Proceedings of the National Academy of Sciences of the United States of America
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Proc. Natl. Acad. Sci. U.S.A. · May 2019
Multicenter StudyExploratory trial of a biepitopic CAR T-targeting B cell maturation antigen in relapsed/refractory multiple myeloma.
Relapsed and refractory (R/R) multiple myeloma (MM) patients have very poor prognosis. Chimeric antigen receptor modified T (CAR T) cells is an emerging approach in treating hematopoietic malignancies. Here we conducted the clinical trial of a biepitope-targeting CAR T against B cell maturation antigen (BCMA) (LCAR-B38M) in 17 R/R MM cases. ⋯ CAR T cells were high in most cases with stable response but low in 6 out of 7 relapse/PD cases. Notably, positive anti-CAR antibody constituted a high-risk factor for relapse/PD, and patients who received prior autologous hematopoietic stem cell transplantation had more durable response. Thus, biepitopic CAR T against BCMA represents a promising therapy for R/R MM, while most adverse effects are clinically manageable.
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Proc. Natl. Acad. Sci. U.S.A. · Aug 2018
Multicenter StudyPatient-physician gender concordance and increased mortality among female heart attack patients.
Very interesting study covering 20 years of Floridian ED patient admissions for myocardial infarct, looking specifically at the influence of gender-discordance between patient and doctor.
The headline finding was that female heart-attack patients experienced lower survival when treated by a male physician than when by a female physician. Baseline mortality across all patients was 11.9%, with a 1.5% absolute survival decrease when compared to male patients treated by female physicians.
Although on the surface this absolute effect size could be misinterpreted as small, it represents a 12% relative risk difference – quite meaningful when we are considering mortality from the leading cause of death in the U.S.
Could the researchers suggest a reason?
The authors identified two interesting points:
- Female patients treated in EDs with a higher percentage or a higher number of female physicians were more likely to survive. Although true of both care from a female or male physician, the beneficial survival effect of a greater female physician presence, was more marked when treated by a male doctor.
- Female patients treated by male physicians were also more likely to survive when the male physician had previously seen more female patients (0.02% increased survival for each female patient seen in the last quarter!).
summary"These results suggest a reason why gender inequality in heart attack mortality persists: Most physicians are male, and male physicians appear to have trouble treating female patients." – Greenwood, 2018
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Proc. Natl. Acad. Sci. U.S.A. · Oct 2015
Randomized Controlled Trial Multicenter StudyPlacebo analgesia and its opioidergic regulation suggest that empathy for pain is grounded in self pain.
Empathy for pain activates brain areas partially overlapping with those underpinning the first-hand experience of pain. It remains unclear, however, whether such shared activations imply that pain empathy engages similar neural functions as first-hand pain experiences. To overcome the limitations of previous neuroimaging research, we pursued a conceptually novel approach: we used the phenomenon of placebo analgesia to experimentally reduce the first-hand experience of pain, and assessed whether this results in a concomitant reduction of empathy for pain. ⋯ In a second step, we used a psychopharmacological manipulation (n = 50) to determine whether these effects can be blocked via an opioid antagonist. The administration of the opioid antagonist naltrexone blocked placebo analgesia and also resulted in a corresponding "normalization" of empathy for pain. Taken together, these findings suggest that pain empathy may be associated with neural responses and neurotransmitter activity engaged during first-hand pain, and thus might indeed be grounded in our own pain experiences.
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Proc. Natl. Acad. Sci. U.S.A. · Mar 2010
Multicenter StudyToward discovery science of human brain function.
Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a priori hypotheses. Resting-state functional MRI (R-fMRI) constitutes a candidate approach capable of addressing this challenge. ⋯ These results demonstrate that independent R-fMRI datasets can be aggregated and shared. High-throughput R-fMRI can provide quantitative phenotypes for molecular genetic studies and biomarkers of developmental and pathological processes in the brain. To initiate discovery science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon_1000/.