tbuckley/cabot-search huggingface dataset:
PT-112 in advanced metastatic castrate-resistant prostate cancer (mCRPC), as monotherapy or in combination with PD-L1 inhibitor avelumab: Findings from two phase I studies.
Authors: Alan Haruo Bryce, Roxana Stefania Dronca, Brian Addis Costello, Jeffrey R. Infante, Tyler David Ames, Jose Jimeno, Daniel D. Karp
Journal: Journal of Clinical Oncology (2020)

83 Background: PT-112, the first pyrophosphate conjugate in Phase I/II clinical development, induces robust immunogenic cell death and is osteotropic, prompting study in mCRPC during Phase I. We report safety and efficacy findings in the mCRPC sub-population given PT-112 monotherapy (NCT02266745) or in combination with avelumab (“PAVE”) (NCT03409458, ongoing). Methods: Patients (pts) received PT-112 days 1, 8, 15 of a 28d cycle; pts on the PAVE combination also received 800 mg avelumab days 1 and 15; all enrolled during dose escalation or at PT-112 doses previously deemed safe. Pts on therapy (Tx) for ≥2 cycles or who stopped Tx due to progressive disease or treatment-related adverse events (TRAEs) were evaluated for exploratory efficacy. Results: 10 pts on PT-112 (200-420 mg/m 2 ) and 18 pts on PAVE (150-200 mg/m 2 PT-112) were evaluable for safety. The most common PT-112 TRAEs were thrombocytopenia (70%, grade (Gr) ≤3) and fatigue (40%, Gr ≤2) with mono-Tx; nausea (50%, Gr ≤2) and fatigue (39%, Gr ≤2) with PAVE. Mono-Tx pts had 6.5 median prior lines of Tx; 2/7 pts with measurable disease (MD) had reductions in target lesions; prostate specific antigen (PSA) declined in 3/10 pts, 1 with ≥50% reduction; and serum alkaline phosphatase (ALP) reductions were seen in 9/10 pts. PAVE pts had 5.5 median prior lines of Tx; radiographic reductions were seen in 2/9 pts with MD; PSA declined in 6/14 pts, 3 with ≥50% decrease, with 1 responder progression free 11.3 months (microsatellite stable). An additional response is ongoing at 4 mos, with 93% PSA decrease and 48% reduction in target lesions (PIK3CBmut &amp; PTEN loss). 13/14 pts with bone metastases had ALP reductions. Pain improvement, opioid cessation and improved performance status were noted in both cohorts. Conclusions: PT-112 was well-tolerated with evidence of efficacy in mCRPC as mono-Tx and in combination with avelumab in heavily pre-treated pts. Bone pain improvement and nearly universal observation of ALP reduction suggest marked therapeutic activity of PT-112 in bone metastases. Serologic / RECIST responses and prolonged disease control in multiple pts substantiate further development of PT-112 in mCRPC. Clinical trial information: NCT02266745, NCT03409458.
Detection of significant prostate cancer through magnetic resonance imaging targeted biopsy of PI-RADS3 lesions in African American patients based on prostate specific antigen density threshold of 0.15 ng/ml<sup>2</sup>: Analysis of patient population from the Vattikuti Urology Institute.
Authors: Shaheen Riadh Alanee, Musatafa Deebajah, Zade Roumayah, Ali Dabaja, James O. Peabody, Mani Menon
Journal: Journal of Clinical Oncology (2020)

286 Background: A prostate specific antigen density (PSAD) threshold of 0.15 ng/ml 2 have been suggested for significant cancer detection in PI-RADS 3 lesions to avoid unnecessary magnetic resonance imaging targeted biopsy (MRI-TB) of these lesions. However, the performance of this threshold in African American (AA) patients is not well characterized. Methods: We analyzed our institutional data base of MRI-TB to identify the rate of significant prostate cancer (Pca) detection in PI-RADS3 lesions in AA patients stratified by PSAD threshold of &lt; 0.15 vs. ≥0.15 ng/ml 2 and lesion size of &lt; 1 cm vs ≥ 1 cm. Significant prostate cancer was defined as Gleason grade group 2 or higher on MRI-TB of the PI-RADS 3 lesion. Results: Of 768 patients included in the database, 211 (27.5%) patients identified themselves as AAs. Mean age of AA patients was 63 years and mean PSAD was 0.21. Sixty nine (32.7%) AA patients were found to have PI-RADS 3 lesions. Mean PSAD of AA patients with PI-RADS 3 lesions was 0.21 ng/ml 2 as well. Fifty percent of AA patients with PI-RADS 3 lesions had PSAD ≥0.15 ng/ml 2 . Significant Pca detection rate for AA patients with PI-RADS 3 lesions was 9% for PSAD of ≥ 0.15 vs. 0.03% percent for AA patients with PSAD &lt; 0.15 ng/ml 2 (OR 7.056, CI 1.017-167.9, P=0.04). Stratification by lesion size (&lt; 1 cm vs. &gt; 1 cm) resulted in missing 0% percentage of significant Pca when only AA patients with PSAD ≥ 0.15 ng/ml2 and lesion size ≥ 1 cm received MRI-TB. Conclusions: We report on the performance of a reported PSAD density threshold in detecting significant Pca in one of the largest series of AA patients receiving MRI-TB of the prostate. Our results have direct clinical implications when counseling AA patients with PI-RADS 3 lesion on whether they should undergo MRI-TB of such lesions.
Biopsy positivity in prostate cancer patients undergoing mpMRI-targeted radiation dose escalation.
Authors: Jessica Meshman, Benjamin Farnia, Radka Stoyanova, Isildinha Reis, Matthew Abramowitz, Alan Dal Pra, Eric M. Horwitz, Alan Pollack
Journal: Journal of Clinical Oncology (2020)

