tbuckley/cabot-search huggingface dataset:
The Clinical Investigator as an Endangered Species
Authors: J B Wyngaarden
Journal: New England Journal of Medicine (1980)

THIS paper deals with the physician-investigator as an endangered species and with the future of clinical research. Clinical research includes the wide range of activities extending from epidemiology to studies of patients, to laboratory studies of specimens and tissues. Clinical research is usually conducted by physician-investigators working in a clinical department of a medical school or in a clinical division of an institute. An increasing number of Ph.D.'s are also engaging in clinical research, but this paper will be largely devoted to the physician-investigator. For several years there has been a declining interest in biomedical research on the part of . . .
Tumor progression versus bone scan “flare” in new lesions detected on early bone scans in patients with chemo-naïve metastatic castration resistant prostate cancer (mCRPC) treated with placebo or enzalutamide.
Authors: Yangmin M. Ning, Clara Chen, Virginia Ellen Maher, James Xunhai Xu, Geoffrey Kim, Richard Pazdur
Journal: Journal of Clinical Oncology (2016)

305 Background: To differentiate between bone metastasis progression vs. Tc 99m scan “flare” in new lesions on early bone scans ( ≤ 12 wks), ≥ 2 additional lesions on a confirmatory scan (6 wks later) are proposed. This reduces the risk of misreading scan “flare” as progression in responding patients (pts). Independent central review (ICR) of scans from placebo (PLC)-controlled trials can help evaluate the role of confirmatory scans as PLC should neither delay progression nor elicit scan “flare”. Methods: The ICR datasets from a randomized PLC-controlled trial of enzalutamide (ENZ) in pts with chemo-naïve mCRPC were examined. Pts with ≥ 2 new lesions on Week 9 bone scans who underwent confirmatory scans were analyzed. Scan “flare” was defined as unconfirmed progression associated with responses in PSA ( ≥ 50% decline). Results: Summarized in the table. Confirmed progression on Week 9 bone scans occurred more in pts on PLC than in pts on ENZ (57% vs. 14%). In pts with unconfirmed progression, scan “flare” occurred in 80% of pts on ENZ. Of the pts with unconfirmed progression who had PSA progression, nearly 60% progressed on follow-up scans. Conclusions: The findings from this large PLC-controlled trial provide strong evidence for performing confirmatory bone scans to verify tumor progression in new lesions on early bone scans in mCRPC. For pts with unconfirmed progression, early PSA progression appears associated with progression on follow-up scans. [Table: see text]
Reappraisal Of The p16INK4A/Prb Pathway and Telomerase Activity, Markers Of Cell Activation and Aging, In Adult Acute Lymphoblastic Leukemia: A Graall Study
Authors: Martine Ffrench, Wei W Chien, Régine Catallo, Amel Chebel, Laurence Baranger, Xavier Thomas, Marie-Christine Bene, PharmSciD, Luc M Gerland, Aline Schmidt, Kheira Beldjord, Nathalie Klein, Martine Escoffre-Barbe, Thibault Leguay, Huguet Françoise, Fabrice Larosa, Sandrine Hayette, Adriana Plesa, Norbert Ifrah, Hervé Dombret, Gilles Andre Salles, Agnès Chassevent
Journal: Blood (2013)
Language Ability after Early Detection of Hearing Impairment
Authors: John Grima
Journal: New England Journal of Medicine (2006)

I was surprised that the article by Kennedy et al. (May 18 issue)1 about language acquisition in deaf children did not mention signing or sign language. Deaf children cannot hear. This creates natural limits on the effectiveness of speech as a medium for the acquisition of language. Hearing parents can and do learn to sign. Deaf children gain real language competence through signing. The introduction of sign language into the infant's environment as the result of hearing screening should be the test of the efficacy of screening and progress in language acquisition.
Soundings: Breaking bad news
Authors: Liam Farrell
Journal: BMJ (2001)

Breaking bad news is quite all right with me; as La Rochefoucald said, “We all have strength enough to bear the troubles of others.” However, I often try to soften the blow with the gift of music: “Your Auntie Rose is dead,” sung to the tune of “Happy Birthday”; or the gift of humour: “You have two months to live, gosh, but that was from last month, and this is February”; or the gift of charades, which is tricky, as medical terms don't lend themselves to mime—once I had to abandon a consultation prematurely, as the patient was in pain and was nowhere near getting “You have a big pilonidal sinus.”

