tbuckley/cabot-search huggingface dataset:
Preferences and knowledge gaps among pediatric oncologists regarding the care of childhood cancer survivors: A survey of nearly 1,200 physicians
Authors: T. O. Henderson, F. Hlubocky, L. Diller, C. Daugherty
Journal: Journal of Clinical Oncology (2009)

6561 Background: Pediatric oncologists' attitudes and knowledge about the long-term follow-up (LTFU) care of childhood cancer survivors (CCS) have not been well described. Methods: We surveyed pediatric oncologists' self-reported attitudes and knowledge regarding the LTFU care of CCS. Following a pre-notification letter, surveys with a $5 gift card were mailed to 1,173 U.S. pediatric oncologists in November 2008. A second mailing for non-responders is planned. Results: With surveys still arriving, 536 have been returned (46% response rate). Median age of respondents is 47 years (range: 32–82 years); 56% men; 69% work in a children's hospital; 17% in a cancer center; 3% in a private practice. Respondents have practiced a median 14 years (range: 1–50 years) and see a median of 23 patients/week (range: 0–250 patients/week). 70% of respondents say their center has a LTFU clinic. Choosing from closed-ended responses: 37% say they prefer to follow CCS as long as possible, 21% prefer for the patients to be followed by a physician other than themselves, and 29% are willing to follow them in the absence of a more suitable physician. In describing comfort levels in caring for CCS (1 = very uncomfortable; 7 = very comfortable), respondents were most comfortable with survivors &lt; 21 years (mean 6.2 + 1.4). For CCS &gt;21 but &lt;30 years, respondents were less comfortable (mean 5.0 + 1.5), and were uncomfortable caring for CCS &gt; 30 years (mean 3.3 + 1.7). 84% of respondents report eventually referring CCS to a LTFU program (40%), to a primary care physician (23%) or to an adult oncologist (12%). In a clinical vignette of 29 year old women exposed to mantle radiation and anthracyclines (150 mg/m2) for Hodgkin's lymphoma at 16 years of age: 30% of respondents did not appropriately recommend yearly breast cancer surveillance (based on Children's Oncology Group LTFU guidelines); 41% of respondents did not appropriately recommend cardiac surveillance; and 15% of respondents did not appropriately recommend yearly thyroid screening. Conclusions: Pediatric oncologists express a range of preferences with regard to LTFU of CCS and CCS over 21 years of age. Many appear unfamiliar with LTFU surveillance recommendations. No significant financial relationships to disclose.
Early and Transient Microchimerism Associated with Complete Remission after Adoptively Transferred Haploidentical NK Cells Against High Risk Myelodysplastic Syndrome and Refractory Acute Myeloid Leukemia
Authors: Andreas T Björklund, Mattias Carlsten, Marie Schaffer, Lisa Liu, Sarah A. Cooley, Jeffrey S. Miller, Emma Watz, Marzia Palma, Lotta Hansson, Björn E Wahlin, Lars Möllgård, Hans Hagglund, Pontus Blomberg, Per T. Ljungman, Eva Hellström-Lindberg, Hans-Gustaf Ljunggren, Karl-Johan Malmberg
Journal: Blood (2014)
Estrogen-induced phosphorylation of P53 at Ser15 in aging HMEC in the absence of estrogen receptor
Authors: R. Hass, A. Scharf, H.-J. Lück, H. Kühnle
Journal: Journal of Clinical Oncology (2005)

615 Background: A variety of studies have established primary human mammary epithelial cells (HMEC) as an ex vivo model. It was of interest therefore, to investigate aging-related functional alterations in response to estrogen treatment as part of a hormone replacement therapy (HRT). Method: Primary HMEC were cultured for 5d, 19d, and 50d, respectively. During this aging process, functional changes including cell cycle distribution and estrogen receptor expression were determined by flow cytometry, respectively. Expression of P53 and phosphorylated P53 were detected by Western blot analysis and quantified by a P53 phospho ELISA. Results: Primary HMEC cultures underwent significant morphological and functional changes during the process of aging. Cells in S phase significantly declined after 19d and accumulated in G0/G1 and G2/M phase after 50d. Simultaneously, the initial estrogen receptor expression of 32,3% dropped to less than 1% in 19d and 50d aged HMEC, respectively. Short term treatment of HMEC with 1μM β-estradiol demonstrated unaltered levels of P53 and phosphorylated P53 after 60min. Following 24h of estrogen exposure, however, Western blot analysis revealed a significantly enhanced phosphorylation of P53 at Ser15 in 5d and 19d HMEC populations, respectively. A phospho-P53 ELISA confirmed a more than 2-fold increased Ser15-phosphorylation of P53 in these two HMEC populations following 24h of estrogen stimulation, but no significant changes after 60min, respectively. Conclusions: According to the estrogen receptor depletion in aged HMEC, these data indicated a receptor-independent signaling and thus suggest a dual estrogen mechanism: 1) a receptor-dependent probably short-term transcriptional effect, and 2) a receptor-independent long-term effect associated with P53 phosphorylation and subsequent repair. Whereas these dual estrogen signaling pathways are accompanied by aging-related functional alterations of the breast tissue, this would also complicate HRT to balance protective and damaging effects of estrogen. No significant financial relationships to disclose.
