tbuckley/cabot-search huggingface dataset:
Pharmacokinetics and pharmacodynamics of asparaginases in antibody-negative pediatric patients with higher risk acute lymphoblastic leukemia (ALL): A report from CCG-1961
Authors: F. J. Arce, N. Seibel, P. S. Gaynon, P. N. Tiwari, I. A. Avramis, L. J. Ettinger, H. N. Sather, J. Franklin, C. Fu, S. E. Siegel, V. I. Avramis
Journal: Journal of Clinical Oncology (2006)

9027 Background: Asparaginase (ASNase) induces apoptosis in ALL lymphoblasts by depleting cells of extracellular asparagine (ASN) and possibly glutamine (GLN). On CCG-1961 [Seibel NL et al. Blood 2003; 102(11): 224a (abstract #787)], all patients (pts) received 9 doses of native E.coli-ASNase in induction (IND). Pts with rapid early response (marrow blasts &lt; 25% on Day 7, RER) were randomized to standard intensity therapy and received native ASNase thereafter or to stronger intensity therapy and received PEG-ASNase post induction. All pts with slow early response (marrow blasts ≥ 25% on Day 7, SER) received PEG-ASNase after induction. Pts with clinical allergy to E.coli-ASNase were switched to Erwinase. Methods: Anti-ASNase Antibody (Ab) titers were assayed at the end of IND, prior to Delayed Intensification #1 and prior to starting Maintenance. Amino acid levels were measured in 430 sera from 187 patients with measurable ASNase activity. Results: Population pharmacokinetics (PK) and pharmacodynamics (PD) of the ASNase formulations demonstrated half-lives of native ASNase (6000 IU/m 2 ): 30 hours, PEG-ASNase (2500 IU/m 2 ): 156 hours, and Erwinase (6000 IU/m 2 ): 18 hours. Subsequent exposures to either formulation resulted in increased activity with moderate prolongation of the elimination half-lives. One-hundred forty-two sera from 70 patients with ASNase activity between 0.03 and 1.11 IU/ml, had a mean ± SDEV ASNase activity, ASN levels, and GLN levels of 0.21 ± 0.23 IU/ml, 14.6 ± 17.7 μM, and 300.4 ± 233.8 μM, respectively; with median values of 0.11 IU/ml (range: 0.03–1.114 IU/ml), 4.7 μM (range: 0.38 - 81.34 μΜ), and 270.2 μM (range: 5.3 - 1189.1 μM), respectively. TTEST analyses linked higher ASNase activity with lower ASN levels and greater % ASN deamination. Higher ASNase activity did not assure greater GLN depletion. Conclusions: A sigmoid relationship between ASNase levels and % ASN deamination showed that activity of 0.41 ± 0.24 IU/ml (mean ± SDEV) provided 93% ± 13% ASN deamination. Therefore, &gt;90% ASN deamination required ASNase &gt;0.4 IU/ml. Kaplan-Meier analyses are pending. [Table: see text]
Intratumoral injections of G100 (synthetic TLR4 agonist) increase trafficking of lentiviral vector-induced antigen-specific CD8 T cells to the tumor microenvironment
Authors: Tina C Albershardt, Andrea J Parsons, Peter Berglund, Jan ter Meulen
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts The clinical efficacy of tumor-specific effector T cells can be limited by their proper trafficking to the site of the tumor and the immunosuppressed local environment. Strategies to improve homing of effector cells to tumors and to enhance activity of these effector cells could
Redefinition of Skin Cancer as a Chronic Disease
Authors: Adam Sutton, Ashley Crew, Ashley Wysong
Journal: JAMA Dermatology (2015)

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 Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Dermatology journal
Immunotherapy of liver cancer with hepcortespenlisimut-L: open-label Phase II clinical study in patients with advanced HCC
Authors: Marina G Tarakanovskaya, Jigjidsuren Chinburen, Genden Purevsuren, Chogsom Munkhzaya, Purev Batchuluun, Purev Bat-Ireedui, Dorjiin Dandii, Dandii Oyungerel, Galyna A Kutsyna, Allen I Bain, Vichai Jirathitikal, Aldar S Bourinbaiar
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Increasing number of studies is now devoted to immunotherapy of cancer. We evaluated the clinical benefit of hepcortespenlisimut‐L (V5) – an oral therapeutic vaccine designated by the US FDA as an orphan drug for treatment of hepatocellular carcinoma (HCC). Open-label Phase
Ultra-Low-Dose Buprenorphine as a Time-Limited Treatment for Severe Suicidal Ideation: A Randomized Controlled Trial
Authors: Yoram Yovell, Gali Bar, Moti Mashiah, Yehuda Baruch, Irina Briskman, Jack Asherov, Amit Lotan, Amihai Rigbi, Jaak Panksepp
Journal: American Journal of Psychiatry (2015)