But Joe was a tough call. We'd be gently caressing a slow air on the mandolin and whistle and then Joe would come busting in with the guitar, deafening everyone. We'd tried many schemes. We'd file his strings so that they'd snap. We'd employ women to chat him up, but Joe was no beauty, Ireland is a small country, and we soon ran out of women. We tried fake phone messages that his granny was dead, which strangely worked the first three times. We suggested he try another instrument, which led to the Great Accordion Disaster of 1998.

So the band decided Joe would have to be terminated. The band was being compromised, music and beauty were the real losers, and I was selected to break the bad news. Sticking my finger down my throat in the graceful Irish gesture of farewell, I left to do the terrible deed.

“Me and the boys were thinking,” I started, “that maybe you should . . .” But the words wouldn't come out; I could see a mute appeal in his eyes. Had his senses, so useless when it came to anything musical, subliminally warned him that the knives were out? It felt like kicking a spaniel, of which I have had some experience. I scrutinised his dog-like face, the sagging skin under his eyes, the hairs growing out of his ears, the greying of his stubble; Joe was growing old and maybe beneath the bravado lay the fear of not belonging. Perhaps it was fear that made him play so loudly, just as primitive tribes bang drums to frighten away the demons of the night: deep down Joe was afraid that he was no good.

“Joe,” I tried again, “maybe you should . . .” and then I heard myself damn us to a dread musical Gotterdammerung, “maybe you should bring in the accordion next week.”
Efficacy of Augmentation of Cognitive Behavior Therapy With Weight-Adjusted<scp>d</scp>-Cycloserine vs Placebo in Pediatric Obsessive-Compulsive Disorder
Authors: Eric A. Storch, Sabine Wilhelm, Susan Sprich, Aude Henin, Jamie Micco, Brent J. Small, Joseph McGuire, P. Jane Mutch, Adam B. Lewin, Tanya K. Murphy, Daniel A. Geller
Journal: JAMA Psychiatry (2016)