Abstract 9387: Painless Acute Aortic Dissection is Associated with Poor Functional Outcome: Relationship to Clinical Characteristics and Diagnostic Procedure
Authors: Hiroshi Imamura, Katsunori Mochizuki, Ken-ichi Nitta, Hiroshi Takayama, Tomomi Iwashita, Hiroshi Dohgomori, Kazufumi Okamoto
Journal: Circulation (2012)

Background: Prompt diagnosis of acute aortic dissection (AAD) is essential for successful management. AAD classically presents with severe chest, back, or abdominal pain. However, there have been several documented cases presenting with atypical features. Making diagnosis is difficult when the classic pattern of pain is absent. Hypothesis: The purpose of this study was to investigate the clinical characteristics of patients with painless AAD and to assess the hypothesis that the diagnostic delay in painless AAD might cause poor prognosis. Methods: One hundred and twenty-four patients with AAD were admitted our hospital from 2002 to 2007. After excluding patients with an out-of-hospital cardiac arrest, 98 patients (53 males, 45 females; 66±12 years) were studied. Sixteen patients (17%) had no pain (Painless group) and 82 patients had pain (Painful group). Eighty-one per cent and 70% of patients had a type A dissection, respectively. Results: The time from admission to a definite diagnosis was longer in the Painless group (P=0.004). The diagnosis was made within 1 hour of admission in 40% of patients in the Painless group and in 76% in the Painful group. The Painless group more frequently had a persistent disturbance of consciousness (44% vs 6%, P&lt;0.001); syncope (25% vs 1%, P&lt;0.001); and a focal neurologic deficit (19% vs 2%, P=0.006) as presenting symptoms. Cerebral ischemia (50% vs 1%, P&lt;0.001) and cardiac tamponade (38% vs 13%, P=0.01) were more frequent complications in the Painless group. In-hospital mortality was not significantly different (19% vs 15%). However, the Painless group had a more unfavorable functional outcome on Overall Performance Category (P&lt;0.001). Characteristics associated with unfavorable functional outcome were cerebral ischemia and cardiac tamponade on admission. The time from admission to a definite diagnosis was not significantly related with unfavorable functional outcome. Conclusions: Painless AAD patients often present with a disturbance of consciousness or a neurologic deficit and have higher morbidity. Although it takes more time for definite diagnosis of painless AAD than painful AAD, the major causes for increased morbidity are complications of AAD on admission rather than the diagnostic delay.
<i>p53</i> mutations in advanced cancers: Clinical characteristics and outcomes in a phase I setting.
