tbuckley/cabot-search huggingface dataset:
CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia
Authors: Jeffrey E. Lancet, Geoffrey L. Uy, Jorge E. Cortes, Laura F. Newell, Tara L. Lin, Ellen K. Ritchie, Robert K. Stuart, Stephen A. Strickland, Donna Hogge, Scott R. Solomon, Richard M. Stone, Dale L. Bixby, Jonathan E. Kolitz, Gary J. Schiller, Matthew J. Wieduwilt, Daniel H. Ryan, Antje Hoering, Kamalika Banerjee, Michael Chiarella, Arthur C. Louie, Bruno C. Medeiros
Journal: Journal of Clinical Oncology (2018)

Purpose CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin that delivers a synergistic 5:1 drug ratio into leukemia cells to a greater extent than normal bone marrow cells. Prior clinical studies demonstrated a sustained drug ratio and exposure in vivo and prolonged survival versus standard-of-care cytarabine plus daunorubicin chemotherapy (7+3 regimen) in older patients with newly diagnosed secondary acute myeloid leukemia (sAML). Patients and Methods In this open-label, randomized, phase III trial, 309 patients age 60 to 75 years with newly diagnosed high-risk/sAML received one to two induction cycles of CPX-351 or 7+3 followed by consolidation therapy with a similar regimen. The primary end point was overall survival. Results CPX-351 significantly improved median overall survival versus 7+3 (9.56 v 5.95 months; hazard ratio, 0.69; 95% CI, 0.52 to 0.90; one-sided P = .003). Overall remission rate was also significantly higher with CPX-351 versus 7+3 (47.7% v 33.3%; two-sided P = .016). Improved outcomes were observed across age-groups and AML subtypes. The incidences of nonhematologic adverse events were comparable between arms, despite a longer treatment phase and prolonged time to neutrophil and platelet count recovery with CPX-351. Early mortality rates with CPX-351 and 7+3 were 5.9% and 10.6% (two-sided P = .149) through day 30 and 13.7% and 21.2% (two-sided P = .097) through day 60. Conclusion CPX-351 treatment is associated with significantly longer survival compared with conventional 7+3 in older adults with newly diagnosed sAML. The safety profile of CPX-351 was similar to that of conventional 7+3 therapy.
Novel therapies in urothelial carcinoma: a biomarker-driven approach
Authors: G. Iyer, J.E. Rosenberg
Journal: Annals of Oncology (2018)

Urothelial malignancies, including carcinomas of the bladder, ureters, and renal pelvis comprised ∼8% of new cancer cases in the USA in 2016. In the metastatic setting, 15% of patients exhibit long-term survival following cisplatin-based chemotherapy and in patients with recurrent disease, response rates to second-line chemotherapy are generally 15%-20% with a 3-month progression-free survival. However, recent advances in immunotherapy represent an opportunity to significantly improve patient outcomes. Moreover, the advent of next-generation sequencing has resulted in both an improved understanding of the fundamental genetic changes that characterize urothelial carcinoma (UC) and identification of several candidate biomarkers of response to various therapies. Incorporation of prospective genotyping into clinical trials will allow for the identification and enrichment of patients most likely to respond to specific targeted therapies and chemotherapy. Combining different therapeutic classes to enhance outcomes is also an area of active research in UC.
Electrocardiographic Abnormalities in Patients With Hutchinson-Gilford Progeria Syndrome
Authors: David Filgueiras-Rama, José Rivera Torres, Vicente Andrés
Journal: JAMA Cardiology (2018)

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
Assessment of Pragmatism in Recently Published Randomized Clinical Trials
Authors: Perrine Janiaud, Rafael Dal-Ré, John P. A. Ioannidis
Journal: JAMA Internal Medicine (2018)

