tbuckley/cabot-search huggingface dataset:
High response rate and PFS with PEGPH20 added to nab-paclitaxel/gemcitabine in stage IV previously untreated pancreatic cancer patients with high-HA tumors: Interim results of a randomized phase II study.
Authors: Sunil R. Hingorani, William Proctor Harris, Andrew Eugene Hendifar, Andrea J. Bullock, Xionghua W. Wu, Ya Huang, Ping Jiang
Journal: Journal of Clinical Oncology (2015)

4006 Background: Poor outcomes in pancreatic cancer (PDA) are associated in part with tumor stroma limiting chemotherapy perfusion. PDAs express high levels of hyaluronan (HA), which contributes to elevated interstitial pressures. PEGylated recombinant human hyaluronidase, PEGPH20, depletes HA in tumors. In a Phase Ib study of PEGPH20 with Gemcitabine (Gem), patients (pts) whose tumors were HAhigh had improved ORR, PFS and OS compared to those with tumors that were HALow. Methods: This is an ongoing phase II, open-label, randomized study of PEGPH20 +Nab-Paclitaxel (Nab) + Gem (PAG) vs. Nab + Gem (AG) in previously untreated pts with Stage IV PDA. Pts receive 3 µg/kg twice weekly (Cycle 1) and then weekly (Cycle 2+) PEGPH20 in combination with standard dosing of AG. HA status was tested retrospectively. Primary endpoint is PFS, secondary endpoints include: ORR, OS and Safety. Due to a temporary clinical hold, ORR is from data through April 2014; and PFS is data through December 2014. Results: 146 pts were enrolled and 135 pts received at least one dose of study drug. The mean age was 65.1 yrs. (Range 29-83 yrs), 93% had a KPS of ≥ 80. The most common AEs related to study drugs (PAG vs. AG) were: fatigue (68% vs. 69%), nausea (55% vs. 44%), anemia (42% vs. 53%) peripheral edema (58% vs. 31%) and muscle spasms (55% vs. 2%). There was an imbalance of thromboembolic (TE) events with 42% vs. 25% of subjects having at least one TE event. Overall RR and PFS are shown in the table below. Conclusions: PEGPH20 + Nab/Gem is generally well tolerated in advanced PDA. Patients with HAhigh tumors receiving PAG had greater ORR and longer PFS than HAhigh patients receiving AG. Overall survival will be presented at the time of the meeting. ClinicalTrials.gov Identifier NCT01839487. Clinical trial information: NCT01839487. Endpoint/Population PAG AG P-value ORR N = 135 25/74 (34%) 14/61 (23%) 0.17 HAHigh N = 34 12/17 (71%) 5/17 (29%) 0.02 HALow N = 28 9/18 (50%) 5/10 (50%) 0.94 PFS N = 135 42/74; 5.7 months 39/61; 5.2 months 0.10 HAHigh N = 48 12/25; 9.2 months 15/23; 4.3 months 0.03 HALow N = 58 22/36; 4.8 months 15/22; 5.6 months 0.81
A Manual of Instruction in the Principles of Prompt Aid to the Injured, Designed for Military and Civil Use.
Journal: JAMA (1889)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Book: Global Crises, Global Solutions
Authors: Henry Greenberg
Journal: BMJ (2005)

What an intriguing idea. Convene serious thinkers to create a list of critical issues facing the global community that are amenable to governmental intervention, prune and prioritise the list to the top 10, enlist leading economists to outline the challenges, add thoughtful commentaries, and then rank the final 10. A group called the Copenhagen Consensus under the leadership of Bjorn Lomborg did just this and teamed up with the Economist to disseminate the results. Global Crises, Global Solutions is the result, and disappointing it is, garnering at best two stars.​stars.
Ipilimumab for Patients with Relapse after Allogeneic Transplantation
Authors: Matthew S. Davids, Haesook T. Kim, Pavan Bachireddy, Caitlin Costello, Rebecca Liguori, Alexandra Savell, Alexander P. Lukez, David Avigan, Yi-Bin Chen, Peter McSweeney, Nicole R. LeBoeuf, Michael S. Rooney, Michaela Bowden, Chensheng W. Zhou, Scott R. Granter, Jason L. Hornick, Scott J. Rodig, Masahiro Hirakawa, Mariano Severgnini, F. Stephen Hodi, Catherine J. Wu, Vincent T. Ho, Corey Cutler, John Koreth, Edwin P. Alyea, Joseph H. Antin, Philippe Armand, Howard Streicher, Edward D. Ball, Jerome Ritz, Asad Bashey, Robert J. Soiffer
Journal: New England Journal of Medicine (2016)

