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"Kim, Y. -K."
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SGLT2 inhibition modulates NLRP3 inflammasome activity via ketones and insulin in diabetes with cardiovascular disease
Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events in humans with type 2 diabetes (T2D); however, the underlying mechanism remains unclear. Activation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome and subsequent interleukin (IL)-1β release induces atherosclerosis and heart failure. Here we show the effect of SGLT2 inhibitor empagliflozin on NLRP3 inflammasome activity. Patients with T2D and high cardiovascular risk receive SGLT2 inhibitor or sulfonylurea for 30 days, with NLRP3 inflammasome activation analyzed in macrophages. While the SGLT2 inhibitor’s glucose-lowering capacity is similar to sulfonylurea, it shows a greater reduction in IL-1β secretion compared to sulfonylurea accompanied by increased serum β-hydroxybutyrate (BHB) and decreased serum insulin. Ex vivo experiments with macrophages verify the inhibitory effects of high BHB and low insulin levels on NLRP3 inflammasome activation. In conclusion, SGLT2 inhibitor attenuates NLRP3 inflammasome activation, which might help to explain its cardioprotective effects.
SGLT2 inhibitors, a class of type 2 diabetes medication, reduce cardiovascular events in patients beyond expectation from blood sugar control. Here the authors report a randomized controlled trial showing that SGLT2 inhibitors reduce inflammasome activation in peripheral macrophages, which may contribute to the cardiovascular protection.
Journal Article
Beyond notation : the music of Earle Brown
Earle Brown (1926-2002) was a crucial part of the seminal group of experimental composers known as the New York School, and his work intersects in fascinating ways with that of his colleagues John Cage, Morton Feldman, and Christian Wolff. This book seeks to expand our view of Brown's work, addressing his practices as a painter and composer as well as his collaborations with visual artists Alexander Calder, Robert Rauschenberg, and the American abstract expressionists. The essays collected here explore Brown's compositional methods and their historical place in depth: not only his influential experiments with open form composition and graphic notation, but his interest in collaboration, mixed media, and his engagement with the European avant-garde. The volume includes several short essays by Brown that shed new light on his relationships with colleagues and the ideas that drove his work.
Book
An increase in cancer stem cell population after primary systemic therapy is a poor prognostic factor in breast cancer
Background:
The cancer stem cell (CSC) hypothesis has important clinical implications for cancer therapeutics because of the proposed role of CSCs in chemoresistance. The aim of this study was to investigate changes in the CSC populations before and after primary systemic therapy (PST) and their prognostic role in human breast cancer.
Methods:
Paired samples (before and after PST) of breast cancer tissue were obtained from clinical stage II or III patients (
n
=92) undergoing PST with the regimen of doxorubicin plus docetaxel (AD) (
n
=50) or doxorubicin plus cyclophosphamide (AC) (
n
=42) and subsequent breast resection. The proportions of putative CSCs with CD44+/CD24− or aldehyde dehydrogenase 1+ (ALDH1+) phenotypes were determined by immunohistochemistry.
Results:
A higher proportion of CD44+/CD24− tumour cells and ALDH1 positivity in pre-chemotherapy tissue was correlated with higher histologic grade, oestrogen receptor (ER) negativity, high Ki-67 proliferation index and basal-like subtype of breast cancer. Aldehyde dehydrogenase 1 positivity in pre-chemotherapy biopsy was also associated with a higher rate of pathologic complete response following PST. In comparisons of putative CSC populations before and after PST, the proportions of CD44+/CD24− and ALDH1+ tumour cells were significantly increased after PST. The cases with increased CD44+/CD24− tumour cell populations after PST showed high Ki-67 proliferation index in post-chemotherapy specimens and those with increased ALDH1+ tumour cell population after PST were associated with ER negativity and p53 overexpression. Furthermore, cases showing such an increase had significantly shorter disease-free survival time than those with no change or a reduced number of CSCs, and the survival difference was most notable with regard to the changes of ALDH1+ tumour cell population in the patients who received AC regimen.
Conclusion:
The present study provides the clinical evidence that the putative CSCs in breast cancer are chemoresistant and are associated with tumour progression, emphasising the need for targeting of CSCs in the breast cancer therapeutics.
