tbuckley/cabot-search huggingface dataset:
Phase 1 results of the ODM-208 first-in-human phase 1-2 trial in patients with metastatic castration-resistant prostate cancer (CYPIDES).
Authors: Karim Fizazi, Natalie Cook, Philippe Barthélémy, Alice Bernard-Tessier, Capucine Baldini, Niamh Peters, Pirjo Nykänen, Tarja Ikonen, Pasi Pohjanjousi, Leena Mattila, Lauri Jouhi, Annamari Vuorela, Chris Garratt, Tapio Utriainen
Journal: Journal of Clinical Oncology (2022)

18 Background: ODM-208 is a novel, oral, non-steroidal and selective inhibitor of CYP11A1, the first and rate-limiting enzyme of steroid biosynthesis. ODM-208 suppresses the production of all steroid hormones and their precursors that may activate the androgen receptor (AR) signalling pathway. This is particularly relevant in patients with AR ligand binding domain (LBD) activating somatic point mutations, a mechanism of resistance to hormone-based therapies in metastatic castration-resistant prostate cancer (mCRPC). We report the first results of the first-in-man phase I CYPIDES trial. Methods: ODM-208 was examined in a dose finding phase 1 trial with a 3+3 design in patients with progressive mCRPC who had previously received ≥1 line of AR signalling inhibitor and ≥1 line of taxane-based chemotherapy. ODM-208 was administered up to 150 mg/day with glucocorticoid (GC) and mineralocorticoid replacement therapy and androgen deprivation therapy (ADT). The phase 1 endpoints included dose-limiting toxicities (DLTs), adverse events, pharmacokinetics, pharmacodynamics, PSA and RECIST response, and exploratory genetic profiling. Results: By Jan 22 2021, 41 patients (median age 70 yrs.) had received ODM-208. The dose finding was completed and included doses ranging from 10 to 150 mg/day. 22 (54%) patients had previously received both abiraterone and enzalutamide, and 23 (56%) patients both docetaxel and cabazitaxel. Although tolerated by most patients, the main safety finding was adrenal insufficiency (AI). Overall, 15/41 (37%) patients experienced Grade 3 AI requiring short-term high-dose GC treatment. ODM-208 plasma exposure was dose proportional. Serum testosterone was undetectable after 4 weeks of start of ODM-208 in almost all patients, as were serum DHEA sulphate, androstenedione, 11β-hydroxyandrostenedione, 11-ketotestosterone and pregnenolone. Overall 12/36 (33%) evaluable patients achieved a PSA decline of ≥50%. In evaluable patients with AR LBD mutation 10/15 (67%) achieved a PSA decline of ≥50%. Clinical improvement in symptoms such as pain was also observed in some men. Conclusions: Administration of ODM-208 to mCRPC men pretreated with abiraterone/enzalutamide and taxanes was highly effective in blocking the production of steroid hormones and showed promising antitumor activity, especially in men with AR mutation-positive cancers. The phase 2 dose expansion part of CYPIDES is ongoing. Clinical trial information: NCT03436485.
PLoS Medicine Issue Image | Vol. 3(5) May 2006
Journal: PLoS Medicine (2006)

I began working on this series of images in 2003. They began as an initial response to the striking images I had been seeing in news media and in advertising, both of which often appeared in the same publication. I began collecting images that caught my eye, and then began to turn photocopies of those images, along with drawings, into collages. My aim with this series was to create a series of works that one immediately responds to visually. At the time, I wanted to capture the chaos that was being reported through photojournalists' images, and the relationship these images had with those images advertising luxury that were presented alongside them. The closer I examined this relationship, the more ironic it became. As a citizen of the developed world, I felt saddened by the fact that while we sit in our comfortable homes filled with the latest technologies, we are entertained by the tragedies our news services report to us. In developing this series, the works became about how our personal interior spaces have become invaded by both of these types of images, to the point where one feels unable to escape. This particular piece of the series was made at the height of the SARS epidemic, and features an appropriation of an image taken during the funeral of a very popular performer in Hong Kong, who committed suicide at that time. Simultaneously, Australia was getting involved with the war in Iraq and that period of time seemed very confusing. I became very interested in what was happening with SARS because I had recently been living in Beijing, China, and was quite concerned about my friends who were over there, and felt quite personally affected by the situation. Image Credit: Tammy Wong
Prognostic impact of fibroblast growth factor receptor (FGFR) genomic alterations and outcomes in patients with metastatic urothelial.
Authors: Elena Sevillano, Rodrigo Madurga, Juan Francisco Rodriguez Moreno, Arantzazu Barquin, Monica Yagüe, Paloma Navarro, María Barba, Miguel Quiralte, Jesús García-Donas
Journal: Journal of Clinical Oncology (2022)