Discussion | The recommendation by the ACIP was informed by the Centers for Disease Control and Prevention model, which assumed a high probability of postherpetic neuralgia and 100% adherence. 1In this modeling study, we found that neither ACIP recommendation would be cost-effective, unless adherence to the 2-dose regimen approached 100%.Using a more realistic estimate, we found it cost-effective to begin vaccination at 55 years of age and offer ZVL recipients a booster after 5 years.This discrepancy highlights the cautions required in interpreting costeffectiveness findings and the importance of scrutinizing underlying assumptions.Adherence of 100% is unlikely for several reasons.The coverage of single-dose ZVL was only 30% in 2015, partly owing to cost. 5 At $280 for the series, RZV is now the most expensive adult vaccine.Reimbursement will also be an issue, especially in people 65 years or older, because Medicare covers zoster vaccine under part D with substantial copayments. 6The 2-dose regimen will require an additional office visit, potentially resulting in extra work loss.Finally, the 6% of patients with a severe local reaction after the first dose may be particularly hesitant to return. Conclusions |The new recommendations of the ACIP for RZV do not appear to be cost-effective unless 100% of patients receive both doses.Given our best estimates, vaccination with RZV at 55 years of age and a booster at least 5 years after ZVL would offer better value.Clinicians may consider vaccination earlier for patients who are very likely to comply with a second dose.In all cases, efforts should be made to enhance compliance with the full series.
Recurrent/Residual Intracranial Phosphaturic Mesenchymal Tumor Revealed on 68Ga-DOTATATE PET/CT
Authors: Jie Ding, Ling Wang, Shu Zhang, Fang Li, Li Huo
Journal: Clinical Nuclear Medicine (2018)

Phosphaturic mesenchymal tumors are benign tumors causing majority of tumor-induced osteomalacia. These tumors are most commonly located in the lower extremities followed by craniofacial regions. However, intracranial lesion is very rare. Here we describe Ga-DOTATATE PET/CT findings of a recurrent intracranial phosphaturic mesenchymal tumor in a 68 year old woman.
Passive Smoking Induces Atherogenic Changes in Low-Density Lipoprotein
Authors: MiiaValkonen, TimoKuusi
Journal: Circulation (1998)

Background—According to the American Heart Association, passive smoking is an important risk factor for coronary heart disease (CHD), but the mechanisms underlying this association are not fully understood. We studied the acute effect of passive smoking on the factors that influence the development of CHD: the antioxidant defense of human serum, the extent of lipid peroxidation, and the accumulation of LDL cholesterol in cultured human macrophages, the precursors of foam cells in atherosclerotic lesions. Methods and Results—Blood samples were collected during 2 ordinary working days from healthy, nonsmoking subjects (n=10) before and after (up to 5.5 hours) spending half an hour in a smoke-free area (day 1) or in a room for smokers (day 2). Passive smoking caused an acute decrease (1.5 hours after exposure) in serum ascorbic acid (P<.001) and in serum antioxidant defense (P<.001), a decreased capacity of LDL to resist oxidation (P<.01), and the appearance of increased amounts of lipid peroxidation end pro...
<i>Staphylococcus aureus</i> small colony variants: Prevalence in chronic rhinosinusitis and induction by antibiotics
Authors: Guimin Zhang, Yin Zhao, Andrew J. Hayes, Alkis J. Psaltis, Peter‐John Wormald, Sarah Vreugde
Journal: Allergy (2018)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Impact of immunopathology on the antituberculous activity of pyrazinamide
Authors: Landry Blanc, Jansy Passiflora Sarathy, Nadine Alvarez Cabrera, Paul O’Brien, Isabela Dias-Freedman, Marizel Mina, James Sacchettini, Radojka M. Savic, Martin Gengenbacher, Brendan K. Podell, Brendan Prideaux, Thomas Ioerger, Thomas Dick, Véronique Dartois
Journal: The Journal of Experimental Medicine (2018)

