tbuckley/cabot-search huggingface dataset:
Randomized trial comparing day 8 infusion of cisplatin (VP8) with day 1 infusion (VP1) in vinorelbine/cisplatin chemotherapy (VP) for advanced non-small cell lung cancer (NSCLC): Reduced episode of day 15 neutropenia with VP8
Authors: H.-J. Sohn, S.-W. Kim, C. Suh, E.-K. Kim, H.-J. Yang, W. S. Kim, T.-S. Shim, Y.-M. Oh, J. S. Lee
Journal: Journal of Clinical Oncology (2004)

7327 Background: The combination of vinorelbine (V) and cisplatin (P) has significant activity in advanced NSCLC. But the usual day 1 infusion of P and V (day 1 and 8) produce severe grade (G) 3/4 neutropenia. We experienced less severe neutropenic episode when P was infused on day 8 instead of day 1. So, we performed a randomized trial comparing day 8 infusion of P with day 1 infusion in VP. Methods: Eligibility required chemotherapy naïve, stage IIIB/IV, and measurable NSCLC. Patients (Pts) received P 75 mg/m2on either day 1 or day 8 with V 25 mg/m2 on day 1 and 8, every 4 weeks. In the 1st cycle of VP, weekly CBC was checked. Primary end point was comparing the neutropenic toxicity. Results: From July 2002 to April 2003, Forty-eight (23 VP1: 25 VP8) pts were randomized. Age (≤ 60 v > 60), performance status (ECOG 0–1 v 2), stage (IIIB v IV), and histology (squamous v non-squamous) were well balanced between two groups. The median number of cycles was 4 in both groups. Forty-six patients (23 VP1: 23 VP8) were evaluable for the toxicity in the 1st cycle of VP. G4 neutropenic toxicity in the 1st cycle is given in the table below. Less G4 neutropenia was observed in VP8 groups (43% v 9%, p=0.017). In the 1st cycle of VP1, three febrile neutropenic episodes were reported. Non-hematologic toxicities were mild and not different between two groups. Forty-one (21 VP1: 20 VP8) pts were evaluable for response, and response rates for VP1 and VP8 were 38% (95% CI, 15–61) and 60% (95% CI, 36–84), respectively (p=0.36). After a median follow-up of 10.4 months (2.1–17.6), 1-year survival rates were 60% and 63%, respectively. Conclusions: Compared with VP1, VP8 produced significantly less episode of day 15 G4 neutropenia. Overall response rates and 1-year survival rates were not significantly different. No significant financial relationships to disclose.
Spontaneous Mutation Rate in the Smallest Photosynthetic Eukaryotes
Authors: Marc Krasovec, Adam Eyre-Walker, Sophie Sanchez-Ferandin, Gwenael Piganeau
Journal: Molecular Biology and Evolution (2017)

Mutation is the ultimate source of genetic variation, and knowledge of mutation rates is fundamental for our understanding of all evolutionary processes. High throughput sequencing of mutation accumulation lines has provided genome wide spontaneous mutation rates in a dozen model species, but estimates from nonmodel organisms from much of the diversity of life are very limited. Here, we report mutation rates in four haploid marine bacterial-sized photosynthetic eukaryotic algae; Bathycoccus prasinos, Ostreococcus tauri, Ostreococcus mediterraneus, and Micromonas pusilla. The spontaneous mutation rate between species varies from μ = 4.4 × 10−10 to 9.8 × 10−10 mutations per nucleotide per generation. Within genomes, there is a two-fold increase of the mutation rate in intergenic regions, consistent with an optimization of mismatch and transcription-coupled DNA repair in coding sequences. Additionally, we show that deviation from the equilibrium GC content increases the mutation rate by ∼2% to ∼12% because of a GC bias in coding sequences. More generally, the difference between the observed and equilibrium GC content of genomes explains some of the inter-specific variation in mutation rates.
First-in-human phase I study of LY2780301, an oral P70S6K/AKT inhibitor, in patients with refractory solid tumors.
Authors: Emiliano Calvo, Karim Adnane Benhadji, Analia Azaro, Ignacio Duran, Guillem Argiles, Valentina Boni, Ute Ohnmacht, Johan Wallin, William Mark Bumgardner, Jordi Rodon Ahnert
Journal: Journal of Clinical Oncology (2012)