Authors: Rabih Said, David S. Hong, Jennifer J. Wheler, Aung Naing, Gerald Steven Falchook, Siqing Fu, Filip Janku, Ralph Zinner, Sarina Anne Piha-Paul, Carla L Warneke, Apostolia Maria Tsimberidou, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2012)

10607 Background: p53 mutation is one of the most common mutations in human tumors and plays an important role in apoptosis, genomic stability and inhibition of angiogenesis. Methods: We retrospectively reviewed 121 consecutive patients (pts) with solid tumors referred to the Clinical Center for Targeted Therapy (Phase I program) who were tested for p53 mutation, and compared clinical characteristics and outcomes in p53 positive vs. wild-type (wt) pts. Results: Of the 121 tested pts, 65 (53.7%) were p53 mutation-positive. The presence of p53 mutation was not associated with sex and race. Tumors with p53 mutation metastasized more often to the liver (44 pts (67.7%) with mutated p53 vs. 26 pts (46.4%) with wt p53, p=0.0264); there was no difference in metastasis to the bones, lungs, brain, soft tissues and adrenals. p53 mutation also showed a trend toward an association with PTEN-loss (13 out of 43 (30%) with p53 mutated vs. 4 out of 37 (11%) with wt p53, p=0.053). Among pts with the p53 mutation, the best median progression-free survival (PFS) prior to phase I trial entry was 10.97 months (range 0.85–29.04 months) when the treatment regimen included bevacizumab and 4.37 months (range 0.92–14.98 months) when the treatment did not include bevacizumab (P=0.0046). Among patients with wt p53, there was no significant difference in PFS between bavacizumab-containing regimens and regimens without bevacizumab. The median OS from diagnosis was 7.7 years (95% CI 6.32–9.84 years) vs. 11.8 years (95% CI 10.37 years, not attained) for p53 mutant vs. wild-type disease (p = 0.03). Univariate analysis for OS from diagnosis showed that mutated p53, Hispanic race (vs. Caucasians) and the shorter time from diagnosis to metastasis were associated with a worse prognosis. Conclusions: Tumors with p53 mutation have a more aggressive clinical behavior, metastasize more to the liver and may have a higher rate of PTEN loss compared to tumors with wt p53; In addition, anti-angiogenic agents may be of therapeutic value in p53-mutated pts.
Safety of total therapy II with or without thalidomide (THAL) for newly diagnosed myeloma: A study of 475 consecutive patients
Authors: E. J. Anaissie, J. Jacobson, A. B. Fassas, M. Zangari, R. Thertulien, F. VanRhee, G. Talamo, G. Tricot, C. Wendling, C. K. Davis, K. Hollmig, B. Barlogie
Journal: Blood (2003)
Illness Among Flyers
Authors: H M LUYKX, B L MURRAY
Journal: JAMA (1963)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Molecular responses with nilotinib 800 mg daily as first-line treatment of chronic myeloid leukemia in chronic phase: Results of a phase II trial of the GIMEMA CML WP
Authors: G. Martinelli, F. Castagnetti, A. Poerio, M. Breccia, F. Palandri, G. Alimena, F. Pane, G. Saglio, M. Baccarani, G. Rosti
Journal: Journal of Clinical Oncology (2009)

7074 Background: Nilotinib has a higher binding affinity and selectivity for Abl with respect to imatinib (IM). To investigate the efficacy and the safety of nilotinib 400 mg BID in untreated, early chronic phase (ECP) CML patients (pts), the GIMEMA CML WP is conducting a multicentric, phase II study trial (ClinicalTrials.gov NCT00481052 ). Methods: 73 pts have been enrolled between June 2007 and February 2008. The median age was 51 years (range 18–83). Median follow-up is currently 210 days (range 68–362). Results: All 73 pts and 48/73 (66%) completed 3 and 6 months on treatment, respectively. Response at 3 and 6 months (ITT): CHR rate was 100% and 98%, CCgR rate 78% and 96%, respectively. A MMR was achieved by 3% after 1 month on treatment, but this proportion rapidly increased to 22% after 2 months, 59% after 3 months and 74% after 6 months. One patient progressed at 6 months to accelerated-blastic phase with the T315I mutation. The median daily average dose was close to the intended dose, 789 mg (range 261 - 800); 34/73 pts (47%) interrupted nilotinib at least once, with a median interruption of 15 days (range 2–98). The dose of nilotinib at the last visit was 400 mg BID for 52 pts (71%), 400 mg daily for 20 pts (27%), and 200 mg daily for 1 patient (1%). AEs (grade 3/4) were manageable with appropriate dose adaptations: hematologic toxicity was recorded so far in 4 pts (5%); the most frequent biochemical laboratory abnormalities (grade 3) were total bilirubin increase (15%), GOT/GPT increase (11%), and lipase increase (4%). Only 1 episode of grade 4 lipase increase was recorded. It is noteworthy, considering the 48 cases with at least 6 months of follow-up, that the incidence of any grade 2 and 3 non-hematologic adverse event, decreased from 50% and 8% (first 3 months) to 23% and 6% (second trimester), respectively. In 16 pts (22%), transient and not clinically relevant ECG abnormalities have been recorded; 2 more pts (3%) revealed a transient and uneventful QTc prolongation (&gt;450 but &lt;499 msec). Conclusions: In ECP Ph-pos CML pts both cytogenetic and molecular responses to nilotinib are substantially faster than the responses to IM. Supported by: FIRB 2006. No significant financial relationships to disclose.