537 Background: FGFR mutations/translocations are druggable targets in metastatic urothelial cancer (mUC). However, the prognostic effect of these genomic alterations (GA) and their role in the response to conventional therapy remain poorly characterized. Methods: We undertook an observational retrospective study in four Academic Hospitals in Madrid, Spain. Clinical and molecular information of patients diagnosed of Urothelial Cancer (UC) between January 2010 and December 2020 was systematically reviewed. The objective of this work was to compare the outcome of mUC patients with GA in the FGFR 2-3 genes versus wild type tumors. Analyses for detection of FGFR translocations and mutations using DNA isolated from formalin-fixed and paraffinized tumor tissue samples consisted of either next-generation sequencing (Foundation One test; n = 68) or qualitative real-time polymerase chain reaction–based assays (n = 9) with TFGFR or QIAGEN therascreen® tests that evaluated somatic mutations within the FGFR2-3 gene: R248C, S249C, G370C and Y373C and fusions: FGFR3-TACC3v3, FGFR3-TACC3v1 and FGFR3-BAIAP2L1, FGFR2-BICC1 and FGFR2-CASP7. Overall response rate (ORR), Progression Free Survival (PFS) and Overall Survival (OS) were determined and Cox-regression analysis were performed to assess the prognostic impact of these alterations. Results: We identified 201 patients diagnosed with UC. Genomic profiling was available in 77 mUC with 28 patients harboring any FGFR GA. Regarding ORR to first line a trend towards a better outcome was identified in FGFR GA (mutation/translocation/fusion) vs wild type cases (57,7% vs 45,5%, p=0,46). However, median OS was significantly worse among FGFR GA (mutation/translocation) vs FGFR wt tumours (13.8 vs 26.2 months, p=0,021). Prognostic factors associated with an unfavorable outcome in multivariable analysis were visceral metastases (HR 7,29 95% CI 1.6-32,3), ECOG &gt;1 (HR 7,03 95% CI 2,59-19,1), first line treatment with checkpoint inhibitors (HR 2,67; 95% CI 1,06-6,74) and the presence of FGFR GAs (HR 2,98, 95% CI 1.37-6.5). Conclusions: Despite a better response to first line treatment, overall FGFR GA showed to be an independent risk factor in mUC. Thus, this determination should be included in new prognostic models.[Table: see text]
Practice of Obstetrics, Designed for the Use of Students and Practitioners of Medicine.
Journal: JAMA (1907)

The same classification has been followed in this as in the previous editions. The size of the book has been reduced 100 pages, but 140 new illustrations have been added. The following subjects have been rewritten: Development of embryo, fetus, fetal membranes and fetal structures, chorioepithelioma malignum, treatment of placenta prævia, toxemia of pregnancy, etiology of eclampsia, ectopic gestation, treatment of pelvic deformity, morbidity of the puerperium, indications for the induction of abortion and premature labor, use of forceps, Cesarean section, vaginal Cesarean section, Porro operation, and complete and incomplete hysterectomy. New subjects added are: Appendicitis complicating pregnancy, tapeworm in pregnancy, fibroma moluscum gravidarum (illustration), hematoma of the vulva (illustration), lactation atrophy of the uterus and breasts, brachial birth paralysis, vaginal incision and drainage (illustration), new history charts for institution work. The illustrations are good and the schematic drawings which accompany many of them add greatly to their value.
Childhood asthma.
Authors: H. Blair, I. M. Anderson
Journal: BMJ (1968)