Cognitive behavior therapy (CBT) among youth with obsessive-compulsive disorder (OCD) is effective, but many patients remain symptomatic after intervention. d-cycloserine, a partial agonist at the N-methyl-d-aspartate receptor in the amygdala, has been associated with enhanced CBT outcome for OCD among adults but requires evaluation among youth.To examine the relative efficacy of weight-adjusted d-cycloserine (25 or 50 mg) vs placebo augmentation of CBT for youth with OCD and to assess if concomitant antidepressant medication moderated effects.In a placebo-controlled randomized clinical trial, 142 youths (age range, 7-17 years) enrolled between June 1, 2011, and January 30, 2015, at 2 academic health science centers (University of South Florida and Massachusetts General Hospital) with a primary diagnosis of OCD were randomized in a double-blind fashion to d-cycloserine plus CBT or placebo plus CBT. Intent-to-treat analysis was performed.Patients were randomly assigned in a 1:1 ratio to either 10 sessions of d-cycloserine plus CBT or placebo plus CBT. d-cycloserine (25 or 50 mg) or placebo was taken 1 hour before sessions 4 through 10.Children's Yale-Brown Obsessive Compulsive Scale at randomization, biweekly, midtreatment, and posttreatment. Secondary outcomes included the Clinical Global Impressions-Severity or Clinical Global Impressions-Improvement, remission status, Children's Depression Rating Scale, Multidimensional Anxiety Scale for Children, and Children's Obsessive-Compulsive Impact Scale-Parent Version.The study cohort comprised 142 participants. Their mean (SD) age was 12.7 (2.9) years, and 53.5% (76 of 142) were female. A mixed-effects model using all available data indicated significant declines in the Children's Yale-Brown Obsessive Compulsive Scale total score and Clinical Global Impressions-Severity. No significant interaction between treatment group and changes in the Children's Yale-Brown Obsessive Compulsive Scale and Clinical Global Impressions-Severity indicated that the d-cycloserine plus CBT group and the placebo plus CBT group declined at similar rates per assessment point on the Children's Yale-Brown Obsessive Compulsive Scale total score (estimate, -2.31, 95% CI, -2.79 to -1.83 and estimate, -2.03, 95% CI, -2.47 to -1.58, respectively) and Clinical Global Impressions-Severity (estimate, -0.29, 95% CI, -0.35 to -0.22 and estimate, -0.23, 95% CI, -0.29 to -0.17, respectively). No group differences in secondary outcomes were present. Antidepressant medication use at baseline did not moderate changes for either group.d-cycloserine augmentation of CBT did not confer additional benefit relative to placebo among youth with OCD. Other augmentation approaches should be examined to enhance outcome.clinicaltrials.gov Identifier: NCT00864123.
P-173 Outcomes of palliative gastrectomy in 549 asymptomatic patients with advanced gastric cancer
Authors: V. Fanotto, C. Fontanella, S. Cordio, G. Pasquini, M. Baretti, R. Filippi, G. Rosati, D. Santini, R. Giampieri, S. Di Donato, G. Tomasello, O. Brunetti, M. Caporale, F. Bergamo, A. Avallone, M. Scartozzi, S. Lutrino, D. Melisi, L. Antonuzzo, A. Pellegrino, G. Aprile
Journal: Annals of Oncology (2016)
Predictive Factors for Response and Survival in Patients with Myelodysplastic Syndromes (MDS) after Hypomethylating Agent (HMA) Failure: Primary Resistance (PriRes) Vs. Secondary Resistance (SecRes)
Authors: Koji Sasaki, Elias Jabbour, Naveen Pemmaraju, Naval G. Daver, Tapan M. Kadia, Courtney D. DiNardo, Sherry Pierce, Gautam Borthakur, Hagop M. Kantarjian, Guillermo Garcia-Manero
Journal: Blood (2014)
Is Season of Birth Important for Multiple Sclerosis Risk?
Authors: Jennifer S. Graves
Journal: JAMA Neurology (2016)

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 Neurology 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 Neurology journal
Interim results of a randomized phase II study of PEGPH20 added to nab-paclitaxel/gemcitabine in patients with stage IV previously untreated pancreatic cancer.
Authors: Sunil R. Hingorani, William Proctor Harris, Tara Elisabeth Seery, Lei Zheng, Darren Sigal, Andrew Eugene Hendifar, Fadi S. Braiteh, Mark Zalupski, Ari David Baron, Nathan Bahary, Andrea Wang-Gillam, Noelle K. LoConte, Gregory M. Springett, Paul S. Ritch, Aram F. Hezel, Wen Wee Ma, Venu Gopal Bathini, Xionghua W. Wu, Ping Jiang, Andrea J. Bullock
Journal: Journal of Clinical Oncology (2016)

