tbuckley/cabot-search huggingface dataset:
Early Parenteral Nutrition in Critical Illness
Authors: Emanuele Cereda, Carlo Marena, Riccardo Caccialanza
Journal: JAMA (2013)

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Published glioblastoma clinical trials from 1980 to 2013: Lessons from the past and for the future.
Authors: Stuart A. Grossman, Susannah G. Ellsworth
Journal: Journal of Clinical Oncology (2016)

e13522 Background: Recently, the NCI and industry have strongly encouraged the conduct of randomized phase II glioblastoma (GBM) trials in an attempt to reduce false positive results and prevent ineffective therapies from advancing to expensive and lengthy phase III trials. However, inclusion of an internal control arm is unappealing to patients and physicians and increases the size of trials thereby reducing the number of novel therapies that can be studied. This analysis was conducted to document study design and outcomes over a 33 year period. Methods: Peer reviewed publications from 1980 to 2013 were identified in Pubmed using the search terms "glioblastoma" and "Phase I, II or III". The search was restricted to papers in English; pediatric studies and those enrolling multiple histologies were excluded. Data from each study was recorded regarding: 1) study phase, 2) newly diagnosed or recurrent disease, 3) number of accrued patients, 4) experimental agents/approach used, and 5) study location. Results: 570 studies (15 pilot, 136 phase I, 317 phase II, 68 phase I/II, and 30 phase III) were identified using the above criteria. 32,758 patients were enrolled of which 19,670 were accrued to phase I/II studies. Of the phase I/II studies, 20 (5%) were randomized (2,882 patients) and 365 (95%) were single-arm studies (16,788 patients); 170 (44%) were for newly diagnosed GBM, 200 (52%) for recurrent disease, and 14 (4%) for either. 53% of trials were conducted in the US. A wide variety of agents/approaches were studied including systemic and local chemotherapy, radiosensitizers, immunotherapy, gene therapy, and cytostatic, anti-angiogenic, and anti-inflammatory agents. Conclusions: Clinical GBM trials conducted over a period of 33 years, which accrued almost 33,000 patients, identified only one novel agent (temozolomide) which modestly improves median survival (12 to 14.6 months) and lacks curative potential. Given: 1) the very low rate of therapeutic success, 2) the available historical controls, and 3) that < 5% of GBM patients enter clinical trials, single arm phase II studies might maximize accruals and most efficiently screen novel agents/approaches to identify potentially active therapies for this refractory malignancy.
Assessing Homicides by and of U.S. Law-Enforcement Officers
Authors: Alex E. Crosby, Bridget Lyons
Journal: New England Journal of Medicine (2016)

“Legal intervention deaths” of civilians — cases in which someone is killed by a law-enforcement or other peace officer while that officer is on duty — and occupational homicides of law-enforcement officers have garnered increasing attention in the United States, owing to numerous recent high-profile incidents. These events are not only devastating to the victims’ families and the directly affected communities or neighborhoods; they also erode the relationship between law-enforcement agencies and the diverse populations they serve. Though these killings account for a small percentage of total U.S. homicides, they represent a significant public health burden and can incite further . . .
68Ga-PSMA-11 Dynamic PET/CT Imaging in Primary Prostate Cancer
Authors: Christos Sachpekidis, Klaus Kopka, Matthias Eder, Boris A. Hadaschik, Martin T. Freitag, Leyun Pan, Uwe Haberkorn, Antonia Dimitrakopoulou-Strauss
Journal: Clinical Nuclear Medicine (2016)