3005 Background: LY2780301is an oral potent, highly selective ATP competitive inhibitor against p70S6 kinase and AKT. We report on safety, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor activity from the first-in-men study of LY2780301 in solid tumors. Methods: Eligible pts (ECOG≤1) had relapsed solid tumors, adequate hematologic, renal, and hepatic functions. Using a predictive pre-clinical PK/PD model and non-clinical toxicology data, a total daily dose of 100-1000 mg, was selected. LY2780301 was given either once or twice daily for 28-day cycle until disease progression. Dose escalation (3+3 design) was based on CTCAE V4 toxicities. The primary objective was to define the recommended phase 2 dose of LY2780301. Secondary objectives were PK, PD (pS6 in skin), and preliminary antitumor activity. Results: 32 patients were treated at dose levels from 100mg – 500mg total daily dose. LY2780301 was well tolerated at all dose levels No dose-limiting toxicities were observed in cycle 1. Common toxicities potentially related to study therapy included: constipation (7pts), fatigue (5pts), nausea (4pts), diarrhea (3pts), and vomiting (3pts). Grade 3/4 toxicities potentially related to study therapy were: anemia (3pts), increased ALT/AST (1pt), and increased GGT (1pt). Average number of cycles received across all dose levels was 2. There were no partial or complete responses; best response observed was prolonged stable disease for 6.5 cycles. Plasma exposures of LY278030 exceeded predicted efficacious dose in all pts (AUC 0-24H &gt;25000 ng*hr/mL). Increase in exposure with dose was observed (QD or BID) with significant inter-pt variability. The exposure increase was less than linear with dose. Preliminary PK parameters are CL/F 4.5L/h and t1/2 of 24 hours. pS6 assessment in skin showed inhibition in &gt; 50% of pts receiving 400-500 mg per day. Positive correlation with the exposure of the didesmethyl metabolite was observed. Conclusions: LY2780301displayed favorable safety profile, and high PK exposures in the range of efficacious dose. The recommended dose will be defined in the range between 300 and 500 mg. Further exploration of PK/PD effect in mesothelioma is ongoing.
Spectroscopic Photoacoustic Molecular Imaging of Breast Cancer using a B7-H3-targeted ICG Contrast Agent
Authors: Katheryne E. Wilson, Sunitha V. Bachawal, Lotfi Abou-Elkacem, Kristen Jensen, Steven Machtaler, Lu Tian, Jürgen K. Willmann
Journal: Theranostics (2017)

Purpose: Breast cancer imaging methods lack diagnostic accuracy, in particular for patients with dense breast tissue, and improved techniques are critically needed.The purpose of this study was to evaluate antibody-indocyanine green (ICG) conjugates, which undergo dynamic absorption spectrum shifts after cellular endocytosis and degradation, and spectroscopic photoacoustic (sPA) imaging to differentiate normal breast tissue from breast cancer by imaging B7-H3, a novel breast cancer associated molecular target.Methods: Quantitative immunohistochemical staining of endothelial and epithelial B7-H3 expression was assessed in 279 human breast tissue samples, including normal (n=53), benign lesions (11 subtypes, n=129), and breast cancers (4 subtypes, n=97).After absorption spectra of intracellular and degraded B7-H3-ICG and Isotype control-ICG (Iso-ICG) were characterized, sPA imaging in a transgenic murine breast cancer model (FVB/N-Tg(MMTVPyMT)634Mul) was performed and compared to imaging of control conditions [B7-H3-ICG in tumor negative animals (n=60), Iso-ICG (n=30), blocking B7-H3+B7-H3-ICG (n=20), and free ICG (n=20)] and validated with ex vivo histological analysis.Results: Immunostaining showed differential B7-H3 expression on both the endothelium and tumor epithelium in human breast cancer with an area under the ROC curve of 0.93 to differentiate breast cancer vs non-cancer.Combined in vitro/in vivo imaging showed that sPA allowed specific B7-H3-ICG detection down to the 13 nM concentration and differentiation from Iso-ICG.sPA molecular imaging of B7-H3-ICG showed a 3.01-fold (P<0.01)increase in molecular B7-H3-ICG signal in tumors compared to control conditions.Conclusions: B7-H3 is a promising target for both vascular and epithelial sPA imaging of breast cancer.Leveraging antibody-ICG contrast agents and their dynamic optical absorption spectra allows for highly specific sPA imaging of breast cancer.
Heart Failure With Reduced Ejection Fraction in Human Immunodeficiency Virus Infection
Authors: Gerald S. Bloomfield, G. Michael Felker
Journal: JAMA Cardiology (2017)