336 Background: Radiation (RT) dose escalation improves prostate cancer outcomes, but when the whole gland is treated to high doses complications can arise. We used prostate multiparametric MRI (mpMRI) findings for targeted dose escalation (MTDE) in prospective clinical trials in which prostate biopsy at 2-3 years after completion of RT was planned. Biopsy positivity is a known predictor of biochemical failure. These findings are compared to those in another cohort in which standard whole gland RT doses were used. Methods: Patients enrolled on three investigator initiated clinical trials incorporating MTDE (n=30) were eligible for inclusion. All patients were assessed for response by prostate biopsy 2-3 years after RT. Patients were compared to a reference group treated with standard RT doses to the whole prostate on a randomized trial at Fox Chase Cancer Center (FCCC trial). Univariable and multivariable analysis (MVA) was performed to assess for correlation with biopsy positivity, defined as carcinoma with or without RT effect. Results: Of those treated with MTDE: 3 (10%) were low, 23 (77%) intermediate, and 4 (13%) high risk. Assuming an α/β ratio of 1.5, MTDE patients received an equivalent dose (EQD2) of 76 Gy to the prostate, with focal dose escalation to an EQD2 of 98-122 Gy to mpMRI lesions. The MTDE cohort was compared with 115 patients from the FCCC trial, where 23 (20%) were low, 74 (64%) intermediate, and 18 (16%) high risk. The FCCC trial patients received an EQD2 of 76 Gy (n=64) or 84.24 Gy (n=51) without boost. Median time from RT to biopsy was 2 years (range, 1.6-3.3). The post-treatment biopsy results were negative in 50% (n=73), atypical in 12% (n=17), carcinoma with RT effect in 31% (n=45) and frank carcinoma in 7% (n=10). On MVA, patients with tumor volume &gt;20% were more likely to have positive post-RT biopsies (OR: 3.21, 95% CI: 1.34-7.68, p= 0.009). MTDE patients were less likely to have positive post-RT biopsies, 10% vs. 45%, (OR: 0.13, 95% CI: 0.03-0.46, p=0.002). Conclusions: Focal dose-escalation to mpMRI-defined lesions significantly reduces biopsy positivity, a measure associated with long term outcomes including distant metastasis.
Maternal Vitamin D and Offspring Bone Mineral Parameters and Growth
Authors: Elisa Holmlund-Suila, Helena H. Hauta-alus, Sture Andersson
Journal: JAMA Pediatrics (2020)

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 Pediatrics 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 Pediatrics journal
Continuation of Annual Screening Mammography and Breast Cancer Mortality in Women Older Than 70 Years
Authors: Xabier García-Albéniz, Miguel A. Hernán, Roger W. Logan, Mary Price, Katrina Armstrong, John Hsu
Journal: Annals of Internal Medicine (2020)