Purpose The aim of our study is to assess the pharmacokinetics and biodistribution of 68Ga-PSMA-11 in patients suffering from primary prostate cancer (PC) by means of dynamic and whole-body PET/CT. Materials and methods Twenty-four patients with primary, previously untreated PC were enrolled in the study. All patients underwent dynamic PET/CT (dPET/CT) scanning of the pelvis and whole-body PET/CT studies with 68Ga-PSMA-11. The evaluation of dPET/CT studies was based on qualitative evaluation, SUV calculation, and quantitative analysis based on two-tissue compartment modeling and a noncompartmental approach leading to the extraction of fractal dimension (FD). Results A total of 23/24 patients (95.8%) were 68Ga-PSMA-11 positive. In 9/24 patients (37.5%), metastatic lesions were detected. PC-associated lesions demonstrated the following mean values: SUVaverage = 14.3, SUVmax = 23.4, K1 = 0.24 (1/min), k3 = 0.34 (1/min), influx = 0.15 (1/min), and FD = 1.27. The parameters SUVaverage, SUVmax, k3, influx, and FD derived from PC-associated lesions were significantly higher than respective values derived from reference prostate tissue. Time-activity curves derived from PC-associated lesions revealed an increasing 68Ga-PSMA-11 accumulation during dynamic PET acquisition. Correlation analysis revealed a moderate but significant correlation between PSA levels and SUVaverage (r = 0.60) and SUVmax (r = 0.57), and a weak but significant correlation between Gleason score and SUVaverage (r = 0.33) and SUVmax (r = 0.28). Conclusion 68Ga-PSMA-11 PET/CT confirmed its capacity in detecting primary PC with a detection rate of 95.8%. Dynamic PET/CT studies of the pelvis revealed an increase in tracer uptake in PC-associated lesions during the 60 minutes of dynamic PET acquisition, a finding with potential applications in anti-PSMA approaches.
Longitudinal follow-up of quality of life in gastrointestinal cancer patients after curative surgery in South Korea.
Authors: Dae Young Zang, Hyun Ae Jung, Boram Han, Jung Hoon Kim, Dae Ro Choi, Hyeong Su Kim, Geundoo Jang, Jung Hye Kwon, Ho Young Kim, Jung Han Kim, Joo Young Jung, Hyo Jung Kim, Hyunsook Yoon, Young Suk Park, Hyun Woo Lee, Seok Yun Kang, Ji Woong Cho, Hun Ho Song
Journal: Journal of Clinical Oncology (2016)

697 Background: Early detection of cancer and improved treatment have led to higher survival rates and an increasing number of long-term survivors in oncology practice. But there are few longitudinal Quality of Life (QoL) studies in patients who experienced cancer surgery. To investigate the longitudinal change in QoL of elderly gastrointestinal cancer patients, we designed prospective study for QoL in resected gastrointestinal cancer patients. Methods: A prospective longitudinal cohort study was designed. Patients from Hallym, Ajou, and Samsung medical center in South Korea were enrolled consecutively from February to September of 2012. Patients over 55 years old who received curative resection due to gastrointestinal cancer were included. They were given questionnaires every 6 months since then, and we’ve been using EORTC QLQ C-30 as quality of life scale. We selected patients using propensity score matching(PSM). The mean scores of the patients completing the interview at the 3 time points were compared using mixed model. Results: A total of 353 patients with gastrointestinal cancer were interviewed at baseline. We dichotomized patients into 2 groups ( &lt; 70 years old vs. &gt; = 70 years old). There were significant difference in ECOG performance status between 2 groups. After balancing with PSM, we selected 272 patients. Overall QoL did not show significant difference between 2 groups at baseline interview. After repeated interview, the score of global health status, physical functioning, and pain showed significantly higher in younger group ( &lt; 70 years old). But other items didn't show significant difference.Especially patients in both group felt financial difficulty increased. Conclusions: Although the elderly gastrointestinal cancer patients showed lower score in global health status, physical function, they preserved relatively well in other functional status after curative surgery. Most patients felt increased financial burden.
Developing a one-team approach to meet three infusion centers’ staffing needs.
Authors: Laurie Winkelbauer, Ellie Stull, Ann Yager
Journal: Journal of Clinical Oncology (2016)

