and Policy Issues that Arise from the Clinical Application of Whole Genome Sequencing in Cancer Patients
Authors: H. Lim, A. Virani, A. Fok, A. Karsan, D. Renouf, K.A. Gelmon, S. Yip, S. Chia, S. Sun, A. Tinker, S.J. Lee, R. Rassekh, R. Deyell, R. Roscoe, S. Jones, E. Pleasance, M. Marra, J. Laskin
Journal: Annals of Oncology (2014)
Letter from Sarajevo: On a front line
Authors: L. Jones
Journal: BMJ (1995)

Like the patients, doctors in Sarajevo depend largely on humanitarian aid; everyone in the public sector has worked without pay for almost three years. The hospital is on a front line; yet the psychiatric department continues to function, even conducting large scale studies of psychosocial aspects of war in Bosnia-Hercegovina. The type of inpatient morbidity and treatment patterns have changed. A plethora of psychosocial rehabilitation programmes has emerged, including counselling, drop in centres, and attending to special needs of elderly people, schoolchildren, and women. The most prominent psychological symptoms were exhaustion at the prospect of a third winter of war and bewilderment at the Western stereotype of Bosnians as Muslim fundamentalists.
P1198 : Histological stage is relevant for risk-stratification in primary biliary cirrhosis
Authors: M. Carbone, S.J. Sharp, M.A. Heneghan, J.M. Neuberger, G.M. Hirschfield, A.K. Burroughs, D. Thorburn, A. Bathgate, M. Aldersley, C. Adgey, P. Trembling, K. Williamson, L. Jopson, R.T. Lim, N.J. Wareham, H.J. Cordell, G.J. Alexander, J.E. Jones, R.N. Sandford, S.E. Davies, G.F. Mells
Journal: Journal of Hepatology (2015)
Abstract 17695: Femoral Artery Distensibility and Intima Media Thickness (IMT), but Not the Ankle Brachial Index, Are Associated With Measures of Physical Function: The San Diego Population Study (SDPS)
Authors: Christina L Wassel, Matthew A Allison, Emma J Barinas-Mitchell, Joachin H Ix, Nancy S Jenny, Julie O Denenberg, Dena E Rifkin, Belinda J McQuaide, Antoinette Marasco, Michael H Criqui
Journal: Circulation (2014)

Background: Lower extremity peripheral artery disease (PAD), even when asymptomatic, is associated with decreased functional status and mobility. The ankle brachial index (ABI), the standard for PAD diagnosis, may not decrease significantly until substantial lower extremity obstructive disease exists, and when apparent declines in physical function may already be present. Thus, we examined the association of measures of femoral artery atherosclerosis and distensibility, which may be better earlier indicators of pre-clinical lower extremity disease, with measures of physical function. Methods: The SDPS includes 1103 non-Hispanic white, African-American, Hispanic and Asian men and women, average age 70, who participated in a clinic exam between 2007-11. Initial data read from ultrasound images of the superficial and common femoral arteries from the 2007-11 exam is currently available on 295 of 1103 participants. Linear regression was used to assess the associations of femoral artery IMT, distensibility, and...
From HRCT to morphology in diffuse parenchymal lung diseases(DPLDs)
Authors: Anna Benova, Natalia Stoeva, Anton Penev, Tsvetan Minchev, Galia Kirova, Polina Dakova, Diana Lekova
Journal: European Respiratory Journal (2014)