Suicidal ideation and behavior currently have no quick-acting pharmacological treatments that are suitable for independent outpatient use. Suicidality is linked to mental pain, which is modulated by the separation distress system through endogenous opioids. The authors tested the efficacy and safety of very low dosages of sublingual buprenorphine as a time-limited treatment for severe suicidal ideation.This was a multisite randomized double-blind placebo-controlled trial of ultra-low-dose sublingual buprenorphine as an adjunctive treatment. Severely suicidal patients without substance abuse were randomly assigned to receive either buprenorphine or placebo (in a 2:1 ratio), in addition to their ongoing individual treatments. The primary outcome measure was change in suicidal ideation, as assessed by the Beck Suicide Ideation Scale at the end of each of 4 weeks of treatment.Patients who received ultra-low-dose buprenorphine (initial dosage, 0.1 mg once or twice daily; mean final dosage=0.44 mg/day; N=40) had a greater reduction in Beck Suicide Ideation Scale scores than patients who received placebo (N=22), both after 2 weeks (mean difference -4.3, 95% CI=-8.5, -0.2) and after 4 weeks (mean difference=-7.1, 95% CI=-12.0, -2.3). Concurrent use of antidepressants and a diagnosis of borderline personality disorder did not affect the response to buprenorphine. No withdrawal symptoms were reported after treatment discontinuation at the end of the trial.The time-limited, short-term use of very low dosages of sublingual buprenorphine was associated with decreased suicidal ideation in severely suicidal patients without substance abuse. Further research is needed to establish the efficacy, safety, dosing, and appropriate patient populations for this experimental treatment.
Artesunate–mefloquine versus chloroquine for treatment of uncomplicated Plasmodium knowlesi malaria in Malaysia (ACT KNOW): an open-label, randomised controlled trial
Authors: Matthew J Grigg, Timothy William, Jayaram Menon, Prabakaran Dhanaraj, Bridget E Barber, Christopher S Wilkes, Lorenz von Seidlein, Giri S Rajahram, Cielo Pasay, James S McCarthy, Ric N Price, Nicholas M Anstey, Tsin W Yeo
Journal: The Lancet Infectious Diseases (2015)
Perceptions regarding the value of the physical examination in patients with advanced cancer: A survey study.
Authors: Kunal C. Kadakia, David Hui, Gary B. Chisholm, Susan Frisbee-Hume, Janet L. Williams, Eduardo Bruera
Journal: Journal of Clinical Oncology (2014)

9609 Background: Despite its clinical utility, progressive reliance on technology can lead to devaluing the physical examination in patients with advanced cancer. The primary objective was to determine whether these patients have a positive or negative perception of the physical examination. Secondarily, to determine if these perceptions are related to interpersonal/relational values (symbolic) or diagnostic/objective values (pragmatic). Methods: One-hundred and fifty patients with cancer receiving concurrent oncology and palliative care were administered a 26-item survey regarding their overall perception of the physical examination. The primary outcome, patient responses to “I believe my experience while undergoing physical examinations has been overall: very negative (-5) to very positive (+5)”, was analyzed using the Sign test. Other items were predefined as symbolic or pragmatic statements and responses from strongly disagree (1) to strongly agree (5) were further analyzed. Multivariable logistic regression was utilized to test for associations between baseline characteristics and the primary outcome. Results: Most patients (83%) found the overall experience of being examined to be highly positive (median=4, interquartile range [IQR]=2-5, p=<0.0001). Patients valued both the pragmatic (median=5, IQR=4-5) and symbolic (median=4, IQR=4-5) aspects of the physical examination. Increasing age was independently associated with a more positive perception of the physical examination (odds ratio=1.07 per year, 95% confidence interval 1.02-1.12, p=0.01). Conclusions: Patients with advanced cancer find the physical examination to be a highly positive aspect of their care. These benefits are perceived as having both symbolic and pragmatic value. The physical examination should remain a cornerstone of clinical encounters.
Formation of Solid Human Mammary Carcinoma In Vitro
Authors: Richard A. Knazek, Marc E. Lippman, Harish C. Chopra
Journal: JNCI Journal of the National Cancer Institute (1977)