Loss of donor-mediated immune antitumor activity after allogeneic hematopoietic stem-cell transplantation (HSCT) permits relapse of hematologic cancers. We hypothesized that immune checkpoint blockade established by targeting cytotoxic T-lymphocyte–associated protein 4 with ipilimumab could restore antitumor reactivity through a graft-versus-tumor effect.
The Consult Guys - Serving Up Advice: A Waiter With Hematuria
Authors: Geno J. Merli, Howard H. Weitz
Journal: Annals of Internal Medicine (2016)

Web Exclusives21 June 2016The Consult Guys - Serving Up Advice: A Waiter With HematuriaFREEGeno J. Merli, MD and Howard H. Weitz, MDGeno J. Merli, MDSearch for more papers by this author and Howard H. Weitz, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W16-0006 SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The Consult Guys bring a new perspective to the art and science of medicine with lively discussion and analysis of real-world cases and situations.For more videos from and information on The Consult Guys, visit www.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Disclosures: Geno J. Merli, MD, reports the following: Research grants/contracts: Bristol-Myers Squibb, Janssen, Portola; Consultancies: Bristol-Myers Squibb, Janssen. Howard H. Weitz, MD, reports that he has no financial relationships or interests to disclose. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCorrection: The Consult Guys - A Real Headache: Anticoagulation and a Subdural Hematoma 21 June 2016Volume 164, Issue 12Page: CG1KeywordsDisclosureResearch grantsResearch reporting guidelines ePublished: 21 June 2016 Issue Published: 21 June 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.Loading ...
Improving patient participation in a breast cancer survivorship program at a safety net hospital.
Authors: Shakuntala Shrestha, Pam Khosla, Janos Molnar, Maria Eugenia Corona, Sofia M Garcia
Journal: Journal of Clinical Oncology (2016)

60 Background: To provide comprehensive services and meet Commission on Cancer (CoC) accreditation requirements, we developed and evaluated a customized breast cancer SCP template and delivery model. Objective: To implement and pilot test survivorship care plan (SCP) delivery for breast cancer survivors. Methods: Clinicians at a safety net hospital partnered with investigators at an academic institution to start a breast cancer survivorship care program. We developed an SCP template that is CoC-complaint and responsive to input gathered in 2 focus groups with breast cancer survivors (n = 12) and interviews with staff (n = 8). Oncologists and nurses identified and referred English-speaking women who had completed breast cancer treatment. Participants completed baseline measures prior to receiving individualized SCPs in a survivorship consultation visit with a dedicated APN. In response to high no-show rates, we expanded clinic scheduling to harmonize with participants' other medical appointments. Interim feasibility results for our ongoing study are presented here. Results: A total of 154 patients were screened to reach target enrollment (n= 80) within 20 months. Participant median age was 60 ± 11; 71% were African American, 14% Hispanic; 11% Non-Hispanic White and 92% had household incomes &lt; $20,000. Average times were: 30 ± 13.4 minutes for abstracting patient clinical information in preparation for the survivorship visit; 25 ± 16 minutes for completing individual SCPs; 22±7.65 minutes to review / deliver the SCPs with patients. The difference in no-show rate between first 3-month recruitment period (clinic limited to one day/week) and next 17 months (clinic appointment expanded to accommodate patients' schedule) was statistically significant, p = 0.028. Conclusions: Tailoring SCP templates and delivery models to the needs of a safety net hospital aided the sustainability of a new survivorship clinic. Patient non-adherence to scheduled visits was significantly improved by expanding clinic hours. Significant clinician time was spent preparing SCPs and a level 4 visit (25 minutes) does not adequately reflect this effort. This study is funded by the American Cancer Society, Illinois Division (Grant# 254698).
A Phase I Trial of the Small Molecule Pan-Bcl-2 Family Inhibitor Obatoclax Mesylate (GX15-070) Administered by 24 Hour Infusion Every 2 Weeks to Patients with Myeloid Malignancies and Chronic Lymphocytic Leukemia (CLL).
Authors: Gautam Borthakur, Susan O’Brien, Farhad Ravandi-Kashani, Francis Giles, Aaron D. Schimmer, Jean Viallet, Hagop Kantarjian
Journal: Blood (2006)
Elimination of epithelial-like and mesenchymal-like breast cancer stem cells to inhibit metastasis following nanoparticle-mediated photothermal therapy
Authors: Hayley J. Paholak, Nicholas O. Stevers, Hongwei Chen, Joseph P. Burnett, Miao He, Hasan Korkaya, Sean P. McDermott, Yadwinder Deol, Shawn G. Clouthier, Tahra Luther, Qiao Li, Max S. Wicha, Duxin Sun
Journal: Biomaterials (2016)
Personal Views: Freddie
Authors: Simon Stephenson
Journal: BMJ (2003)

