tbuckley/cabot-search huggingface dataset:
A phase II study of talimogene laherparepvec followed by talimogene laherparepvec + nivolumab in refractory T cell and NK cell lymphomas, cutaneous squamous cell carcinoma, Merkel cell carcinoma, and other rare skin tumors (NCI #10057).
Authors: Ann W. Silk, Nicole R. LeBoeuf, Guilherme Rabinowits, Igor Puzanov, Melissa Amber Burgess, Sumana Devata, Dirk Moore, James Steven Goydos, Helen X. Chen, Howard Kaufman, Andrew Zloza, Janice M. Mehnert
Journal: Journal of Clinical Oncology (2018)

TPS219 Background: Talimogene laherparepvec, a modified herpes virus agent, induces a response in 65% of injected melanoma tumors. The combination of talimogene laherparepvec with ipilimumab or pembrolizumab appears promising in clinical trials of advanced melanoma. Talimogene laherparepvec-based therapy may be effective in other cancers of the skin and lymph nodes that are anatomically accessible for intratumoral injection. Methods: This phase II study will evaluate intratumoral talimogene laherparepvec monotherapy in 4 parallel disease cohorts: 1) Refractory T cell and NK cell lymphomas including cutaneous T cell lymphoma, 2) Merkel cell carcinoma 3) Cutaneous squamous cell carcinoma and 4) Other advanced/refractory non-melanoma skin cancers. Lymphoma patients must be refractory to or intolerant of all standard life-prolonging therapies. Skin cancer patients must be advanced/unresectable or refractory to one or more treatments including surgery, radiation therapy, or medical therapy. Prior PD-1-directed therapy is allowed. If an objective response is not achieved by Week 12, the PD-1 blocking antibody nivolumab will be added. The primary endpoint is the response rate with talimogene laherparepvec and secondary endpoints include response rate with the combination and overall survival. Using a two-stage design, if 1 or more response is observed in the first 9 patients in each parallel cohort, 8 additional patients will be accrued for a total sample size of 36 to 68 patients across the 4 disease cohorts. Tumor biopsies of injected lesions are mandatory at baseline and Week 6, and optional at Week 16 and the time of progression. Optional biopsies of non-injected lesions (when applicable) at Week 6 and 16 will be analyzed to identify biomarkers of systemic immunity. Tumor tissue and/or blood will be assayed for PD-L1 expression, RNA profiling, immune cell profiling, HVEM, NECTIN 1/2, IDO, tryptophan and L-kynurenine, mutational load, TIL TCR clonality, and prior exposure to herpes simplex type 1 virus and Merkel cell polyomavirus. Clinical trial information: NCT02978625.
IMPACT OF REVASCULARIZATION ON ABSOLUTE MYOCARDIAL BLOOD FLOW AS ASSESSED BY SERIAL [15O]H2O PET IMAGING: A COMPARISON WITH FRACTIONAL FLOW RESERVE
Authors: Roel Driessen, Ibrahim Danad, Wijnand Stuijfzand, Stefan Schumacher, Juhani Knuuti, Adriaan Lammertsma, Albert van Rossum, Niels Van Royen, Pieter Raijmakers, Paul Knaapen
Journal: Journal of the American College of Cardiology (2018)
Biopolymer strategy for the treatment of Wilson's disease
Authors: Miroslav Vetrik, Jana Mattova, Hana Mackova, Jan Kucka, Pavla Pouckova, Olivia Kukackova, Jiri Brus, Sebastian Eigner-Henke, Ondrej Sedlacek, Ludek Sefc, Petr Stepanek, Martin Hruby
Journal: Journal of Controlled Release (2018)
Adjuvant enzalutamide (Enza) for men with non-metastatic high-risk prostate cancer (HRPCa) after radical prostatectomy (RP).
Authors: Moshe Chaim Ornstein, Andrew J. Stephenson, Paul Elson, Allison Janine Tyler, Pam Profusek, Kimberly D Allman, Pedro C. Barata, Cristina Magi-Galluzzi, Amr Farouk Fergany, Robert Stein, Khaled Fareed, Georges-Pascal Haber, Steven C. Campbell, Jihad Kaouk, Petros Grivas, Brian I. Rini, Eric A. Klein, Jorge A. Garcia
Journal: Journal of Clinical Oncology (2018)