116 Background: Our cancer service line provides infusion services for oncology patients at three locations. The numbers of chairs vary by location from 10 to 30. Each location has a nurse manager. Staff are hired for specific locations. Hours of operation differ at each location, depending on patient needs. With increasing pressure to streamline operations and maintain productivity, along with challenges of RN vacancies and growing volumes, efforts were needed to coordinate staffing between locations to ensure best utilization of resources. Methods: The leadership team met to identify opportunities for improvement and develop an action plan. Issues identified included: Locations worked in silos to manage staffing issues and patient volumes. Decisions were made without consideration of the other locations; Staff were reluctant to float; Lack of consistent communication and comradery among managers/leads; Critical decisions were made inconsistently by staff; Lack of communication to senior management and physician leadership when capacity and staffing situations were occurring. Strategies were proposed to address the issues. Phone huddles with leadership from all locations are held daily to discuss staffing, patient scheduling and concerns. A tool was developed to assist with decision making related to staffing and patient scheduling. A “One Team” approach was implemented for staffing with the expectation that staff would float to cover staffing needs at the other locations. Processes were standardized across all units to ensure staff feel competent when floating. Results: Several positive outcomes have been noted since changes were implemented 10 months ago. Staff are more willing to float and have bought into the “One Team” concept. Cross coverage of staffing vacancies occurs daily, allowing for better and more cost effective utilization of staff across locations. Decisions to block schedules are made by managers using the developed tool. There is improved awareness of critical staffing and capacity issues by senior leadership and physician leaders. Conclusions: Implementing a One Team staffing approach to cover three infusion center locations increases staff productivity and allows for fluctuations in patient volumes.
High-Throughput Mutational Profiling Of Post-Myeloproliferative Neoplasm Acute Myeloid Leukemia Reveals Frequent Mutations In NRAS In JAK2V617F-Negative Post-MPN AML
Authors: Raajit K. Rampal, Sean M. Devlin, Anna Sophia Mckenney, Kristina M. Knapp, Minal Patel, Kai Wang, Michelle K. Nahas, Roman Yelensky, Geoff A. Otto, Doron Lipson, Philip J. Stephens, Vincent A. Miller, Taghi Manshouri, Srdan Verstovsek, Ross L. Levine
Journal: Blood (2013)
Fewer people are quitting smoking, say NHS stop smoking services
Authors: Susan Mayor
Journal: BMJ (2016)

The numbers of people setting a date to quit smoking or who successfully quit have fallen for the fourth consecutive year, figures from NHS “stop smoking services” in England have shown.1

A total of 382 500 people set a smoking quit date through these NHS services from April 2015 to March 2016. This is 15% lower than the figures reported the previous year by the services, which provide a range of resources in the local community to help people stop smoking, and 37% …
A first-in-human phase 1 study to evaluate the brain-penetrant PI3K/mTOR inhibitor GDC-0084 in patients with progressive or recurrent high-grade glioma.
Authors: Patrick Y. Wen, Timothy Francis Cloughesy, Alan Olivero, Xuyang Lu, Lars Mueller, Alexandre Fernandez Coimbra, Elizabeth Robins Gerstner, Jordi Rodon Ahnert
Journal: Journal of Clinical Oncology (2016)

2012 Background: GDC-0084 is a potent, oral, selective, brain-penetrant small molecule inhibitor of phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) kinase. A first-in-human, phase 1 dose escalation study was conducted in patients with high-grade glioma. Methods: GDC-0084 was administered orally, once daily on a continuous dosing schedule to evaluate the safety and pharmacokinetic (PK) characteristics. Plasma samples for PK analysis were collected on Day 1 and Day 8 or Day 15 of Cycle 1. Fluorodeoxyglucose positron emission tomography (FDG-PET) was performed at baseline and on-treatment. Results: 47 pts enrolled in eight successive dose escalation cohorts (2-65 mg). Dose-limiting toxicities (DLTs) reported were one case of Gr 2 bradycardia and Gr 3 myocardial ischemia (15 mg), Gr 3 stomatitis (45 mg) and two cases of Gr 3 mucosal inflammation (65 mg); the MTD was 45 mg. The most frequent adverse events (AE) attributed to GDC-0084 were fatigue, hyperglycemia, nausea, hypertriglyceridemia, rash, hypophosphatemia, decreased appetite, diarrhea, and stomatitis. PK data showed linear and dose proportional increases in exposure, with a half-life supportive of once daily dosing (t1/2 ~19 hr). At a dose of 45 mg steady-state concentrations were consistent with antitumor activity observed in xenograft models. On FDG-PET, 5 of 27 (18.5%) evaluable patients show a metabolic PR. Additionally, at doses of ≥45 mg QD, a trend towards decreased median SUV in normal brain was observed, suggesting CNS penetration of the study drug. In two available exploratory specimens, GDC-0084 was detected at similar levels in brain tumor and brain tissue, with a brain tissue/tumor to plasma ratio of >1 and >0.5 for total and free drug, respectively. Of the evaluable patients, 26 patients (55.3%) had a best overall response of progressive disease, 19 patients (40.4%) had stable disease. Conclusions: The safety profile demonstrated classic Pi3K/mTOR-inhibitor related AEs. FDG-PET and concentration data from brain tumor tissue suggest that GDC-0084 crosses the blood brain barrier, with a uniform distribution throughout the brain. Clinical trial information: NCT01547546.
Application of multinomial (MN) phase II designs in trials of targeted agents.
Authors: R. Jamal, R. A. Goodwin, D. Tu, W. Walsh, E. A. Eisenhauer
Journal: Journal of Clinical Oncology (2010)