At 12 years old, he'd already been unwell for a long time: congestive cardiac failure secondary to cardiomyopathy; a rare cause of this condition in my limited clinical practice but common in the population he came from. He'd been receiving maximal therapy for months now, his dutiful carers ensuring he took his furosemide and enalapril every day, going so far as to grind them up into his meals when he—as happened increasingly often—refused to take them.
Treat signs of sepsis with same urgency as chest pain, says NICE
Authors: Ingrid Torjesen
Journal: BMJ (2016)

Doctors should treat patients with suspected sepsis with the same urgency as those who present with chest pains, says new UK guidance from the National Institute for Health and Care Excellence.1

Health professionals need to think about the possibility of sepsis in far more patients—all patients who may be infected, said NICE in its evidence based guideline for identifying and treatment sepsis.

Saul Faust from the University of Southampton and chair of the group that developed the guideline said, “Sepsis can be difficult to diagnose with certainty. We want clinicians to start asking, ‘Could this be sepsis?’ much earlier on so that they can rule it out or get people the treatment they need.”

He added, “Just like most people with chest pain are not having a heart attack, the majority of people with an infection will not have sepsis. …
P37 Development of a Stable, Clinically Relevant, Fully Monitored and Managed Reproducible Model of Paracetamol Induced Acute Liver Failure in the Pig
Authors: A Proven, C Thiel, P Leckie, K Thiel, M Schenk, R Jalan, N Davies
Journal: Gut (2010)

Introduction  Acute liver failure (ALF) is a rare but devastating clinical condition, a common cause of which is paracetamol overdose. Advances in treatment options for ALF have been hampered by the lack of a representative large animal model.  Aim  This study was designed to develop a clinically relevant, fully monitored and managed model of ALF that would develop the clinical, biochemical, haemodynamic and inflammatory characteristics of the human equivalent.  Method  Initial studies were performed in 36 landrace pigs to define a dose, which resulted in 100% mortality. We developed the model in 3 female pigs that were subjected to full intensive care but without any paracetamol administration and 8 pigs that were treated with paracetamol. After an overnight fast, 11 pigs [weighing 35-45 kg] were intubated and ventilated under general anaesthetic for the duration of the experiment. Catheters were placed for blood pressure monitoring, haemofiltration, urine measurement and triple lumen central intravenous lines for fluids, drugs and sampling. An ICP bolt was inserted and a separate catheter for cerebral microdialysis. Placebo (n=3) or a loading dose (0.25 g Kg-1) then hourly bolus? of paracetamol (n=8) were given via the jejunostomy to keep the serum paracetamol concentration 350 - 450 mg dl-1. Paracetamol was stopped when Quick index of 30% was reached. Animals were supported with fluids, glucose, fresh frozen plasma, inotropes, renal haemofiltration and mechanical ventilation until time of death.  Results  The paracetamol overdosed animals developed typical changes of ALF manifested by attenuated mean arterial pressure requiring large amounts of fluid resuscitation (2.5 litres per hour) and inotropic support (noradrenaline; 15-150 ?g kg-1 hr-1) and increased intracranial pressure (p 160 s, creatinine (0.58±0.17 vs 1.45±0.13 mg kg-1, p  Conclusion  We have developed a stable, fully monitored and managed model of paracetamol induced ALF which exhibits the clinical, haemodynamic, biochemical and inflammatory characteristics of ALF that is suitable for interventional studies of novel therapies for this devastating rare disease.
Enteroviral Postencephalitic Parkinsonism With Evidence of Impaired Presynaptic Dopaminergic Function
Authors: Michel Toledano, Nicholas W. S. Davies
Journal: JAMA Neurology (2016)