In the 1970s, inclusion of pyrazinamide (PZA) in the drug regimen of tuberculosis (TB) patients for the first 2 mo achieved a drastic reduction of therapy duration. Until now, however, the mechanisms underlying PZA’s unique contribution to efficacy have remained controversial, and animal efficacy data vary across species. To understand how PZA kills bacterial populations present in critical lung lesion compartments, we first characterized a rabbit model of active TB, showing striking similarities in lesion types and fates to nonhuman primate models deemed the most appropriate surrogates of human TB. We next employed this model with lesion-centric molecular and bacteriology readouts to demonstrate that PZA exhibits potent activity against Mycobacterium tuberculosis residing in difficult-to-sterilize necrotic lesions. Our data also indicate that PZA is slow acting, suggesting that PZA administration beyond the first 2 mo may accelerate the cure. In conclusion, we provide a pharmacodynamic explanation for PZA’s treatment-shortening effect and deliver new tools to dissect the contribution of immune response versus drug at the lesion level.
Impaired Production and Diurnal Regulation of Vascular RvD <sub>n-3 DPA</sub> Increase Systemic Inflammation and Cardiovascular Disease
Authors: Romain A. Colas, Patricia R. Souza, Mary E. Walker, Maudrian Burton, Zbigniew Zasłona, Annie M. Curtis, Raquel M. Marques, Jesmond Dalli
Journal: Circulation Research (2018)

Diurnal mechanisms are central to regulating host responses. Recent studies uncovered a novel family of mediators termed as specialized proresolving mediators that terminate inflammation without interfering with the immune response.Herein, we investigated the diurnal regulation of specialized proresolving mediators in humans and their role in controlling peripheral blood leukocyte and platelet activation.Using lipid mediator profiling and healthy volunteers, we found that plasma concentrations of n-3 docosapentaenoic acid-derived D-series resolvins (RvDn-3 DPA) were regulated in a diurnal manner. The production and regulation of these mediators was markedly altered in patients at risk of myocardial infarct. These changes were associated with decreased 5-lipoxygenase expression and activity, as well as increased systemic adenosine concentrations. We also found a significant negative correlation between plasma RvDn-3 DPA and markers of platelet, monocyte, and neutrophil activation, including CD63 and CD11b. Incubation of RvDn-3 DPA with peripheral blood from healthy volunteers and patients with cardiovascular disease significantly and dose-dependently decreased platelet and leukocyte activation. Furthermore, administration of RvD5n-3 DPA to ApoE-/- (apolipoprotein E deficient) mice significantly reduced platelet-leukocyte aggregates, vascular thromboxane B2 concentrations, and aortic lesions.These results demonstrate that peripheral blood RvDn-3 DPA are diurnally regulated in humans, and dysregulation in the production of these mediators may lead to cardiovascular disease.
Direct burden of oncologic disease in a socialized health care system: Using acute myeloid leukemia as an example.
Authors: Marta Isabel De Correia Pereira, Emilia Cortesao, Ana Espadana, Gilberto P Marques, Catarina Geraldes, Adriana Teixeira
Journal: Journal of Clinical Oncology (2012)

e12040 Background: Portugal has a socialized national healthcare system (NHS), rated 12 th overall by WHO (2000), that exempts oncologic patients from paying the direct costs of treatment. It has a per capita Gross Domestic Product of $22 699 (International Monetary Fund, 2011), less than 50% of the US, and was severely affected by the international Financial Crisis, requiring a bail-out; in this scenario, the state budget for health for 2012 is approximately $9900 million. Adult acute myeloid leukemia (AML) is a relatively rare cancer, with standardized non-surgical inpatient treatment protocols (outside clinical trials) that are subject to little variation between centers and over time, characteristics that make it an ideal example to evaluate the impact of oncologic disease on a socialized healthcare system. Methods: We reviewed all new diagnoses of AML over a five-year period (2006 to 2010) in one of the 7 national centers that treat adult AML, to estimate the yearly expenditure with direct costs. Results: Over the period considered, 192 new adult cases were diagnosed (38.4 cases per year, 47% male), with a median age of 63 years; 43.8% were 65 or over. The 2009 National Directive assumes the daily cost of one hospitalization for uncomplicated adult “acute leukemia” [sic] to be $1250, with an average hospital stay of 12.2 days, amounting to $15 250; minor complications increase this to $2400 and 19.5 days, and major complications to $6 480 times 25 days, or $162 000. An allogeneic HSC transplant (allo-HSC) costs $9 605 daily, over 35.5 days, or $340 800. Assuming induction and one cycle of consolidation in under-65 cases, this Hospital would spend between $700 000 (no complications in either cycle) and $7 million (all cases with major complications in both cycles) on new cases per year. Additional cycles and allo-HSC push the estimate towards $1-10 million. Conclusions: While chronic metabolic, cardiovascular and respiratory diseases consume the bulk of resources, the burden of oncologic disease on a socialized NHS is marked. AML ideally exemplifies how a small number of patients can consume vast resources: as this estimate shows, Portugal could expect to spend $7-70 million of the 2012 health budget on new cases of AML alone.
Venous Thromboembolism Incidence and Prophylaxis Use After Gastrectomy Among Korean Patients With Gastric Adenocarcinoma
Authors: Yoon Ju Jung, Ho Seok Seo, Cho Hyun Park, Hae Myung Jeon, Ji-Il Kim, Hyeon Woo Yim, Kyo Young Song
Journal: JAMA Surgery (2018)