Bevacizumab in unresectable hepatocellular carcinoma (HCC) for patients without metastasis and without invasion of the portal vein
Authors: J. D. Schwartz, M. Schwartz, D. Lehrer, E. Cohen, M. Sung, M. Kinkhabwala, A. Siegel, S. Holloway, A. Ocean, S. Wadler
Journal: Journal of Clinical Oncology (2006)

4144 Background: HCC is a vascular tumor in which angiogenesis contributes to pathogenesis. VEGF-inhibition has not been previously attempted in cirrhosis or HCC. Methods: We enrolled patients with unresectable HCC to treatment with bevacizumab at 5 mg/kg or 10 mg/kg every 14 days to assess safety and preliminary efficacy. Inclusion criteria were BR &lt; 3.0 mg/dl, transaminases 75K and PT within 4 seconds of normal. Additional criteria included no history of myocardial infarction, stroke, or condition requiring ongoing antiplatelet or antithrombotic therapy. Results: Initial safety assessments for patients treated for at least 8 weeks indicate that 10 of 11 patients treated at 5 mg/kg and 7 of 8 patients treated at 10mg/kg tolerated therapy with acceptable toxicity. Of the first 28 patients treated at either dose, four have had therapy discontinued because of adverse events (including one grade 3 transient ischemic attack). Three patients had serious esophageal bleeding which was likely secondary to progression of HCC and liver disease (although contribution of drug to these events cannot be excluded). The protocol has been modified to identify and treat esophageal varices prior to enrollment. Other toxicities have included grade 2 fatigue, abdominal pain, gastric ulcer, hypertension, hyperbilirubinemia, rash and proteinuria and grade 1 gingivitis, diarrhea, vomiting and epistaxis. Of the initial 25 patients evaluable for efficacy, 5 had progressive disease within 16 weeks. Two patients had PR and 18 had SD. Median time-to-progression was 6.5 months (range 3.9–24.2). Nineteen of 25 (76%) patients had HCC that progressed following transplant, surgery, RFA or embolization procedures. Conclusions: Bevacizumab can be given safely at both 5 mg/kg and 10 mg/kg in HCC patients with localized, unresectable HCC, preserved liver function and no significant esophageal varices. Preliminary results suggest significant disease-modifying effect (80% disease-control rate); median time-to-progression to-date has exceeded 6-months. [Table: see text]
SP0085 Co-Ordinating Care: The Role of the General Practitioner
Authors: S. Bergman
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> The general practitioner (GP) has a unique role in the care of people with rheumatic disorders. The main possibilities lie within early detection of the rheumatic disease and knowledge in how to diagnose and treat common co-morbidities. The GP could also be a link between specialised rheumatology care and paramedical resources in primary care. There are however great differences in how care is organised in different countries and thus how the possibilities within primary care are utilised. Lessons could be learned from how GPs work in collaboration with rheumatologists and other caregivers in different settings, with the patients' best in focus. <h3>Disclosure of Interest</h3> None Declared
Phase I evaluation of CYT997, a novel cytotoxic and vascular-disrupting agent, in patients with advanced cancer
Authors: J. Lickliter, A. Francesconi, G. Smith, M. Burge, A. Coulthard, S. Rose, M. Griffin, A. Wilks, D. Wyld, P. Vasey
Journal: Journal of Clinical Oncology (2008)

3504 Background: CYT997 binds α-tubulin, inhibits microtubule assembly and demonstrates potent anti-tumour and vascular- disrupting activity in preclinical models. A phase I dose-finding study in patients with advanced cancer has now been completed. Methods: CYT997 was administered by continuous IV infusion over 24 hours, with doses repeated every 3 weeks. Doses were escalated using a standard phase I design (3 patients per dose level) for patients 1–18; subsequently, an accelerated titration design was used. Pharmacodynamic effects on tumour vasculature were assessed with DCE-MRI scans, circulating endothelial cell (CEC) assays and von Willebrand