Journal Article
Clinical impact of positron emission tomography or positron emission tomography/computed tomography in the posttherapy surveillance of endometrial carcinoma: evaluation of 88 patients
The objective of this study was to evaluate the validity and clinical impact of positron emission tomography (PET) or positron emission tomography/computed tomography (PET/CT) using 18-fluoro-2-deoxy-D-glucose in the posttherapy surveillance of patients with endometrial carcinoma. Eighty-eight patients previously treated for histopathologically diagnosed endometrial adenocarcinoma underwent 99 PET or PET/CT scans at follow-up visits at Asan Medical Center, Seoul, Korea, between 2001 and 2007. The standard of reference for tumor recurrence consisted of histopathologic confirmation or follow-up information at least 6 months after PET or PET/CT. Of the 88 patients, 24 underwent PET (n= 11) and/or PET/CT (n= 14) scans due to suspected disease recurrence. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of PET and/or PET/CT in detecting recurrence in these patients were 100%, 83.3%, 96%, 95%, and 100%, respectively. Especially, PET/CT revealed true-positive findings in three patients with elevated tumor markers but negative CT findings. The remaining 64 patients underwent PET (n= 8) and/or PET/CT (n= 66) as part of routine posttherapy surveillance; these patients were asymptomatic, with no evidence of disease. The sensitivity, specificity, accuracy, PPV, and NPV of PET and/or PET/CT in detecting recurrence in these patients were all 100%. Clinical decisions on treatment were changed in 14 (21.9%) patients by introducing PET or PET/CT into their conventional posttherapy surveillance program. PET and/or PET/CT were highly effective in discriminating true recurrence in patients with suspected recurrence, highly sensitive in detecting recurrence in asymptomatic patients, and had impacts on clinical decisions in a considerable portion of patients.
Journal Article
The Impact of Real-Time Documentation of In-Hospital Medication Changes on Preventing Undocumented Discrepancies at Discharge and Improving Physician-Pharmacist Communication: A Retrospective Cohort Study and Survey
Transitional medication safety is crucial, as miscommunication about medication changes can lead to significant risks. Unclear or incomplete documentation during care transitions can result in outdated or incorrect medication lists at discharge, potentially causing medication errors, adverse drug events, and inadequate patient education. These issues are exacerbated by extended hospital stays and multiple care events, making accurate medication recall challenging at discharge.
Thus, we aimed to investigate how real-time documentation of in-hospital medication changes prevents undocumented medication changes at discharge and improves physician-pharmacist communication.
We conducted a retrospective cohort study in a tertiary hospital. Two pharmacists reviewed medical records of patients admitted to the acute medical unit from April to June 2020. In-hospital medication discrepancies were determined by comparing preadmission and hospitalization medication lists and it was verified whether the physician's intent of medication changes was clarified by documentation. By a documentation rate of medication changes of 100% and <100%, respectively, fully documented (FD) and partially documented (PD) groups were defined. Any undocumented medication changes at discharge were considered a \"documentation error at discharge\". Pharmacists' survey was conducted to assess the impact of appropriate documentation on the pharmacists.
After reviewing 400 medication records, patients were categorized into FD (61.3%) and PD (38.8%) groups. Documentation errors at discharge were significantly higher in the PD than in the FD group. Factors associated with documentation errors at discharge included belonging to the PD group, discharge from a non-hospitalist-managed ward, and having three or more intentional discrepancies. Pharmacists showed favorable attitudes towards physician's documentation.
Appropriate documentation of in-hospital medication changes, facilitated by free-text communication, significantly decreased documentation errors at discharge. This analysis underlines the importance of communication between pharmacists and hospitalists in improving patient safety during transitions of care.
Journal Article
James Turrell : a retrospective
\"Published in conjunction with a major retrospective, this comprehensive volume illuminates the origins and motivations of James Turrell's incredibly diverse and exciting body of work--from his Mendota studio days to his monumental work-in-progress Roden Crater. Whether he's projecting shapes on a flat wall or into the corner of a gallery space, James Turrell is perpetually asking us to \"go inside and greet the light\"--evoking his Quaker upbringing. In fact, all of Turrell's work has been influenced by his life experiences with aviation, science, and psychology, and as a key player in Los Angeles's exploding art scene of the 1960s. Enhanced by thoughtful essays and an illuminating interview with the artist, this monograph explores every aspect of Turrell's career to date--from his early geometric light projections, prints, and drawings, through his installations exploring sensory deprivation and seemingly unmodulated fields of colored light, to recent two-dimensional experiments with holograms. It also features an in-depth look at Roden Crater, a site-specific intervention into the landscape near Flagstaff, Arizona, which will be presented through models, plans, photographs, and drawings. Fans of this highly influential artist will find much to savor in this wide-ranging and beautiful book, featuring specially commissioned new photography by Florian Holzherr.\"--Publisher's website.
Book
Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer
In patients with metastatic HER2-positive breast cancer that had progressed after primary therapy, treatment with the antibody–drug conjugate trastuzumab deruxtecan resulted in a higher response rate and longer progression-free survival than trastuzumab emtansine. Since trastuzumab deruxtecan was associated with interstitial pulmonary fibrosis, close monitoring of pulmonary function is warranted.
Journal Article