3074 Background: The commonly used Fleming (FL) and Gehan phase II designs make recommendations on activity or early termination based on response rate (RR). The MN design, by incorporating early progression (PD) and RR, has been shown to perform more efficiently than FL or Gehan as assessed by appropriate early stopping for inactivity in phase II trials of cytotoxic agents (Dent S, 2001). Because RR is a controversial endpoint for targeted agent trials, we compared the performance of MN versus FL designs in a series of NCIC CTG phase II trials. Methods: We applied two MN stopping rules (MNA and MNB) to 15 trials evaluating single agent targeted therapies. All trials were conducted using a FL design (Ho: proportion responding pr≤5% vs. Ha: pr≥20%). The hypotheses were as follows: for MNA: Ho: pr≤5% OR proportion with PD pp≥60% vs. Ha pr≥20% and pp≤40%; for MNB: Ho: pr≤5% AND pp≥60% vs. Ha pr≥20% or pp≤40%. The trial would stop at stage 1 by MNA if either the response OR the PD criterion for stopping were met and by MNB only if both the response AND the PD criteria for stopping were met. Sequential patient data were reviewed in each trial to tabulate a stop/go decision at the end of stage 1 based on FL, MNA and MNB and also to determine if each agent was considered active by that design at end of study. Results: FL stopped 8/15 trials: of 7 trials completing stage 2, only 2 met FL criteria for activity. The MNA rule would have stopped 12/15 trials, including 2 that the same design would have accepted as active based on the final data. FL and MNA disagreed on early stopping in 4/15 trials, all of which were eventually rejected by FL. MNB did not recommend early stopping in any trial. Conclusions: Using the PD hypotheses noted: MNA, which considered both RR and PD in assessing activity, stopped trials early more often than FL. MNB, which required only one of RR or PD to assess activity, never stopped a trial early. We plan to repeat this exercise using additional PD hypotheses to determine levels that would change MNB performance. No. of trials (n = 15) Stopped end stage 1 Continued to stage 2 “Active” at end of study Active at end of study and rejected stage 1 FL 8 7 2 N/A MNA 12 3 5 2 MNB 0 15 At least 2* 0 * Stage 2 sample size for MNB design exceeded number pts actually enrolled in all cases so only rarely could activity be determined. No significant financial relationships to disclose.
Rapidly progressive acute chest syndrome in individuals with sickle cell anemia: a distinct acute chest syndrome phenotype
Authors: Shruti Chaturvedi, Djamila L. Ghafuri, Jeffrey Glassberg, Adetola A. Kassim, Mark Rodeghier, Michael R. DeBaun
Journal: American Journal of Hematology (2016)

Current definitions of acute chest syndrome (ACS) in sickle cell anemia (SCA) do not account for rapid progression of respiratory compromise. In this two-center retrospective cohort study, we tested the hypothesis that in children and adults with ACS and respiratory failure (≤24 hours after onset of respiratory symptoms) have a distinct ACS phenotype associated with multiorgan failure when compared to those with ACS that have a more subacute and protracted course. We identified 173 individuals (97 children <20 years and 76 adults ≥20 years) with SCA and at least one episode of ACS. Only one ACS episode was considered per individual. Rapidly progressive ACS occurred in 21% (n = 16) of adults, but only 2.1% (n = 2) of children. Compared to adults without rapidly progressive ACS, adults with rapidly progressive ACS more frequently developed acute kidney injury (68.8% vs. 3.3%, P < 0.001), hepatic dysfunction (75.0% vs. 15.0%, P < 0.001), altered mental status (43.8% vs. 11.7%, P < 0.001), multiorgan failure (93.8% vs. 10%, P < 0.001), and death (6.3% vs. 0%, P = 0.05). Clinical and laboratory covariates that were evaluable on the first day of respiratory symptoms were evaluated to identify predictors of rapidly progressive ACS. On multivariable analysis, decline in platelet count at presentation was the only predictor of rapidly progressive ACS [odds ratio 4.82 (95% CI 1.20-19.39), P = 0.027]. In conclusion, rapidly progressive ACS is a distinct phenotype that occurs more frequently in adults, is preceded by thrombocytopenia, and is associated with multiorgan failure. Am. J. Hematol. 91:1185-1190, 2016. © 2016 Wiley Periodicals, Inc.
Sentinel lymph node in gastric cancer.
Authors: Luisa Quaresma, Antonio Caldeira Fradique, Alexandra Pupo, Gualdino Silva, Guedes Da Silva, Ligia Bruno Da Costa, Mario Oliveira, Jorge Esteves, Mateus Marques, Gonçalo Fernandez
Journal: Journal of Clinical Oncology (2015)

