58 research outputs found
LocoMMotion: a prospective, non-interventional, multinational study of real-life current standards of care in patients with relapsed and/or refractory multiple myeloma
Despite treatment advances, patients with multiple myeloma (MM) often progress through standard drug classes including proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies (mAbs). LocoMMotion (ClinicalTrials.gov identifier: NCT04035226) is the first prospective study of real-life standard of care (SOC) in triple-class exposed (received at least a PI, IMiD, and anti-CD38 mAb) patients with relapsed/refractory MM (RRMM). Patients (N = 248; ECOG performance status of 0â1, â„3 prior lines of therapy or double refractory to a PI and IMiD) were treated with median 4.0 (range, 1â20) cycles of SOC therapy. Overall response rate was 29.8% (95% CI: 24.2â36.0). Median progression-free survival (PFS) and median overall survival (OS) were 4.6 (95% CI: 3.9â5.6) and 12.4 months (95% CI: 10.3âNE). Treatment-emergent adverse events (TEAEs) were reported in 83.5% of patients (52.8% grade 3/4). Altogether, 107 deaths occurred, due to progressive disease (n = 74), TEAEs (n = 19), and other reasons (n = 14). The 92 varied regimens utilized demonstrate a lack of clear SOC for heavily pretreated, triple-class exposed patients with RRMM in real-world practice and result in poor outcomes. This supports a need for new treatments with novel mechanisms of action
Farnesoid X Receptor (FXR) Activation and FXR Genetic Variation in Inflammatory Bowel Disease
Contains fulltext :
96924.pdf (publisher's version ) (Open Access)BACKGROUND: We previously showed that activation of the bile salt nuclear receptor Farnesoid X Receptor (FXR) protects against intestinal inflammation in mice. Reciprocally, these inflammatory mediators may decrease FXR activation. We investigated whether FXR activation is repressed in the ileum and colon of inflammatory bowel disease (IBD) patients in remission. Additionally, we evaluated whether genetic variation in FXR is associated with IBD. METHODS: mRNA expression of FXR and FXR target gene SHP was determined in ileal and colonic biopsies of patients with Crohn's colitis (n = 15) and ulcerative colitis (UC; n = 12), all in clinical remission, and healthy controls (n = 17). Seven common tagging SNPs and two functional SNPs in FXR were genotyped in 2355 Dutch IBD patients (1162 Crohn's disease (CD) and 1193 UC) and in 853 healthy controls. RESULTS: mRNA expression of SHP in the ileum is reduced in patients with Crohn's colitis but not in patients with UC compared to controls. mRNA expression of villus marker Villin was correlated with FXR and SHP in healthy controls, a correlation that was weaker in UC patients and absent in CD patients. None of the SNPs was associated with IBD, UC or CD, nor with clinical subgroups of CD. CONCLUSIONS: FXR activation in the ileum is decreased in patients with Crohn's colitis. This may be secondary to altered enterohepatic circulation of bile salts or transrepression by inflammatory signals but does not seem to be caused by the studied SNPs in FXR. Increasing FXR activity by synthetic FXR agonists may have benefit in CD patients
'Gut health': a new objective in medicine?
'Gut health' is a term increasingly used in the medical literature and by the food industry. It covers multiple positive aspects of the gastrointestinal (GI) tract, such as the effective digestion and absorption of food, the absence of GI illness, normal and stable intestinal microbiota, effective immune status and a state of well-being. From a scientific point of view, however, it is still extremely unclear exactly what gut health is, how it can be defined and how it can be measured. The GI barrier adjacent to the GI microbiota appears to be the key to understanding the complex mechanisms that maintain gut health. Any impairment of the GI barrier can increase the risk of developing infectious, inflammatory and functional GI diseases, as well as extraintestinal diseases such as immune-mediated and metabolic disorders. Less clear, however, is whether GI discomfort in general can also be related to GI barrier functions. In any case, methods of assessing, improving and maintaining gut health-related GI functions are of major interest in preventive medicine
Virtual seismometers in the subsurface of the Earth from seismic interferometry
The Earthâs interior can be imaged by analysing the records
of propagating seismic waves. However, the global array
of permanent seismometers that record seismic energy is
confined almost exclusively to land-based sites. This limits
the resolution of subsurface images, and results in relatively
few local measurements from areas of great geological
and tectonic interest (for example, the mid-ocean ridges
and the Tibetan plateau)1. Here we use an unconventional
form of seismic interferometry2â5 to turn earthquakes into
virtual seismometers located beneath the Earthâs surface.
Seismic waves generated by one earthquake lead to transient
strain in the subsurface at other locations around the
globe. This strain can be quantified from seismograms of
independent earthquakes that have occurred in those locations.
This technique can therefore provide information on the
subsurface strain in regions of the globe that lack instrumental
networks. Applying our method to earthquakes in Alaska
and the southwestern United States, we show that the
information that can be obtained from these earthquakes
about other such events is consistent with that provided by
instrumental seismometers. Our approach may allow realtime,
non-invasive, subsurface seismic strain monitoring,
particularly in areas remote frominstrumental networks
- âŠ