tbuckley/cabot-search huggingface dataset:
377 Characterization of peripheral biomarkers of GS-1423, a first in class bifunctional anti-CD73-TGFβ receptor II- trap molecule, in a phase 1 dose escalation study in patients with advanced solid tumors
Authors: Marianna Zavodovskaya, Anthony Tolcher, Michael Gordon, James Strauss, Kathleen Mahoney, Ping Cheng Yi, Rick Sorensen, Xiaoyun Yang, Kai-Wen Lin, Biao Li, Anna Seto, Matthew Peach, Audrey Goddard, Tianling Chen, Juliane Jürgensmeier
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background GS-1423 is a first-in-class bifunctional molecule comprised of an anti-CD73 antibody fused to the extracellular domain of TGFβ receptor II (TGFβRII). GS-1423 is designed to inhibit CD73-mediated adenosine production and neutralize active TGFβ within the tumor microenvironment. Dual antagonism of these 2 broadly immunosuppressive barriers is anticipated to facilitate productive anti-tumor immunity. Methods This open label Phase 1a study ( NCT03954704 ) evaluated the safety, tolerability, and pharmacokinetics of GS-1423. Exploratory biomarkers included the evaluation of the inhibition of GS-1423 targets, i.e.CD73 and TGFβ, in the periphery. Biomarker assessments were performed in serial blood samples from patients receiving GS-1423 every two weeks (Q2W). Biomarker assays, unless otherwise stated, were custom built and qualified to measure the following: 1) TGF-beta 1/2/3 (Luminex, Bio-Rad) in platelet poor plasma, 2) CD73 target occupancy (TO) on B and CD8 T cells in whole blood, 3) free soluble CD73 (sCD73) not bound to GS-1423, and 4) sCD73 activity in platelet poor plasma. Biomarker values were plotted longitudinally by patient and by dose. Results A dose dependent decrease in TGF-beta 1/2/3 in plasma of patients was observed on treatment. There was no detectable TGFβ at the 20 mg/kg dose level and above at 2 hours post first dose and for the duration of the Q2W dosing interval. A dose dependent increase in CD73 TO on B and CD8 T cells was also observed with treatment, and complete TO was achieved at 20 mg/kg and above at 2 hours post first dose for the duration of the Q2W dosing interval. Free sCD73 decreased at 2 hours post first dose, while remaining above the lower limit of quantitation, and then increased above baseline after 24 hours post-dose at the 3 mg/kg dose level and above. The sCD73 activity in blood correlated with changes in free sCD73 levels. Conclusions Blood biomarker analyses of GS-1423 in patients with advanced solid tumors demonstrated undetectable soluble TGFβ1/2/3 and complete TO of CD73 on B and T cells at the 20 mg/kg dose level and above. The mechanism underlying the increase in sCD73 following GS-1423 treatment remains to be elucidated. Ethics Approval The study obtained ethics approval from the IRB/IEC and all participants gave informed consent before taking part in the study.
Monoclonal and Oligoclonal Anti-PF4 Antibodies Mediate VITT
Authors: Bandana Singh, Adam Kanack, Antonios Bayas, Gemlyn George, Mouhamed Yazan Abou Abou-Ismail, Mindy Kohlhagen, Monika Christ, Markus Naumann, Karen A Moser, Kristi J Smock, Alison Grazioli, David L Murray, Anand Padmanabhan
Journal: Blood (2021)
Characterization of Residual CLL Following Long-Term Bruton Tyrosine Kinase Inhibitor Therapy
Authors: Shanmugapriya Thangavadivel, Alexander Pan, Xi Chen, Chen Song, Claire Snyder, Kerry Rogers, Seema A Bhat, Adam S Kittai, Bradley W Blaser, James S. Blachly, Pearlly S. Yan, John C. Byrd, Jennifer A. Woyach
Journal: Blood (2021)
Private providers must increase access to training in cataract surgery, ophthalmologists say
Authors: Gareth Iacobucci
Journal: BMJ (2021)

Private providers are now delivering almost half of NHS cataract surgery and must rapidly increase access to surgical training, the Royal College of Ophthalmologists has urged.

In a position statement setting out its views on the delivery of NHS cataract surgery the college also called on private providers to help ensure equitable access for all patients needing surgery and to contribute to the financial viability of NHS eye care units by performing a mix of routine and complex procedures.1

The college noted that 46% of NHS cataract procedures in England were carried out by the independent sector in April 2021, up from 11% in 2016. Though recognising that this shift has been vital to meeting demand, given the limited capacity …
Health Care Access and Use Among Adults with Diabetes During the COVID-19 Pandemic — United States, February–March 2021
Authors: Mark É. Czeisler, Catherine E. Barrett, Karen R. Siegel, Matthew D. Weaver, Charles A. Czeisler, Shantha M.W. Rajaratnam, Mark E. Howard, Kai McKeever Bullard
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Diabetes affects approximately one in 10 persons in the United States† and is a risk factor for severe COVID-19 (1), especially when a patient's diabetes is not well managed (2). The extent to which the COVID-19 pandemic has affected diabetes care and management, and whether this varies across age groups, is currently unknown. To evaluate access to and use of health care, as well as experiences, attitudes, and behaviors about COVID-19 prevention and vaccination, a nonprobability, Internet-based survey was administered to 5,261 U.S. adults aged ≥18 years during February-March 2021. Among respondents, 760 (14%) adults who reported having diabetes currently managed with medication were included in the analysis. Younger adults (aged 18-29 years) with diabetes were more likely to report having missed medical care during the past 3 months (87%; 79) than were those aged 30-59 years (63%; 372) or ≥60 years (26%; 309) (p<0.001). Overall, 44% of younger adults reported difficulty accessing diabetes medications. Younger adults with diabetes also reported lower intention to receive COVID-19 vaccination (66%) compared with adults aged ≥60 years§ (85%; p = 0.001). During the COVID-19 pandemic, efforts to enhance access to diabetes care for adults with diabetes and deliver public health messages emphasizing the importance of diabetes management and COVID-19 prevention, including vaccination, are warranted, especially in younger adults.
CC-99282 is a Novel Cereblon (CRBN) E3 Ligase Modulator (CELMoD) Agent with Enhanced Tumoricidal Activity in Preclinical Models of Lymphoma
Authors: Soraya Carrancio, Lynda Groocock, Preethi Janardhanan, Diana Jankeel, Ryan Galasso, Carla Guarinos, Rama K. Narla, Matthew Groza, Jim Leisten, Daniel W. Pierce, Mark Rolfe, Antonia Lopez-Girona
Journal: Blood (2021)