88 Background: Management of HRPCa is a clinical challenge. Novel AR inhibitors could potentially impact outcome in HRPCa men following RP. We conducted a phase II study evaluating the efficacy/safety of Enza in men with HRPCa following RP. Methods: HRPCa pts (≥pT3a, GS≥8, iPSA ≥20 ng/mL, +ve lymph nodes (LN), or ≥35% chance of biochemical recurrence (BCR) at 5 yrs based on MSKCC’s nomogram) with undetectable PSA within 3 months from RP were eligible. Enza 160mg PO daily was given in 28-day cycles until disease progression, intolerability, consent withdrawal, or study completion at 24 months. Accrual goal was N=40 to provide 80% power to detect a 75% decrease in the risk of BCR from historical 55% rate. BCR was defined as PSA ≥0.2ng/mL on 2 consecutive lab results or any PSA rise that resulted in subsequent therapy. Results: 42 men enrolled. Median age 59 (range 43-70), based on biopsy 45% were GS7; 36% GS8, 19% GS9. 76% men had cT1, 24% cT2, median iPSA was 8.2 (range 2-77). On prostatectomy pathology: 50% had pT3b; 52% +ve margins; 50% SVI; 24% had +LN. 37 (88%) pts completed 24 planned cycles. Of the 5 pts who did not complete all cycles, 3 withdrew consent for toxicity (2 had G3 fatigue, 1 had G3 fatigue and arthralgias/myalgias), 1 had rising PSA requiring subsequent therapy, and 1 had financial concerns. With median follow-up of 31 months (range 2.5-44.5), 37 (88%) pts remain free of BCR. Of the 5 pts who developed BCR, 4 completed all 24 months on therapy. Median time to BCR was 31 months (range 13-40). Most common adverse events (AE) are listed (Table). Conclusions: Adjuvant Enza in men with HRPCa following RP is safe and relatively well-tolerated. Long-term safety, efficacy, and genomic correlations (including tumor RNA expression) are ongoing. Clinical trial information: NCT01927627. [Table: see text]
Notable Year for Novel Drugs
Authors: Rebecca Voelker
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
The enrollment status of patients with brain metastases in metastatic renal cell carcinoma: A query of clinicaltrials.gov.
Authors: Tri Cao Le, James Brugarolas
Journal: Journal of Clinical Oncology (2017)

e16070 Background: Clinical trials routinely exclude patients with brain metastases in metastatic renal cell carcinoma (mRCC). However, the degree to which such patients are excluded has not been documented. Routine exclusion of such patients limits applicability of trial results and obfuscates potential benefit in this subpopulation. This study aims to systematically determine the status of central nervous system (CNS) disease exclusion, with or without leptomeningeal disease, in clinical trial enrollment in interventional studies of mRCC. Methods: ClinicalTrials.gov was systematically queried to characterize the CNS exclusion criteria among open, interventional trials in mRCC. Results: Of 121 open trials, 29 (24%) strictly excluded patients with CNS metastasis. 69 trials (57%) enrolled patients with CNS metastasis with contingencies (i.e. prior CNS-directed local therapy, and/or lack of neurologic symptoms). Two trials (2%) enrolled patients with CNS metastasis without exception. 21 trials (17%) did not specify enrollment criteria with respect to CNS disease. In multivariate analysis of the effect of trial phase, location, sponsor, treatment type, and histologic subtype on CNS exclusion criteria, only location had a statistically significant effect. Trials performed exclusively within the United States had higher odds of excluding patients with CNS metastases than global trials (OR = 8.889, 95% CI: 1.405-56.251, p = 0.023) or trials performed exclusively outside of the United States (OR = 2.778, 95% CI: 1.054-1.758, p = 0.053). Conclusions: Due to the high rate of exclusion of patients with brain metastases in mRCC, many trial results cannot be reliably generalized to this subpopulation. Consideration should be given to looking at the effect of new systemic therapies on patients with CNS metastases to clarify benefit or harm in this subpopulation.
Thiol-capped Bi nanoparticles as stable and all-in-one type theranostic nanoagents for tumor imaging and thermoradiotherapy
Authors: Nuo Yu, Zhaojie Wang, Jiulong Zhang, Zixiao Liu, Bo Zhu, Jing Yu, Meifang Zhu, Chen Peng, Zhigang Chen
Journal: Biomaterials (2018)
Genital Lymphoma Presenting as Pyrexia of Unknown Origin
Authors: Shrikant Solav, Ajit Yadav, Deepak Salunke
Journal: Clinical Nuclear Medicine (2010)