The guidelines by the National Comprehensive Cancer Network and the American Society for Clinical Oncology recommend the routine use of thromboprophylaxis for patients with gastric adenocarcinoma. However, many physicians in Asian countries use venous thromboembolism (VTE) prophylaxis much less often because of the perceived lower VTE incidence in this population.To evaluate the incidence of postgastrectomy VTE in Korean patients with gastric adenocarcinoma, and to identify the complications and evaluate the efficacy and safety of VTE prevention methods.The Optimal Prophylactic Method for Venous Thromboembolism After Gastrectomy in Korean Patients (PROTECTOR) randomized clinical trial was conducted between August 1, 2011, and March 31, 2015. Patients with histologically confirmed gastric adenocarcinoma presenting to a single center (Seoul St Mary's Hospital in Seoul, South Korea) were enrolled. Patients were randomized to either an intermittent pneumatic compression (IPC)-only group or an IPC+low-molecular-weight (LMW) heparin sodium group. The data were analyzed on intention-to-treat and per protocol bases. Data analysis was performed from April 1, 2016, to October 30, 2017.Venous thromboembolism incidence was the primary outcome. Postoperative complications, particularly those associated with VTE prophylaxis methods, were the secondary end point.Of the 682 patients enrolled and randomized, 447 (65.5%) were male and 245 (34.5%) were female, with a mean (SD) age of 57.67 (12.94) years. Among the 666 patients included in the analysis, the overall incidence of VTE was 2.1%. The incidence of VTE was statistically significantly higher in the IPC-only group compared with the IPC+LMW heparin group (3.6%; 95% CI, 2.05%-6.14% vs 0.6%; 95% CI, 0.17%-2.18%; P = .008). Among the 14 patients (2.1%) with VTE, 13 were asymptomatic and received a deep vein thrombosis diagnosis, whereas 1 patient received a symptomatic pulmonary thromboembolism diagnosis. The overall incidence of bleeding complications was 5.1%. The incidence of bleeding complications was significantly higher in the IPC+LMW heparin group compared with the IPC-only group (9.1% vs 1.2%; P < .001). No cases of VTE-associated mortality were noted.Use of IPC alone is inferior to the use of IPC+LMW heparin in preventing postoperative VTE. Because LMW heparin is associated with a high bleeding risk, further study is needed to stratify the patients at high risk for perioperative development of VTE.ClinicalTrials.gov Identifier: NCT01448746.
Trends in Insurance Coverage for Gender-Affirming Surgeries
Authors: Justin D. Arnold, Amy E. Nelson, Erin M. Loubier
Journal: JAMA Surgery (2018)

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
Assessment of microsatellite instability (MSI) in cell free DNA (cfDNA) of colorectal cancers (CRC) patients (pts).
Authors: Afsaneh Barzi, Mihaela Campan, Jonas Petterson, Lan Du, Tiffany Long, Louis Dubeau, Heinz-Josef Lenz, Pamela Ward
Journal: Journal of Clinical Oncology (2018)