Randomized trials have shown that initiating breast cancer screening between ages 50 and 69 years and continuing it for 10 years decreases breast cancer mortality. However, no trials have studied whether or when women can safely stop screening mammography. An estimated 52% of women aged 75 years or older undergo screening mammography in the United States.To estimate the effect of breast cancer screening on breast cancer mortality in Medicare beneficiaries aged 70 to 84 years.Large-scale, population-based, observational study of 2 screening strategies: continuing annual mammography, and stopping screening.U.S. Medicare program, 2000 to 2008.1 058 013 beneficiaries aged 70 to 84 years who had a life expectancy of at least 10 years, had no previous breast cancer diagnosis, and underwent screening mammography.Eight-year breast cancer mortality, incidence, and treatments, plus the positive predictive value of screening mammography by age group.In women aged 70 to 74 years, the estimated difference in 8-year risk for breast cancer death between continuing and stopping screening was -1.0 (95% CI, -2.3 to 0.1) death per 1000 women (hazard ratio, 0.78 [CI, 0.63 to 0.95]) (a negative risk difference favors continuing). In those aged 75 to 84 years, the corresponding risk difference was 0.07 (CI, -0.93 to 1.3) death per 1000 women (hazard ratio, 1.00 [CI, 0.83 to 1.19]).The available Medicare data permit only 8 years of follow-up after screening. As with any study using observational data, the estimates could be affected by residual confounding.Continuing annual breast cancer screening past age 75 years did not result in substantial reductions in 8-year breast cancer mortality compared with stopping screening.National Institutes of Health.
Thunderstorm Asthma: In Search For Relationships With Airborne Pollen And Fungal Spores From 23 Sites In Bavaria, Germany. A Rare Incident Or A Common Threat?
Authors: Athanasios Damialis, Daniela Bayr, Vivien Leier-Wirtz, Franziska Kolek, Maria Plaza, Sigrid Kaschuba, Stefanie Gilles, Jose Oteros, Jeroen Buters, Annette Menzel, Annette Straub, Stefanie Seubert, Claudia Traidl-Hoffmann, Michael Gerstlauer, Christoph Beck, Andreas Philipp
Journal: Journal of Allergy and Clinical Immunology (2020)
A study of the drug tildrakizumab in psoriasis patients
Authors: K. Reich, R.B. Warren, L. Iversen, L. Puig, I. Pau‐Charles, A. Igarashi, M. Ohtsuki, M. Falqués, M. Harmut, S. Rozzo, M.G. Lebwohl, W. Cantrell, A. Blauvelt, D. Thaçi
Journal: British Journal of Dermatology (2020)

Psoriasis is a common skin condition that causes red and scaly patches of skin. About 2% of people worldwide suffer from psoriasis. The authors of this study wanted to see how well the drug tildrakizumab treats psoriasis and the side effects it may have with long-term use. In order to do so, they combined information from two clinical trials called reSURFACE 1 and reSURFACE 2. The authors examined the improvement of psoriasis symptoms using a scoring method named PASI (Psoriasis Area Severity Index) for a period of three years. This method grades the severity of a person's psoriasis and helps to measure any improvement. In clinical trials, success is measured by the proportion of patients who achieve a “PASI 75” or “PASI 90”, which means a 75% or 90% reduction of the PASI score from the beginning of the treatment. Additionally, an excellent response to treatment can also be described by reaching a low PASI score such as a PASI score of less than 3 or less than 1 point. The authors found a high proportion of patients achieving an improvement in PASI during the first year that was well maintained with continued tildrakizumab 100 or 200 mg and, after three years, 80% and 60% of patients, respectively, achieved a PASI 75 and a PASI 90. Looking at PASI scores, 70% and 50% of patients, respectively, maintained a PASI score of less than 3 and less than 1, after three years. Even the patients who initially had a poor response (i.e. not much improvement) to tildrakizumab showed an improvement over time, if the treatment was maintained. Patients previously treated with etanercept (another drug for psoriasis) unsuccessfully, saw an improvement of their psoriasis with only two doses of tildrakizumab, with 80% and 40% of patients, respectively, achieving a PASI 75 and a PASI 90. Very few undesirable effects were seen, and no new or unexpected side effects were reported. The most frequent side effect was nasopharyngitis, which is commonly known as a cold. Severe infections, malignancies, or cardiovascular effects were uncommon and comparable to placebo (an inactive substance, like a “sugar pill”), indicating no increased risk of these events with tildrakizumab. In conclusion, tildrakizumab proved to be a good treatment for psoriasis for as long as three years, which is safe and has very few side effects. This is a summary of the study: Long-term efficacy and safety of tildrakizumab for moderate-to-severe psoriasis: pooled analyses of two randomized phase III clinical trials (reSURFACE 1 and reSURFACE 2) through 148 weeks
Children’s health and wellbeing must be prioritised by governments, experts urge
Authors: Elisabeth Mahase
Journal: BMJ (2020)

The health and future of every child worldwide is under threat from climate change, ecological degradation, migrating populations, conflict, pervasive inequalities, and predatory commercial practices, a landmark report from over 40 child and adolescent health experts has warned.1

The report, published in The Lancet Commissions , highlighted exploitative marketing practices that push heavily processed fast food, sugary drinks, alcohol, and tobacco at children as a distinct threat.