Fever/pyrexia of unknown origin is defined as temperature >38.5°C lasting for >3 weeks, of which at least 2 weeks have been spent in thorough investigations. We present a case of an elderly gentleman who had pyrexia of unknown origin and whose PET scan was useful to localize the site of extranodal lymphoma. An 80-year-old gentleman presented with intermittent fever for past 2 months. He reported loss of appetite and subsequent weight loss. There was no demonstrable abnormality on clinical examination. His blood cytology, blood biochemistry, and conventional radiology were unremarkable. He was referred for a whole-body F-18 FDG PET/CT scan. The study revealed intense metabolic activity within the penis. Clinically, there were no signs of inflammation in the genitals. On a follow-up visit, tenderness was observed during per rectal examination. Another follow-up sonography revealed inflammation in the epididymis. Hence, he underwent biopsy of the testicle and scrotal tissue, which revealed non-Hodgkin lymphoma.
Impact of Donor Type in Patients with AML Given Allogeneic Hematopoietic Cell Transplantation After Low-Dose TBI-Based Regimen
Authors: Frédéric Baron, Myriam Labopin, Annalisa Ruggeri, Jan J. Cornelissen, Ellen Meijer, Henrik Sengeloev, Dietger Niederwieser, Marco R. De Groot, Harry C. Schouten, Noel Milpied, Didier Blaise, Bipin N. Savani, Eliane Gluckman, Mohamad Mohty, Arnon Nagler
Journal: Clinical Cancer Research (2018)

Abstract Purpose: We assessed the impact of donor type in acute myeloid leukemia (AML) patients transplanted with 2 Gy total body irradiation (TBI)-based nonmyeloablative conditioning regimen. Patients and Methods: Data from 1,715 adult patients, with AML in CR1 or CR2 were included in this retrospective survey. Results: Donors consisted either of HLA-matched sibling donors (MSD, n = 701), 10/10 HLA-matched unrelated donors (MUD, n = 611), HLA-haploidentical donors (haplo, n = 112) or single or double umbilical cord bloods (CBT, n = 291). Chronic graft-versus-host disease (GVHD) was less frequent in CBT (28%) and in haplo (30%) patients than in MSD (50%) and MUD (51%) recipients (P &amp;lt; 0.001). Two-year incidence of relapse was 32%, 30%, 34%, and 34% in MSD, MUD, CBT and haplo patients, respectively (P = 0.7). Two-year overall (OS) and GVHD-free relapse-free survival (GRFS) were 59% and 29% in MSD patients, 56% and 39% in CBT recipients, 53% and 23% in MUD recipients, and 43% and 37% in haplo patients, respectively. In multivariate analyses, MUD patients had lower GRFS than MSD patients beyond day 100 (HR 1.3, P = 0.001) while CBT was associated with a better GRFS than MSD beyond day 100 (HR 0.6, P = 0.002). Conclusions: In this large cohort of AML patients transplanted following low-dose TBI-based conditioning, the relapse incidence was not affected by donor type suggesting that the intensity of GVL effects might be comparable with these four transplant approaches. Furthermore, CBT was associated with better GRFS beyond day 100 than MSD while the opposite was observed for MUD. Clin Cancer Res; 24(12); 2794–803. ©2018 AACR.
Should gatifloxacin be included in the model list of essential medicines?
Authors: Chen-Yuan Chiang, Arnaud Trébucq, Alberto Piubello, Hans L. Rieder, Armand Van Deun
Journal: European Respiratory Journal (2018)