In view of the increasing popularity of this technique since the introduction of Marcaine (marketed in 10-ml.ampoules containing bupivacaine 0.5 % + adrenaline 1: 200,000) we feel that these effects should be more widely known and that the use of the undiluted solu- tion should be actively avoided.-Weare, etc.,
LINEAR CRANIOTOMY.
Journal: JAMA (1891)

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
Hormonal treatment for newly diagnosed metastatic prostate cancer: A population-based study of 15,435 cases from the California Cancer Registry (2009-2018).
Authors: David Joseph Benjamin, Dimitra Fellman, Anshu Shrestha, Arash Rezazadeh
Journal: Journal of Clinical Oncology (2022)

22 Background: Androgen deprivation therapy (ADT) is considered standard of care in the treatment of metastatic prostate cancer (mPC). Over the past ten years, the approval of novel androgen receptor-axis-targeted therapies has changed the treatment landscape of mPC. All these novel therapies have only been approved for use in addition to ADT. Despite these new therapeutic advances, it remains unclear how often men with mPC receive standard of care treatment with ADT. Methods: Male adults aged 20 years and older with newly diagnosed metastatic (stage IV) prostate cancer between 2009 and 2018 were identified through the California Cancer Registry (n = 15,435). Patient characteristics including age, year of diagnosis, race/ethnicity, insurance status, socioeconomic status (SES), Charlson co-morbidity score, and death within 3 months of diagnosis were analyzed. Results: 23.1% (n = 3,568) of men with newly diagnosed mPC did not receive ADT. The highest rate of receiving ADT was in men between ages 75-84 (79.6%), and the lowest rate was in men aged over 85 (72.0%) as shown in the table. There was a trend toward more newly diagnosed men receiving ADT in 2018 (81.3%) compared to 2009 (68.8%). Asian men (n = 1077) had a larger proportion of receiving ADT (79.7%), followed by American Indian men (n = 152; 76.4%), Hispanic men (n = 2,368; 75.1%), non-Hispanic White (n = 6,790; 75.6%), and lastly non-Hispanic Black men (n = 1,312; 74.8%). Men from the highest SES had the highest rate of receiving ADT (77.3%), and lowest rate was in lowest SES (73.5%). There was no significant difference among men not receiving hormonal therapy based off Charlson comorbidity score: 0 (26.0%), 1-2 (25.3%), and 3+ (24.9%). Conclusions: Despite significant advancements in the treatment of mPC in recent years, nearly a quarter of patients in California did not receive ADT, which is the backbone for all new systemic therapies. Further statistical analysis of this data set is currently ongoing. This data set might be able to help addressing some of the prostate cancer care disparities in California. [Table: see text]
Abstract 273: Alpha-Delta Ratio Peak Appears Early After Return of Spontaneous Circulation in the Continuous Electroencephalogram of Patients With Good Outcome After Cardiac Arrest
Authors: Joo Suk Oh, Sang Hoon Oh, Kyu Nam Park
Journal: Circulation (2018)

Introduction: Several studies have shown that the alpha-delta ratio (ADR) is associated with ischemic brain injury. Recently, an animal study has revealed that the ADR reaches the maximum point at 11 hours after ROSC, followed by downward curve (ADR peak) in the continuous EEG recordings of the rats with good outcome after cardiac arrest. We examined the existence of the early ADR peak after cardiac arrest in human. Methods: This is a prospective, observational study. Forty patients who survived out-of-hospital cardiac arrest underwent 33°C-targeted temperature management. We induced 33°C within 5 hours after ROSC and maintained for 24 hours, followed by 12 hours of rewarming period. All patients received sedative and paralytic agents until the restoration of normothermia. We started continuous EEG monitoring within 20 hours after ROSC until 72 hours after ROSC or mental recovery. We calculated alpha (8 - 13 Hz) and delta (0.5 - 4 Hz) frequency bands and computed ADR in the bifrontal channel (F3 - F4), bicentral channel (C3 - C4) and biparietal channel (P3 - P4). We did not remove artifact nor seizure events. Therefore, the whole continuous recordings were analyzed. Good neurologic outcome was defined as cerebral performance category 1 and 2 one month after ROSC. Results: Twenty-five patients showed poor outcome, while 15 patients showed good outcome. The figure is showing mean ADR ± SD change over time. The ADR reaches its highest amplitude 10 hours after ROSC and gradually decreases in the patients with good outcome regardless of the recording channel. However, the 10-hour ADR was not significantly different between the groups due to the large variances. Conclusions: Similar to the rats, the ADR peak appears early in the human patients with good outcome. However, due to the highly variable trend, application of ADR peak as a prognostic marker is limited. Regardless, the ADR implicates the crucial window of brain recovery time and remains an important subject requiring further study.
New Appliances
Authors: M K SYKES
Journal: BMJ (1960)