672 Background: While there is accumulating evidence that tumor specific mutations can be accurately detected in cfDNA, the determination of MSI status in cfDNA has not been investigated, perhaps because the complexity of detecting tumor instability embedded within stutter amplification patterns generated from normal cfDNA was considered too challenging to allow the detection of altered microsatellite profiles. We explored the possibility of detecting MSI in cfDNA. Methods: Circulating cfDNA was isolated from Streck tubes from 13 patients with CRC; 6 pts had serial collections. Isolation and testing of cfDNA for MSI was performed using kits purchased from Promega. Microsatellite alterations were scored by comparing the amplicon stutter profiles of 5 mononucleotide markers generated from cfDNA to those present in genomic DNA extracted from buffy coats from the same pts. MSI was diagnosed based on a shift in the size of a predominant stutter peak together with a commensurate shift in the stutter profile resulting in the appearance of at least one new stutter in tumor-derived DNA compared to matched germline DNA. MSI was scored high when 30% or more of the markers showed MSI or low if present in less than 30% of the biomarkers examined. Results: No MSI was detected in 3 pts with microsatellite stable tumors and 2 Lynch syndrome pts with no evidence of disease. Five of six pts with MSI high tumors (sporadic and Lynch syndrome) had a detectable MSI high biomarker profile in cfDNA at baseline. Four pts with positive MSI in cfDNA started immunotherapy and had a decline in the relative amounts of tumor-derived microsatellite alleles in their subsequent specimens. The pt with MSI high in the primary tumor and no MSI in cfDNA had rapid progression on immunotherapy. Two other pts with MSI high who responded deeply to check point inhibitors had no evidence of MSI in cfDNA at the time of their specimen collection. In each case with MSI in cfDNA, the electrophoretic profile matched that in the respective primary tumor. Conclusions: Detection of MSI in cfDNA is feasible and may be reflective of burden of the disease. A prospective study to establish the validity of cfDNA in the diagnosis and follow up care in pts with metastatic CRC is planned.
An open label, randomized, parallel, phase II trial to evaluate the efficacy and safety of cremophor-free, polymeric micelle formulation of paclitaxel compared to paclitaxel in subjects with ovarian cancer.
Authors: Yong-Man Kim, Shin-Wha Lee, Chi Heum Cho, Soo-Young Hur, Byoung-Gie Kim, Jae Hoon Kim, Seung Cheol Kim, Seok-Mo Kim, Young-Tae Kim, Hee Sug Ryu, Soon-Beom Kang
Journal: Journal of Clinical Oncology (2013)

5568 Background: Cremorphor EL, used to enhance drug solubility, may add to paclitaxel’s toxicities such as hypersensitivity reactions or peripheral neuropathy. This multi-institutional phase II trial is to evaluate the efficacy and safety of Cremophor-Free, Polymeric Micelle Formulation of Paclitaxel (Genexol-PM) compared to Paclitaxel (Genexol) as a combined chemotherapy with carboplatin in patients with advanced epithelial ovarian cancer. Methods: In this phase II, randomized, parallel study, patients with FIGO stage IC-IV epithelial ovarian cancer after debulking surgery received intravenously Genexol-PM 260 mg/m2 or Genexol 175 mg/m2 combined with carboplatin iv (AUC 5) on day 1 of every 3-week cycle for a maximum of six cycles. The primary endpoint was composite response by GCIG CA-125 Response and Response Evaluation Criteria In Solid Tumors (RECIST). Secondary and exploratory endpoints included overall survival, progression-free survival, time to tumor progression, and safety and tolerability. Results: A total of 102 patients were randomized to Genexol-PM plus carboplatin (n = 51) or Genexol plus carboplatin (n = 51). Composite response rate in patients with or without measurable disease was 88.0% in the Genexol-PM plus carboplatin group and 77.1% in the Genexol plus carboplatin group. Noninferiority of Genexol-PM plus carboplatin compared with Genexol plus carboplatin was confirmed for composite response rate by CA-125/RECIST criteria. There were no differences in progression-free survival and overall tumor progression between the groups. Although there was a higher rate of grade 3 neutropenia in the Genexol-PM plus carboplatin group, the overall rate of hemodynamic adverse events was comparable between the 2 groups. There was no difference in peripheral neuropathy and hypersensitivity. No unexpected safety concerns were identified in this study. Conclusions: High-dose of Genexol-PM in combination with carboplatin was well tolerated, and its response rate was noninferior to that of Genexol plus carboplatin in patients with advanced epithelial ovarian cancer. Clinical trial information: NCT01276548.