We read with great interest the paper by Falzon et al. [1], which reported that gatifloxacin and moxifloxacin have been recommended by the World Health Organization (WHO) for both longer and shortened regimens in the treatment of rifampicin-resistant (RR) and multidrug-resistant (MDR) tuberculosis (TB). Gatifloxacin and moxifloxacin belong to the latest generation of fluoroquinolones that have comparable early bactericidal and sterilising activity in the treatment of TB. Gatifloxacin has been used in the treatment of bacterial infections and MDR-TB [2]. Gatifloxacin was also used in a clinical trial (OFLOTUB) comparing a 4-month gatifloxacin-based regimen with the standard 6-month regimen for the treatment of rifampicin-susceptible pulmonary TB [3]. The gatifloxacin-based shortened treatment was highly effective, achieving >84% treatment success among MDR-TB patients in Bangladesh, Cameroon and Niger [2]. Moxifloxacin may not be a valid alternative to gatifloxacin in the treatment of multidrug-resistant tuberculosis <http://ow.ly/uLby30hBItG>
Nearly half of doctors wouldn’t recommend the profession
Authors: Abi Rimmer
Journal: BMJ (2015)

Nearly half (44%) of doctors wouldn’t recommend their profession to others, a survey has found.

A survey of 102 doctors carried out by Wesleyan, a financial services provider, found that 44% of doctors would not recommend the profession, an increase from 30% in 2014. However, doctors were more likely to recommend their career than other …
A Supramolecular Approach for Liver Radioembolization
Authors: Silvia J. Spa, Mick M. Welling, Matthias N. van Oosterom, Daphne D. D. Rietbergen, Mark C. Burgmans, Willem Verboom, Jurriaan Huskens, Tessa Buckle, Fijs W. B. van Leeuwen
Journal: Theranostics (2018)

Hepatic radioembolization therapies can suffer from discrepancies between diagnostic planning (scout-scan) and the therapeutic delivery itself, resulting in unwanted side-effects such as pulmonary shunting.We reasoned that a nanotechnology-based pre-targeting strategy could help overcome this shortcoming by directly linking pre-interventional diagnostics to the local delivery of therapy.Methods: The host-guest interaction between adamantane and cyclodextrin was employed in an in vivo pre-targeting set-up.Adamantane (guest)-functionalized macro albumin aggregates (MAA-Ad; d = 18 µm) and (radiolabeled) Cy5 and β-cyclodextrin (host)-containing PIBMA polymers ( 99m Tc-Cy5 0.5 CD 10 PIBMA 39 ; MW ~ 18.8 kDa) functioned as the reactive pair.Following liver or lung embolization with ( 99m Tc)-MAA-Ad or ( 99m Tc)-MAA (control), the utility of the pre-targeting concept was evaluated after intravenous administration of 99m Tc-Cy5 0.5 CD 10 PIBMA 39 .Results: Interactions between MAA-Ad and Cy5 0.5 CD 10 PIBMA 39 could be monitored in solution using confocal microscopy and were quantified by radioisotope-based binding experiments.In vivo the accumulation of the MAA-Ad particles in the liver or lungs yielded an approximate ten-fold increase in accumulation of 99m Tc-Cy5 0.5 CD 10 PIBMA 39 in these organs (16.2 %ID/g and 10.5 %ID/g, respectively) compared to the control.Pre-targeting with MAA alone was shown to be only half as efficient.Uniquely, for the first time, this data demonstrates that the formation of supramolecular interactions between cyclodextrin and adamantane can be used to drive complex formation in the chemically challenging in vivo environment. Conclusion:The in vivo distribution pattern of the cyclodextrin host could be guided by the pre-administration of the adamantane guest, thereby creating a direct link between the scout-scan (MAA-Ad) and delivery of therapy.
Comment on Burrows et al. Declining Rates of Hospitalization for Selected Cardiovascular Disease Conditions Among Adults Aged ≥35 Years With Diagnosed Diabetes, U.S., 1998–2014. Diabetes Care 2018;41:293–302
Authors: José M. de Miguel-Yanes, Manuel Méndez-Bailón, Rodrigo Jiménez-García, Ana López-de-Andrés
Journal: Diabetes Care (2018)