It warned that in some countries, children are exposed to as many as 30 000 advertisements on television alone every year, and that this …
Response to immunotherapy, platinum-based chemotherapy or their combination in metastatic urothelial carcinoma (MUC) with or without FGFR-3 alterations: Single cohort experience.
Authors: Laura Ferrer-Mileo, Adela Rodriguez, Nuria González, Mayra Orrillo, Natalia Jiménez, Mercedes Marín-Aguilera, Leonardo Rodriguez-Carunchio, Aleix Prat, Begona Mellado, Oscar Reig
Journal: Journal of Clinical Oncology (2020)

560 Background: Fibroblast growth factor receptor-3 (FGFR-3) is a promising target therapy in metastatic urothelial carcinoma. Its role in patient’s clinical outcome and treatment response is unclear. We present data for overall survival (OS) and response to platinum-based treatment, immunotherapy and combination (platinum plus immunotherapy) in MUC. Methods: Enrolled patients were diagnosed with muscle-invasive urothelial cancer (MIUC) between 2/2009-6/2019 at Clinic Hospital of Barcelona, Spain. All have been screened for FGFR-3 alterations using next-generation sequencing or qualitative real-time polymerase chain reaction-based assays in tumour or blood. Demographic, pathology, treatments and treatment response were collected retrospectively. Results: 101 patients with MIUC were screened, 99% had progressed to metastatic stage. At diagnosis 32.67% were metastatic. 77% were man and median age was 68y (38-85y). Median follow-up (FU) since metastatic disease was 16.25 months (1.2-89.72m) with 69.31% of patients had died at cut-off. 32% presented FGFR-3 alteration (fusion =1 and mutation=31). FGFR-3 altered more frequently had papillary histology than FGFR-3 wild type tumours (69 vs 26%, p&lt;0.05). No statistical differences were detected between both groups for gender, age, stage at diagnosis, median FU, primary tumour site (upper vs lower tract) or previous history of non-invasive urothelial carcinoma. 58% patients received 1 st line platinum-based chemotherapy, 25% immunotherapy and 8% the combination of both (9% with other therapies). FGFR-3 altered tended to present more benefit (complete, partial response or stable disease) with platinum-based chemotherapy than FGFR-3 wild type (81% vs 62%) but without reach statistical significance. No differences were detected for immunotherapy or combination therapies. Moreover, OS was similar for FGFR-3 altered (median 14.6m) and FGFR-3 wild- type (median 17.1 m) (HR 0.76, p=0.3). Conclusions: In our series, no significant differences related to response to first line therapy or survival was observed.
Long-term health-related quality of life in pediatric brain tumor survivors receiving proton radiotherapy at &amp;lt;4 years of age
Authors: Bree R Eaton, Saveli Goldberg, Nancy J Tarbell, Miranda P Lawell, Sara L Gallotto, Elizabeth A Weyman, Karen A Kuhlthau, David H Ebb, Shannon M MacDonald, Torunn I Yock
Journal: Neuro-Oncology (2020)

Abstract Background The purpose of this analysis is to report long-term health-related quality of life (HRQoL) among brain tumor survivors treated with proton therapy (PRT) at a very young age. Methods Fifty-nine children &amp;lt;4 years old received PRT between 2000 and 2011. Forty families participated. HRQoL was assessed by child self-report (CSR; age ≥5) and parent proxy report (PPR; age 2+) using the PedsQL Core. Results The median age was 2.5 years (range, 0.3–3.8) at PRT and 9.1 years (5.5–18) at last follow-up. The most common diagnoses were ependymoma (n = 22) and medulloblastoma (n = 7). Median follow-up is 6.7 years (3–15.4). Follow-up mean CSR and PPR scores were: total core (78.4 and 72.9), physical (82.9 and 75.2), psychosocial (76.0 and 71.6), emotional (74.4 and 70.7), social (81.2 and 75.1), and school (72.4 and 69.9). Parent-reported HRQoL fell within a previously defined range for healthy children in 37.5% of patients, and for children with severe health conditions in 45% of patients. PPR HRQoL was stable from baseline to last follow-up among all domains except for social functioning. History of gastrostomy tube was significantly associated with poorer CSR and PPR HRQoL on multivariable analysis. Ninety percent of children functioned in a regular classroom, 14 (36%) used a classroom aid, 9 (23%) used an outside tutor, and 18 (46%) had an individualized education plan. Conclusion Long-term HRQoL among brain tumor survivors treated with PRT at a very young age is variable, with over a third achieving HRQoL levels commensurate with healthy children. Key Points 1. One third of survivors reported long-term HRQoL scores comparable to those of healthy children. 2. Treatment for hydrocephalus or a feeding tube was associated with significantly lower HRQoL. 3. Total core HRQoL scores remained stable from baseline to last follow-up.
Phase Ib study of niraparib plus androgen receptor-targeted therapy (ART) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Fred Saad, Kim N. Chi, Neal D. Shore, Julie Nicole Graff, Edwin M. Posadas, Byron M. Espina, Eugene Zhu, Anasuya Hazra, Branislav Bradic, Shinta Cheng, Vinny Hayreh, Arash Rezazadeh
Journal: Journal of Clinical Oncology (2020)