Proton Pump Inhibitors and Dementia IncidenceTo the Editor Dietary aluminum ingestion is theorized to be neurotoxic and play a causative role in the onset and progression of dementia. 1-3A recent meta-analysis showed that individuals chronically exposed to aluminum were 71% more likely to develop Alzheimer disease (odds ratio, 1.71; 95% CI, 1.35-2.18). 4any strong antacids contain aluminum hydroxide and are often taken for years by patients with peptic ulcer disease or gastroesophageal reflux before they are prescribed proton pump inhibitors, and concurrent with their use.Gomm and colleagues 5 do not correct for the use of aluminum-containing antacids when calculating the association of dementia with proton pump inhibitor use.How much of their observed association of proton pump inhibitor use with dementia is actually due to long-term ingestion of aluminum antacids, either currently or in the past?
Body Mass Index Is a Prognostic Factor in Adults with Newly Diagnosed Acute Myeloid Leukemia: A Retrospective Multi-Institutional Study in Japan
Authors: Taiki Ando, Etsuko Yamazaki, Haruka Teshigawara, Fujii Eriko, Yoshimi Ishii, Wataru Yamamoto, Kenji Motohashi, Takayoshi Tachibana, Maki Hagihara, Kenji Matsumoto, Masatsugu Tanaka, Hashimoto Chizuko, Koharazawa Hideyuki, Fujimaki Katsumichi, Jun Taguchi, Naoto Tomita, Hiroyuki Fujita, Heiwa Kanamori, Shin Fujisawa
Journal: Blood (2015)
Immunotherapy targeting pyroglutamate-3 Aβ: prospects and challenges
Authors: Holger Cynis, Jeffrey L. Frost, Helen Crehan, Cynthia A. Lemere
Journal: Molecular Neurodegeneration (2016)

Immunization against amyloid-β (Aβ) peptides deposited in Alzheimer's disease (AD) has shown considerable therapeutic effect in animal models however, the translation into human Alzheimer's patients is challenging. In recent years, a number of promising Aβ immunotherapy trials failed to reach primary study endpoints. Aside from uncertainties in the selection of patients and the start and duration of treatment, these results also suggest that the mechanisms underlying AD are still not fully understood. Thorough characterizations of protein aggregates in AD brain have revealed a conspicuous heterogeneity of Aβ peptides enabling the study of the toxic potential of each of the major forms. One such form, amino-terminally truncated and modified pyroglutamate (pGlu)-3 Aβ peptide appears to play a seminal role for disease initiation, qualifying it as novel target for immunotherapy approaches.
Pooled analysis of the reports of carfilzomib, panobinostat, and elotuzumab combinations in patients with refractory/relapsed multiple myeloma
Authors: Liping Liu, Ningning Zhao, Wenjun Xu, Zhixin Sheng, Lida Wang
Journal: Journal of Hematology & Oncology (2016)

The purpose of this study was to better understand the efficacy and safety of carfilzomib, panobinostat, and elotuzumab combinations in patients with refractory/relapsed multiple myeloma(R/RMM). We retrieved and reviewed published reports including carfilzomib, panobinostat, and elotuzumab combination regimens for patients with R/RMM. We identified 20 prospective studies that evaluated 2220 patients. Carfilzomib combination regimens produced an overall response rate (ORR ≥ PR) of 61 % in the 1211 relapsed/refractory patients. At least very good partial response (VGPR) was 29 % in patients with carfilzomib combinations. Finally, 49 % of the 597 patients achieved ORR in patients receiving panobinostat-containing combinations. At least VGPR was 16 % in patients with panobinostat combinations. Three hundred twenty-eight of these 449 patients (73 %) receiving elotuzumab-containing combinations achieved ORR. And at least VGPR was 37 %. And, the vital nonhematologic adverse events (AEs) were cardiac events and pneumonia. Carfilzomib, panobinostat, and elotuzumab combination regimens produced clinical benefits in patients with R/RMM.
The liquid biopsy as a new ally to fight cancer?
Authors: L. Orgiano, A. Dessi, L. Demurtas, A. Puzzoni, A. Cubeddu, M.G. Pusole, R. Mascia, G. Astara, C. Madeddu, E. Massa, V. Pusceddu, M. Scartozzi
Journal: Annals of Oncology (2015)
Phase Ib trial of docetaxel, prednisone, and pazopanib, in men with metastatic castration resistant prostate cancer (mCRPC).
Authors: Daniel J. George, Susan Halabi, Patrick Healy, Sarah Gemberling, Carolyn Winters, Kelly Mundy, Michael Roger Harrison, Russell Zelig Szmulewitz, Andrew J. Armstrong
Journal: Journal of Clinical Oncology (2016)