factor (vWF) plasma levels. Results: 31 patients (M/F: 15/16; median age 57, range 21–75) were treated on study. A total of 99 cycles of CYT997 were administered (median 2/patient, range 1–6) over 12 dose levels (7 - 358 mg/m2). Doses up to 202 mg/m2 were well tolerated. However, dose-limiting toxicities were observed at 269 and 358 mg/m2, consisting of grade-3 prolonged QTc interval (n=2) and grade-4 dyspnea in a patient with a history of thoracic radiation. All toxicities were reversible. PK profiles revealed dose-dependent linear increases in Cmax and AUC values. vWF-antigen plasma levels increased significantly following CYT997 doses of 202 mg/m2 and above (mean 136% of baseline, standard deviation 23%), whereas no increase was observed at lower dose levels (p<.00001). In addition, a marked increase in CD146+ CD31+ 7-AADdim apoptotic CECs was observed in one patient at the highest dose level. DCE-MRI assessments (including histogram analyses) were evaluable in 11 patients who received ≥ 65 mg/m2 of CYT997. Statistically-significant changes in tumour Ktrans values consistent with vascular disruption were observed in 7 of these patients. No objective responses were seen among 22 evaluable patients; however, 17 patients had stable disease for a median of 4 cycles (range 2–6). Conclusions: CYT997 was well tolerated at doses associated with vascular targeting activity. The recommended dose for phase II evaluation is 202 mg/m2. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Cytopia Research Pty Ltd Cytopia Research Pty Ltd Cytopia Research Pty Ltd Cytopia Research
Healthiron: a longitudinal population study defining the burden of disease in HFE-associated hereditary hemochromatosis
Authors: K. J. Allen, L. C. Gurrin, N. J. Osborne, C. C. Constantine, M. B. Delatycki, A. J. Nicoll, C. E. McLaren, M. Bahlo, A. S. Fletcher, A. E. Nisselle, S. Forrest, C. D. Vulpe, G. J. Anderson, G. G. Giles, D. R. English, J. L. Hopper, J. K. Olynyk, L. W. Powell, D. M. Gertig
Journal: American Journal of Hematology (2007)
One week on/one week off regimen of temozolomide: Phase II trial in recurrent glioma
Authors: W. Wick, A. Wick, J. Schuth, M. Platten, G. Reifenberger, M. Weller
Journal: Journal of Clinical Oncology (2007)

2032 Background: Evaluation of toxicity and efficacy of a one week on/one week off temozolomide regimen in patients with recurrent gliomas. Methods: Ninety adult patients (median Karnofsky performance score 90; median age 51 years) with recurrent gliomas (9 patients with low-grade gliomas, 11 with anaplastic gliomas, 64 with GBM, and 6 with other brain tumors) accrued in one center received chemotherapy with temozolomide at 150 mg/m2/d (days 1–7 and 15–21 every four weeks) with individual dose adjustments according to hematological toxicity. Results: A total of 906 treatment weeks was delivered. Grade 4 hematotoxicity according to the common terminology criteria for adverse events (CTCEA v 3.0) was observed in 24 treatment weeks (2.6%). CTCEA grade 4 lymphopenia eventually developed in 11 patients (12%). There were no cumulative lymphopenia or opportunistic infections. The progression-free survival (PFS) rate at 6 months for the patients with GBM was 43.8%. The median PFS was 24 weeks (95% CI, 17 to 26 weeks), the median survival time (MST) from diagnosis of progression was 38 weeks (95% CI, 30 to 46 weeks), the 1-year survival rate from progression was 23%. O6-methylguanine DNA methyltransferase (MGMT) gene promoter methylation in the tumor tissue was not associated with longer PFS (p=0.37, log-rank test). Conclusions: This data imply that the one week on/one week off schedule is feasible, safe and effective and clearly warrant investigation in randomized studies. In contrast, protracted low-dose temozolomide at 75 mg/m2 has been shown to be toxic, resulting in cumulative lymphopenia and opportunistic infections. Compared with protracted low-dose temozolomide 1 the one week on/one week off schedule was far less toxic. In addition this dosing schedule may circumvent the disadvantage of an unmethylated MGMT gene promoter by depleting MGMT. [Table: see text]