An established line of human breast carcinoma, MCF-7, when cultured within the artificial capillary system, formed solid masses of tissue. Acinar and ductular patterns developed, having the ultrastructural appearance of breast tissue that responds to exogenous hormones.
Prediction of response and survival in patients with chronic-phase chronic myeloid leukemia treated with omacetaxine mepesuccinate: logistic regression and landmark analyses
Authors: M Wetzler, H M Kantarjian, F E Nicolini, J H Lipton, L Akard, M Baccarani, H J Khoury, E Li, M Munteanu, J Cortes
Journal: Blood Cancer Journal (2015)

Although many chronic myeloid leukemia (CML) patients initially do well with tyrosine kinase inhibitors (TKIs), some patients develop resistance or intolerance to multiple TKIs and need further therapy. Omacetaxine mepesuccinate (omacetaxine), a protein synthesis inhibitor, represents a new class of treatment that can produce major cytogenetic response (MCyR) in patients with CML who have developed resistance or intolerance to TKIs. The US Food and Drug Administration approved subcutaneous omacetaxine for treatment of CML in chronic-phase (CP) and accelerated-phase patients, with resistance or intolerance to two or more TKIs based on efficacy analysis of a subset of patients from two phase 2, open-label, international, multicenter studies.1, 2 Among the 76 evaluable patients with CML-CP in the efficacy analysis, MCyR was reported in 14 patients (18.4%), including confirmed complete cytogenetic response (CCyR) in six patients (7.9%), with a median MCyR duration of 12.5 months.2, 3 Median progression-free survival (PFS) and overall survival (OS) in CML-CP patients were 9.6 months (95% confidence interval (CI) 6.8–11.3 months) and 40.3 months (95% CI 23.8 months–not reached), respectively.
Contraceptive and hormonal treatment options for women with history of venous thromboembolism
Authors: Manon C Stam-Slob, Cornelis B Lambalk, Marcel A van de Ree
Journal: BMJ (2015)

#### The bottom line

For women with a history of venous thromboembolism, we recommend:

A 28 year old woman, recently diagnosed as having a first deep venous thrombosis (DVT), visits her general practitioner. She has no predisposing factors (such as surgery, trauma, or malignancy), and tests show no familial thrombophilia risk factors, such as factor V Leiden. She had been using a combined oral contraceptive containing ethinylestradiol 30 µg and levonorgestrel 150 µg but was advised at the hospital to stop this as it increased her risk of getting another DVT. She now asks about contraceptive options that do not put her at risk for another DVT, particularly hormonal options, as she has been told they are more effective than non-hormonal contraceptives.

Venous thromboembolism (VTE) is a common disease with an overall annual incidence of 1 in 1000 people and an estimated mortality rate of 370 000 deaths per year in six European countries.1 2 The overall incidence of a recurrent thrombotic event is 20-30% in 10 years, with the highest rate in the months after discontinuation of anticoagulation therapy.3 As the risk of VTE is increased in women using combined oral contraceptives (that is, containing both oestrogen and progestogen) and hormone replacement therapy, this article aims to provide advice for women with a history of VTE who require contraception or hormone replacement therapy. …
Gastrointestinal metastases from melanoma: Does surgical resection improve survival when performed in combination with immunotherapy?
Authors: Gary B. Deutsch, Daniel D. Kirchoff, Mariel Bailey, Sarah Vitug, Devin C. Flaherty, Leland Jay Foshag, Anton Bilchik, Mark B. Faries
Journal: Journal of Clinical Oncology (2015)