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 Cardiology 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 Cardiology journal
Prognostic significance of VEGF receptor I and II expression in patients with acute myeloid leukemia
Authors: S. A. Patel, J. Yang, G. Kashef, K. Kojouri, M. Hashmi, G. B. Selby, H. Ozer, R. Kamble, M. A. Kharfan-Dabaja
Journal: Journal of Clinical Oncology (2004)

9623 Background: Advances in the molecular biology of AML have confirmed the negative prognostic value of angiogenesis; and uncovered potential molecular targets including VEGF. VEGF stimulation is mediated by various receptor tyrosine kinases like VEGFR-I(Flt-1) and VEGFR-II(KDR/Flk-1), among others. Methods: A retrospective analysis (01/94–11/03) evaluating the prognostic significance of expression of VEGF receptor I/II on bone marrows (BM) of patients (pts) with AML was performed. Both medical records and BM biopsy samples were required for analysis. 62 pts were identified; 40 were excluded due to unavailable records and BM. 22 pts were eligible for analysis with a median age of 48.5 y (20–90), M/F(15/7). Expression of VEGFR-I and VEGFR-II was determined by immunohistochemistry with a monoclonal Ab against the Flt-1 and KDR/Flk-1 respectively. Staining ≥ 1% of myeloid blasts was defined as positive. Overall survival (OS) is defined as time interval in months (mos) from date of diagnosis to date of death, or if patient alive, through end of study. Log-rank statistic was used to compare OS among groups. A two-tailed p value of < 0.05 was considered significant. Results: Median survival (MS) among VEGFR-I(−) pts(n= 17, 8/17 died) was longer compared to VEGFR-I(+) pts (n= 5, 3/5 died)[26 vs. 11 mos, p=0.5244]. Similarly, MS among VEGFR-II (−) pts (n=16, 6/16 died) was longer compared to VEGFR-II (+) pts (n=6, 5/6 died) [not reached (NR) vs. 18.5 mos, p=0.1445]. Subsequently, we compared MS for the group VEGFR-I(−) /VEGFR-II(−) (n= 13, 5/13 died) vs.VEGFR-I and/or VEGFR-II (+) (n=9, 6/9 died)[NR vs. 26 mos, p=0.3493]. Finally, MS for the group VEGFR-I(−) /VEGFR-II(−) (n= 13, 5/13 died) was significantly longer than the group VEGFR-I(+) /VEGFR-II(+) (n=2, 2/2 died) [NR vs. 7 months, p=0.0378]. Conclusion: Our study provides evidence of the negative prognostic significance of dual expression of VEGFR-I and II in AML. Expression of either VEGFR-I or VEGFR-II suggests a trend for worse outcome that did not reach statistical significance perhaps due to the limited size of our sample. Our study highlights the importance of VEGFR-I and VEGFR-II as potential targets for therapy in AML. No significant financial relationships to disclose.
Improving oral chemotherapy documentation in a breast medical oncology outpatient practice.
Authors: Aarti Sonia Bhardwaj, Katherine FitzPatrick, Kathleen Hynes, David Bivens, Micheal McLean, Jenna Enson, Marilyn J. Hammer, Randall F. Holcombe
Journal: Journal of Clinical Oncology (2017)