439 Background: Poor outcome in pancreatic cancer (PDA) is associated partly with stromal hyaluronan (HA) accumulation, which compromises chemotherapy perfusion. PEGPH20, PEGylated recombinant human hyaluronidase, potentiates chemotherapy by depleting HA in tumors. Methods: In an ongoing, phase II, open-label, randomized study of PEGPH20+nab-paclitaxel (Nab)+Gemcitabine (Gem) (PAG) vs Nab+Gem (AG) in previously untreated stage IV PDA, pts receive PEGPH20 3 µg/kg twice weekly (C1), then weekly (C2+) with standard AG dosing. HA status was tested retrospectively. After a temporary clinical hold (Apr-Jul 2014) for an imbalance in thromboembolic (TE) events (29% PAG vs 15% AG), the protocol was amended to exclude high-TE-risk pts and add enoxaparin (LMWH) prophylaxis. Endpoints are PFS and TE events (primary); PFS and ORR by HA level and OS (secondary). Efficacy and safety data through Dec 2014 are for pts enrolled up to clinical hold (Stage 1); TE data are through Sep 2015 (Stage 2). Results: 135 pts were treated (74 PAG, 61 AG). PFS results are shown below (median follow-up 7 mo). In HA-high pts receiving PAG vs AG, ORR was 52% (1 CR) vs 24% (P=.038); ORR was 37% vs 38% in HA-low pts. OS was 12 mo vs 9 mo (HR=0.62) despite 12/23 PAG pts discontinuing PEGPH20 at clinical hold. Common ADRs (PAG vs AG) included peripheral edema (58% vs 31%), muscle spasms (55% vs 1.6%), and neutropenia (32% vs 18%). TE events were: Stage 1 42% vs 25% (no LMWH); Stage 2 (with LMWH; 40 mg/d or 40 mg/d increased to 1 mg/kg/d) 28% vs 29%; (1 mg/kg/d) 5% vs 6%; overall (40 mg/d or 1 mg/kg/d) 13% each arm (to be updated). Conclusions: Pts with HA-high tumors receiving PAG, vs AG, showed significant improvements in PFS and ORR and a trend toward improved OS. PAG was well tolerated, with TE events reduced with LMWH prophylaxis. A global phase III trial of PAG will initiate Q1 2016. Clinical Trial Information: NCT01839487. Clinical trial information: NCT01839487. [Table: see text]
Rupture of Splenic-Artery Aneurysm
Authors: Gioacchino Sisto Parrella
Journal: New England Journal of Medicine (1955)

NEXT to those of the aorta, aneurysms of the splenic artery are the most common intra-abdominal aneurysms.1 In spite of this, the disease is rarely recognized before surgery or autopsy. In a collected series of 144 cases reported by Cosgrove, Watts and Kaump,2 the preoperative diagnosis was made in only 10. The hope for survival in these cases rests on immediate diagnosis. The surgeon must be alert to the possibility of this condition, particularly in the advanced stages of pregnancy. Tonge3 mentions only 2 survivals after surgery of ruptured splenic-artery aneurysms in pregnancy, whereas Dobson, Morse and Covert4 have presented . . .
High Progression-Free Survival At 10 Years After Tandem Autologous/Nonmyeloablative Allogeneic Transplants For Multiple Myeloma In a Cohort Of 93 Patients: Impact Of Disease Remission Status At Transplant and Chronic Graft-Versus-Host Disease
Authors: Imran Ahmad, Sandra Cohen, Silvy Lachance, Guy Sauvageau, Thomas Kiss, Lambert Busque, Denis-Claude Roy, Jean-Sebastien Delisle, Lea Bernard, Richard LeBlanc, Jean Roy
Journal: Blood (2013)
Pancreatic Tumors in Male Rats Elicited by Corn Oil Gavage
Authors: Nathan Mantel
Journal: JNCI Journal of the National Cancer Institute (1986)

Journal Article Pancreatic Tumors in Male Rats Elicited by Corn Oil Gavage Get access Nathan Mantel Nathan Mantel Mathematics, Statistics and Computer Science, The American University, 4900 Auburn Avenue, Bethesda, Maryland 20814 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 77, Issue 1, July 1986, Page 305, https://doi.org/10.1093/jnci/77.1.305 Published: 01 July 1986
Radiotherapy for Hepatocellular Carcinoma: New Indications and Directions for Future Study
Authors: Nitin Ohri, Laura A Dawson, Sunil Krishnan, Jinsil Seong, Jason C Cheng, Shiv K Sarin, Milan Kinkhabwala, Mansoor M Ahmed, Bhadrasain Vikram, C Norman Coleman, Chandan Guha
Journal: JNCI Journal of the National Cancer Institute (2016)

Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide; its incidence is increasing in the United States. Depending on disease extent and underlying liver status, patients may be treated with local, locoregional, and/or systemic therapy. Recent data indicates that radiotherapy (RT) can play a meaningful role in the management of HCC. Here, we review published experiences using RT for HCC, including the use of radiosensitizers and stereotactic RT. We discuss methods for performing preclinical studies of RT for HCC and biomarkers of response. As a part of the HCC Working Group, an informal committee of the National Cancer Institute's Radiation Research Program, we suggest how RT should be implemented in the management of HCC and identify future directions for the study of RT in HCC.
DDEL-05DIFFERENTIAL BLOOD-BRAIN BARRIER (BBB) PERMEABILITY OF ALKYLPHOSPHOCHOLINE (APC) ANALOGS ANALYZED USING AN IN VITRO PLURIPOTENT STEM CELL-DERIVED BRAIN MICROVASCULAR ENDOTHELIAL CELL SYSTEM
Authors: Paul Clark, Abraham Al-Ahmad, Tongcheng Qian, Ray Zhang, Justin Jeffery, Hannah Wilson, Sean Palecek, Jamey Weichert, Eric Shusta, John Kuo
Journal: Neuro-Oncology (2015)

BACKGROUND: Agents with cancer specificity against the highly aggressive glioblastoma (GBM) have potential diagnostic, intraoperative visualization, and therapeutic applications. Recently reported alkylphosphocholine (APC) analogs demonstrated tumor selectivity in 55 rodent and human cancer and cancer stem cell models, including GBM. Although these APC analogs strongly label GBM, their permeability across an intact blood-brain barrier (BBB) vasculature remains unknown. METHODS: APC analogs -124I-CLR1404 (PET radiotracer), CLR1501 (green fluorescence), CLR1502 (near infrared fluorescence) - were obtained from Cellectar Biosciences, and tested for permeability across an in vitro BBB composed of human induced pluripotent stem cell (iPSC)-derived brain microvascular endothelial cells (BMECs). This in vitro BBB Transwell system consistently exhibits satisfactory barrier tightness as marked by a high transendothelial electrical resistance (TEER > 1000 Ω-cm2) and functional drug efflux transporters. We investigated the permeability of these different APC analogs by measuring changes in cell diffusion rates using the clearance method and assessed the contribution of drug efflux transporters using pharmacological inhibitors. RESULTS: APC analogs demonstrated limited diffusion across the BBB with permeability values (Pe, x10−5 cm/min) of 40.8 ± 15.1 (124I-CLR1404), 34.4 ± 14.0 (CLR1501), and 35.4 ± 17.5 (CLR1502); compared to impermeable sucrose (12.95 ± 2.49) and highly permeable diazepam (174.0 ± 28.57). Only the fluorescent analogs CLR1501 and CLR1502, and not CLR1404, were substrates for drug efflux transporters, and MRP or BCRP inhibition (using MK571 and Ko143, respectively) increased permeability of these compounds 3-fold. Interestingly, inhibition of P-gp did not affect permeability of any compounds. CONCLUSIONS: Limited BBB diffusion of APC analogs helps explain the excellent GBM to normal brain ratios achievable in initial human trials. Addition of fluorescent moieties to APCs resulted in greater BMEC efflux via MRP and BCRP, and transporter inhibition may help optimize APC analog delivery to GBM during fluorescence-guided neurosurgical resection. Overall, characterizing BBB permeability of APC analogs will help guide future applications of these agents against brain tumors.
Optimizing PD-L1 as a biomarker of response with pembrolizumab (pembro; MK-3475) as first-line therapy for PD-L1–positive metastatic non-small cell lung cancer (NSCLC): Updated data from KEYNOTE-001.
Authors: Naiyer A. Rizvi, Edward B. Garon, Natasha Leighl, Matthew David Hellmann, Amita Patnaik, Leena Gandhi, Joseph Paul Eder, Reshma A. Rangwala, Gregory Lubiniecki, Jin Zhang, Kenneth Emancipator, Charlotte M. Roach, Ruth Rutledge, Rina Hui, Myung-Ju Ahn, Leora Horn, Enriqueta Felip, Enric Carcereny Costa
Journal: Journal of Clinical Oncology (2015)