In their paper, Burrows et al. (1) used U.S. National (Nationwide) Inpatient Sample (NIS) data (1998–2014) to estimate the number of discharges for cardiovascular disease conditions as first-listed diagnoses in people aged ≥35 years. They found significant decreases over time in the age-adjusted hospitalization rates for acute coronary syndrome (average annual percentage change \[AAPC\] \[confidence limits\] −4.6% …
INFLUENCE OF CONTINUOUS SINUSOIDAL STENT DESIGN ON IRREGULAR PROTRUSION AND ARTERIAL HEALING OF CULPRIT LESIONS IN PATIENTS WITH ACUTE CORONARY SYNDROME (CSI: ACC STUDY)
Authors: Daisuke Izumi, Kohei Unno, Hiromasa Ito, Itaru Goto, Katsuyuki Tone, Shigetoshi Sakabe, Masahide Horiguchi, Takeshi Takamura, Ken-Ichi Maeno, Tetsuya Seko, Atsunobu Kasai
Journal: Journal of the American College of Cardiology (2018)
The impact of visual impairment on Health-Related Quality of Life (HRQoL) scores in brain tumour patients
Authors: Sana Sharrack, Alexis J Joannides, William Sage, Stephen Price
Journal: Neuro-Oncology (2018)

Brain tumour patients have significant disability and symptom burden. Health-Related Quality of Life (HR-QoL) scores can be useful when assessing the impact brain tumours have on their QoL. 1. To determine whether there are any statistically significant differences in HRQoL scores in brain tumour patients with visual impairment compared to those without. 2. To compare pre- and post-operative HR-QoL scores in patients whose vision was not impaired pre-operatively but that deteriorated post-operatively, and assess whether there were any statistically significant differences in each of the QoL dimensions. 3. To see if there was an association between visual impairment and a) tumour type and b) tumour location. Suitable patients confirmed to have brain tumours were recruited at neuro-oncology clinics from 2010–2013. We analysed HR-QoL scores from a total of 175 patients, either pre- or post-operatively (or for a minority of patients, both). 1. The mean HRQoL scores for all of the QoL domains were higher (equating to higher functionality) in patients without visual impairment compared to those with and this was statistically significant (p=<0.05) for a) Global Health b) Role c) Emotional and d) Cognitive functioning. 2. Comparisons of HRQoL scores pre- and post-operatively in 11 patients who had no visual impairment pre-operatively but whose vision deteriorated post-operatively reveals statistically significant (p=<0.05) decreases in global health and cognitive functioning post-operatively. 3. There was no association between visual impairment and type of tumour but a strong association between visual impairment and occipital tumours. 1. Visual impairment has a huge impact on brain tumour patients' QoL. 2. HRQoL scores may be very useful as primary outcome measures in the future. 3. Surgical intervention in brain tumour patients often results in huge deteriorations in their QoL and hence may not always be in the patients' best interest.
Medical leadership requires “profound shift in self-image and social role”
Authors: Matthew Limb
Journal: BMJ (2015)

Doctors looking to succeed in medical leadership roles need a “profound shift in self-image and social role,” says a report by the management consultancy firm Hay Group. The paper says that doctors need to be given more support at key stages to make the challenging transition “from professional to leader.”1