122 Background: Poly ADP-ribose polymerase (PARP) inhibitor and abiraterone acetate + prednisone (AA+P) has activity in pts with mCRPC regardless of DNA repair gene defects (DRD). Methods: This phase 1b study (Bedivere; NCT02924766) began with a 3+3 dose escalation of niraparib (Part 1), followed by expansion (Part 2) of the recommended phase 2 dose (RP2D) of nira + AA+P. Pts with mCRPC received nira 200 or 300 mg/day with AA+P. Dose-limiting toxicities (DLTs) were evaluated the first 28 days. Serial PK for nira were collected on cycle 1 day 1 (C1D1) over 24 h; PK for nira and abiraterone were collected on C2D1 over 10 h. Results: Nira 200 mg + 1000 mg AA+P was selected as the RP2D dose. 4 pts in 200 mg cohort and 8 pts in 300 mg cohort were enrolled in Part 1. During Part 1, 1 patient in the 300 mg cohort had two DLTs: Gr 3 fatigue and Gr 4 increased gamma glutamyltransferase. Therefore, the 200 mg dose was evaluated in 15 pts in Part 2. In 19 total pts treated with 200 mg niraparib, 12 (63%) pts had Gr 3-4 AEs, 5 (26%) pts had an AE with outcome of drug discontinuation and 1 (5%) patient had an AE with outcome of death (general physical health deterioration; unrelated). AEs of special interest were: 6 pts (32%) thrombocytopenia, 6 pts (32%) hypertension, 5 pts (26%) anemia and 3 pts (16%) neutropenia of any grade. 21% pts in 200 mg cohort had treatment emergent serious AE (TESAE) while 50% treated with 300 mg had TESAE. The exposure (AUC 24h ) on Day 1 of Cycle 2 for 200 mg niraparib with 1000 mg of AA were 17745±9380 ng.h/mL and 712±140 ng.h/mL, respectively. These exposures are consistent with single agent PK. Summaries of all responses will be provided, including a patient with primarily bone disease and carrying an ATM mutation who had a circulating tumor cell conversion and was on study treatment for 22.1 mo. Conclusions: The safety and PK findings support the choice of nira 200 mg in combination with AA+P in pts with mCRPC. The efficacy of nira + AA+P is being evaluated in an ongoing phase 3 MAGNITUDE study (NCT03748641). Clinical trial information: NCT02924766.
Liver-Resident Memory CD8( ) T Cells Form a Front-Line Defense against Malaria Liver-Stage Infection (vol 45, pg 889, 2016)
Authors: Daniel Fernandez-Ruiz, Wei Yi Ng, Lauren E Holz, Joel Z Ma, Ali Zaid, Yik Chun Wong, Lei Shong Lau, Vanessa Mollard, Anton Cozijnsen, Nicholas Collins, Jessica Li, Gayle M Davey, Yu Kato, Sapna Devi, Roghieh Skandari, Michael Pauley, Jonathan H Manton, Dale I Godfrey, Asolina Braun, Szun Szun Tay, Peck Szee Tan, David G Bowen, Friedrich Koch-Nolte, Bjorn Rissiek, Francis R Carbone, Brendan S Crabb, Mireille Lahoud, Ian A Cockburn, Scott N Mueller, Patrick Bertolino, Geoffrey I McFadden, Irina Caminschi, William R Heath
Journal: Immunity (2019)
Associations of adverse childhood experiences with educational attainment and adolescent health and the role of family and socioeconomic factors: A prospective cohort study in the UK
Authors: Lotte C. Houtepen, Jon Heron, Matthew J. Suderman, Abigail Fraser, Catherine R. Chittleborough, Laura D. Howe
Journal: PLoS Medicine (2020)

Experiencing multiple adverse childhood experiences (ACEs) is a risk factor for many adverse outcomes. We explore associations of ACEs with educational attainment and adolescent health and the role of family and socioeconomic factors in these associations.