8026 Background: Platinum doublets provide 6-mo PFS and 12-mo OS for treatment-naive, metastatic NSCLC without driver mutations. Preliminary data from KEYNOTE-001 revealed robust antitumor activity and manageable toxicity for the anti–PD-1 antibody pembro in treatment-naive NSCLC. In these patients (pts), PD-L1 positivity correlated with improved ORR, PFS, and OS. We explored the relationship between PD-L1 expression levels and efficacy in treatment-naive pts in KEYNOTE-001. Methods: 101 treatment-naive, PD-L1+ metastatic NSCLC pts were randomized 1:1 to pembro 10 mg/kg Q2W or Q3W (11 pts randomized to 2 or 10 mg/kg Q3W). Pembro was given until unacceptable toxicity, PD, or pt/investigator decision. PD-L1 expression was assessed by IHC (22C3 antibody). Staining of tumor cells or stroma by a prototype assay was used for enrollment. In a prospectively defined validation set (n = 90), the percentage of PD-L1–stained tumor cells was determined with a clinical trial assay. Response was assessed centrally every 9 wk by RECIST 1.1. Results: There were no significant between-dose differences in ORR, PFS, or OS; 11% of pts experienced gr 3-5 drug-related AEs. In the validation set (38-wk median follow-up), ORR and DCR were highest and PFS was longest in pts with ≥50% PD-L1 tumor cell staining (Table); there was a trend toward longer OS (immature data). Conclusions: Pembro demonstrateddurable antitumor activity and manageable toxicity profile as first-line therapy for PD-L1+ metastatic NSCLC, with the greatest efficacy observed in pts with PD-L1 staining in ≥50% of tumor cells. These data demonstrate that PD-L1 expression in tumor cells identifies those NSCLC pts most likely to respond to pembro. The efficacy and safety of pembro as first-line therapy for PD-L1+NSCLC is being examined in ongoing, controlled clinical trials. Clinical trial information: NCT01295827. PD-L1+ Tumor Cells n ORR, % (95% CI) DCR, % (95% CI) Median, mo (95% CI) PFS OS ≥50% 17 47 (23-72) 77 (50-93) NR (2.4-NR) NR (NR-NR) 1%-49% 31 19 (8-38) 71 (52-86) 4.4 (3.6-6.4) NR (8.6-NR) <1% 7 14 (0.4-58) 57 (18-90) 3.4 (2.1-4.2) 7.3 (3.4-NR) Total 90 24 (16-35) 68 (57-77) 6.0 (4.1-8.6) NR (10.6-NR) NR, not reached.
PD-007 CXCR4, CXCR7 and CXCL12 expression is not a prognostic predictive factor in patients with resected pancreatic cancer - results from the CONKO-001 trial
Authors: J. Striefler, L. Wislocka, M. Sinn, U. Pelzer, C. Denkert, A. Juehling, S. Bischoff, M. Bahra, B. Hendrik, H. Oettle, H. Riess, P. Lohneis
Journal: Annals of Oncology (2016)
Efficacy and Safety of Autologus Hematopoietic Cell Transplantation in Elderly Patients with Multiple Myeloma: A Retrospective Israeli Multi-Site Cohort Study
Authors: Yael C Cohen, Tsila Zuckerman, Moshe Yeshurun, Galit Perez, Hila Magen, Israel Henig, Itai Levi, Liat Shargian, Svetlana Trestman, Uri Rouvio, Elizabeth Naparstek, Eti Ganon-Elazar, Irit Avivi, Ron Ram
Journal: Blood (2014)