e15014 Background: In the European Union, Portugal is the country with the highest incidence of gastric cancer. The prognostic value of lymph node metastasis in gastric carcinoma was accepted long ago. More recently it was put in evidence the more precise meaning of the relationship between the number of metastatic nodes and the number of resected lymph nodes - r N), which reinforces the importance of lymphadenectomy .However, it is essential that we develop new technology for diagnosing lymph node metastasis prior to surgery.In the early twenty-first century, Japanese authors started the discussion of the importance of the concept of sentinel lymph node(SLN) applied to the staging and treatment of gastric carcinoma.Has the intra-operative identification of the SLN in gastric carcinoma some value in a most accurate N staging? Methods: The study will be applied to patients with gastric carcinoma with preoperative staging T1, T2 or T3 N0.The size of the tumor is less than 4 cm;All patients will be treated according to the group's protocol ,both in terms of gastric resection extension as in terms of D2 lymphadenectomy Sub serosal peritumoral injection of indocyanine green in the four quadrants Identification of lymphatic routes and wait 5 minutes All nodes that blush in 5 minutes after injection are harvested by dissection of the basin, identified the location according to the japonese classification and sent to pathology Results: A total of 20 patients were operated. An average of 40 nodes were resected per patient.The average of SLN harvested per patient was 4.The location of the SNL was related with the location of the tumor. The false negative rate was 16.6%. The sensitivity of the method was 83.3% The Identification rate was 92.85% Conclusions: The authors wish to present the most frequent locations of sentinel lymph node in gastric cancer which depend on the tumor location.The fact that about 40 nodes per patient were collected, on average, gives greater power to the study. A patient is correctly staged as N0 with this extent of dissection and, on the other hand, a negative sentinel node is considered more likely to be a true negative. The indocyanine green dye seems very promising as a marker for the sentinel node identification in gastric carcinoma.
Highlights of the Year in JACC 2013
Authors: Anthony N. DeMaria, Eric D. Adler, Jeroen J. Bax, Ori Ben-Yehuda, Gregory K. Feld, Barry H. Greenberg, Jennifer L. Hall, Mark A. Hlatky, Wilbur Y.W. Lew, João A.C. Lima, Ehtisham Mahmud, Alan S. Maisel, Sanjiv M. Narayan, Steven E. Nissen, David J. Sahn, Sotirios Tsimikas
Journal: Journal of the American College of Cardiology (2014)
Culex mosquitoes are experimentally unable to transmit Zika virus
Authors: Fadila Amraoui, Célestine Atyame-Nten, Anubis Vega-Rúa, Ricardo Lourenço-de-Oliveira, Marie Vazeille, Anna Bella Failloux
Journal: Eurosurveillance (2016)

We report that two laboratory colonies of Culex quinquefasciatus and Culex pipiens mosquitoes were experimentally unable to transmit ZIKV either up to 21 days post an infectious blood meal or up to 14 days post intrathoracic inoculation. Infectious viral particles were detected in bodies, heads or saliva by a plaque forming unit assay on Vero cells. We therefore consider it unlikely that Culex mosquitoes are involved in the rapid spread of ZIKV.
High Transferrin Saturation Is Associated with Lower Monocytic Ferritin Heavy Chain Expression in Sickle Cell Anemia Patients
Authors: Kleber Yotsumoto Fertrin, Carolina Lanaro, Carla Fernanda Franco-Penteado, Dulcinéia Martins Albuquerque, Betania Lucena Hatzlhofer, Mariana Rezende Bandeira Mello, Marcos André Cavalcanti Bezerra, Aderson da Silva Araujo, Fernando Ferreira Costa
Journal: Blood (2014)