275 Background: Docetaxel prednisone (DP) is a standard of care for men with metastatic castrate resistant prostate cancer (mCRPC) with median progression-free survival (PFS) of 4-6 months and overall survival (OS) of 19 months, supporting a need for further treatment options. Pazopanib (PAZO) is a multi-targeted kinase inhibitor of VEGF receptors approved for treatment of kidney cancer and sarcoma. We performed a two center, Phase Ib study of DP + PAZO to evaluate the safety and early efficacy in mCRPC. Methods: This is a 2 site phase 1 DOD Prostate Cancer Clinical Trials Consortium trial of DP + PAZO once daily with ongoing ADT in men with mCRPC. The primary endpoint was safety; secondary endpoints included evaluation of a maximum tolerated dose (MTD) through a dose escalation and expansion design, pharmacokinetic assessments, PSA and radiographic responses, and toxicity. Results: Twenty-five men were treated over 6 dose levels using a 3+3 design. Pegfilgrastim (Neu) was added to the regimen after myelosuppression limited dose escalation. With Neu, our target MTD of D 75 mg/m2; P 10 mg QD and PAZO 800 mg QD was reached. Eleven additional patients were accrued at this dose level for a total of 36 patients. 17 patients had received prior Abi and/or Enza. The most common AEs were alopecia (86%), fatigue (69%), diarrhea (58%), and nausea (53%), and the most common Grade 3-5 SAEs were neutropenia (33%) and leukopenia (19%). Three deaths attributed to study treatment occurred: one from pneumonitis, one from respiratory failure, and one from intracranial hemorrhage. The proportion of 30%, 50% and 90 % PSA declines were 69%, 58% and 25%, respectively. The objective response rate was 31% (11/36). Median PFS was 18.6 months (95% CI: 6.5, 27.7) and OS was 22.2 months (95% CI: 14.7, -). Predicted median OS using the Halabi nomogram was 20.9 months (95% CI: 19.2, 23.0) with 23%, 34% and 43% of patients in low, intermediate and high risk groups, respectively. Conclusions: DP + PAZO (with Neu) were tolerable at full doses and demonstrated a surprisingly long PFS and high objective response rate in a relatively poor risk group of mCRPC patients. These data support further randomized studies of DP + Pazo in Abi/Enza refractory patients. Clinical trial information: NCT01385228.
Ursodeoxycholic acid in advanced polycystic liver disease: A phase 2 multicenter randomized controlled trial
Authors: Hedwig M.A. D’Agnolo, Wietske Kievit, R. Bart Takkenberg, Ioana Riaño, Luis Bujanda, Myrte K. Neijenhuis, Ellen J.L. Brunenberg, Ulrich Beuers, Jesus M. Banales, Joost P.H. Drenth
Journal: Journal of Hepatology (2016)
P-274 Pembrolizumab for patients with previously treated, mismatch repair–deficient microsatellite instability–high advanced colorectal carcinoma: phase 2 KEYNOTE-164 study
Authors: Le Dung, André Thierry, Kim Tae Won, Van Cutsem Eric, Jäger Dirk, Geva Ravit, Hara Hiroki, Kim Tae You, Yoshino Takayuki, Burge Matthew, Taniguchi Hiroya, Elez Elena, Atreya Chloe, Bendell Johanna, Koshiji Minori, Wang Ruixue, Kang S. Peter, Diaz Luis
Journal: Annals of Oncology (2016)
Case 42-1987
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Jeffrey D. Bernhard, Randall J. Margolis
Journal: New England Journal of Medicine (1987)

Presentation of CaseA 15-year-old boy was admitted to the hospital because of a progressive cutaneous disorder.He was born of an uneventful full-term third pregnancy and vaginal delivery and apparently developed normally as an infant. Soon after his first year of life hyperpigmented macules and hypopigmented papular lesions developed over the exposed areas of his skin and gradually spread to affect most of his body. At the age of three years he became blind in the right eye, and in more recent years vision was impaired in the left eye. He never attended school. Through the years his mother . . .
Seborrheic Dermatitis
Authors: Luigi Naldi, Alfredo Rebora
Journal: New England Journal of Medicine (2009)

A 35-year-old man reports itching, redness, and scaling in his scalp, eyebrows, and external auditory canal. He has tried several over-the-counter dandruff shampoos, with only temporary relief, and is increasingly embarrassed by this problem. Physical examination reveals greasy scaling on the scalp and erythema with yellowish scales in the nasolabial creases. How should his case be managed?
Nurofen advertisement was misleading, says watchdog
Authors: Clare Dyer
Journal: BMJ (2016)

The UK advertising watchdog has banned a TV advertisement because it misled consumers by suggesting that Reckitt Benckiser’s branded ibuprofen product, Nurofen Joint and Back Pain Relief, could target particular areas of the body.

In a decision that could signal a crackdown on the marketing of general painkillers for specific purposes, the Advertising Standards Authority (ASA) ruled that the ad was misleading because it “implied that the product had a special mechanism which meant it specifically targeted back and joint pain, and was especially effective at relieving those sources of …