Kate Wilson, the report’s author, told BMJ Careers, “Organisations should start developing those leadership skills early, so doctors don’t simply transition into formal leadership roles and [find that] suddenly the whole world changes. The NHS really needs doctors to see …
Correlation of MECA-79-positive high endothelial venule density with clinical outcomes in upper tract urothelial carcinoma patients treated with radical nephroureterectomy.
Authors: Yasuhiro Hashimoto, Hayato Yamamoto, Tohru Yoneyama, Atsushi Imai, Shingo Hatakeyama, Takahiro Yoneyama, Takuya Koie, Chikara Ohyama
Journal: Journal of Clinical Oncology (2018)

417 Background: High endothelial venules (HEVs) are present in lymph nodes and tertiary lymphoid organs. It has been reported that low HEV density is associated with the poor prognosis of several carcinomas. MECA-79 antibody recognizes L-selectin ligand (6-sulfosialyl Lewis X glycan) expressed in HEV. In the present study, we examined whether MECA-79 positive HEV density was associated with clinical outcomes of patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). Methods: Eighty-eight patients with UTUC who underwent RNU at the Hirosaki University hospital between January 2008 and December 2016 were enrolled. Tissue microarray for MECA-79 was performed, and HEV densities were calculated. HEV density &lt; 1.5/mm 2 was defined as HEV (−); HEV density ≥1.5/mm 2 was defined as HEV(+). Results: Of 88 patients, 64 (72.7%) were male and 24 (27.2%) were female. The average age was 68.5 years (range, 36–84 years). Fifty-three patients (60.2%) had previously undergone neoadjuvant chemotherapy. The mean observation period was 39.0 months. Twenty-one (23.8%) patients developed recurrence, whereas 16 (33.3%) patients died during follow-up. Five-year cause-specific survival (CSS) rate was 66.1%, and five-year disease-free survival (DFS) rate was 70.7%. In our cohort, 25 (28.4%) patients were found to be HEV(−), whereas 63 (71.5%) were found to be HEV(+). The mean HEV density was 6.3/mm 2 (0-41.6). The 5-year DFS rates for HEV (+) and HEV (−) patients were 78.0% and 53.9%, respectively, with a statistically significant difference between the groups. (log-rank, p = 0.042). Moreover, the 5-year CSS rates for HEV (+) and HEV (−) patients were 72.5% and 53.4%, respectively, with a statistically significant difference between the groups. (log-rank, p = 0.0036). Conclusions: Low MECA-79-positive HEV density may be associated with poor prognosis of patients with UTUC treated with RNU. Despite the small sample size and preliminary nature of our study, our study provides valuable insights to guide future research.
ASSESSMENT OF MORTALITY RISK IN FRAIL PATIENTS WITH CRITICAL LIMB ISCHEMIA UNDERGOING REVASCULARIZATION
Authors: Osamu Iida, Mitsuyoshi Takahara, Yoshimitsu Soga, Nobuyoshi Azuma Azuma, Shinsuke Nanto, Toshiaki Mano
Journal: Journal of the American College of Cardiology (2018)
USE OF DIRECT ORAL ANTICOAGULANTS IN DIALYSIS PATIENTS WITH ATRIAL FIBRILLATION IN THE UNITED STATES
Authors: Konstantinos Siontis, Ashley Eckard, Nicole Bhave, Peter Noseworthy, Nilay Shah, Xiaoxi Yao, Kevin He, Austin Stack, Rajesh Balkrishnan, Rajiv Saran, Brahmajee Nallamothu
Journal: Journal of the American College of Cardiology (2018)
DOES VALVE CHOICE MATTER? A THEORETICAL MODEL COMPARING PROSTHESIS-PATIENT MISMATCH AMONG TRANSCATHETER VALVES IN TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Gilbert Hin-Lung Tang, Syed Zaid, Hasan Ahmad, Ryan Kaple, Jason Kovacic, Cenap Undemir, Asaad Khan, Martin Cohen, Steven Lansman, Samin K. Sharma, Annapoorna Subhash Kini
Journal: Journal of the American College of Cardiology (2018)