71 Background: The safe administration of oral chemotherapy is a challenging yet important process to ensure patient safety. Comprehensive initial and subsequent documentation especially regarding dosage and toxicities in the plan of care for patients receiving oral chemotherapy can be instrumental in improving patient safety by ensuring comprehensive health information is available to all health team members. Methods: We are undertaking a rapid cycle improvement project to improve initial and subsequent documentation of new oral chemotherapy care plans by increasing our compliance with the number of components of an oral chemotherapy care plan (as outlined by QOPI’s 13 standards). We performed a baseline chart audit to confirm our current low level of compliance. We then created a process to use smart phrases that include necessary QOPI elements for progress notes upon new prescription of oral chemotherapy as well as smart phrases for subsequent patient initiated telephone encounters regarding oral chemotherapy, that feed into a universal “med note” location. Post implementation, we will perform a chart audit to determine our updated compliance. Staff satisfaction with the old vs the new process will be compared to verify that we have created a more efficient system to answer patient questions regarding oral chemotherapy. Results: Baseline chart audit revealed the number of components of an oral chemotherapy care plan (as per QOPI standards) documented in the EMR was 43% (i.e contained 5/13 components). A Pareto chart confirmed that underutilization of current EMR resources and lack of knowledge regarding QOPI standards were common reasons for poor oral chemotherapy documentation. Implementation of smart phrases for documentation for initial patient encounters and subsequent telephone encounters is currently in process to determine our new level of compliance with QOPI standards for a sustained and meaningful improvement. Conclusions: This quality improvement initiative was designed to improve patient safety by enhancing documentation of an oral chemotherapy care plan in the EMR and also to create a more efficient system to answer and document patient phone calls regarding oral chemotherapy.
Prostate cancer screening: Rise and fall?
Authors: François Eisinger, Jean Francois Morere, Chantal Touboul, Xavier B. Pivot, Yvan Coscas, Jean-Yves Blay, Christine Lhomel, Jérôme Viguier
Journal: Journal of Clinical Oncology (2013)

1562 Background: Our previously published data showed a fast increasing rate of prostate cancer screening in men aged 50-74 from 36% in 2005 to 48% in 2008. According to their expressed wish either to continue to be tested annually or to start prostate cancer screening, the rate of testing was expected to rise to 70% in 2011. We report here the actual rate of prostate cancer screening. Methods: Three nationwide observational surveys (EDIFICE opinion polls) were carried out by telephone (2005, 2008, and 2011). The target was a representative sample of more than 1,500 subjects living in France and aged 40-74. Precision of results for the samples was + 3.2% with a 95% confidence interval (CI). Results: In this survey population (men aged 50-74), the rate of screening reported remained stable between 2008 and 2011 (48% and 49% respectively). However, there were some differences according to age with a decreasing rate for men aged 50 to 59 years: 44% in 2008 vs 37% in 2011 (p=0.11) and an increasing rate for men aged 60 to 74 years: 53% in 2008 vs 62% in 2011 (p=0.04). Comparing privileged versus underserved populations, significant differences were found with a relative decrease in attendance of those of higher professional status (p=0.034) and from higher income groups (p=0.015); the difference was not significant for educational attainment (p=0.147). For household with a monthly income above 2500 €, the screening rate decreased from 61% in 2008 to 51% in 2011, while for an income below 2500 €, the rate increased from 36% in 2008 to 44% in 2011. Conclusions: A plateau or even reduction in prostate cancer screening is observed, possibly due to a progressive recognition of the controversy on prostate cancer screening by the population, which previously engaged only the experts. After previously being more likely to take up prostate cancer screening, the backlash is mainly observed in the younger, wealthier groups. This “fall”, according to many health agencies should not be seen as a health threat. Health institutions and medical practitioners should, however, be aware of this trend, to avoid general mistrust of cancer screening as a whole.
Outcomes of young patients with Waldenstrom macroglobulinemia (WM).
Authors: Nishanth Vallumsetla, Jonas Paludo, Stephen Maxted Ansell, Morie A. Gertz, Angela Dispenzieri, Martha Lacy, Francis Buadi, David Dingli, Suzanne R. Hayman, Ronald S. Go, Robert A. Kyle, Vincent Rajkumar, Shaji Kumar, Prashant Kapoor
Journal: Journal of Clinical Oncology (2014)