340 Background: Prior studies have shown the benefits of metastasectomy and more recently, immunotherapy, in Stage IV melanoma. We report the largest series of gastrointestinal (GI) melanoma metastases, in order to clarify the role of surgical resection in the setting of systemic treatment options. Methods: A review of our institutional melanoma database identified all patients with hollow viscus GI metastases diagnosed between 1971 and 2013. Patient age and sex; primary tumor location, thickness and ulceration; GI-metastasis free interval; and types of treatment were analyzed. The primary endpoint was melanoma-specific survival (MSS), measured from the diagnosis of GI metastases. Survival analyses compared combination therapy to immunotherapy (i.e. vaccine, interleukin-2, interferon, ipilimumab) or surgery alone. Operative patients were further stratified by surgical intent (curative or palliative). Results: The 393 study patients had a median GI-metastasis free interval of 49.5 (0 – 416.0) months from the initial diagnosis; their mean age at GI metastases was of 53.5 ± 14.1 years. Median MSS was 20.0 months with surgery plus immunotherapy (n=160), 13.0 months with surgery alone (n=111), 8.0 months with immunotherapy alone (n=64), and 5.0 months with neither treatment (n=58) (p&lt;0.001). By multivariable analysis, age at GI metastasis diagnosis (HR=1.014; p=.014), truncal melanoma site (HR=1.659; p=.017), immunotherapy (HR=0.675; p=.030), and metastasectomy (HR=0.544; p&lt;.001) were significant predictors of MSS. Surgical intent was known in 98 patients: curative surgery had a median MSS of 30.0 months (n=49) and palliative surgery had a median MSS of 12.0 months (n=49) (p=.015). Conclusions: Treatment of GI melanoma metastases should use a combination of metastasectomy and immunotherapy, instead of either modality alone. Select patients are likely to obtain an enhanced benefit from GI metastasectomy, specifically curative surgery, in the setting of newer immunotherapy options.
Viral integration signature in multifocal hepatocellular carcinoma during occult hepatitis B virus infection: a single-cell sequencing analysis
Authors: Han-Jie Wu, Yu-Dong Xia, Hui-Fang Liang, Arian Laurence, Wei-Yang Li, Gui-Bo Li, Zhi-Kun Zhao, Kui Wu, Yong Hou, Jing-Jing Yu, Wei Xiao, Guo-Ping Wang, Peng-Cheng Zhu, Yi-Xin Jian, Wei Chen, Ming Zhou, Xun Xu, Xiu-Qing Zhang, Huan-Ming Yang, Jun Wang, Qian Chen, Xiao-Ping Chen
Journal: The Lancet (2015)
Early discharge after stroke
Authors: T. B. Wyller, A. Rudd, C. Wolfe, K. Tilling, R. Beech
Journal: BMJ (1998)

Editor—There are three reasons why Rudd et al may be at fault when they conclude that early discharge of patients with stroke has no clinical importance.1

Firstly, the authors used the Barthel index as the main outcome measure. This scale is insensitive to change at higher scores.2 More than 1 in 10 of the patients had a maximum Barthel score at randomisation, and improvement therefore cannot be shown in these patients with this index. The study was powered to detect a 3.5 point difference in the Barthel index. To be able to detect such a difference, the Barthel score should have been ⩽16.5 at the start of the study. Only about two thirds of the patients, however, seem to have had this low score, so a difference of this magnitude is unlikely to have occurred. Moreover, the most probable effects of early discharge are on the psychosocial level3 and thus are not measured by the index. 

Secondly, outcomes were assessed after one year. Most functional improvement after stroke takes place during the first few months.4 Different treatment strategies may influence the speed of this, and such effects may be clinically important even if they disappear within a year. 

Thirdly, nearly two weeks elapsed before half the patients had been randomised, and some were not randomised until considerably later. Thus the authors had no opportunity to start the intervention—that is, prepare for early discharge—during the first important weeks.5

The study provides important though insufficient information for clear conclusions to be drawn on the role of early discharge. Such conclusions should preferably be based on several studies with common, appropriate outcome measures.5
Prevalence of interstitial lung disease (ILD) in a lung cancer screening program using low-dose computer tomography (CT)
Authors: María Sánchez-Carpintero Abad, Luis Seijo Maceiras, Mόnica Ferreira, Montes Uxua, Alcaide Ana Belén, Campo Aranzazu, Juan Pablo De Torres, Pueyo Jesús, Bastarrika Gorka, Zulueta Francés Javier
Journal: European Respiratory Journal (2011)

Introduction: The prevalence of ILD in asymptomatic smokers is unknown. Unsuspected ILD can easily be detected by low-dose screening CTs.

Materials and methods: We conducted a retrospective review of CTs from 2418 individuals enrolled in the University of Navarre's lung cancer screening program between 2003 and 2010. Subjects were asymptomatic current or former smokers at least 40 years old, with a cumulative tobacco exposure > 10 pack-years. The prevalence of ILD on baseline CT was assessed initially by 2 independent radiologists. ILD was confirmed and characterized by a panel including a third radiologist and a pulmonologist.

Results: The prevalence of ILD in our study was 1.8%. The median age of subjects with ILD was 57 years (IQR: 51-68). Most were male (70%) and continued to smoke (71%) with a cumulative tobacco exposure of 35 pack-years (IQR: 23-47). The most common radiographic pattern was reticular disease (68%), followed by ground glass opacities (59%), bronchiolitis (15%), honeycombing (11%), and nodular (5%). The majority of subjects had peripheral (77%) and bilateral (96%) disease. Lymphadenopathy was rare (9%). The prevalence of emphysema in subjects with ILD was high (80%). Bronchial wall thickening (59%) and coronary calcifications (46%) were also common. Lung function was preserved in this asymptomatic cohort with a mean FEV1 of 97% (IQR: 78-108).