data received from the same individuals on previous occasions, and, if the comparison indicated the development of a pathological condition, would send out notices asking the persons in question to seek medical help.The same datahandling systems might be used to construct a giant " Index Medicus " which would help the physician to cietermine the pathological cause of any set of symptoms pr'-sented by a patient and to prescribe a cure for it.New Appliances
Buccal Oxytocin
Authors: T M MCCALLA, F A HASKINS
Journal: BMJ (1964)

In past estimates of protein requirements the F.A.0.3 has been guided by nitrogen balance without the increments made by the working party.The B.M.A. committee4 and the National Research Council of the U.S.A.5 have been guided by intakes.As a result the discrepancies between the recom- mended allowances are often large.Thus for girls aged 16- 20 the allowance recommended by the F.A.O. is 38 g. daily, as opposed to 88 g. recommended by the B.M.A. and 100 g. by the National Research Council.For the year 1961 the B.M.A. estimate of the protein requirement of the average person, with an allowance for wastage, was virtually identical with the average share of the total protein available in this country at a retail level, which worked out at 85.7 g. daily.A point which the non-expert may not fully realize is the small proportion of the ingested protein which is used for growth after the first year of life.Thus rapidly growing European boys aged 13-14 ingest on an average 1.8 g. of protein per kg. of body weight daily, but use only 0.07 g. per kg., or about 4 %, for growth.We may expect, therefore, that the adequacy of the protein intake, as judged by its power to promote growth, will be much influenced by factors affecting the efficiency of its utilization.These will include the other components of the diet and hormones.A factor which
Pulmonary eosinophilia.
Authors: I W Grant
Journal: Thorax (1990)

Background: Endobronchial stents have a clear role in the palliation of patients with malignant central airway obstruction, but peripheral (lobar) airway obstruction is still a debatable indication for stenting. However dispnea or more frequently post-obstructive pneumonia, seriously interferes with the administration of additional treatment such as chemotherapy or radiotherapy, usually when tumor of the left upper lobe may impairs the lower lobe bronchus9s patency. We report our experience with self-expandable metallic stents (SEMSs) in patients with symptomatic neoplastic stenosis in which eleven patients had a stenosis confined to a lower lobe bronchus. Methods: Between May 2010 and August 2012, 31 SEMSs were implanted in 29 patients with malignant (n=28) tracheobronchial strictures and broncho-oesophageal fistula (n=1). Barthel Index (BI), MRC scale and a four points endoscopic score for the degree of secretions accumulated were used in follow up evaluations at day 1, 30 days, 3 and 6 moths post stent placement. Results. Stent deployment was successful in all patients without procedure related complications with immediate significant improvement of symptoms (BI p&lt;0,001;MRC p&lt;0,001). The mean follow-up duration was 150 dys ± SD 53. Overall stent-related complications were seen in 16,2 % of patients. Conclusions: We suggest that stenting of peripheral airways should be performed early to prevent the infective event. Furthermore the amount of recovered lung tissue consequent to stent placement is clinically and radiologically significant.
Impact of rectal spacer on toxicity reduction in men treated with proton versus photon therapy.
Authors: Vishal Ramesh Dhere, Ashesh B. Jani, Benjamin Walker Fischer-Valuck, Sherrie Cooper, Joseph W. Shelton, Bruce Warren Hershatter, Subir Goyal, Yuan Liu, Karen D. Godette, Pretesh R. Patel, Sagar Anil Patel
Journal: Journal of Clinical Oncology (2022)