8609 Background: WMis infrequentin young population, and data in patients (pts) ≤50 years of age are sparse. We present outcomes of a large cohort of young WM pts seen at Mayo Clinic, Rochester between 01/2000-12/2013. Methods: Sixty-nine (10.7%) of 640 consecutive pts were ≤50 years at diagnosis. Overall survival (OS) was calculated with Kaplan-Meier method and years of life lost were computed based on expected mortality for the age group. Results: Males constituted 65% of pts. Nine (14%) pts had familial WM. Patient characteristics and therapy related information are tabulated. Median follow up (FU) was 8years from diagnosis and 7.8 years from initial therapy. Eight-year OS was 84%from frontline therapy (median 14.8 years). Of all deaths (n=18), only 1 was non WM related. Over 30 years of FU, the average years of life lost were 10.8 years. Stem cells were successfully harvested from 10 of the 12 attempted. Only 5 (8%) pts underwent autologous stem cell transplantation (ASCT), one of whom had ASCT post transformation. In the non-transformed pts, ASCT was used as salvage therapy after a median of 6.5 regimens. Among these pts, median FU was 4.6 years from ASCT and median OS was not reached. Of 67 pts treated, 65 (97%) received rituximab (R) during their disease course. Overall, 6/25 (24%) who received nucleoside analogs (NA) developed therapy related myelodysplastic syndrome (t-MDS) or transformed lymphoma compared to 1/42 (2%) who received non NA based therapy (p=0.009). These events occurred at a median of 7.6 years from NA therapy. Median number of regimens utilized was 3.75. Conclusions: Despite its indolent course, WM remains a major cause of morbidity and mortality in young pts with this cancer. NA-based therapy is best avoided in this population due to high risk of developing t-MDS or transformation. Although effective, ASCT appears to be an underutilized approach. Parameters Median (Range) Symptoms/signs % Initial therapy % Age (years) 45 (31-50) Constitutional 43 R Monotherapy 24 Hemoglobin (g/dL) 10 ( 5.4-14.6) Paresthesias 17 DRC 15 Platelet count (109/L) 220 (80-501) Hyperviscosity 23 NA-based 22 β2 Microglobulin (mcg/ml) 2.7 (1.3-7.8) Lymphadenopathy 29 Chlorambucil-based 10 IgM (mg/dl) 4501 (68-14400) Splenomegaly 14 Other therapies 28
Acceptance of Surgical Treatment for Adolescent Obesity
Authors: Simon Erridge, Swathikan Chidambaram, En Lin Goh
Journal: JAMA Surgery (2017)

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 Surgery 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 Surgery journal
In Reply
Authors: Jennifer L. Steel, T. Clark Gamblin, David A. Geller, Marion C. Olek, Brian I. Carr
Journal: Journal of Clinical Oncology (2007)

which these relationships are found.A more parsimonious explanation is that associations are primarily due to measurement confounds between health status (objective and perceived) and affect.This explanation requires many fewer assumptions and is increasingly being accepted. 11 Finally, the accompanying Editorial uses these results to call for more aggressive treatment of depression and depressive symptoms.The prevalence of major depression, the condition for which there are empirically based treatment guidelines, is certainly lower in this and other samples than what one would infer from equating elevated scores with the disorder.Recognition and treatment of major depressive disorder is a realistic goal in the cancer care center.Also, research efforts are needed to demonstrate efficacious treatments for the more diffuse construct of "elevated distress" given the lack of evidence for the efficacy of antidepressants in the absence of a diagnosis of major depression.Patients need accurate information on which to base their decisions concerning psychological treatment, and the rationale with which they are presented should not be based on premature claims for survival and immunologic benefits.