Transbronchial Lung Biopsy(TBLB) can give a specific diagnosis in 29-79% of the patients with DPLD(AU Wells and N Hirani).In this retrospective study we assessed the use of TBLB in 61 patients(pts) with diffuse nodular,infiltrative,reticular and ground glass opacity(GGO)images on HRCT.We performed bronchoscopy with TBLB in all 61 patients.15 of them underwent additional surgical biopsy by Videoassisted Thoracoscopy(VATS). Results :We compared the radiological images to histological findings.34(55%)patients had diffuse reticular pattern on HRCT, 37(60.65%)nodular, 39(63.93%)infiltrates, 33(54.09%)GGO. Reticular pattern correlated with infiltrates and GGO in the same patient,while nodular was not significantly related to the rest.TBLB resulted in histological diagnosis in 36(59%)pts.VATS was applied to 15 of the pts with non-conclusive histology from TBLB.It resulted in histological yield in 14 more pts.We got definite histology in 50 pts:12 malignancies,10 sarcoidosis,10 tuberculosis,3 usual interstitial pneumonia(UIP),5 nonspecific interstitial pneumonia(NSIP),4 bronchiolitis obliterans and organizing pneumonia(BOOP),2 desquamative interstitial pneumonia(DIP),1pulmonary embolism,2 pulmonary oedema and 1Wegener granulomatosis.There was no strong correlation between HRCT images and histological findings.Weak positive correlation(r=0.36) was found between nodular pattern and sarcoidosis and weak negative between infiltrates and sarcoidosis(r=-0.42) and between nodular pattern and NSIP(r=-0.37).In 11(18%) patients the histology did not contribute to the final diagnosis. Conclusion :DPLDs are clinical entities with overlapping imaging features on HRCT. TBLB can obtain morphological diagnosis in around 60% of the patients.
Summary of results in patients with metastatic renal cell cancer (RCC) from phase I studies of RAD001 (everolimus)
Authors: L. L. Porter, H. A. Burris, S. F. Jones, S. Calvert, V. A. Papadimitrakopoulou, K. Hazell, N. Shand, D. Lebwohl, J. Baselga, I. Judson
Journal: Journal of Clinical Oncology (2006)

14599 Background: Activation of mammalian target of rapamycin (mTOR) is implicated in the pathogenesis of RCC. Hereditary RCC in tuberous sclerosis pts is associated with loss of function of TS complex genes and resultant activation of mTOR. In non-hereditary RCC, mutation of VHL reduces opposition to mTOR-dependant upregulation of HIF. HIF-1α stimulates growth-factor-mediated activities (VEGF, PDGF, TGFα) supporting tumor-growth and proliferation. RAD001, an orally bioavailable inhibitor of mTOR, could have a role in the treatment of pts with RCC. Methods: All pts with metastatic RCC treated in two phase 1 studies of RAD001 in advanced solid cancer were reviewed. Changes in tumor were assessed using RECIST. Results: There were 12 pts (8.2% of total study population) with histology of clear cell (10 pts), papillary (1 pt), sarcomatoid (1 pt). Dosing was either weekly (20 mg:1 pt, 50 mg:2 pts, 70 mg:4 pts) or daily (10 mg:5 pts). 8 pts were male, 4 female. Median age 60 yrs (range: 44–76). Baseline performance status (WHO) was 0 (2 pts) or 1 (10 pts). Metastatic sites included lung (9 pts), bone (7 pts), liver (2 pts). 10 pts had failed prior drug therapy including IL-2 (2 pts), bevacizumab &amp; erlotinib (7 pts), others (5 pts). Most frequent suspected drug reactions (3 pts or more) were: fatigue, diarrhea, rash, anorexia, mucositis, nausea, abdominal distension, vomiting, headache. Gr.3 events in single pts comprised: hypertriglyceridemia, hyperglycemia, epistaxis with prolonged bleeding time. 6 pts were progression-free at 6 months, 4 pts beyond 12 months (max. 20 months ongoing). Partial response apparent in 1 pt (papillary) on D334 is ongoing at D502. Conclusions: Advanced RCC pts can benefit from RAD001 as indicated by prolonged stable disease in half the cohort. Tumor shrinkaqe may appear only after several months of treatment. Toxicity is mostly mild and similar to patients with other tumor types. Further studies of RAD001 in pts with RCC are planned. [Table: see text]