247 Background: Dose escalation in prostate cancer (PCa) radiotherapy (RT) is limited by toxicity to surrounding tissue, including the rectum. Rectal spacers improve bowel toxicity in men treated with photons (i.e. IMRT). However, the relative benefit of rectal spacers in men treated with protons remains unknown. Further, proton therapy may result in high-dose exposure to the anterior rectal wall due to lateral penumbra with conventional opposed lateral beam arrangement. We hypothesize that rectal spacers will confer greater toxicity benefit in the setting of proton therapy compared with photon therapy. Methods: We conducted an IRB approved, single institution, retrospective review of patients receiving definitive conventional or moderate hypofractionated photon IMRT or pencil-beam scanning proton RT for localized PCa from 2018-2021. Four cohorts were compared: Photon with (Ph+RS) or without (Ph-RS) rectal spacer, and proton with (Pr+RS) or without (Pr-RS) rectal spacer. Rates of pelvic nodal treatment were equivalent between protons and photons within the +/- rectal spacer cohorts. Acute (&lt;3 months) and late (≥ 3 month) toxicity was compared amongst the four cohorts. Cumulative incidence of physician-reported grade 1-2 gastrointestinal (GI) toxicity (CTCAE V5.0) was compared using Chi-square or Fisher’s exact test. Patient-reported bowel toxicity was evaluated using International Prostate Expanded Prostate Composite Index- Clinical Practice (EPIC-CP) and compared using linear mixed modeling. Results: 164 patients were eligible for analysis: 38 Ph-RS, 50 Ph+RS, 26 Pr-RS, &amp; 50 Pr+RS. Median follow-up was 17.6 months. In men treated with protons, physician-reported acute G1-2 GI toxicity was significantly lower in men with versus without rectal spacer (6.12 vs 30.77%, Pr+RS vs Pr-RS, respectively; p=0.009) and there was a trend towards lower late G1-2 GI toxicity (8.51 vs 26.09%, Pr+RS vs Pr-RS, respectively; p=0.08). In men treated with photons, there were no significant differences in physician-reported acute or later GI toxicity with versus without rectal spacer. No significant differences in patient-reported outcomes were observed with versus without spacer in the proton or photon cohorts. Conclusions: Rectal spacer use was associated with a lower CTCAE grade 1-2 acute GI toxicity in men treated with protons, and this difference was not observed in men treated with photons. While this study is limited by low sample size, a relatively greater benefit of rectal spacer with proton vs. photon therapy was observed. Further prospective analyses in larger cohorts are ongoing to validate these hypothesis-generating findings.
Free Papers
Authors: M. Grotz, M. Stalp, L. Bastian, G. Regel, H. Tscheme, Yoshihiko Suzuki, Kazuhiro Kasai, Keiitchi Ikegami, Wang Ning Yuan, Tetsuo Yukioka, Hiroharu Matsuda, Shuji Shimazaki, H. G. Bone, P. J. Schenarts, D. Harper, L. D. Traber, D. L. Traber, R. Stjletto, T. H. Bötel, E. Brück, L. Gotzen, G. Hernandez, A. Dougnac, D. Angus, M. Ojeda, J. Castro, E. Labarca, L. Castillo, M. Andresen, G. Bugedo, O. Diaz, D. Arriagada, J. Dagnino, M. Zuleika, T. Mphanza, C. Rozario
Journal: Intensive Care Medicine (1996)
Author Correction: The mitochondrial protein Opa1 promotes adipocyte browning that is dependent on urea cycle metabolites
Authors: Camilla Bean, Matteo Audano, Tatiana Varanita, Francesca Favaretto, Marta Medaglia, Marco Gerdol, Lena Pernas, Fabio Stasi, Marta Giacomello, Stèphanie Herkenne, Maheswary Muniandy, Sini Heinonen, Emma Cazaly, Miina Ollikainen, Gabriella Milan, Alberto Pallavicini, Kirsi H. Pietiläinen, Roberto Vettor, Nico Mitro, Luca Scorrano
Journal: Nature Metabolism (2022)