Conclusions: The prevalence of ILD in our screening population was higher than expected. Most of these individuals ignore the diagnosis, continue smoking, and have preserved lung function.
Capecitabine plus oxaliplatin (XELOX) versus bolus 5-fluorouracil/leucovorin (5-FU/LV) as adjuvant therapy for stage III colon cancer: Survival follow-up of study NO16968 (XELOXA).
Authors: Hans-Joachim Schmoll, Josep Tabernero, Jean Alfred Maroun, Filippo G. De Braud, Timothy Jay Price, Eric Van Cutsem, Mark Hill, Silke Hoersch, Karen Rittweger, Daniel G. Haller
Journal: Journal of Clinical Oncology (2012)

388 Background: The MOSAIC trial demonstrated that adding oxaliplatin to 5-FU/LV (FOLFOX4) improved 3-year disease-free survival (DFS) compared to infusional and bolus 5-FU/LV as adjuvant therapy in patients (pts) with stage II/III colon cancer [André et al. NEJM 2004]. A significant survival advantage for FOLFOX4 versus 5-FU/LV was not evident until after median duration of follow-up had exceeded 6 years [André et al. JCO 2009]. Study NO16968 demonstrated that XELOX was superior to bolus 5-FU/LV as adjuvant therapy in pts with stage III colon cancer in terms of DFS at 57 months median follow-up (HR 0.80; 95% CI 0.69–0.93; p=0.0045) [Haller et al. JCO 2011]. The difference between treatment groups in overall survival (OS) was not significant at 59 months median follow-up (HR=0.87; p=0.1486). Data from the planned final analysis of NO16968 are presented. Methods: Pts with resected stage III colon cancer were randomized to receive XELOX (8 cycles, 24w) or bolus 5-FU/LV (Mayo Clinic, 6 cycles; 24w or Roswell Park, 4 cycles; 32w). The primary study endpoint was DFS. Secondary endpoints included OS. Results: The ITT population included 1886 pts (XELOX, n=944; 5-FU/LV, n=942). After a median follow-up of 74 months, the HR (XELOX vs 5-FU/LV) for DFS was 0.80 (95% CI 0.69–0.93; p=0.0038). Seven-year DFS rates were 63% for XELOX and 56% for 5-FU/LV. After a median follow-up of 83 months, the HR for OS was 0.83 (95% CI 0.70–0.99; p=0.0367). Absolute 7-year OS rates were 73% with XELOX and 67% with 5-FU/LV. After adjusting for stratification and prognostic variables, HRs remained essentially unchanged for both DFS (0.79; 95% CI 0.68–0.91; p=0.0016) and OS (0.84; 95% CI 0.71–1.00; p=0.0477). Locoregional / systemic treatments after recurrence were given in 230 (24%) XELOX pts and 308 (33%) 5-FU/LV pts. Conclusions: The combination of oxaliplatin and capecitabine improves OS significantly compared with 5-FU/LV in the adjuvant treatment of stage III colon cancer after a median follow-up of 83 months; these data are comparable to those achieved with FOLFOX4 in the MOSAIC trial. XELOX is an effective adjuvant therapy option for pts with resected stage III colon cancer.
Chest pain in children - Evaluation of 136 consecutive cases
Authors: Tita Butenko, Marina Praprotnik, Malena Aldeco, DuÅ¡anka Lepej, UroÅ¡ Krivec
Journal: European Respiratory Journal (2012)

Chest pain (CP) is a common complaint among children. In many cases the source of pain can be identified by a thorough history and physical examination. Further diagnostic evaluation is warranted in doubtful cases. Aim: To identify the causes of CP in children referred to the emergency department (ED) and to compare results with the published data. Methods: All cases referred to ED for CP in one year period (2010-11) were retrospectively analyzed. Causes of CP were divided in: cardiac-related and noncardiac-related, the latter being further subdivided in: idiopathic (IC), musculoskeletal (MC), respiratory (RC), gastrointestinal (GC) and miscellaneous (MSC) causes. The results were compared with data from the literature. Results: Records from 136 children (66 girls), mean age 12.2 years (SD±3.7 years), were included. The most frequent group - 55 (40.4%) had IC, followed by MC in 35 (25.7%) children. RC were present in 17 (12.5%), GC in 13 (9.6%), and MSC in 6 children (4.4%). Our results in all groups did not differ from data in other studies. Cardiac causes were present in 10 children (7.4%), which is in line with up to 15% of cases in published data. Potentially fatal conditions were diagnosed in 6 (4.4%) children. None died or suffered significant sequellae. Conclusion: Our results are in line with published data from major centers. Benign conditions represent the majority of causes of CP. Nevertheless, CP in children should be evaluated with care since potentially fatal conditions can also be present in this age group.